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1035 条记录 (耗时 0.04 秒)

    Mercaptoketones and mercaptoalcohols and a process for their preparation
    73.
    发明授权
    Mercaptoketones and mercaptoalcohols and a process for their preparation 失效
    巯基酮和巯基醇及其制备方法

    公开(公告)号：US6160132A

    公开(公告)日：2000-12-12

    申请号：US358010

    申请日：1999-07-21

    申请人： Jeremy Ian Levin

    发明人： Jeremy Ian Levin

    IPC分类号： C07C319/20 ,  C07C323/60 ,  C07D307/33 ,  C07D307/08

    CPC分类号： C07D307/33 ,  C07C319/20 ,  C07C323/60

    摘要： This invention relates to matrix metalloproteinase (MMP) inhibiting compounds of the formula: ##STR1## where R.sup.1 is C.sub.1 -C.sub.12 alkyl, straight or branched and optionally substituted by halogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, amino, carboxyl, C.sub.1 -C.sub.6 alkoxycarbonyl, carboxamido, nitrile, mono- or di-(C.sub.1 -C.sub.6)alkylamino, thio, C.sub.1 -C.sub.6 alkylthio, aryl, --Oaryl or --OCH.sub.2 aryl where aryl is optionally substituted with C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, carboxy, halogen, cyano, nitro, carboxamido, or hydroxy; and C.sub.1 -C.sub.6 alkanesulfonyloxy. R.sup.2 is .alpha.-OH or .beta.-OH and R.sup.6 is H or R.sup.2 and R.sup.6 together are carbonyl; the chemical intermediates; and processes for the preparation of these compounds and the intermediates thereto.Matrix metalloproteinases (MMP) are a family of zinc-containing calcium dependent proteinases, including stromelysins, collagenases, and gelatinases. These MMP enzymes are capable of degrading the proteinaceous components of connective tissue and appear to be involved in tissue remodeling, i.e., wound healing and connective tissue turnover. Unexpectedly, the mercaptoalcohols with the S-configuration at the hydroxyl-bearing carbon have been found to be at least 4 times more potent than the analogous (R)-alcohols both in vitro and in vivo in inhibiting the MMP enzyme.

    摘要翻译： 本发明涉及下式的基质金属蛋白酶（MMP）抑制化合物：其中R1是直链或支链的C1-C12烷基，任选被卤素，羟基，C 1 -C 6烷氧基，氨基，羧基，C 1 -C 6烷氧基羰基，甲酰氨基， 腈，单 - 或二 - （C 1 -C 6）烷基氨基，硫代，C 1 -C 6烷硫基，芳基， - 芳基或-OCH 2芳基，其中芳基任选被C 1 -C 6烷基，C 1 -C 6烷氧基，羧基，卤素，氰基， 硝基，甲酰氨基或羟基; 和C 1 -C 6烷磺酰氧基。 R2是α-OH或β--OH，R6是H或R2，R6一起是羰基; 化学中间体; 以及这些化合物及其中间体的制备方法。 基质金属蛋白酶（MMP）是含锌钙依赖性蛋白酶的家族，包括基质溶胶蛋白，胶原酶和明胶酶。 这些MMP酶能够降解结缔组织的蛋白质组分，并且似乎参与组织重塑，即伤口愈合和结缔组织切换。 出乎意料的是，在含羟基的碳上具有S-构型的巯基醇在体外和体内都抑制MMP酶的效力比类似的（R） - 醇的效力高至少4倍。

    Beta-thiopropionyl-amino acid derivatives and their use as beta-lactamase inhibitors
    74.
    发明授权
    Beta-thiopropionyl-amino acid derivatives and their use as beta-lactamase inhibitors 失效
    β-硫代丙酰氨基酸衍生物及其作为β-内酰胺酶抑制剂的用途

    公开(公告)号：US6156774A

    公开(公告)日：2000-12-05

    申请号：US284098

    申请日：1999-04-07

    申请人： John Hargreaves Bateson ,  Desmond John Best ,  Brian Peter Clarke ,  Martin Leonard Gilpin ,  David Witty

    发明人： John Hargreaves Bateson ,  Desmond John Best ,  Brian Peter Clarke ,  Martin Leonard Gilpin ,  David Witty

    IPC分类号： A61K31/198 ,  A61K31/341 ,  A61K31/343 ,  A61K31/381 ,  A61K31/403 ,  A61K31/41 ,  A61K31/4166 ,  A61K31/4192 ,  A61K31/4406 ,  A61K31/4409 ,  A61P31/04 ,  C07C323/60 ,  C07C327/32 ,  C07D209/86 ,  C07D213/30 ,  C07D307/42 ,  C07D307/54 ,  C07D307/91 ,  C07D333/16 ,  C07D333/24 ,  C07D409/06 ,  A61K31/44 ,  C07D401/02

    CPC分类号： C07D307/91 ,  C07C323/60 ,  C07C327/32 ,  C07D209/86 ,  C07D213/30 ,  C07D307/54 ,  C07D333/16 ,  C07D333/24 ,  C07D409/06

    摘要： Mercapto amino acid derivatives of formula (I), wherein R is hydrogen, a salt-forming cation of a in vivo hydrolysable ester-forming group; R.sub.1 is selected from (a) and (b) in which A is a monocyclic aryl or heteroaryl ring and B is a monocyclic aryl, alicyclic or heterocyclic ring, C and D are independently --Z.sub.p --(CR.sub.8 CR.sub.9).sub.q -- or --(CR.sub.8 CR.sub.9).sub.q --Z.sub.p -- where p is 0 or 1, q is 0 to 3 provided that p+q in C is not 0, R.sub.8 and R.sub.9 are independently hydrogen or (C.sub.1-6)alkyl or together represent oxo and Z is O, NR.sub.10 or S(O).sub.x where R.sub.10 is hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl and x is 0-2, and wherein C and D are linked ortho to one another on each of the rings A and B in formula (b); R.sub.2 is hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl; R.sub.3 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms, (C.sub.3-7)cycloalkyl, fused aryl(C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl--(CH.sub.2).sub.m --X--(CH.sub.2).sub.n, heterocyclyl or heterocyclyl--(CH.sub.2).sub.m --X--(CH.sub.2).sub.n, where m is 0 to 3, n is 1 to 3 and X is O or S(O).sub.x where x is 0-2 or a bond; R.sub.4 is hydrogen or an in vivo hydrolysable acyl group; and R.sub.5 and R.sub.6 are independently hydrogen and (C.sub.1-6)alkyl or together represent (CH.sub.2).sub.r, where r is 2 to 5; for use in treatment of bacterial infections in humans or animals by administration in combination with a .beta.-lactam antiobiotic.

    摘要翻译： PCT No.PCT / EP97 / 05709 Sec。 371日期1999年4月7日 102（e）日期1999年4月7日PCT 1997年10月10日PCT公布。 公开号WO98 / 17639 日期：1998年4月30日式（I）的巯基氨基酸衍生物，其中R是氢，体内可水解的酯形成基团的成盐阳离子; R1选自（a）和（b），其中A是单环芳基或杂芳基环，B是单环芳基，脂环族或杂环，C和D独立地是-Zp-（CR8CR9）q-或 - （CR8CR9 ）q-Zp-其中p为0或1，q为0至3，条件是C中的p + q不为0，R8和R9独立地为氢或（C1-6）烷基或一起代表氧代，Z为O， NR10或S（O）x，其中R10是氢，（C1-6）烷基或芳基（C1-6）烷基，x是0-2，并且其中C和D在每个环A上彼此原子连接 和式（b）中的B; R2是氢，（C1-6）烷基或芳基（C1-6）烷基; R3是氢，任选被至多三个卤素原子取代的（C 1-6）烷基，（C 3-7）环烷基，稠合芳基（C 3-7）环烷基，（C 3-7）环烷基（C 2-6）烷基，（C 2 -6）链烯基，（C2-6）炔基，芳基，芳基 - （CH2）mX-（CH2）n，杂环基或杂环基 - （CH2）mX-（CH2）n，其中m为0-3，n为1 至3且X为O或S（O）x，其中x为0-2或键; R4是氢或体内可水解的酰基; 并且R 5和R 6独立地为氢和（C 1-6）烷基或一起代表（CH 2）r，其中r为2至5; 用于通过与β-内酰胺抗生素联合施用来治疗人或动物中的细菌感染。

    .beta.-thiopropionyl-aminoacid derivatives and their use as .beta.-lactamase inhibitors
    78.
    发明授权
    .beta.-thiopropionyl-aminoacid derivatives and their use as .beta.-lactamase inhibitors 失效
    β-硫代丙酰基 - 氨基酸衍生物及其作为β-内酰胺酶抑制剂的用途

    公开(公告)号：US6048852A

    公开(公告)日：2000-04-11

    申请号：US125245

    申请日：1999-01-13

    申请人： John Hargreaves Bateson ,  David R Witty ,  Brian Charles Gasson ,  Desmond John Best ,  David John Payne

    发明人： John Hargreaves Bateson ,  David R Witty ,  Brian Charles Gasson ,  Desmond John Best ,  David John Payne

    IPC分类号： A61K31/00 ,  A61K31/195 ,  A61K31/198 ,  A61K31/215 ,  A61K31/216 ,  A61K31/34 ,  A61K31/341 ,  A61K31/38 ,  A61K31/381 ,  A61K31/403 ,  A61K31/404 ,  A61K31/405 ,  A61K31/425 ,  A61K31/426 ,  A61K31/43 ,  A61K31/545 ,  A61K45/06 ,  A61P31/00 ,  A61P31/04 ,  A61P43/00 ,  C07C323/41 ,  C07C323/60 ,  C07C327/30 ,  C07D209/20 ,  C07D209/26 ,  C07D215/14 ,  C07D231/12 ,  C07D233/96 ,  C07D277/20 ,  C07D277/30 ,  C07D307/54 ,  C07D333/24 ,  C07D333/26 ,  C07D333/60

    CPC分类号： C07D333/60 ,  A61K45/06 ,  C07C323/60 ,  C07D209/20 ,  C07D215/14 ,  C07D231/12 ,  C07D233/96 ,  C07D277/30 ,  C07D307/54 ,  C07D333/24 ,  C07C2101/02

    摘要： A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a .beta.-lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, ##STR1## wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R.sub.1 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C.sub.1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C.sub.1-6)alkylcarbonyloxy, (C.sub.1-6)alkoxycarbonyl, formyl or (C.sub.1-6)alkylcarbonyl group, (C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl(C.sub.1-6)alkyl, heterocyclyl or heterocyclyl(C.sub.1-6)alkyl; R.sub.2 is hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl; R.sub.3 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms, (C.sub.3-7)cycloalkyl, fused aryl(C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n, heterocyclyl or heterocyclyl-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n, where m is 0 to 3, n is 1 to 3, each R.sub.10 and R.sub.11 is independently hydrogen or (C.sub.1-4)alkyl and X is O, S(O).sub.x where x is 0-2, or a bond; R.sub.4 is hydrogen, or an in vivo hydrolysable acyl group; and R.sub.5 and R.sub.6 are independently hydrogen and (C.sub.1-6)alkyl or together represent (CH.sub.2).sub.p where p is 2 to 5. Some compounds are claimed per se.

    摘要翻译： PCT No.PCT / EP97 / 00516 Sec。 371日期1999年1月13日 102（e）1999年1月13日PCT PCT 1997年2月3日PCT公布。 出版物WO97 / 30027 PCT 日期1997年8月21日一种治疗人或动物细菌感染的方法，其包括与β-内酰胺抗生素组合施用治疗有效量的式（I）的氨基酸衍生物或其药学上可接受的盐，溶剂合物 或其体内可水解的酯，其中：R为氢，形成盐的阳离子或体内可水解的酯形成基团; 羟基，氨基，硝基，羧基，（C 1-6）烷基羰基氧基，（C 1-6）烷氧基，（C 1-6）烷氧基， 烷氧基羰基，甲酰基或（C1-6）烷基羰基，（C3-7）环烷基，（C3-7）环烷基（C2-6）烷基，（C2-6）烯基，（C2-6）炔基，芳基， C 1-6）烷基，杂环基或杂环基（C 1-6）烷基; R2是氢，（C1-6）烷基或芳基（C1-6）烷基; R3是氢，任选被至多三个卤素原子取代的（C 1-6）烷基，（C 3-7）环烷基，稠合芳基（C 3-7）环烷基，（C 3-7）环烷基（C 2-6）烷基，（C 2 -6）烯基，（C 2-6）炔基，芳基，芳基 - （CHR 10）m X-（CHR 11）n，杂环基或杂环基 - （CHR 10）m X-（CHR 11）n，其中m为0至3，n为1 至3，每个R 10和R 11独立地为氢或（C 1-4）烷基，X为O，S（O）x，其中x为0-2，或键; R4是氢或体内可水解的酰基; 并且R 5和R 6独立地为氢和（C 1-6）烷基或一起代表（CH 2）p，其中p为2至5.一些化合物本身是要求的。