Arylsulfonylamino hydroxamic acid derivativesA compound of formula (I) wherein n, X, R, R and Q are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S) and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.Following formula: compound or its pharmaceutical salts: wherein n is 1-6;x is or 1, r wherein 1be defined as follows: azetidine, pyrrolidyl, piperidyl, morpholinyl, thio-morpholinyl, indolinyl, iso-dihydro-indole-group, tetrahydric quinoline group, tetrahydro isoquinolyl, piperazinyl or be selected from the diaza-bicyclo alkyl ring of following bridging: wherein r is 1,2 or 3; m is 1 or 2; andp is 0 or 1; each heterocyclic radical wherein can randomly be selected from following group by one or two and replace: hydroxyl, (c 1-c 6) alkyl, (c 1-c 6) alkoxyl group, (c 1-c 10) acyl group, (c 1-c 10) acyloxy, (c 6-c 10) aryl, (c 5-c 9) heteroaryl, (c 6-c 10) aryl (c 1-c 6) alkyl, (c 5-c 9) heteroaryl (c 1-c 6) alkyl, hydroxyl (c 1-c 6) alkyl, (c 1-c 6) alkoxyl group (c 1-c 6) alkyl, (c 1-c 6) acyl-oxygen (c 1-c 6) alkyl, (c 1-c 6) alkyl sulfide, (c 1-c 6) alkyl sulfide (c 1-c 6) alkyl, (c 6-c 10) aryl sulphur, (c 6-c 10) aryl sulphur (c 1-c 6) alkyl, r 9r 10n, r 9r 10nso 2, r 9r 10nco, r 9r 10nco (c 1-c 6) alkyl, wherein r 9and r 10independent separately is hydrogen, (c 1-c 6) alkyl, (c 6-c 10) aryl, (c 5-c 9) heteroaryl, (c 6-c 10) aryl (c 1-c 6) alkyl or (c 5-c 9) heteroaryl (c 1-c 6) alkyl or r 9and r 10constitute azetidine together with its banded n, tetramethyleneimine, piperidines, morpholine or thiomorpholine ring; r 12so 2, r 12so 2nh is r wherein 12be trifluoromethyl, (c 1-c 6) alkyl, (c 6-c 10) aryl, (c 5-c 9) heteroaryl, (c 6-c 10) aryl (c 1-c 6) alkyl or (c 5-c 9) heteroaryl (c 1-c 6) alkyl; r 13conr 9, r wherein 9be to define as above and r 13be hydrogen, (c 1-c 6) alkyl, (c 1-c 6) alkoxyl group (c 6-c 10) aryl, (c 5-c 9) heteroaryl, (c 1-c 6) aryl (c 1-c 6) alkyl (c 6-c 10) aryl (c 1-c 6) alkoxyl group or (c 5-c 9) heteroaryl (c 1-c 6) alkyl; r 14ooc, r 14oo (c 1-c 6) alkyl, wherein r 14be (c 1-c 6) alkyl, (c 6-c 10) aryl, (c 5-c 9) heteroaryl, (c 6-c 10) aryl (c 1-c 6) alkyl, 5-2,3-indanyl, chr 5ocor 6, r wherein 5be hydrogen or (c 1-c 6) alkyl and r 6be (c 1-c 6) alkyl, (c 1-c 6) alkoxyl group or (c 6-c 10) aryl; ch 2conr 6r 8, its r 7and r 8independent separately is hydrogen or (c 1-c 6) alkyl or can form azetidine together with its bonded nitrogen, tetramethyleneimine, piperidines, morpholine or thiomorpholine ring; or r 15o (c 1-c 6) alkyl, wherein r 15be h 2n (chr 16) co, wherein r 16it is the amino acid whose side chain of natural d-or l-; r 1be (c 1-c 6) aryl, (c 5-c 9) heteroaryl, (c 6-c 10) aryl (c 1-c 6) alkyl, 5-2,3-indanyl, chr 5ocor 6or ch 2conr 7r 8, r wherein 5, r 6, r 7and r 8as above definition; r 3and r 4be selected from independently of one another: hydrogen, (c 1-c 6) alkyl, trifluoromethyl, trifluoromethyl (c 1-c 6) alkyl, (c 1-c 6) alkyl (difluoro methylene), (c 1-c 3) alkyl (difluoro methylene) (c 1-c 3) alkyl, (c 6-c 10) aryl, (c 5-c 9) heteroaryl, (c 6-c 10) aryl (c 1-c 6) alkyl, (c 5-c 9) heteroaryl (c 1-c 6) alkyl, (c 6-c 10) aryl (c 6-c 10) aryl, (c 6-c 10) aryl (c 6-c 10) aryl (c 1-c 6) alkyl, (c 3-c 4) cycloalkyl, (c 3-c 6) cycloalkyl (c 1-c 6) alkyl, hydroxyl (c 1-c 6) alkyl, (c 1-c 10) acyl-oxygen (c 1-c 6) alkyl, (c 1-c 6) alcoxyl (c 1-c 6) alkyl, (c 1-c 10) amido (c 1-c 6) alkyl, piperidyl, (c 1-c 6) the alkylpiperidine base, (c 6-c 10) aryl (c 1-c 6) alcoxyl (c 1-c 6) alkyl, (c 5-c 9) heteroaryl (c 1-c 6) alcoxyl (c 1-c 6) alkyl, (c 1-c 6) alkyl sulfide (c 1-c 6) alkyl, (c 6-c 10) aryl sulphur (c 1-c 6) alkyl, (c 1-c 6) alkyl sulfenyl (c 1-c 6) alkyl, (c 6-c 10) aryl sulfinyl (c 1-c 6) alkyl, (c 1-c 6) alkyl sulfonyl (c 1-c 6) alkyl, (c 6-c 10) aryl sulfonyl (c 1-c 6) alkyl, amino (c 1-c 6) alkyl, (c 1-c 6) alkylamino (c 1-c 6) alkyl, ((c 1-c 6) alkylamino) 2(c 1-c 6) alkyl, r 17co (c 1-c 6) alkyl, r wherein 17be r 14o or r 7r 8n r wherein 7, r 8and r 14definition as above; or r 18(c 1-c 6) alkyl, wherein r 18be piperazinyl, (c 1-c 10) the acyl piperazine base, (c 6-c 10) arylpiperazinyl, (c 5-c 9) the heteroaryl piperazine, (c 1-c 6) alkylpiperazine, (c 6-c 10) aryl (c 1-c 6) alkylpiperazine base, (c 5-c 9) heteroaryl (c 1-c 6) alkylpiperazine base, morpholinyl, thio-morpholinyl, piperidyl, pyrrolidyl, piperidyl, (c 1-c 6) alkylpiperidine, (c 6-c 10) arylpiperidine, (c 5-c 9) heteroaryl piperidine, (c 6-c 10) aryl (c 1-c 6) alkylpiperidine, (c 5-c 9) heteroaryl (c 1-c 6) alkylpiperidine base or (c 1-c 10) the acylpiperidine base; or r 3and r 4form (c together 3-c 6) cycloalkyl, epoxy hexane, sulfo-hexanaphthene, 2,3-indanyl or 1,2,3,4-tetralin ring or following formula group r wherein 21be hydrogen, (c 1-c 10) acyl group, (c 1-c 6) alkyl, (c 6-c 10) aryl (c 1-c 6) alkyl, (c 5-c 9) heteroaryl (c 1-c 6) alkyl or (c 1-c 6) alkyl sulphonyl; and q is (c 1-c 6) alkyl, (c 6-c 10) aryl, (c 6-c 10) aryl oxide (c 6-c 10) aryl, (c 6-c 10) aryl (c 6-c 10) aryl, (c 6-c 10) aryl (c 6-c 10) aryl (c 1-c 6) alkyl, (c 6-c 10) aryl oxide (c 5-c 9) heteroaryl, (c 5-c 9) heteroaryl, (c 1-c 6) alkyl (c 6-c 10) aryl, (c 1-c 6) alcoxyl (c 6-c 10) aryl, (c 6-c 10) aryl (c 1-c 6) alco...
아릴설포닐아미노 하이드록삼산 유도체본 발명은 관절염, 암, 조직 궤양, 각막반 분해, 재발협착증, 치주 질병, 수포성표피박리증, 공막염 및 매트릭스 메탈로프로테이나제 활성이 특징인 다른 질병, AIDS, 패혈증, 패혈성 쇼크 및 TNF의 생성이 포함되는 다른 질병으로 구성된 군에서 선택된 질병의 치료에 유용한 하기 화학식 I의 화합물에 관한 것이다:화학식 I상기 식에서,n, X, R3, R4 및 Q는 상기 정의된 바와 같다. 또한, 본 발명의 화합물은 표준 비-스테로이드성 염증치료 약물(NSAID'S) 및 진통제와의 조합 치료, 및 아드리아마이신, 다우노마이신, 시스-플라티늄, 에토포시드, 탁솔, 탁소테레 및 다른 알칼로이드, 예를 들면 빈크리스틴과 혼합되어 암의 치료에 사용될 수 있다. 하기 화학식 I의 화합물 또는 이의 약학적으로 허용가능한 염: 화학식 I [이미지] 상기 식에서, n은 1 내지 6이고; X는 OR1이고, 이때 R1은 아제티디닐, 피롤리디닐, 피페리디닐, 모르폴리닐, 티오모르폴리닐, 인돌리닐, 이소인돌리닐, 테트라하이드로퀴놀리닐, 테트라하이드로이소퀴놀리닐, 피페라지닐 또는 [이미지] [이미지] [이때, r은 1, 2 또는 3이고, m은 1 또는 2이고, p는 0 또는 1이고, 각각의 이종환상 기는 하이드록시, (C1-C6)알킬, (C1-C6)알콕시, (C1-C10)아실, (C1-C10)아실옥시, (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬, (C5-C9)헤테로아릴(C1-C6)알킬, 하이드록시(C1-C6)알킬, (C1-C6)알콕시(C1-C6)알킬, (C1-C6)아실옥시(C1-C6)알킬, (C1-C6)알킬티오, (C1-C6)알킬티오(C1-C6)알킬, (C6-C10)아릴티오, (C6-C10)아릴티오(C1-C6)알킬, R9R10N, R9R10NSO2, R9R10NCO, R9R10NCO(C1-C6)알킬(이때, R9 및 R10은 각각 독립적으로 수소, (C1-C6)알킬, (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬 또는 (C5-C9)헤테로아릴(C1-C6)알킬이거나 또는 R9 및 R10은 이들이 결합된 질소와 함께 아제티디닐, 피롤리디닐, 피페리디닐, 모르폴리닐 또는 티오모르폴리닐 고리를 형성할 수 있다), R12SO2, R12SO2NH(이때, R12는 트리플루오로메틸, (C1-C6)알킬, (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬 또는 (C5-C9)헤테로아릴(C1-C6)알킬이다), R13CONR9(이때, R9는 상기 정의된 바와 같고, R13은 수소, (C1-C6)알킬, (C1-C6)알콕시, (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬(C6-C10)아릴(C1-C6)알콕시 또는 (C5-C9)헤테로아릴(C1-C6)알킬이다), R14OOC, R14OOC(C1-C6)알킬(이때, R14는 (C1-C6)알킬, (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬, 5-인다닐, CHR5OCOR6(이때, R5는 수소 또는 (C1-C6)알킬이고, R6은 (C1-C6)알킬, (C1-C6)알콕시 또는 (C6-C10)아릴이다)이다), CH2CONR7R8(이때, R7 및 R8은 각각 독립적으로 수소 또는 (C1-C6)알킬이거나 또는 이들이 결합된 질소와 함께 아제티디닐, 피롤리디닐, 피페리디닐, 모르폴리닐 또는 티오모르폴리닐 고리를 형성한다), 또는 R15O(C1-C6)알킬(이때, R15는 H2N(CHR16)CO이고, R16은 천연 D- 또는 L-아미노산의 측쇄이다)에서 선택된 하나 또는 두 개의 기로 선택적으로 치환될 수 있다]로 구성된 군에서 선택된 가교된 디아자비사이클로알킬 고리이고; R1은 (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬, 5-인다닐, CHR5OCOR6 또는 CH2CONR7R8(이때, R5, R6, R7 및 R8은 상기 정의된 바와 같다)이고; R3 및 R4는 각각 독립적으로 수소, (C1-C6)알킬, 트리플루오로메틸, 트리플루오로메틸(C1-C6)알킬, (C1-C6)알킬(디플루오로메틸렌), (C1-C3)알킬(디플루오로메틸렌)(C1-C3)알킬, (C6-C10)아릴, (C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알킬, (C5-C9)헤테로아릴(C1-C6)알킬, (C6-C10)아릴(C6-C10)아릴, (C6-C10)아릴(C6-C10)아릴(C1-C6)알킬, (C3-C6)사이클로알킬, (C3-C6)사이클로알킬(C1-C6)알킬, 하이드록시(C1-C6)알킬, (C1-C10)아실옥시(C1-C6)알킬, (C1-C6)알콕시(C1-C6)알킬, (C1-C10)아실아미노(C1-C6)알킬, 피페리딜, (C1-C6)알킬피페리딜, (C6-C10)아릴(C1-C6)알콕시(C1-C6)알킬, (C5-C9)헤테로아릴(C1-C6)알콕시(C1-C6)알킬, (C1-C6)알킬티오(C1-C6)알킬, (C6-C10)아릴티오(C1-C6)알킬, (C1-C6)알킬설피닐(C1-C6)알킬, (C6-C10)아릴설피닐(C1-C6)알킬, (C1-C6)알킬설포닐(C1-C6)알킬, (C6-C10)아릴설포닐(C1-C6)알킬, 아미노(C1-C6)알킬, (C1-C6)알킬아미노(C1-C6)알킬, ((C1-C6)알킬아미노)2(C1-C6)알킬, R17CO(C1-C6)알킬(이때, R17은 R14O 또는 R7R8N이고, 이때, R7, R8 및 R14는 상기 정의된 바와 같다), 또는 R18(C1-C6)알킬(이때 R18은 피페라지닐, (C1-C10)아실피페라지닐, (C6-C10)아릴피페라지닐, (C5-C9)헤테로아릴피페라지닐, (C1-C6)알킬피페라지닐, (C6-C10)아릴(C1-C6)알킬피페라지닐, (C5-C9)헤테로아릴(C1-C6)알킬피페라지닐, 모르폴리닐, 티오모르폴리닐, 피페리디닐, 피롤리디닐, 피페리딜, (C1-C6)알킬피페리딜, (C6-C10)아릴피페리딜, (C5-C9)헤테로아릴피페리딜, (C6-C10)아릴(C1-C6)알킬피페리딜, (C5-C9)헤테로아릴(C1-C6)알킬피페리딜 또는 (C1-C6)아실피페리딜이다)로 구성된 군에서 선택되거나; 또는 R3 및 R4는 함께 (C3-C4)사이클로알킬, 옥사사이클로헥실, 티오사이클로헥실, 인다닐 또는 테트랄리닐 고리를 형성하거나 또는 하기 일반식 [이미지]의 기이고(이때, R21은 수소, (C1-C10)아실, (C1-C6)알킬, (C6-C10)아릴(C1-C6)알킬, (C5-C9)헤테로아릴(C1-C6)알킬 또는 (C1-C6)알킬설포닐이다); Q는 (C1-C6)알킬, (C6-C10)아릴, (C6-C10)아릴옥시(C6-C10)아릴, (C6-C10)아릴(C6-C10)아릴, (C6-C10)아릴(C6-C10)아릴(C1-C6)알킬, (C6-C10)아릴옥시(C5-C9)헤테로아릴, (C5-C9)헤테로아릴, (C1-C6)알킬(C6-C10)아릴, (C1-C6)알콕시(C6-C10)아릴, (C6-C10)아릴(C1-C6)알콕시(C6-C10)아릴, (C6-C10)아릴(C1-C6)알콕시(C1-C6)알킬, (C5-C9)헤테로아릴옥시(C6-C10)아릴, (C1-C6)알킬(C5-C9)헤테로아릴, (C1-C6)알콕시(C5-C9)헤테로아릴, (C6-C10)아릴(C1-C6)알콕시(C5-C9)헤테로아릴, (C5-C9)헤테로아릴옥시(C5-C9)헤테로아릴, (C6-C10)아릴옥시(C1-C6)알킬, (C5-C9)헤테로아릴옥시(C1-C6)알킬, (C1-C6)알킬(C6-C10)아릴옥시(C6-C10)아릴, (C1-C6)알킬(C5-C9)헤테로아릴옥시(C6-C10)아릴, (C1-C6)알킬(C6-C10)아릴옥시(C5-C9)헤테로아릴, (C1-C6)알콕시(C6-C10)아릴옥시(C6-C10)아릴, (C1-C6)알콕시(C5-C9)헤테로아릴옥시(C6-C10)아릴 또는 (C1-C6)알콕시(C6-C10)아릴옥시(C5-C9)헤테로아릴이고, 이때 각각의 아릴 기는 선택적으로 플루오로, 클로로, 브로모, (C1-C6)알킬, (C1-C6)알콕시 또는 퍼플루오로(C1-C3)알킬로 치환될 수 있고, 단, X가 아제티디닐, 피롤리디닐, 모르폴리닐, 티오모르폴리닐, 인돌리닐, 이소인돌리닐, 테트라하이드로퀴놀리닐, 테트라하이드로이소퀴놀리닐, 피페라지닐, (C1-C10)아실피페라지닐, (C1-C6)알킬피페라지닐, (C6-C10)아릴피페라지닐, (C5-C9)헤테로아릴피페라지닐 또는 가교된 디아자비사이클로알킬 고리로 정의된 경우, 이는 치환되어야만한다. 