The present invention relates to a novel pyrazolopyridine compound or a pharmaceutically acceptable salt thereof which are useful as a medicament.
1. Background Art
Some pyrazolopyridine compounds to be useful as psychostimulant, antihypertensive agent, remedy for renal failure, diuretics or the like are known (e.g. EP-0299209, EP-0379979, etc).
2. Disclosure of Invention
The present invention relates to a novel pyrazolopyridine compound and a pharmaceutically acceptable salt thereof useful as a medicament; the processes for the preparation of said pyrazolopyridine compound or a salt thereof; a pharmaceutical composition comprising, as an active ingredient, said pyrazolopyridine compound or a pharmaceutically acceptable salt thereof; a use of said pyrazolopyridine compound or a pharmaceutically acceptable salt thereof as a medicament; and a method for using said pyrazolopyridine compound for the therapeutic purpose, which comprises administering said pyrazolopyridine compound or a pharmaceutically acceptable salt thereof to a human being or an animal.
The pyrazolopyridine compound or a pharmaceutically acceptable salt thereof is an adenosine antagonist (especially, A1 receptor antagonist) and possesses various pharmacological actions such as cognitive enhancing action, analgesic action, locomotor action, antidepressant action, diuretic action, cardioprotective effect, cardiotonic action, vasodilating action (e.g. cerebral vasodilating action, etc), the action of increasing the renal blood flow, renal protective effect, improvement of renal function, enhancing action of lipolysis, inhibition of anaphylactic bronchoconstriction, acceleration of the insulin release, the action of increasing the production of erythropoietin, inhibiting action of platelet aggregation, or the like; useful as cognitive enhancer, antidementia drug, psychostimulant, analgesic, cardioprotective agent, antidepressant, ameliorants of cerebral circulation, tranquilizer, drug for heart failure, cardiotonic agent, antihypertensive agent, drug for renal failure (renal insufficiency), drug for renal toxicity, renal protective agent, drug for improvement of renal function, diuretic, drug for edema, antiobesity, antiasthmatic, bronchodilator, drug for apnea, drug for gout, drug for hyperuricemia, drug for sudden infant death syndrome (SIDS), ameliorants of immunosuppressive action of adenosine, antidiabetic agent, drug for ulcer, drug for pancreatitis, drug for Mxc3xa9nixc3xa8re""s syndrome, drug for anemia; drug for thrombosis, drug for myocardial infarction, drug for obstruction, drug for arteriosclerosis obliterans, drug for thrombophlebitis, drug for cerebral infarction, drug for transient ischemic attack, drug for angina pectoris, or the like; and useful for the prevention and/or treatment of depression, dementia (e.g. Alzheimer""s disease, cerebrovascular dementia, Parkinson""s disease, etc), anxiety, pain, cerebrovascular disease (e.g. stroke, etc), heart failure; hypertension (e.g. essential hypertension, nephrogenous hypertension, etc); circulatory insufficiency (acute circulatory insufficiency) cuased by, for example, the ischemia/reperfusion injury (e.g. myocardial ischemia/reperfusion injury, cerebral ischemia/reperfusion injury, peripheral ischemia/reperfusion injury, etc), shock (e.g. endotoxin shock, hemorrhagic shock, etc), surgical procedure, or the like; post-resuscitation asystole; bradyarrhythmia; electro-mechanical dissociation; hemodynamic collapse; SIRS (systemic inflammatory response syndrome); multiple organ failure; renal failure (renal insufficiency) (e.g. acute renal failure, etc), renal toxicity [e.g. renal toxicity induced by a drug such as cisplatins, gentamicin, FR-900506 (disclosed in EP-0184162), cyclosporin (e.g. cyclosporin A) or the like; glycerol, etc], nephrosis, nephritis, edema (e.g. cardiac edema, nephrotic edema, hepatic edema, idiopathic edema, drug edema, acute angioneurotic edema, hereditary angioneurotic edema, carcinomatous ascites, gestational edema, etc); obesity, bronchial asthma, gout, hyperuricemia, sudden infant death syndrome, immunosuppression, diabetes, ulcer such as peptic ulcer (e.g. gastric ulcer, duodenal ulcer, etc), pancreatitis, Mxc3xa9nixc3xa8re""s syndrome, anemia; myocardial infarction, thrombosis (e.g. arterial thrombosis, cerebral thrombosis, etc), obstruction, arteriosclerosis obliterans, thrombophlebitis, cerebral infarction, transient ischemic attack, angina pectoris, or the like.
The novel pyrazolopyridine compound of the present invention can be shown by the following formula (I). 
wherein R1 is aryl, and
R2 is cyclo(lower)alkyl which may have one or more suitable substituent(s);
cyclo(lower)alkenyl which may have one or more suitable substituent(s);
lower alkyl substituted with aryl and acyl;
aryl which may have one or more suitable substituent(s);
saturated 3 to 8-memberd heteromonocyclic group containing 1 to 4 nitrogen atom(s) which may have one or more suitable substituent(s);
unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) which may have one or more suitable substituent(s); or
saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) which may have one or more suitable substituent(s).
The object compound (I) or a salt thereof of the present invention can be prepared by the following reaction schemes. 
wherein
R1 and R2 are each as defined above,
Ra2 is cyclo(lower)alkyl having oxo, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having oxo, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having oxo, which may have one or more suitable substituent(s);
unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having oxo, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having oxo, which may have one or more suitable substituent(s); or saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having oxo, which may have one or more suitable substituent(s);
Rb2 is cyclo(lower)alkyl having hydroxy, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having hydroxy, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having hydroxy, which may have one or more suitable substituent(s);
unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having hydroxy, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having hydroxy, which may have one or more suitable substituent(s); or
saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having hydroxy, which may have one or more suitable substituent(s);
Rc2 is cyclo(lower)alkyl having oxo, which may have one or more suitable substituent(s); or
cyclo(lower)alkenyl having oxo, which may have one or more suitable substituent(s),
Rd2 is cyclo(lower)alkyl having lower alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having acyl(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having cyano(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having heterocyclic(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having lower alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having acyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having acyl(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having cyano(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having heterocyclic(lower)alkylidene, which may have one or more suitable substituent(s);
Re2 is cyclo(lower)alkyl having protected carboxy, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having protected carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having protected carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having N-protected carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having protected carboxy(lower)alkoxyimino, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having protected carboxy, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having protected carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having protected carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having N-protected carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having protected carboxy(lower)alkoxyimino, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having protected carboxy(lower)alkyl, which may have one or more suitable substituent(s);
unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having protected carboxy(lower)alkyl, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having protected carboxy(lower)alkyl, which may have one or more suitable substituent(s); or
saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having protected carboxy(lower)alkyl, which may have one or more suitable substituent(s);
Rf2 is cyclo(lower)alkyl having carboxy, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having N-carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having carboxy(lower)alkoxyimino, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having carboxy, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having N-carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having carboxy(lower)alkoxyimino, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having carboxy(lower)alkyl, which may have one or more suitable substituent(s); or
saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
Rg2 is cyclo(lower)alkyl having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
Rh2 is cyclo(lower)alkyl having amidated carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkyl having amidated carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having amidated carboxy(lower)alkyl, which may have one or more suitable substituent(s);
cyclo(lower)alkenyl having amidated carboxy(lower)alkylidene, which may have one or more suitable substituent(s);
a compound of the formula 
xe2x80x83is cyclo(lower)alkane having epoxy, which may have one or more suitable substituent(s);
cyclo(lower)alkene having epoxy, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 nitrogen atom(s) having epoxy, which may have one or more suitable substituent(s);
unsaturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 nitrogen atom(s) having epoxy, which may have one or more suitable substituent(s);
saturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 oxygen atom(s) having epoxy, which may have one or more suitable substituent(s); or saturated condensed heterocyclic compound containing 1 to 4 oxygen atom(s) having epoxy, which may have one or more suitable substituent(s); and
X is an acid residue.
In addition to the processes as mentioned above, the object compound (I) or a salt thereof can be prepared, for example, according to the procedures as illustrated in Examples in the present specification or the similar manners thereto.
In starting compounds, there may be the novel compounds. They can be prepared, for example, according to the procedures as illustrated in Preparations in the present specification or the similar manners thereto.
It is to be noted that the object compound (I) may include the geometrical isomer(s) due to the double bond(s) and/or the stereo isomer(s) due to the asymmetric carbon atom(s). In this regard, one isomer can be converted to another according to a conventional manner in this field of the art.
Suitable pharmaceutically acceptable salts of the object compound (I) are conventional ones and include a metal salt such as an alkali metal salt (e.g. sodium salt, potassium salt, etc) and an alkaline earth metal salt (e.g. calcium, salt, magnesium salt, etc), an ammonium salt, an organic base salt (e.g. trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,Nxe2x80x2-dibenzylethylenediamine salt, etc), an organic acid salt (e.g. acetate, trifluoroacetate, maleate, tartrate, fumarate, methanesulfonate, benzenesulfonate, formate, toluenesulfonate, etc), an inorganic acid salt (e.g. hydrochloride, hydrobromide, hydriodide, sulfate, phosphate, etc), a salt with an amino acid (e.g. arginine, aspartic acid, glutamic acid, etc), and the like.
In the above and following descriptions of the present specification, suitable examples and illustrations of the various definitions which the present invention includes within the scope thereof are explained in detail as follows.
The term xe2x80x9clowerxe2x80x9d is intended to mean 1 to 6 carbon atom(s) unless otherwise indicated.
The term xe2x80x9chigherxe2x80x9d is intended to mean 7 to 20 carbon atoms unless otherwise indicated.
Suitable xe2x80x9carylxe2x80x9d may include phenyl, naphthyl, dihydronaphthyl (e.g., 1,2-dihydronaphthyl, 1,4-dihydronaphthyl, etc), tetrahydronaphthyl (e.g. 1,2,3,4-tetrahydronaphthyl, etc), indenyl, anthryl, and the like; in which the preferred one may be (C6-C10)aryl, and the more preferred one may be phenyl and tetrahydronaphthyl.
Said xe2x80x9carylxe2x80x9d ay nave one or more (preferably 1 to 3) suitable substituent(s) selected from the group consisting of hydroxy; oxo; lower alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, t-butoxy, pentyloxy, hexyloxy, etc); acyl(lower)alkoxy [in which the preferred one may be carboxy(lower)alkoxy or lower alkoxycarbonyl(lower)alkoxy; and the like, in which the preferred substituent(s) may be hydroxy; oxo; (C1-C4)alkoxy; carboxy(C1-C4)alkoxy; or (C1-C4)alkoxycarbonyl(C1-C4)alkoxy, and the more preferred one may be hydroxy; oxo; methoxy; carboxymethoxy; or methoxycarbonylmethoxy.
Suitable xe2x80x9clower alkylxe2x80x9d may include straight or branched ones such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl or the like, in which the preferred one may be (C1-C4)alkyl and the more preferred one may be methyl, ethyl or propyl.
Suitable xe2x80x9clower alkylidenexe2x80x9d may include methylene, ethylidene, propylidene, 1-methylethylidene, butylidene, pentylidene, hexylidene, and the like, in which the preferred one may be (C1-C4)alkylidene, and the more preferred one may be methylene.
Suitable xe2x80x9ccyclo(lower)alkylxe2x80x9d may be cyclo(C3-C8)alkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or the like, in which the preferred one may be cyclo(C5-C7)alkyl such as cyclopentyl, cyclohexyl or cycloheptyl.
Said xe2x80x9ccyclo(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) selected from the group consisting of oxo; protected oxo (e.g. lower alkylenedioxy group such as ethylenedioxy, or the like; etc); hydroxy, protected hydroxy [e.g. acyloxy; tri(lower)alkylsilyloxy such as trimethylsilyloxy, t-butyldimethylsilyloxy, or the like; etc]; hydroxy(lower)alkyl (e.g. hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 1-hydroxymethylethyl, 4-hydroxybutyl, 2-hydroxymethyl-2-methylethyl, 5-hydroxypentyl, 3-hydroxyhexyl, etc) [in which the preferred one may be hydroxy(C1-C4)alkyl and the more preferred one may be 2-hydroxyethyl]; acyl; lower alkyl; lower alkylidene; acyl(lower)alkyl; acyl(lower)alkylidene; cyano; cyano(lower)alkyl (e.g. cyanomethyl, 2-cyanoethyl, 2-cyanopropyl, 1-cyanomethylethyl, 4-cyanobutyl, 2-cyanomethyl-2-methylethyl, 5-cyanopentyl, 3-cyanohexyl, etc) [in which the preferred one may be cyano(C1-C4)alkyl, and the more preferred one may be cyanomethyl]; cyano(lower)alkylidene (e.g. cyanomethylene, 2-cyanoethylidene, 2-cyanopropylidene, 4-cyanobutylidene, 5-cyanopentylidene, 3-cyanohexylidene, etc) [in which the preferred one may be cyano(C1-C4)alkylidene, and the more preferred one may be cyanomethylene]; heterocyclic(lower)alkylidene which may have one or more suitable substituent(s); hydroxyimino; lower alkoxyimino (e.g. methoxyimino, ethoxyimino, propoxyimino, butoxyimino, t-butoxyimino, pentyloxyimino, hexyloxyimino, etc) [in which the preferred one may be (C1-C4)alkoxyimino, and the more preferred one may be methoxyimino]; acyl(lower)alkoxyimino [in which the preferred one may be carboxy(lower)alkoxyimino or protected carboxy(lower)alkoxyimino, the more preferred one may be carboxy(lower)alkoxyimino or lower alkoxycarbonyl(lower)alkoxyimino, the much more preferred one may be carboxy(C1-C4)alkoxyimino or (C1-C4)alkoxycarbonyl(C1-C4)alkoxyimino, and the most preferred one may be carboxymethoxyimino or t-butoxycarbonylmethoxyimino]; acyloxyimino [in which the preferred one may be hydroxysulfonyloxyimino]; hydrazono; acylhydrazono [in which the preferred one may be carbamoylhydrazono]; and the like.
Suitable xe2x80x9ccyclo(lower)alkenylxe2x80x9d may be cyclo(C3-C8)alkenyl such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl or the like, in which the preferred one may be cyclo(C5-C7)alkenyl such as cyclopentenyl, cyclohexenyl or cycloheptenyl, and the more preferred one may be cyclohexenyl or cycloheptenyl.
Said xe2x80x9ccyclo(lower)alkenylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified above for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
Suitable xe2x80x9cacylxe2x80x9d may include lower alkanoyl (e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, pivaloyl, hexanoyl, etc); carboxy; protected carboxy; hydroxysulfonyl; and the like.
Suitable xe2x80x9cprotected carboxyxe2x80x9d may be
(1) an esterified carboxy, in which concrete examples of esterified carboxy may be the ones such as lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, sopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, z-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, 1-cyclopropylethoxycarbonyl, etc) which may have suitable substituent(s), for example, lower alkanoyloxy(lower)alkoxycarbonyl [e.g. acetoxymethoxycarbonyl, propionyloxymethoxycarbonyl, butyryloxymethoxycarbonyl, valeryloxymethoxycarbonyl, pivaloyloxymethoxycarbonyl, 1-acetoxyethoxycarbonyl, 1-propionyloxyettoxycarbonyl, pivaloyloxymethoxycarbonyl, 2-propionyloxyethoxycarbonyl, hexanoyloxymethoxycarbonyl, etc]; lower alkanesulfonyl(lower)alkoxycarbonyl [e.g. 2-mesylethoxycarbonyl, etc]; mono(or di or tri)halo(lower)alkoxycabronyl [e.g. 2-iodoethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, etc]; lower alkenyloxycarbonyl [e.g. vinyloxycarbonyl, allyloxycarbonyl, etc]; lower alkynyloxycarbonyl [e.g. ethynyloxycarbonyl, propynyloxycarbonyl, etc]; ar(lower)alkoxycarbonyl [preferably mono- (or di- or tri-)phenyl(lower)alkoxycarbonyl] which may have suitable substituent s) [e.g. benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, phenethyloxycarbonyl, trityloxycarbonyl, benzhydryloxycarbonyl, bis(methoxyphenyl)methoxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 4-hydroxy-3,5-di-t-butylbenzyloxycarbonyl, etc]; aryloxycarbonyl which may have suitable substituent(s) [e.g. phenoxycarbonyl, 4-chlorophenoxycarbonyl, tolyloxycarbonyl, 4-t-butylphenoxycarbonyl, xylyloxycarbonyl, mesityloxycarbonyl, cumenyloxycarbonyl, etc]; or the like;
(2) amidated carboxy, in which concrete examples of amidated carboxy may be carbamoyl; N-(lower)alkylcarbamoyl (e.g. N-methylcarbamoyl, N-ethylcarbamoyl, N-isopropylcarbamoyl, N-butylcarbamoyl, N-pentylcarbamoyl, N-hexylcarbamoyl, etc);
N-(higher)alkylcarbamoyl (e.g. N-heptylcarbamoyl, N-(2-methylhepryl)carbamoyl, N-nonylcartbamoyl, N-decanylcarbamoyl, N-tricyclo[3.3.1.13,7]-decanylcarbamoyl, N-undecanylcarbamoyl, N-(bicyclo[4.3.2]urdecanyl)carbamoyl, N-dodecanylcarbamoyl, N-tridecanylcarbamoyl, N-tetradecanylcarbamoyl, N-pentadecanylcarbamoyl, N-hexadecanylcarbamoyl, N-heptadecanylcarbamoyl, N-octadecanylcarbamoyl, N-nonadecanylcarbamoyl, N-icosanylcarbamoyl, etc);
N,N-di(lower)alkylcarbamoyl [e.g. N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, N,N-dipropylcarbamoyl, N,N-di(t-butyl)carbamoyl, N-pentyl-N-hexylcarbamoyl, etc];
N-lower alkyl-N-ar(lower)alkylcarbamoyl (e.g. N-methyl-N-benzylcarbamoyl, etc);
N-carboxy(lower)alkylcarbamoyl [e.g. N-carboxymethylcarbamoyl, N-(2-carboxyethyl)carbamoyl, N-(2-carboxypropyl)carbamoyl, N-(3-carboxypropyl)carbamoyl, N-(1-carboxymethylethyl)carbamoyl, N-(4-carboxybutyl)carbamoyl, N-(2-carboxymethyl-2-methylethyl)carbamoyl, N-(5-carboxypentyl)carbamoyl, N-(3-carboxyhexyl)carbamoyl, etc];
N-protected carboxy(lower)alkylcarbamoyl, in which the preferred one may be N-esterified carboxy(lower)alkylcarbamoyl, and the more preferred one may be N-lower alkoxycarbonyl(lower)alkylcarbamoyl [e.g. N-(methoxycarbonylmethyl)carbamoyl, N-(ethoxycarbonylmethyl)carbamoyl, N-(2-ethoxycarbonylethyl)carbamoyl, N-(2-t-butoxycarbonylethyl)carbamoyl, N-(3-methoxycarbonylpropyl)carbamoyl, N-(1-propoxycarbonylpropyl)carbamoyl, N-(1-isopropoxycarbonylmethylethyl)carbamoyl, N-(butoxycarbonylmethyl)carbamoyl, N-(t-butoxycarbonylmethyl)carbamoyl, N-(4-isobutoxycarbonylbutyl)carbamoyl, N-(2-t-butoxycarbonylmethyl-2-methylethyl)carbamoyl, N-(3-pentyloxycarbonylpentyl)carbamoyl, N-(6-hexyloxycarbonylhexyl)carbamoyl, N-[(1-cyclopropylethoxy)carbonylmethyl]carbamoyl, etc];
N-lower alkyl-N-carboxy(lower)alkylcarbamoyl [e.g. N-methyl-N-(carboxymethyl)carbamoyl, N-methyl-N-(2-carboxyethyl)carbamoyl, N-ethyl-N-(2-carboxypropyl)carbamoyl, N-propyl-N-(3-carboxypropyl)carbamoyl, N-isopropyl-N-(1-carboxymethylethyl)carbamoyl, N-butyl-N-(4-carboxybutyl)carbamoyl, N-t-butyl-N-(2-carboxymethyl-2-methylethyl)carbamoyl, N-pentyl-N-(5-carboxypentyl)carbamoyl, N-hexyl-N-(3-carboxyhexyl)carbamoyl, etc];
N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl, in which the preferred one may be N-lower alkyl-N-esterified carboxy(lower)alkylcarbamoyl, and the more preferred one may be N-lower alkyl-N-lower alkoxycarbonyl(lower)alkylcarbamoyl [e.g. N-methyl-N-(methoxycarbonylmethyl)carbamoyl, N-methyl-N-(ethoxycarbonylmethyl)carbamoyl, N-methyl-N-(2-ethoxycarbonylethyl)carbamoyl, N-ethyl-N-(2-t-butoxycarbonylethyl)carbamoyl, N-propyl-N-(3-methoxycarbonylpropyl)carbamoyl, N-isopropyl-N-(1-propoxycarbonylpropyl)carbamoyl, N-propyl-N-(1-isopropoxycarbonylmethylethyl)carbamoyl, N-butyl-N-(butoxycarbonylmethyl)carbamoyl, N-isobutyl-N-(t-butoxycarbonylmethyl)carbamoyl, N-butyl-N-(4-isobutoxycarbonylbutyl)carbamoyl, N-methyl-N-(2-t-butoxycarbonylmethyl-2-methylethyl)-carbamoyl, N-pentyl-N-(3-pentyloxycarbonylpentyl)-carbamoyl, N-hexyl-N-(6-hexyloxycarbonylhexyl)carbamoyl, N-ethyl-N-[(1-cyclopropylethoxy)carbonylmethyl]carbamoyl, etc];
N-hydroxy(lower)alkylcarbamoyl [e.g. N-hydroxymethylcarbamoyl, N-(2-hydroxyethyl)carbamoyl, N-(1-hydroxyethyl)carbamoyl, N-(3-hydroxypropyl)carbamoyl, N-(1-hydroxybutyl)carbamoyl, N-(2-hydroxymethyl-2-methylethyl)carbamoyl, N-(5-hydroxypentyl)carbamoyl, N-(3-hydroxyhexyl)carbamoyl, etc]; a group of the formula: 
xe2x80x83(wherein a group of the formula: 
xe2x80x83is N-containing heterocyclic group which may have one or more suitable substituent(s), in which N-containing heterocyclic group may contain the other hetero atom(s) such as N, O or S in its ring; or the like; or the like.
Suitable aforesaid xe2x80x9cN-containing heterocyclic groupxe2x80x9d may include saturated or unsaturated, monocyclic or polycyclic heterocyclic group such as unsaturated 3 to 8-membered (more preferably 5 to 7-membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, azepinyl (e.g. 1H-azepinyl, etc), pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl and its N-oxide, dihydropyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (e.g. 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc), tetrazolyl (e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc) etc;
saturated 3 to 8-membered (more preferably 5 to 7-membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, perhydroazepinyl (e.g. perhydro-1H-azepinyl, etc), pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc;
unsaturated condensed heterocyclic group containing 1 to 4 nitrogen atom(s), for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, etc;
saturated condensed heterocyclic group containing 1 to 4 nitrogen atom(s), for example, 7-azabicyclo[2.2.1]-heptyl, 3-azabicyclo [3.2.2]nonanyl, etc;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, dihydrooxazinyl (e.g. 5,6-dihydro-4H-dihydro-1,3-oxazinyl, etc), oxazolyl, isoxazolyl, oxadiazolyl (e.g. 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc), etc;
saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, morpholinyl, sydnonyl, etc;
unsaturated condensed heterocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, etc;
unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolyl, isothiazolyl, thiadiazolyl (e.g. 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc), dihydrothiazinyl, etc;
saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur. atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl, thiomorpholinyl, etc;
unsaturated condensed heterocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzothiadiazolyl, etc; in which the preferred one may include saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s),
saturated 3 to 8-membered heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), and saturated 3 to 8-membered heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s).
xe2x80x9cN-containing heterocyclic groupxe2x80x9d thus defined may have one or more referably 1 to 3) suitable substituent(s) such as lower alkyl as mentioned above; hydroxy(lower)alkyl ,e.g. hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxybutyl, 1-methyl-1-hydroxymethylethyl, 4-hydroxypentyl, 3-hydroxyhexyl, etc); lower alkoxy(lower)alkyl (e.g. methoxymethyl, 2-methoxyethyl, 1-ethoxyethyl, 3-propoxypropyl, 2-(t-butoxy)butyl, 5-pentyloxypentyl, 3-hexyloxyhexyl, etc); acyloxy(lower)alkyl such as lower alkanoyloxy(lower)alkyl (e.g. acetoxymethyl, 1-acetoxyethyl, 2-acetoxyethyl, 2-propionyloxyethyl, 3-propionyloxypropyl, 2-butyryloxybutyl, 4-pivaloyloxypentyl, 6-hexanoyloxyhexyl, etc) or the like; protected carboxy such as lower alkoxycarbonyl as mentioned above; carboxy; ar(lower)alkyl such as phenyl(lower)alkyl (e.g. benzyl, phenethyl, etc), di-phenyl(lower)alkyl (e.g. benzhydryl, etc) or tri-phenyl(lower)alkyl (e.g. trityl, etc); lower alkylamino (e.g. methylamino, ethylamino, propylamino, butylamino, t-butylamino, pentylamino, hexylamino, etc); acyl such as lower alkanoyl as mentioned before; or the like.
Suitable xe2x80x9cacylxe2x80x9d moiety in the terms xe2x80x9cacyl(lower)alkoxyxe2x80x9d, xe2x80x9cacyl(lower)alkylxe2x80x9d, xe2x80x9cacyl(lower)alkylidenexe2x80x9d, xe2x80x9cacyloxyxe2x80x9d, xe2x80x9cacyl(lower)alkoxyiminoxe2x80x9d, xe2x80x9cacyloxyiminoxe2x80x9d, and xe2x80x9cacylhydrazonoxe2x80x9d can be referred to the ones exemplified before for xe2x80x9cacylxe2x80x9d.
Suitable xe2x80x9clower alkylxe2x80x9d moiety in the term xe2x80x9cacyl(lower)alkylxe2x80x9d may be the ones as exemplified before for xe2x80x9clower alkylxe2x80x9d.
Suitable example of acyl(lower)alkylxe2x80x9d may be carboxy(lower)alkyl such as carboxymethyl, 2-carboxyethyl, 3-carboxypropyl, 1-carboxymethylethyl, 4-carboxybutyl, 2-carboxymethyl-2-methylethyl, 5-carboxypentyl, 3-carboxyhexyl, or the like, lower alkanoyl(lower)alkyl such as acetylmethyl, formylmethyl, 2-acetylethyl, 3-propionylpropyl, 4-butyrylbutyl, 3-pentanoylpentyl, 6-hexanoylhexyl, or the like, in which the preferred one may be carboxy(C1-C4)alkyl or (C1-C4)alkanoyl(C1-C4)alkyl, and the more preferred one may be carboxymethyl, 2-carboxyethyl, 3-carboxypropyl or acetylmethyl.
Another suitable example of xe2x80x9cacyl(lower)alkylxe2x80x9d may be protected carboxy(lower)alkyl, in which the preferred one may be esterified carboxy(lower)alkyl, the more preferred one may be lower alkoxycarbonyl(lower)alkyl such as methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 1-propoxycarbonylpropyl, 2-isopropoxycarbonylpropyl, butoxycarbonylmethyl, t-butoxycarbonylmethyl, 4-isobutoxycarbonylbutyl, 3-pentyloxycarbonylpentyl, 6-hexyloxycarbonylhexyl, (1-cyclopropylethoxycarbonyl)methyl, or the like, or phenyl(lower)alkoxycarbonyl(lower)alkyl such as benzyloxycarbonylmethyl, 2-benzyloxycarbonylethyl, 1-phenethyloxycarbonylethyl, 3-benzyloxycarbonylpropyl, 2-benzyloxycarbonylbutyl, 2-phenethyloxycarbonylmethyl-2-methylethyl, 3-benzyloxycarbonylpentyl, 6-benzyloxycarbonylhexyl, or the like, the much more preferred one may be (C1-C4)alkoxycarbonyl-(C1-C4)alkyl, or phenyl(C1-C4)alkoxycarbonyl(C1-C4)alkyl, and the most preferred one may be methoxycarbonylmethyl, ethoxycarbonylmethyl, t-butoxycarbonylmethyl, 2-benzyloxycarbonylethyl or 3-benzyloxycarbonylpropyl.
In aforesaid xe2x80x9cprotected carboxy(lower)alkyl, another preferred one may be amidated carboxy(lower)alkyl, in which the more preferred one may be carbamoyl(lower)-alkyl, N-(lower)alkylcarbamoyl(lower)alkyl, N,N-di-(lower)alkylcarbamoyl(lower)alkyl, N-carboxy(lower)-alkylcarbamoyl (lower)alkyl, N-lower alkoxycarbonyl-(lower)alkylcarbamoyl(lower)alkyl, N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkyl, N-lower alkyl-N-lower alkoxycarbonyl(lower)alkylcarbamoyl(lower)alkyl, N-hydroxy(lower)alkylcarbamoyl(lower)alkyl, or a group of the formula: 
[wherein A1 is lower alkyl, and the group of the formula: 
xe2x80x83is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s), saturated 3 to 8-membered heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), or
saturated 3 to 8-membered heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), each of which may have 1 to 3 suitable substituent(s) selected from the group consisting of lower alkyl, lower alkanoyl, mono-(or di- or tri-)-phenyl(lower)alkyl and lower alkylamino);
the much more preferred one may be carbamoyl(C1-C4)alkyl, N-(C1-C4)alkylcarbamoyl(C1-C4)alkyl, N,N-di(C1-C4)-alkylcarbamoyl(C1-C4)alkyl, N-carboxy(C1-C4)alkyl-carbamoyl(C1-C4)alkyl, N-(C1-C4)alkoxycarbonyl(C1-C4)-alkylcarbamoyl(C1-C4)alkyl, N-(C1-C4)alkyl-N-carboxy-(C1-C4)alkylcarbamoyl(C1-C4)alkyl, N-(C1-C4)alkyl-N-(C1-C4)alkoxycarbonyl(C1-C4)-alkylcarbamoyl(C1-C4)alkyl, N-hydroxy(C1-C4)-alkylcarbamoyl(C1-C4)alkyl, or a group of the formula: 
xe2x80x83[wherein A1 is (C1-C4)alkyl, and the group of the formula: 
xe2x80x83is 1-pyrrolidinyl; piperidino which may have 1 to 3 (C1-C4)alkylamino;
1-piperazinyl which may have 1 to 3 (C1-C4)alkyl, (C1-C4)alkanoyl or tri-phenyl(C1-C4)alkyl; morpholino; or thiomorpholin-4-yl], and the most preferred one may be carbamoylmethyl, 3-carbamoylpropyl, (N-methylcarbamoyl)methyl, 3-(N-methylcarbamoyl)propyl, (N,N-dimethylcarbamoyl)methyl, 3-(N,N-dimethylcarbamoyl)-propyl, (N-carbcxymethylcarbamoyl)methyl, [N-(2-carboxyethyl)carbamoyl]methyl, [N-(3-carboxypropyl)carbamoyl]methyl, 3-(N-carboxymethylcarbamoyl)propyl, (N-t-butoxycarbonylmethylcarbamoyl)methyl, (N-(2-t-butoxycarbonylethyl)carbamoyl]methyl, [N-(3-methoxycarbonylpropyl)carbamoyl]methyl, 3-(N-ethoxycarbonylmethylcarbamoyl)propyl, (N-methyl-N-carboxymethylcarbamoyl)methyl, [(N-methyl-N-(2-carboxyethyl)carbamoyl]methyl, (N-methyl-N-ethoxycarbonylmethylcarbamoyl)methyl, [N-methyl-N-(2-ethoxycarbonylethyl)carbamoyl]methyl, [N-(2-hydroxyethyl)carbamoyl]methyl, pyrrolidin-1-ylcarbonylmethyl, piperidinocarbonylmethyl, (4-methylaminopiperidino)carbonylmethyl, (4-methylpiperazin-1-yl)carbonylmethyl, (4-acetylpiperazin-1-yl)carbonylmethyl, piperazin-1-ylcarbonylmethyl, (4-tritylpiperazin-1-yl)carbonylmethyl, morpholinocarbonylmethyl, or thiomorpholin-4-ylcarbonylmethyl.
Suitable xe2x80x9clower alkylidenexe2x80x9d moiety in the terms xe2x80x9cacyl(lower)alkylidenexe2x80x9d and xe2x80x9cheterocyclic(lower)alkylidene which may have one or more suitable substituent(s)xe2x80x9d may be the ones as exemplified before for xe2x80x9clower alkylidenexe2x80x9d.
Suitable example of xe2x80x9cacyl(lower)alkylidenexe2x80x9d may be carboxy(lower)alkylidene such as carboxymethylene, 2-carboxyethylidene, 2-carboxypropylidene, 4-carboxybutylidene, 5-carboxypentylidene, 3-carboxyhexylidene, or the like, in which the preferred one may be carbcxy(C1-C4)alkylidene, and the more preferred one may be carboxymethylene.
Another suitable example of xe2x80x9cacyl(lower)alkylidenexe2x80x9d may be protected carboxy(lower)alkylidene, in which the preferred one may be esterified carboxy(lower)alkylidene, the more preferred one may be lower alkoxycarbonyl(lower)alkylidene such as methoxycarbonylmethylene, ethoxycarbonylmethylene, 2-ethoxycarbonylethylidene, 1-propoxycarbonylpropylidene, 2-isopropoxycarbonylpropylidene, butoxycarbonylmethylene, t-butoxycarbonylmethylene, 4-isobutoxycarbonylbutylidene, 3-pentyloxycarbonylpentylidene, 6-hexyloxycarbonylhexylidene, (1-cyclopropylethoxycarbonyl)methylene, or the like, the much more preferred one may be (C1-C4)alkoxycarbonyl-(C1-C4)alkylidene, and the most preferred one may be methoxycarbonylmethylene, ethoxycarbonylmethylene, t-butoxycarbonylmethylene.
Suitable xe2x80x9cheterocyclicxe2x80x9d moiety in the term xe2x80x9cheterocyclic(lower)alkylidene which may have one or more suitable substituent(s)xe2x80x9d can be referred to the ones as exemplified before for xe2x80x9cN-containing heterocyclic groupxe2x80x9d, in which the preferred one may be unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) or unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), in which the more preferred one may be dihydrooxazinyl or tetrazolyl.
xe2x80x9cHeterocyclic(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 4) suitable substituent(s) (preferably on its heterocyclic moiety) such as lower alkyl, or the like.
Suitable xe2x80x9csaturated 3 to 8-membered heteromonocyclic-group containing 1 to 4 nitrogen atom(s)xe2x80x9d in the term xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which may have one or more suitable substituent(s)xe2x80x9d may include perhydroazepinyl (e.g. perhydro-1H-azepinyl, etc) pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, and; the like;
in which the preferred one may be 5 to 7-membered one, and the more preferred one may be pyrrolidinyl, or piperidyl.
Suitable xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d in the term xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which may have one or more suitable substituent(s)xe2x80x9d may include azepinyl (e.g. 1H-azepinyl, etc) pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl and its N-oxide, dihydropyridyl, pyrimidinyl, dihydropyrimidinyl (e.g. 1,2-dihydropyrimidinyl, etc), tetrahydropyrimidinyl (e.g. 1,2,3,4-tetrahydropyrimidinyl, etc), pyrazinyl, pyridazinyl, triazolyl (e.g. 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc), tetrazolyl (e.g. 1H-tetrazolyl, 2H-tetrazolyl) and the like; in which the preferred one may be 5 to 7-membered one, and the more preferred one may be tetrahydropyrimidinyl.
Suitable xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d in the term xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) which may have one or more suitable substituent(s)xe2x80x9d may include perhydrofuryl, perhydropyranyl, dioxanyl, and the like; in which the preferred one may be 5 to 7-membered one, and the more preferred one may be perhydrofuryl.
Suitable xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d in the term xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) which may have one or more suitable substituent(s)xe2x80x9d may include perhydrochromanyl, perhydroisochromanyl, perhydrobenzofuryl (e.g. perhydrobenzo[b]furyl, perhydrobenzo[c]furyl, etc), and the like;
in which the preferred one may be perhydrobenzofuryl.
Aforesaid xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d, xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d, xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d and xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d each may have one or more (preferably 1 to 4) suitable substituent(s) selected from the group consisting of oxo; hydroxy; lower alkyl as mentioned before; acyl as mentioned before (in which the preferred one may be protected carboxy, the more preferred one may be lower alkoxycarbonyl, and the most preferred one may be t-butoxycarbonyl); acyl(lower)alkyl as mentioned before (in which the preferred one may be carboxy(lower)alkyl or protected carboxy(lower)alkyl, the more preferred one may be carboxy(lower)alkyl or lower alkoxycarbonyl(lower)alkyl, and the most preferred one may be carboxymethyl, methoxycarbonyimethyl, or ethoxycarbonylmethyl); and the like.
Suitable xe2x80x9clower alkylxe2x80x9d, xe2x80x9carylxe2x80x9d and xe2x80x9cacylxe2x80x9d in the term xe2x80x9clower alkyl substituted with aryl and acylxe2x80x9d can be referred to the ones as exemplified above for xe2x80x9clower alkylxe2x80x9d moiety in the term xe2x80x9cacyl(lower)alkylxe2x80x9d, xe2x80x9carylxe2x80x9d and xe2x80x9cacylxe2x80x9d, respectively.
Suitable example of xe2x80x9clower alkyl substituted with aryl and acylxe2x80x9d may be lower alkyl substituted with phenyl and carboxy such as xcex1-carboxybenzyl, 1-carboxy-2-phenylethyl, 1-carboxymethyl-2-phenylethyl, 4-carboxy-2-phenylbutyl, 1-benzyl-2-carboxy-1-methylethyl, 5-phenyl-3-carboxypentyl, 4-phenyl-3-carboxyhexyl, or the like, in which the preferred one may be (C1-C4)alkyl substituted with phenyl and carboxy, and the more preferred one may be xcex1-carboxybenzyl.
Suitable xe2x80x9ccyclo(lower)alkane having epoxyxe2x80x9d may include epoxycyclobutane, epoxycyclopentane, epoxycyclohexane, epoxycycloheptane, epoxycyclooctane, and the like.
Suitable xe2x80x9ccyclo(lower)alkene having epoxyxe2x80x9d may include 3,4-epoxycyclopentene, 4,5-epoxycyclohexene, 3,4-epoxycycioheptene, 5,6-epoxycyclooctene, and the like.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic compound-containing 1 to 4 nitrogen atom(s) having epoxyxe2x80x9d is a heterocyclic compound corresponding to xe2x80x9csaturated 3 to 8 membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d which has epoxy as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 nitrogen atom(s) having epoxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cUnsaturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 nitrogen atom(s) having epoxyxe2x80x9d is a heterocyclic compound corresponding to xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d which has epoxy as its substituent and this xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 nitrogen atom(s) having epoxyxe2x80x9d may have one or more preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 oxygen atom(s) having epoxyxe2x80x9d is a heterocyclic compound corresponding to xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d which has epoxy as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic compound containing 1 to 4 oxygen atom(s) having epoxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cSaturated condensed heterocyclic compound containing 1 to 4 oxygen atom(s) having epoxyxe2x80x9d is a heterocyclic compound corresponding to xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d which has epoxy as its substituent and this xe2x80x9csaturated condensed heterocyclic compound containing 1 to 4 oxygen atom(s) having epoxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having oxoxe2x80x9d is cyclo(lower)alkyl as explained before which has oxo as its substituent and this xe2x80x9ccyclo(lower)alkyl having oxoxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having oxoxe2x80x9d is cyclo(lower)alkenyl as explained before which has oxo as its substituent and this xe2x80x9ccyclo(lower)alkenyl having oxoxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having oxoxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has oxo as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having oxoxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cUnsaturated 3 to 8-membered heteromonocyclic group. containing 1 to 4 nitrogen atom(s) having oxoxe2x80x9d is unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has oxo as its substituent and this xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having oxoxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having oxoxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) which has oxo as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having oxoxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cSaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having oxoxe2x80x9d is saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) which has oxo as its substituent and this xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having oxoxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having hydroxyxe2x80x9d is cyclo(lower)alkyl as explained before which has hydroxy as its substituent and this xe2x80x9ccyclo(lower)alkyl having hydroxyxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having hydroxyxe2x80x9d is cyclo(lower)alkenyl as explained before which has hydroxy as its substituent and this xe2x80x9ccyclo(lower)alkenyl having hydroxyxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having hydroxyxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has hydroxy as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having hydroxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cUnsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having hydroxyxe2x80x9d is unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has hydroxy as its substituent and this xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having hydroxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having hydroxyxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) which has hydroxy as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having hydroxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cSaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having hydroxyxe2x80x9d is saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) which has hydroxy as its substituent and this xe2x80x9csaturated condensed heterocyclic group containing 1 to 4oxygen atom(s) having hydroxyxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having lower alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has lower alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having lower alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having acyl(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has acyl(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having acyl(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified far those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having cyano(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has cyano(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having cyano(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having heterocyclic(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has heterocyclic(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having heterocyclic(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for hose of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having lower alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has lower alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having lower alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having acyl(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has acyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having acyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having acyl(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has acyl(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having acyl(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having cyano(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has cyano(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having cyano(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo (lower) alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having heterocyclic(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has heterocyclic(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having heterocyclic(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having protected carboxyxe2x80x9d is cyclo(lower)alkyl as explained before which has protected carboxy as its substituent and this xe2x80x9ccyclo(lower)alkyl having protected carboxyxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having protected carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has protected carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having protected carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having protected carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has protected carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having protected carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having N-protected carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has N-protected carboxy(lower)alkylcarbamoyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having N-protected carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo (lower) alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having N-lower alkyl-N-protected. carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl-(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having protected carboxy(lower)alkoxyiminoxe2x80x9d is cyclo(lower)alkyl as explained before which has protected carboxy(lower)alkoxyimino as its substituent and this xe2x80x9ccyclo(lower)alkyl having protected carboxy(lower)alkoxyiminoxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having protected carboxyxe2x80x9d is cyclo(lower)alkenyl as explained before which has protected carboxy as its substituent and this xe2x80x9ccyclo(lower)alkenyl having protected carboxyxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified or those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having protected carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has protected carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having protected carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having protected carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has protected carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having protected carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having N-protected carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has N-protected carboxy(lower)alkylcarbamoyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having N-protected carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl (lower) alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has N-lower alkyl-N-protected carboxy(lower)alkylcarbamoyl(lower) alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having N-lower alkyl-N-protected carboxy(lower) alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having protected carboxy(lower) alkoxyiminoxe2x80x9d is cyclo(lower)alkenyl as explained before which has protected carboxy(lower)alkoxyimino as its substituent and this xe2x80x9ccyclo(lower)alkenyl having protected carboxy(lower)alkoxyiminoxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having protected carboxy(lower)alkylxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has protected carboxy(lower)alkyl as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having protected carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cUnsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having protected carboxy(lower)alkylxe2x80x9d is unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has protected carboxy(lower)alkyl as its substituent and this xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having protected carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having protected carboxy(lower)alkylxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) which has protected carboxy(lower)alkyl as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having protected carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cSaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having protected carboxy(lower)alkylxe2x80x9d is saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) which has protected carboxy(lower)alkyl as its substituent and this xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having protected carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having carboxyxe2x80x9d is cyclo(lower)alkyl as explained before which has carboxy as its substituent and this xe2x80x9ccyclo(lower)alkyl having carboxyxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has N-carboxy(lower)alkylcarbamoyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having carboxy(lower)alkoxyiminoxe2x80x9d is cyclo(lower)alkyl as explained before which has carboxy(lower)alkoxyimino as its substituent and this xe2x80x9ccyclo(lower)alkyl having carboxy(lower)alkoxyiminoxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having carboxyxe2x80x9d is cyclo(lower)alkenyl as explained before which has carboxy as its substituent and this xe2x80x9ccyclo(lower)alkenyl having carboxyxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having carboxy(lower)alkylxe2x80x9d may have. one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has N-carboxy(lower)alkylcarbamoyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower) alkenyl having N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having N-lower alkyl-N-carboxy(lower)alkylcarbamoyl(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having carboxy(lower)alkoxyiminoxe2x80x9d is cyclo(lower)alkenyl as explained before which has carboxy(lower)alkoxyimino as its substituent and this xe2x80x9ccyclo(lower)alkenyl having carboxy(lower)alkoxyiminoxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having carboxy(lower)alkylxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has carboxy(lower)alkyl as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cUnsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having carboxy(lower)alkylxe2x80x9d is unsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) which has carboxy(lower)alkyl as its substituent and this xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s) having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9cunsaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atom(s)xe2x80x9d.
xe2x80x9cSaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having carboxy(lower)alkylxe2x80x9d is saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) which has carboxy(lower)alkyl as its substituent and this xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s) having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated 3 to 8-membered heteromonocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cSaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having carboxy(lower)alkylxe2x80x9d is saturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) which has carboxy(lower)alkyl as its substituent and this xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s) having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 3) suitable substituent(s) as exemplified for those of xe2x80x9csaturated condensed heterocyclic group containing 1 to 4 oxygen atom(s)xe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for hose of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having amidated carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkyl as explained before which has amidated carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkyl having amidated carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkyl having amidated carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkyl as explained before which has amidated carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkyl having amidated carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having amidated carboxy(lower)alkylxe2x80x9d is cyclo(lower)alkenyl as explained before which has amidated carboxy(lower)alkyl as its substituent and this xe2x80x9ccyclo(lower)alkenyl having amidated carboxy(lower)alkylxe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
xe2x80x9cCyclo(lower)alkenyl having amidated carboxy(lower)alkylidenexe2x80x9d is cyclo(lower)alkenyl as explained before which has amidated carboxy(lower)alkylidene as its substituent and this xe2x80x9ccyclo(lower)alkenyl having amidated carboxy(lower)alkylidenexe2x80x9d may have one or more (preferably 1 to 2) suitable substituent(s) as exemplified for those of xe2x80x9ccyclo(lower)alkenylxe2x80x9d.
Suitable xe2x80x9can acid residuexe2x80x9d may include halogen (e.g. fluoro, chloro, bromo, iodo), acyloxy such as lower alkanoyloxy (e.g. acetoxy, propionyloxy, etc), sulfonyloxy (e.g. methylsulfonyloxy, p-tolylsulfonyloxy, etc), and the like.
The processes for the preparation of the object compound (I) or a salt thereof (Processes 1 to 8) are explained in detail in the following.
Process 1
The compound (I) or a salt thereof can be prepared by reacting the compound (II) or a salt thereof with the compound (III) or a salt thereof.
Suitable salt of the compound (II) can be referred to an acid addition salt as exemplified for the compound.
Suitable salt of the compound (III) can be referred to the ones as exemplified for the compound (I).
The present reaction may be carried out in a solvent such as water, phosphate buffer, acetone, chloroform, acetonitrile, nitrobenzene, toluene, methylene chloride, ethylene chloride, formamide, N,N-dimethylformamide, methanol, ethanol, sec-butanol, amyl alcohol, diethyl ether, dimethoxyethane, dioxane, tetrahydrofuran, dimethyl sulfoxide, or any other organic solvent which does not adversely affect the reaction, preferably in ones having strong polarities. Among the solvents, hydrophilic solvents may be used in a mixture with water. When the compound (III) is in liquid, it can also be used as a solvent.
The reaction is preferably conducted in the presence, of a base, for example, inorganic base such as alkali metal hydroxide, alkali metal alkoxide, alkali metal carbonate, alkali metal bicarbonate, alkali metal hydride, organic base such as benzyltrimethylammonium hydroxide trialkylamine, and the like.
The reaction temperature is not critical, and the reaction is usually carried out at ambient temperature, under warming or under heating.
The present reaction is preferably carried out in the presence of alkali metal halide [e.g. sodium iodide, potassium iodide, etc], alkali metal thiocyanate [e.g. sodium thiocyanate, potassium thiocyanate, etc] or the like.
Process 2
The compound (Ib) or a salt thereof can be prepared by subjecting the compound (Ia) or a salt thereof to reduction reaction.
Suitable salts of the compounds (Ia) and (Ib) can be referred to the ones as exemplified for the compound (I).
The reduction reaction of this process can be carried out according to a conventional reduction methods in this field or the art (e.g. chemical reduction, catalytic reduction, etc).
Process 3
The compound (Ib) or a salt thereof can be prepared by reacting the compound (II) or a salt thereof with the compound (IV).
The reaction of this process can be carried out according to a similar manner to that in Process 1.
Process 4
The compound (Ia) or a salt thereof can be prepared by subjecting the compound (Ib) or a salt thereof to oxidation reaction.
The oxidation reaction of this process can be carried out according to a conventional oxidation methods in this field of the art.
Process 5
The compound (Id) or a salt thereof can be prepared by subjecting the compound (Ic) or a salt thereof to so-called Wittig type reaction.
Suitable salt of the compounds (Ic) and (Id) can be referred to the ones as exemplified for the compound (I).
The reaction of this process can be carried out by reacting the compound (Ic) or a salt thereof with a so-called Wittig reagent as shown in the following formulae: 
[wherein R3 is aryl or lower alkyl, each as mentioned above,
R5 is lower alkyl as mentioned above,
R4 is hydrogen; acyl as mentioned above; cyano; or heterocyclic group which may have one or more suitable substituent(s) [in which suitable xe2x80x9cheterocyclic groupxe2x80x9d can be referred to the ones as exemplified before for xe2x80x9cN-containing heterocyclic groupxe2x80x9d, and this xe2x80x9cheterocyclic groupxe2x80x9d may have one or more (preferably 1 to 4) suitable substituent(s) such as lower alkyl as mentioned above];
A2 is lower alkylidene, and
A3 is lower alkyl as mentioned above].
The aforesaid Wittig reagents (VI) and (VII) can be prepared according to a usual manner.
The reaction of this process can be carried out in the presence of base such as alkali metal hydride (e.g. sodium hydride, potassium hydride, etc), alkali metal lower alkoxide (e.g. potassium t-butoxide, etc) or the like in case c; using Wittig reagent (VII).
The reaction is usually carried out in a conventional solvent such as diethyl ether, tetrahydrofuran, methylene chloride, benzene, toluene, N,N-dimethylformamide or any other solvent which does not adversely influence the reaction.
The reaction temperature is not critical and the reaction can be carried out under cooling, at room temperature, under warming or under heating.
The reaction condition can be determined according to the kind of the compound (Ic) and the Wittig reagent to be used.
Process 6
The compound (If) or a salt thereof can be prepared by subjecting the compound (Ie) or a salt thereof to elimination reaction of carboxy protective group.
Suitable salts of the compounds (Ie) and (If) can be referred to the ones as exemplified for the compound (I).
This reaction is carried out in accordance with a conventional method such as hydrolysis, or the like.
The hydrolysis is preferably carried out in the presence of a base or an acid including Lewis acid. Suitable base may include an inorganic base and an organic base such as an alkali metal [e.g. sodium, potassium, etc], an alkaline earth metal [e.g. magnesium, calcium, etc], the hydroxide or carbonate or bicarbonate. thereof, trialkylamine [e.g. trimethylamine, triethylamine, etc], picoline, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene, or the like.
Suitable acid may include an organic acid [e.g. formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc] and an inorganic acid [e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, etc]. The elimination using Lewis acid such as trihaloacetic acid [e.g. trichloroacetic acid, trifluoroacetic acid, etc] or the like is preferably carried out in the presence of cation trapping agents [e.g. anisole, phenol, etc].
The reaction s usually carried out in a solvent such as water, an alcohol [e.g. methanol, ethanol, etc], methylene chloride, tetrahydrofuran, dioxane, a mixture thereof or any other solvent which does not adversely influence the reaction. A liquid base or acid can be also used as the solvent.
The reaction temperature is not critical and the reaction is usually carried out under cooling to heating.
Process 7
The compound (I) or a salt thereof can be prepared by subjecting the compound (V) or a salt thereof to cyclization reaction.
Suitable salt of the compound (V) can be referred to acid addition salts as exemplified for the compound (I).
The cyclization reaction of this process can be carried out, for example, by reacting the compound (V) or a salt thereof with glyoxalic acid or its reactive derivative or a salt thereof and the compound of the formula:
H2Nxe2x80x94NHxe2x80x94R2xe2x80x83xe2x80x83(VIII)
(wherein R2 is as defined above) or a salt thereof.
Suitable salt of glyoxalic acid can be referred to a salt with a base as exemplified for the compound (I).
Suitable salt of the compound (VIII) can be referred to an acid addition salt as exemplified for the compound (I).
Suitable reactive derivative of glyoxalic acid may be the ones conventionally used in this field of the art such as an activated ester thereof.
The reaction can be carried out in the presence or absence of a solvent.
The reaction temperature is not critical and the reaction is usually carried out under warming to heating.
Process 8
The compound (Ih) or a salt thereof can be prepared by subjecting the compound (Ig) or its reactive derivative at the carboxy group or a salt thereof to amidation reaction.
Suitable salts of the compounds (Ig) and (Ih) can be referred to the ones as exemplified for the compound (I).
This reaction can be carried out by reacting the compound (Ig) or its reactive derivative at the carboxy group or a salt thereof with an amidation reagent.
This amidation reagent is the xe2x80x9camine compoundxe2x80x9d or its reactive derivative at the amino group or a salt thereof corresponding to the object amide, and the suitable examples thereof may include ammonia; lower alkylamine; higher alkylamine; N,N-di(lower)alkylamine; N-lower alkyl-N-ar(lower)alkylamine; N-carboxy(lower)alkylamine; N-protected carboxy(lower)alkylamine; N-lower alkyl-N-carboxy(lower)alkylamine; N-lower alkyl-N-protected carboxy(lower)alkylamine; N-hydroxy(lower)alkylamine; a compound of the formula: 
(wherein a group of the formula: 
is as defined above); and the like.
Suitable salt of xe2x80x9camine compoundxe2x80x9d can be referred to the ones as exemplified for the compound (I).
Suitable reactive derivative at the carboxy group of the compound (Ig) may include an acid halide, an acid anhydride, an activated amide, an activated ester, and the like. Suitable examples of the reactive derivatives may be an acid chloride; an acid azide; a mixed acid anhydride with an acid such as substituted phosphoric acid [e.g. dialkylphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid, etc.], dialkylphosphorous. acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid [e.g. methanesulfonic acid, etc], aliphatic carboxylic acid [e.g. acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid, trichloroacetic acid, etc] or aromatic carboxylic acid [e.g. benzoic acid, etc]; a symmetrical acid anhydride; an activated amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole, tetrazole or 1-hydroxy-1H-benzotriazole; or an activated ester [e.g., cyanomethyl ester, methoxymethyl ester, dimethyliminomethyl [(CH3)2xe2x95x90CHxe2x80x94] ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenyl thioester, p-nitrophenyl thioester, p-cresyl thioester, carboxymethyl thioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolyl thioester, etc] or an ester. with a N-hydroxy compound [e.g. N,N-dimethylhydroxylamine, 1-hydroxy-2-(1H)-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole, etc], and the like. These reactive derivatives can optionally be selected from them according to the kind of the compound (Ig) to be used.
Suitable reactive derivative at the amino group of xe2x80x9camine compoundxe2x80x9d may include Schiff""s base type imino or its tautomeric enamine type isomer formed by the reaction of xe2x80x9camine compoundxe2x80x9d with a carbonyl compound such as aldehyde, ketone or the like; a silyl derivative formed by the reaction of xe2x80x9camine compoundxe2x80x9d with a silyl compound such as bis(trimethylsilyl)acetamide, mono(trimethylsilyl)acetamide, bis(trimethylsilyl)urea or the like; a derivative formed by reaction of xe2x80x9camine compoundxe2x80x9d with phosphorus trichloride or phosgene, and the like.
The reaction is usually carried out in a conventional solvent such as water, alcohol [e.g. methanol, ethanol, etc], acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide, pyridine or any other organic solvent which does not adversely influence the reaction. These conventional solvent may also be used in a mixture with water.
In this reaction, when the compound (Ig) is used in a free acid form or its salt form, the reaction is preferably carried out in the presence of a conventional condensing agent such as N,Nxe2x80x2-dicyclohexylcarbodiimide; or the like.
The reaction may also be carried out in the presence of an inorganic or organic base such as an alkali metal carbonate, alkali metal bicarbonate, tri(lower)alkylamine (e.g. triethylamine, etc), pyridine, N-(lower)alkylmorpholine, N,N-di(lower)alkylbenzylamine, or the like.
The reaction temperature is not critical, and the reaction is usually carried out under cooling to heating.
The object compound (I) of the present invention is an adenosine antagonist and possesses the various pharmacological actions as stated before.
In order to show this usefulness of the compound (I) of the present invention, the pharmacological test result of the representative compound of the present invention is shown in the following.
Male JCL:SD strain rats aged 9 weeks weighing 280-300 g received cisplatin (4.5 mg/kg) intraperitoneally. Normal rats were injected with an equal amount of saline instead of cisplatin. The effect of repeated intravenous administration of the test compound (0.1 mg/kg, twice a day) on cisplatin induced renal failure was investigated in rats. Cisplatin was given at the same time of the first dose of the test compound (for the test group) or vehicle (saline) (for the control group), and the test compound or vehicle was given for 3 days. The plasma creatinine concentrations were measured in all rats on the 8th day.
3-[2-(2-Carboxymethyl-1-cycloheptenyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine
Male JCL:SD strain rats aged 9 weeks weighing 280-300 g received cisplatin (4.5 mg/kg) intraperitoneally. Normal rats were injected with an equal amount of saline instead of cisplatin. The effect of chronic intravenous administration of the test compound (0.1 mg/kg, twice a day) on cisplatin induced renal failure was investigated in rats. Cisplatin was given 60 minutes after the first dose of the test compound (for the test group) or vehicle (saline) (for the control group), and the test compound or vehicle was given for 8 days. The plasma creatinine concentrations were measured in all rats on the 8th day.
3-[2-(2-Carboxymethyl-1-cyclohexenyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]-pyridine
The pharmaceutical composition of this invention can be used in the form of a pharmaceutical preparation, for example, in solid, semisolid or liquid form, which contains the pyrazolopyridine compound (I) or a pharmaceutically acceptable salt thereof, as an active ingredient in a mixture with an organic or inorganic carrier or excipient suitable for rectal, pulmonary (nasal or buccal inhalation), nasal, ocular, external (topical), oral or parenteral (including subcutaneous, intravenous and intramuscular) administrations or insufflation. The active ingredient may be compounded, for example, with the usual non-toxic, pharmaceutically acceptable carriers for tablets, pellets, troches, capsules, suppositories, creams, ointments, aerosols, powders for insufflation, solutions, emulsions, suspensions, and any other form suitable for use. And, if necessary, in addition, auxiliary, stabilizing, thickening and coloring agents and perfumes may be used. The pyrazolopyridine compound (I) or a pharmaceutically acceptable salt thereof is/are included in the pharmaceutical composition in an amount sufficient to produce the desired aforesaid pharmaceutical effect upon the process or condition of diseases.
For applying the composition to human being or animals, it is preferable to apply it by intravenous, intramuscular, pulmonary, or oral administration, or insufflation. While the dosage of therapeutically effective amount of the pyrazolopyridine compound (I) varies from and also depends upon the age and condition of each individual patient to be treated, in the case of intravenous administration, a daily dose of 0.01-100 mg of the pyrazolopyridine compound (I) per kg weight of human being or animals, in the case of intramuscular administration, a daily dose of 0.1-100 mg of the pyrazolopyridine compound (I) per kg weight of human being or animals, in case of oral administration, a daily dose of 0.5-100 mg of the pyrazolopyridine compound (I) per kg weight of human being or animals generally given for the prevention and/or treatment of aforesaid diseases.
USPTO Backgrounds
USPTO Backgrounds