3-(3-cyclopentyloxy-4-methoxy-phenylsulfonyl)-7-phenylheptanoic acid | 211098-08-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3-cyclopentyloxy-4-methoxy-phenylsulfonyl)-7-phenylheptanoic acid
• 英文别名: 3-(3-Cyclopentyloxy-4-methoxyphenyl)sulfonyl-7-phenylheptanoic acid
• CAS: 211098-08-7
• 化学式: C₂₅H₃₂O₆S
• 分子量: 460.591
• InChiKey: CSNVYWIAXBAJKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  98.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(3-cyclopentyloxy-4-methoxy-phenylsulfonyl)-7-phenylheptanoic acid 在 hydroxylamine resin 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 3-(3-cyclopentyloxy-4-methoxyphenylsulfonyl)-7-phenylheptanohydroxamic acid
  参考文献：
  名称：

  Solid-phase synthesis of an arylsulfone hydroxamate library

  摘要：

  Synthesis of an arylsulfone hydroxamate lead optimization library is presented. Biological activity of representative examples is given to demonstrate the value of this approach for lead optimization. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00285-7
• 作为产物：
  描述：

  二乙基磷乙酸 、 苯戊醛 、 3-cyclopentyloxy-4-methoxybenzene thiol 生成 3-(3-cyclopentyloxy-4-methoxy-phenylsulfonyl)-7-phenylheptanoic acid
  参考文献：
  名称：

  Solid-phase synthesis of an arylsulfone hydroxamate library

  摘要：

  Synthesis of an arylsulfone hydroxamate lead optimization library is presented. Biological activity of representative examples is given to demonstrate the value of this approach for lead optimization. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00285-7

文献信息

• Substituted B-thiocarboxylic acids
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP1486486A2

  公开（公告）日：2004-12-15

  This invention relates to compounds of general formula (I) : wherein    R1 and R3 may be the same or different and each independently represents a group -L1-R5 [where L1 is a direct bond, a straight or branched C1-6alkylene chain, a straight or branched C2-6alkenylene chain, a straight or branched C2-6alkynylene chain or a straight or branched C1-6alkylene chain containing an oxygen or sulfur atom, a phenylene, imino (-NH-) or alkylimino linkage, or a sulfinyl or sulfonyl group, in which each of the alkylene, alkenylene and alkynylene chains may be optionally substituted, the substituents chosen from alkoxy, aryl, carboxy, cyano, cycloalkyl, halogen, heteroaryl, hydroxyl, or oxo; and R5 represents hydrogen, aryl, aroyl, carboxy or an acid bioisostere, cyano, cycloalkyl, cycloalkenyl, heterocycloalkyl, heteroaryl, arylalkoxycarbonyl, -NH-C(=O)-NH2, -C=N-O-C(=O)-NH2, -C(=O)-NY1Y2, -NY1SO2aryl, -NHR6, -SR6, or -OR6];    R2 and R4 may be the same or different and are each independently hydrogen or alkyl; or    R2 and R4 together form a bond; or R1 and R2, or R1 and R3, or R3 and R4 together with the carbon atom(s) to which they are attached form a 3 to 8 membered cycloalkyl or cycloalkenyl ring, optionally substituted by alkyl, arylalkyl, or heteroarylalkyl, and which may optionally contain a heteroatom selected from O, S or NR6; or R1 and R3 together with the carbon atoms to which they are attached form a heteroaryl ring;    Y represents tetrazolyl, 3,5-dioxo-1,2,4-oxadiazolidinyl, 3-hydroxyisoxazolyl or 3-hydroxy-1-methylpyrazolyl;    A1 represents a direct bond, a straight or branched C1-4alkylene chain or a NR6 group;    Ar is a group chosen from : and and    n is 0, 1 or 2;    and N-oxides thereof, and their prodrugs, pharmaceutically acceptable salts, and solvates (e.g. hydrates), thereof. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.

  本发明涉及通式 (I) 的化合物： 其中 R1 和 R3 可以相同或不同，各自独立地代表一个基团 -L1-R5 [其中 L1 是直接键、直链或支链 C1-6 烯链、直链或支链 C2-6 烯链、直链或支链 C2-6 烯链或含有氧原子或硫原子的直链或支链 C1-6 烯链、亚苯基、亚氨基（-NH-）或烷基亚氨基连接，或亚磺酰基或磺酰基，其中每个亚 烷基、亚烯基和亚炔基链可任选被取代，取代基选自烷氧基、芳基、羧基、氰基、 环烷基、卤素、杂芳基、羟基或氧代；R5 代表氢、芳基、芳烷基、羧基或酸生物异构体、氰基、环烷基、环烯 基、杂环烷基、杂芳基、芳基烷氧基羰基、-NH-C(=O)-NH2、-C=N-O-C(=O)-NH2、-C(=O)-NY1Y2、-NY1SO2 芳基、-NHR6、-SR6 或-OR6]； R2 和 R4 可以相同或不同，各自独立地为氢或烷基；或 R2 和 R4 一起形成键；或 R1 和 R2、或 R1 和 R3、或 R3 和 R4 与它们所连接的碳原子一起形成 3 至 8 个成员的环烷基或环 烯基环，可任选被烷基、芳烷基或杂芳基烷基取代，并可任选含有选自 O、S 或 NR6 的杂原子；或 R1 和 R3 与它们所连接的碳原子一起形成杂芳基环； Y 代表四唑基、3,5-二氧代-1,2,4-恶二唑烷基、3-羟基异恶唑基或 3-羟基-1-甲基吡唑基； A1 代表直接键、直链或支链 C1-4 烯链或 NR6 基团； Ar 是选自......的基团 和 和 n 是 0、1 或 2； 及其 N-氧化物，以及它们的原药、药学上可接受的盐和溶解物（如水合物）。 此类化合物可抑制 TNF 的产生或生理效应，并抑制环 AMP 磷酸二酯酶。本发明还涉及包含式（I）化合物的药物组合物、其药物用途及其制备方法。
• SUBSTITUTED $g(b)-THIOCARBOXYLIC ACIDS
  申请人：RHONE-POULENC RORER PHARMACEUTICALS, INC.

  公开号：EP0960096A1

  公开（公告）日：1999-12-01
• SUBSTITUTED BETA-THIOCARBOXYLIC ACIDS
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP0960096B1

  公开（公告）日：2005-04-06
• US6306873B1
  申请人：——

  公开号：US6306873B1

  公开（公告）日：2001-10-23
• [EN] SUBSTITUTED beta -THIOCARBOXYLIC ACIDS<br/>[FR] ACIDES BETA-THIOCARBOXYLIQUES SUBSTITUES
  申请人：RHONE-POULENC RORER PHARMACEUTICALS INC.

  公开号：WO1998032734A1

  公开（公告）日：1998-07-30

  (EN) This invention relates to compounds of general formula (I), wherein R1 and R3 may be the same or different and each independently represents a group -L1-R5, where L1 is a direct bond, a straight or branched C1-6alkylene chain, a straight or branched C2-6alkenylene chain, a straight or branched C2-6alkynylene chain or a straight or branched C1-6alkylene chain containing an oxygen or sulfur atom, a phenylene, imino (-NH-) or alkylimino linkage, or a sulfinyl or sulfonyl group, in which each of the alkylene, alkenylene and alkynylene chains may be optionally substituted, the substituents chosen from alkoxy, aryl, carboxy, cyano, cycloalkyl, halogen, hereroaryl, hydroxyl, or oxo; and R5 represents hydrogen, aryl, aroyl, carboxy or an acid bioisostere, cyano, cycloalkyl, cycloalkenyl, heterocycloalkyl, heteroaryl, arylalkoxycarbonyl, -NH-C(=O)-NH2, -C=N-O-C(=O)-NH2, -C(=O)-NY1Y2, -NY1SO2aryl, -NHR6, -SR6, or -OR6; R2 and R4 may be the same or different and are each independently hydrogen or alkyl; or R2 and R4 together form a bond; or R1 and R2, or R1 and R3, or R3 and R4 together with the carbon atom(s) to which they are attached form a 3 to 8 membered cycloalkyl or cycloalkenyl ring, optionally substituted by alkyl, arylalkyl, or heteroarylalkyl, and which may optionally contain a heteroatom selected from O, S or NR6; or R1 and R3 together with the carbon atoms to which they are attached form a heteroaryl ring; Y represents carboxy or an acid bioisostere; A1 represents a direct bond, a straight or branched C1-4alkylene chain or a NR6 group; Ar is a group chosen from (i) and (ii) and n is 0, 1 or 2; and N-oxides thereof, and their prodrugs, pharmaceutically acceptable salts, and solvates (e.g. hydrates), thereof. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation. (FR) L'invention concerne des composés de formule générale (I), dans laquelle R1 et R3 peuvent être identiques ou différents et représentent chacun indépendamment un groupe -L1-R5 [dans lequel L1 est une liaison directe, une chaîne alkylène C1-6 linéaire ou ramifiée, une chaîne alcénylène C2-6 linéaire ou ramifiée, une chaîne alcynylène C2-6 linéaire ou ramifiée, une chaîne alkylène C1-6 linéaire ou ramifiée contenant un atome d'oxygène ou de soufre, une liaison phénylène, imino (-NH-) ou alkylimino, ou un groupe sulfinyle ou sulfonyle, chaque chaîne alkylène, alcénylène et alcynylène pouvant être éventuellement substituée, les substituants étant choisis parmi alcoxy, aryle, carboxy, cyano, cycloalkyle, halogène, hétéroaryle, hydroxyle ou oxo; et R5 représente hydrogène, aryle, aroyle, carboxy ou un bioisostère acide, cyano, cycloalkyle, cycloalcényle, hétérocycloalkyle, hétéroaryle, arylalcoxycarbonyle, -NH-C(=O)-NH2, -C=N-O-C(=O)-NH2, -C(=O)-NY1Y2, -NY1SO2aryle, -NHR6,-SR6, ou -OR6]; R2 et R4 peuvent être identiques ou différents et représentent chacun hydrogène ou alkyle; ou R2 et R4 forment ensemble une liaison; ou R1 et R2, ou R1 et R3 ou R3 et R4 conjointement avec le ou les atomes de carbone auxquels ils sont attachés forment un cycle cycloalcényle ou cycloalkyle à 3 à 8 éléments, éventuellement substitué par alkyle, arylalkyle ou hétéroarylalkyle et peuvent éventuellement contenir un hétéroatome choisi parmi O, S ou NR6; ou R1 et R3 conjointement avec les atomes de carbone auxquels ils sont attachés forment un cycle hétéroaryle; Y représente carboxy ou un bioisostère acide; A1 représente une liaison directe, une chaîne alkylène C1-4 linéaire ou ramifiée ou un groupe NR6; Ar représente un groupe choisi dans (i) et (ii), et n vaut 0, 1 ou 2. L'invention se rapporte également aux N-oxydes desdits composés, leurs promédicaments, des sels pharmaceutiquement acceptables et des solvates (ex. hydrates) de ceux-ci. Lesdits composés inhibent la production ou les effets physiologiques de TNF et inhibent l'AMP phosphodiestérase. L'invention porte aussi sur des compositions pharmaceutiques comprenant des composés de formule (I), leur utilisation pharmaceutique et leurs méthodes de préparation.