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    • 6. 发明申请
    • DERIVATIVES OF HYDROXAMIC ACID AS METALLOPROTEINASE INHIBITORS
    • 羟基酸作为金属蛋白酶抑制剂的衍生物
    • WO2005019194A1
    • 2005-03-03
    • PCT/GB2004/003558
    • 2004-08-18
    • VERNALIS (OXFORD) LIMITEDLABORATOIRES SERONO S.A.PAIN, GillesDAVIES, Stephen, JohnBOMBRUN, Agnes
    • PAIN, GillesDAVIES, Stephen, JohnBOMBRUN, Agnes
    • C07D295/16
    • C07D213/74C07C259/06C07D211/58C07D213/38C07D217/06C07D239/42C07D241/04C07D251/46C07D265/30C07D295/185C07D317/58C07D333/34
    • Compounds of formula (I) are inhibitors of matrix metalloproteinases, and are of use in the treatment of, for example fibrotic disease, multiple sclerosis, emphysemia, bronchitis and asthma: formula (I) wherein Ar represents an optionally substituted aryl, heteroaryl, C 3 -C 8 cycloalkyl or heterocycloakyl group; R represents hydrogen or C 1 -C 6 alkyl, or C 3 -C 6 cycloalkyl; Alk represents a divalent C 1 -C 5 alkylene or C 2 -C 5 alkenylene radical; and R 1 and R 2 taken together with the nitrogen atom to which they are attached form a first heterocycloalkyl ring which is optionally fused to a second C 3 -C 8 cycloalkyl or heterocycloalkyl ring, the said first and second rings being optionally substituted by at least one group of formula (II): formula (II) wherein m, p and n are independently 0 or 1; Z represents, hydrogen, or an optionally substituted carbocyclic or heterocyclic ring of from 5 to 7 ring atoms which is optionally fused to another optionally substituted carbocyclic or heterocyclic ring of from 5 to 7 ring atoms; Alk 1 and Alk 2 independently represent optionally substituted divalent C 1 -C 3 alkylene radicals; X represents -0-, -S-, -S(O)-, -S(O 2 )-, -C(=O)-, -NH-, -NR 3 -, -S(O 2 )NH-, -S(O 2 )NR 3 -, -NHS(O 2 )-, or -NR 3 S(O 2 )-, where R 3 is C 1 -C 3 alkyl.
    • 式(I)化合物是基质金属蛋白酶抑制剂,可用于治疗,例如纤维化疾病,多发性硬化,肺气肿,支气管炎和哮喘:式(I)其中Ar表示任选取代的芳基,杂芳基,C3 -C8环烷基或杂环烷基; R表示氢或C 1 -C 6烷基或C 3 -C 6环烷基; Alk表示二价C 1 -C 5亚烷基或C 2 -C 5亚烯基; 并且R 1和R 2与它们所连接的氮原子一起形成第一个杂环烷基环,其任选地与第二个C 3 -C 8环烷基或杂环烷基环稠合,所述第一和第二个环任选被至少一个 式(II):式(II)其中m,p和n独立地为0或1; Z表示氢或任选取代的5至7个环原子的碳环或杂环,其任选地与另外任何取代的5至7个环原子的碳环或杂环稠合; Alk 1和Alk 2独立地表示任选取代的二价C1-C3亚烷基; X表示-O - , - S - , - S(O) - , - S(O 2) - , - C(= O) - , - NH - , - NR 3 - , - S(O 2)NH-,-S (O 2)NR 3 - , - NH(O 2) - 或-NR 3 S(O 2) - ,其中R 3是C 1 -C 3烷基。