(R) 3-[(5-methyl-isoxazole-3-carbonyl)-amino]-3-{4-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-phenyl}-propionic acid | 306767-90-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R) 3-[(5-methyl-isoxazole-3-carbonyl)-amino]-3-{4-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-phenyl}-propionic acid
• 英文别名: (3R)-3-[4-[[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]amino]phenyl]-3-[(5-methyl-1,2-oxazole-3-carbonyl)amino]propanoic acid
• CAS: 306767-90-8
• 化学式: C₃₀H₂₇N₅O₆
• 分子量: 553.574
• InChiKey: PFFDYHADBVVRGC-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(2-methylphenylamino)-6-benzoxazolylacetic acid 、 (R) 3-(4-amino-phenyl)-3-[(5-methyl-isoxazole-3-carbonyl)-amino]-propionic acid tert-butyl ester 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 在 三氟乙酸 作用下， 以 N-甲基乙酰胺 、 二氯甲烷 为溶剂， 生成 (R) 3-[(5-methyl-isoxazole-3-carbonyl)-amino]-3-{4-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-phenyl}-propionic acid
  参考文献：
  名称：

  Substituted bicyclic compounds

  摘要：

  该发明涉及一般式(I)的生理活性化合物： 其中Het是一个可选择取代的、饱和的、部分饱和的或完全不饱和的含有至少一个来自O、S或N的杂原子的8到10成员的双环环系统；R 1 是可选择取代的芳基、杂环芳基、烷基、烯基、炔基、环烷基或杂环烷基；R 2 是氢、卤素、低烷基或低烷氧基；Z 1 是NR 5 ；L 1 是一个—R 6 —R 7 —连接（其中R 6 是烷基、烯基或炔基，R 7 是直接键、环烷基、杂环烷基、芳基二基、杂芳基二基、—C(═Z 3 )—NR 5 —、—NR 5 —C(═Z 3 )—、—Z 3 —、—C(═O)—、—C(═NOR 5 )—、—NR 5 —、—NR 5 —C(═Z 3 )—NR 5 —、—SO 2 —NR 5 —、—NR 5 —SO 2 —、—O—C(═O)—、—C(═O)—O—、—NR 5 —C(═O)—O—或—O—C(═O)—NR 5 —）；L 2 是被羟基、氧代、—OR 4 、—O—C(═O)—R 4 、—N(R 8 )—C(═O)—R 9 、—N(R 8 )—C(═O)—OR 9 、—N(R 8 )—SO 2 —R 9 或—NY 3 Y 4 取代的烷基链；Y是羧基或酸生物同位素；以及相应的N-氧化物，它们的前药；以及这些化合物及其N-氧化物和前药的药学上可接受的盐和溶剂。 这些化合物具有有价值的药理特性，特别是调节VCAM-1和纤维连接蛋白与整合素VLA-4（α4β1）相互作用的能力。

  公开号：

  US20020156111A1

文献信息

• SUBSTITUTED BICYCLIC COMPOUNDS
  申请人：Aventis Pharma Limited

  公开号：EP1177181A1

  公开（公告）日：2002-02-06
• US6562851B2
  申请人：——

  公开号：US6562851B2

  公开（公告）日：2003-05-13
• [EN] SUBSTITUTED BICYCLIC COMPOUNDS<br/>[FR] COMPOSES BICYCLIQUES SUBSTITUES
  申请人：AVENTIS PHARMA LTD

  公开号：WO2000068213A1

  公开（公告）日：2000-11-16

  The invention is directed to physiologically active compounds of general formula (I): wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring system containing at least one heteroatom selected from O, S or N; R1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; R2 is hydrogen, halogen, lower alkyl or lower alkoxy; Z?1 is NR5; L1¿ is a -R6-R7- linkage (where R6 is alkylene, alkenylene or alkynylene and R7 is a direct bond, cycloalkylene, heterocycloalkylene, aryldiyl, heteroaryldiyl, -C(=Z?3)-NR5-, -NR5-C(=Z3)-, -Z3¿-, -C(=O)-, -C(=NOR?5)-, -NR5-, -NR5-C(=Z3)-NR5¿-, -SO¿2?-NR?5-, -NR5-SO¿2-, -O-C(=O)-, -C(=O)-O-, -NR5-C(=O)-O- or -O-C(=O)-NR5-); L2 is an alkylene chain substituted by hydroxy, oxo, -OR4, -O-C(=O)-R?4, -N(R8¿)-C(=O)-R?9, -N(R8¿)-C(=O)-OR?9, -N(R8)-SO¿2-R9, or -NY3 Y4; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1)
• Substituted bicyclic compounds
  申请人：——

  公开号：US20020156111A1

  公开（公告）日：2002-10-24

  The invention is directed to physiologically active compounds of general formula (I): 1 wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring system containing at least one heteroatom selected from O, S or N; R 1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; R 2 is hydrogen, halogen, lower alkyl or lower alkoxy; Z 1 is NR 5 ; L 1 is a —R 6 —R 7 — linkage (where R 6 is alkylene, alkenylene or alkynylene and R 7 is a direct bond, cycloalkylene, heterocycloalkylene, aryldiyl, heteroaryldiyl, —C(═Z 3 )—NR 5 —, —NR 5 —C(═Z 3 )—, —Z 3 —, —C(═O)—, —C(═NOR 5 )—, —NR 5 —, —NR 5 —C(═Z 3 )—NR 5 —, —SO 2 —NR 5 —, —NR 5 —SO 2 —, —O—C(═O)—, —C(═O)—O—, —NR 5 —C(═O)—O— or —O—C(═O)—NR 5 —); L 2 is an alkylene chain substituted by hydroxy, oxo, —OR 4 , —O—C(═O)—R 4 , —N(R 8 )—C(═O)—R 9 , —N(R 8 )—C(═O)—OR 9 , —N(R 8 )—SO 2 —R 9 , or —NY 3 Y 4 ; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (&agr;4&bgr;1).

  该发明涉及一般式(I)的生理活性化合物： 其中Het是一个可选择取代的、饱和的、部分饱和的或完全不饱和的含有至少一个来自O、S或N的杂原子的8到10成员的双环环系统；R 1 是可选择取代的芳基、杂环芳基、烷基、烯基、炔基、环烷基或杂环烷基；R 2 是氢、卤素、低烷基或低烷氧基；Z 1 是NR 5 ；L 1 是一个—R 6 —R 7 —连接（其中R 6 是烷基、烯基或炔基，R 7 是直接键、环烷基、杂环烷基、芳基二基、杂芳基二基、—C(═Z 3 )—NR 5 —、—NR 5 —C(═Z 3 )—、—Z 3 —、—C(═O)—、—C(═NOR 5 )—、—NR 5 —、—NR 5 —C(═Z 3 )—NR 5 —、—SO 2 —NR 5 —、—NR 5 —SO 2 —、—O—C(═O)—、—C(═O)—O—、—NR 5 —C(═O)—O—或—O—C(═O)—NR 5 —）；L 2 是被羟基、氧代、—OR 4 、—O—C(═O)—R 4 、—N(R 8 )—C(═O)—R 9 、—N(R 8 )—C(═O)—OR 9 、—N(R 8 )—SO 2 —R 9 或—NY 3 Y 4 取代的烷基链；Y是羧基或酸生物同位素；以及相应的N-氧化物，它们的前药；以及这些化合物及其N-氧化物和前药的药学上可接受的盐和溶剂。 这些化合物具有有价值的药理特性，特别是调节VCAM-1和纤维连接蛋白与整合素VLA-4（α4β1）相互作用的能力。