Novel 2,5-substituted pyrimidines as pde inhibitorsThe invention relates to novel substituted condensed pyrimidine compounds of general formula (I), in which the chemical groupings, substituents and indices are as defined in the description, and to their use as medicaments, in particular as medicaments for the treatment of conditions and diseases that can be treated by inhibition of the PDE4 enzyme.There are the pyrimidines that the 2,5- of below general formula (i) replacesa, b, c each represent n or ch independently of one another；r1represent (c1-c6)-alkyl, (c1-c6)-hydroxy alkyl, (c3-c6)-cycloalkyl, sox-(c1-c6)-alkyl；x is 0,1 or 2；g is the phenyl optionally being replaced by least one substituent group y or the unit of 5- or 6- containing at least one oxygen, sulfur or nitrogen-atoms heteroaryl, and the nitrogen-atoms being present in described heteroaryl can be by r4replace；r4it is hydrogen, (c1-c6)-alkyl, (c1-c6)-haloalkyl, co- (c1-c6)-alkyl, so (c1-c6)-alkyl, so2(c1- c6)-alkyl；y is oh, cn, sh, (c1-c6)-alkyl, (c2-c6)-thiazolinyl, (c2-c6)-alkynyl, (c3-c6)-cycloalkyl, (c1-c6)-alkane epoxide, (c1-c6)-alkylthio group, (c1-c6)-haloalkyl, (c1-c6)-halogenated alkylthio, (c1-c6)-halogenated alkoxy, co2h、co2(c1-c6)-alkyl, cho, co (c1-c6)-alkyl, oco (c1-c6)-alkyl, conh2、conh-(c1-c6)-alkyl, con((c1-c6)-alkyl)2、oco-nh(c1-c6)-alkyl, oco-n ((c1-c6)-alkyl)2、nh2、nh(c1-c6)-alkyl, n ((c1-c6)-alkyl)2, n- pyrrolidinyl, n- piperidyl, n- morpholinyl, nh-co- (c1-c6) alkyl, nh-co2(c1-c6)-alkane base, n (c1-c6)-alkyl-co2(c1-c6)-alkyl, nh-co-nh2、 nh-co-nh(c1-c6)-alkyl, nh-co-n (c1-c6)- alkyl)2、n(c1-c6)-alkyl-co-nh2、n(c1-c6) alkyl-co-nh (c1-c6)-alkyl, n (c1-c6)-alkyl-co-n ((c1-c6)-alkyl)2、nh-so2-(c1-c6)-alkyl, n (c1-c6) alkyl-so2-(c1-c6)-alkyl, s- (c1-c6)-alkyl, so(c1-c6)-alkyl, so2-(c1-c6)-alkyl, so2h、so2oh、so2nh2、so2nh(c1-c6)-alkyl, so2n((c1-c6)- alkyl)2、c(=n)-nh、nhc(=n)-nh2,-n=c=o ,-s-cn, wherein aforesaid alkyl chain following can replace by least one base replaces：oh、cn、(c3-c6)-cycloalkyl, (c1-c6)-alkoxyl, co2h、co2(c1-c6)-alkyl or-nh2；r2and r3represent hydrogen or optionally substituted (c independently of one another1-c6)-alkyl, (c1-c6)-haloalkyl, (c1-c6)- hydroxy alkyl, (c1-c6)-alkoxyl (c1-c6)-alkylidene, (c1-c6)-alkylidene-co2h、(c1-c6)-alkylidene-co2(c1- c6)-alkyl, (c1-c6)-alkylidene-conh2、(c1-c6)-alkylidene-conh (c1-c6)-alkyl, (c1-c6)-alkylidene-con ((c1-c6)-alkyl)2、(c1-c6)-alkylidene-(c3-c6)-cycloalkyl, (c1-c6)-hydroxy alkyl-(c3-c6)-cycloalkylidene, group l1v, group l2w, orr2and r3formed together with the nitrogen-atoms being connected with it optionally by least one substituent xq3- to the 12- unit replacing is single or bicyclic can the extra heterolipid race residue q containing at least one oxygen, sulfur or other nitrogen-atoms, and these are one or more extra nitrogen-atoms are by r5replace；xqrepresentative=o (carbonyl), halogen, oh, cn, sh, (c independently of one another1-c6)-alkyl, (c1-c6)-hydroxy alkyl, (c1- c6)-cyanoalkyl, (c2-c6)-thiazolinyl, (c2-c6)-alkynyl, (c3-c6)-cycloalkyl, (c1-c6)-alkoxyl, (c1-c6)-alcoxyl base (c1-c6)-alkylidene, (c1-c6)-alkylthio group, (c1-c6)-haloalkyl, (c1-c6)-halogenated alkylthio, (c1-c6)-halogen for alkoxyl ,-nh2、nh(c1-c6)-alkyl, n ((c1-c6)-alkyl)2、(c1-c6)-alkylidene-nh (c1-c6)-alkyl, (c1- c6)-alkylidene-n ((c1-c6)-alkyl)2、nh-cho、nh-co(c1-c6)-alkyl, n (c1-c6)-alkyl-co (c1-c6)-alkane base, nh-co-o (c1-c6)-alkyl, n (c1-c6)-alkyl-co-o (c1-c6)-alkyl, nh-co-nh2、 nh-co-nh(c1- c6)-alkyl, nh-co-n ((c1-c6)-alkyl)2、n(c1-c6)-alkyl-co-nh2、n(c1-c6)-alkyl-co-nh (c1-c6)- alkyl, n (c1-c6)-alkyl-co-n ((c1-c6)-alkyl)2、nh-so2-(c1-c6)-alkyl, n (c1-c6)-alkyl-so2-(c1- c6)-alkyl, co2h、co2(c1-c6)-alkyl, cho, co (c1-c6)-alkyl, o-co (c1-c6)-alkyl, co-nh2、co-nh (c1-c6)-alkyl, co-n ((c1-c6)-alkyl)2、o-co-nh(c1-c6)-alkyl, o-co-n ((c1-c6)-alkyl)2、s-(c1- c6)-alkyl, so (c1-c6)-alkyl, so2-(c1-c6)-alkyl, sooh, so2oh、so2nh2、so2nh(c1-c6)-alkyl, so2n ((c1-c6)-alkyl)2、c(=n)-nh、nhc(=n)-nh2,-n=c=o ,-s-cn, wherein aforesaid alkyl chain can be by least one following substituent group replaces：oh、cn、(c3-c6)-cycloalkyl, (c1-c6)-alkoxyl, co2h、co2(c1-c6)-alkyl or-nh2；r5it is hydrogen, (c1-c6)-alkyl, (c1-c6)-haloalkyl, co- (c1-c6)-alkyl, so- (c1-c6)-alkyl, so2-(c1- c6)-alkyl；l1it is key or side chain or the optionally substituted (c of straight chain1-c6)-alkylidene group, it is connected with amide nitrogen；v is optionally by least one substituent xvthe aliphatic series of the single or double ring of 3- to 12- unit replacing or heterolipid race residue, and such as really one or more nitrogen-atoms are present in the heterolipid race residue of described single or double ring, then at least one of these nitrogen-atoms is by r6 replace；xvrepresentative=o (carbonyl), halogen, oh, cn, sh, (c independently of one another1-c6)-alkyl, (c1-c6)-hydroxy alkyl, (c1- c6)-cyanoalkyl, (c2-c6)-thiazolinyl, (c2-c6)-alkynyl, (c3-c6)-cycloalkyl, (c1-c6)-alkoxyl, (c1-c6)-alcoxyl base (c1-c6)-alkylidene, (c1-c6)-alkylthio group, (c1-c6)-haloalkyl, (c1-c6)-halogenated alkylthio, (c1-c6)-halogen for alkoxyl ,-nh2、nh(c1-c6)-alkyl, n ((c1-c6)-alkyl)2、(c1-c6)-alkylidene-nh (c1-c6)-alkyl, (c1- c6)-alkylidene-n ((c1-c6)-alkyl)2、nh-cho、nh-co(c1-c6)-alkyl, n (c1-c6)-alkyl-co (c1-c6)-alkane base, nh-co-o (c1-c6)-alkyl, n (c1-c6)-alkyl-co-o (c1-c6)-alkyl, nh-co-nh2、nh-co-nh(c1-c6)- alkyl, nh-co-n ((c1-c6)-alkyl)2、n(c1-c6)-alkyl-co-nh2、n(c1-c6)-...
PDE 억제제로서의 신규한 2,5-치환된 피리미딘본 발명은, 화학적 그룹화, 치환체 및 지수가 본 명세서에서 정의된 바와 같은 화학식 I의 신규한 치환된 축합된 피리미딘 화합물에 관한 것이며, 또한 약제로서의, 특히 PDE4 효소의 억제에 의해 치료될 수 있는 병태 및 질환 치료용 약제로서의 이들의 용도에 관한 것이다. 화학식 I하기 화학식 I을 갖는 2,5-치환된 피리미딘. 화학식 I[이미지]상기 화학식 I에서,A, B, C는 각각 서로 독립적으로 N 또는 CH를 나타내고;R1은 (C1-C6)-알킬, (C1-C6)-하이드록시알킬, (C3-C6)-사이클로알킬, SOx-(C1-C6)-알킬을 나타내고;x는 0, 1 또는 2이고;G는 임의로 적어도 하나의 치환체 Y로 치환된 페닐 또는 적어도 하나의 산소, 황 또는 질소 원자를 함유하는 5원 또는 6원의 헤테로아릴이며, 상기 헤테로아릴에 존재하는 질소 원자들은 R4로 치환될 수 있고;R4는 수소, (C1-C6)-알킬, (C1-C6)-할로알킬, CO-(C1-C6)-알킬, SO(C1-C6)-알킬, SO2(C1-C6)-알킬이고;Y는 OH, CN, SH, (C1-C6)-알킬, (C2-C6)-알케닐, (C2-C6)-알키닐, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, (C1-C6)-티오알킬, (C1-C6)-할로알킬, (C1-C6)-티오할로알킬, (C1-C6)-할로알콕시, CO2H, CO2(C1-C6)-알킬, CHO, CO(C1-C6)-알킬, OCO(C1-C6)-알킬, CONH2, CONH-(C1-C6)-알킬, CON((C1-C6)-알킬)2, OCO-NH(C1-C6)-알킬, OCO-N((C1-C6)-알킬)2, NH2, NH(C1-C6)-알킬, N((C1-C6)-알킬)2, N-피롤리디닐, N-피페리디닐, N-모르폴리닐, NH-CO-(C1-C6)알킬, NH-CO2(C1-C6)-알킬, N(C1-C6)-알킬-CO2(C1-C6)-알킬, NH-CO-NH2, NH-CO-NH(C1-C6)-알킬, NH-CO-N(C1-C6)-알킬)2, N(C1-C6)-알킬-CO-NH2, N(C1-C6)알킬-CO-NH(C1-C6)-알킬, N(C1-C6)-알킬-CO-N((C1-C6)-알킬)2, NH-SO2-(C1-C6)-알킬, N(C1-C6)알킬-SO2-(C1-C6)-알킬, S-(C1-C6)-알킬, SO(C1-C6)-알킬, SO2-(C1-C6)-알킬, SO2H, SO2OH, SO2NH2, SO2NH(C1-C6)-알킬, SO2N((C1-C6)-알킬)2, C(=N)-NH, NHC(=N)-NH2, -N=C=O, -S-CN이고, 여기서, 상기 언급된 알킬 쇄는 치환체들 OH, CN, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, CO2H, CO2(C1-C6)-알킬 또는 -NH2 중 적어도 하나로 치환될 수 있고; R2 및 R3은 서로 독립적으로 수소 또는 임의로 치환된 (C1-C6)-알킬, (C1-C6)-할로알킬, (C1-C6)-하이드록시알킬, (C1-C6)-알콕시(C1-C6)-알킬렌, (C1-C6)-알킬렌-CO2H, (C1-C6)-알킬렌-CO2(C1-C6)-알킬, (C1-C6)-알킬렌-CONH2, (C1-C6)-알킬렌-CONH(C1-C6)-알킬, (C1-C6)-알킬렌-CON((C1-C6)-알킬)2, (C1-C6)-알킬렌-(C3-C6)-사이클로알킬, (C1-C6)-하이드록시알킬-(C3-C6)-사이클로알킬렌, 그룹 L1V, 그룹 L2W를 나타내거나, 또는 R2와 R3은 이들이 부착되어 있는 질소 원자와 함께, 임의로 적어도 하나의 치환체 XQ로 치환된 3원 내지 12원의 모노사이클릭 또는 바이사이클릭 헤테로지방족 잔기 Q를 형성하고, 상기 Q는 적어도 하나의 산소, 황 또는 추가의 질소 원자를 추가로 함유할 수 있으며, 이들 하나 이상의 추가의 질소 원자들은 R5로 치환되고; XQ는 서로 독립적으로 =O(카보닐), 할로겐, OH, CN, SH, (C1-C6)-알킬, (C1-C6)-하이드록시알킬, (C1-C6)-시아노알킬, (C2-C6)-알케닐, (C2-C6)-알키닐, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, (C1-C6)-알콕시(C1-C6)-알킬렌, (C1-C6)-티오알킬, (C1-C6)-할로알킬, (C1-C6)-티오할로알킬, (C1-C6)-할로알콕시, -NH2, NH(C1-C6)-알킬, N((C1-C6)-알킬)2, (C1-C6)-알킬렌-NH(C1-C6)-알킬, (C1-C6)-알킬렌-N((C1-C6)-알킬)2 NH-CHO, NH-CO(C1-C6)-알킬, N(C1-C6)-알킬-CO(C1-C6)-알킬, NH-CO-O(C1-C6)-알킬, N(C1-C6)-알킬-CO-O(C1-C6)-알킬, NH-CO-NH2, NH-CO-NH(C1-C6)-알킬, NH-CO-N((C1-C6)-알킬)2, N(C1-C6)-알킬-CO-NH2, N(C1-C6)-알킬-CO-NH(C1-C6)-알킬, N(C1-C6)-알킬-CO-N((C1-C6)-알킬)2, NH-SO2-(C1-C6)-알킬, N(C1-C6)-알킬-SO2-(C1-C6)-알킬, CO2H, CO2(C1-C6)-알킬, CHO, CO(C1-C6)-알킬, O-CO(C1-C6)-알킬, CO-NH2, CO-NH(C1-C6)-알킬, CO-N((C1-C6)-알킬)2, O-CO-NH(C1-C6)-알킬, O-CO-N((C1-C6)-알킬)2, S-(C1-C6)-알킬, SO(C1-C6)-알킬, SO2-(C1-C6)-알킬, SOOH, SO2OH, SO2NH2, SO2NH(C1-C6)-알킬, SO2N((C1-C6)-알킬)2, C(=N)-NH, NHC(=N)-NH2, -N=C=O, -S-CN을 나타내고, 여기서, 상기 언급된 알킬 쇄는 치환체들 OH, CN, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, CO2H, CO2(C1-C6)-알킬 또는 -NH2 중 적어도 하나로 치환될 수 있고;R5는 수소, (C1-C6)-알킬, (C1-C6)-할로알킬, CO-(C1-C6)-알킬, SO-(C1-C6)-알킬, SO2-(C1-C6)-알킬이고;L1은 결합이거나, 또는 아미드 질소에 연결된, 임의로 치환된 측쇄 또는 직쇄의 (C1-C6)-알킬렌 그룹이고;V는 임의로 적어도 하나의 치환체 Xv로 치환된 3원 내지 12원의 모노사이클릭 또는 바이사이클릭 지방족 또는 헤테로지방족 잔기이며, 하나 이상의 질소 원자들이 상기 모노사이클릭 또는 바이사이클릭 헤테로지방족 잔기에 존재하는 경우, 이들 질소 원자들 중 적어도 하나는 R6으로 치환되고; XV는 서로 독립적으로 =O(카보닐), 할로겐, OH, CN, SH, (C1-C6)-알킬, (C1-C6)-하이드록시알킬, (C1-C6)-시아노알킬, (C2-C6)-알케닐, (C2-C6)-알키닐, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, (C1-C6)-알콕시(C1-C6)-알킬렌, (C1-C6)-티오알킬, (C1-C6)-할로알킬, (C1-C6)-티오할로알킬, (C1-C6)-할로알콕시, -NH2, NH(C1-C6)-알킬, N((C1-C6)-알킬)2, (C1-C6)-알킬렌-NH(C1-C6)-알킬, (C1-C6)-알킬렌-N((C1-C6)-알킬)2 NH-CHO, NH-CO(C1-C6)-알킬, N(C1-C6)-알킬-CO(C1-C6)-알킬, NH-CO-O(C1-C6)-알킬, N(C1-C6)-알킬-CO-O(C1-C6)-알킬, NH-CO-NH2, NH-CO-NH(C1-C6)-알킬, NH-CO-N((C1-C6)-알킬)2, N(C1-C6)-알킬-CO-NH2, N(C1-C6)-알킬-CO-NH(C1-C6)-알킬, N(C1-C6)-알킬-CO-N((C1-C6)-알킬)2, NH-SO2-(C1-C6)-알킬, N(C1-C6)-알킬-SO2-(C1-C6)-알킬, CO2H, CO2(C1-C6)-알킬, CHO, CO(C1-C6)-알킬, O-CO(C1-C6)-알킬, CO-NH2, CO-NH(C1-C6)-알킬, CO-N((C1-C6)-알킬)2, O-CO-NH(C1-C6)-알킬, O-CO-N((C1-C6)-알킬)2, S-(C1-C6)-알킬, SO(C1-C6)-알킬, SO2-(C1-C6)-알킬, SOOH, SO2OH, SO2NH2, SO2NH(C1-C6)-알킬, SO2N((C1-C6)-알킬)2, C(=N)-NH, NHC(=N)-NH2, -N=C=O, -S-CN을 나타내고, 여기서, 상기 언급된 알킬 쇄는 치환체들 OH, CN, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, CO2H, CO2(C1-C6)-알킬 또는 -NH2 중 적어도 하나로 치환될 수 있고;R6은 수소, (C1-C6)-알킬, (C1-C6)-할로알킬, CO-(C1-C6)-알킬, SO(C1-C6)-알킬, SO2(C1-C6)-알킬이고;L2는 결합이거나, 또는 아미드 질소에 연결된, 임의로 치환된 측쇄 또는 직쇄의 (C1-C6)-알킬렌 그룹이고;W는 임의로 적어도 하나의 치환체 Z로 치환된 페닐 또는 적어도 하나의 산소, 황 또는 질소 원자를 함유하는 5원 또는 6원의 헤테로아릴이고; Z는 서로 독립적으로 할로겐, OH, CN, SH, (C1-C6)-알킬, (C2-C6)-알케닐, (C2-C6)-알키닐, (C3-C6)-사이클로알킬, (C1-C6)-알콕시, (C1-C6)-티오알킬, (C1-C6)-할로알킬, (C1-C6)-티오할로알킬, (C1-C6)-할로알콕시, -NH2, NH(C1-C6)-알킬, N((C1-C6)-알킬)2, N-피롤리디닐, N-피페리디닐, N-모르폴리닐, NH-CHO, NH-CO(C1-C6)-알킬, N(C1-C6)-알킬-CO(C1-C6)-알킬, NH-CO2(C1-C6)-알킬, N(C1-C6)-알킬-CO2(C1-C6)-알킬, NH-CO-NH2, NH-CO-NH(C1-C6)-알킬, NH-CO-N((C1-C6)-알킬)2, N(C1-C6)-알킬-CO-NH2, N(C1-C6)-알킬-CO-NH(C1-C6)-알킬, N(C1-C6)-알킬-CO-N((C1-C6)-알킬)2, NH-SO2-(C1-C6)-알킬, N(C1-C6)-알킬-SO2-(C1-C6)-알킬, CO2H, CO2(C1-C6)-알킬, CHO, CO(C1-C6)-알킬, O-CO(C1-C6)-알킬, CO-NH2, CO-NH(C1-C6)-알킬, CO-N((C1-C6)-알킬)2, O-CO-NH(C1-C6)-알킬, O-CO-N((C1-C6)-알킬)2, S-(C1-C6)-알킬, SO(C1-C6)-알킬, SO2-(C1-C6)-알킬, SO2H, SO2OH, SO2NH2, SO2NH(C1-C6)-알킬, SO2N((C1-C6)-알킬)2, C(=N)-NH, NHC(=N)-NH2, -N=C=O, -S-CN을 나타내고, 여기서, 상기 언급된 알킬 쇄는 치환체들 OH, CN, (C3-C6)-사이클로알킬, (C1-C6)-알...