3-(6-{2-[2-(2-methoxy-phenylamino)-benzoxazol-6-yl]-acetylamino}-pyridin-3-yl)-butyric acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 3-(6-{2-[2-(2-methoxy-phenylamino)-benzoxazol-6-yl]-acetylamino}-pyridin-3-yl)-butyric acid
• 英文别名: 3-[6-[[2-[2-(2-Methoxyanilino)-1,3-benzoxazol-6-yl]acetyl]amino]pyridin-3-yl]butanoic acid
• 化学式: C₂₅H₂₄N₄O₅
• 分子量: 460.489
• InChiKey: HTFKAMFYXWBFIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (RS) methyl 3-{6-[2-(4-amino-3-hydroxy-phenyl)-acetylamino]-pyridin-3-yl}-butyrate 、 异氰酸2-甲氧苯酯 生成 3-(6-{2-[2-(2-methoxy-phenylamino)-benzoxazol-6-yl]-acetylamino}-pyridin-3-yl)-butyric acid
  参考文献：
  名称：

  Substituted bicyclic heteroaryl compounds and their use as integrin antagonists

  摘要：

  该发明涉及一般式(I)的生理活性化合物： R1Z1—Het—L1—Ar1—L2—Y  (I) 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；R1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；Z1代表直链键、烷基链、NR4、O或S(O)n；L1是一个a—R5—R6—连接，其中R5是烷基、烯基或炔基，R6是直链、环烷基、杂环烷基、芳基、杂芳基二烷基、—C(═Z3)—NR4—、—NR4—C(═Z3)—、—Z3—、—C(═O)—、—C(═NOR4)—、—NR4—、—NR4—C(═Z3)—NR4—、—SO2—NR4—、—NR4—SO2—、—O—C(═O)—、—C(═O)—O—、—NR4—C(═O)—O—或—O—C(═O)—NR4—；L2是一个直链；一个可选择取代的烷基、烯基、炔基、环烯基、环烷基、杂芳基二烷基、杂环烷基或芳基连接；一个—[C(═O)—N(R9)—C(R4)(R10)]p—连接；一个—Z4—R11—连接；一个—C(═O)—CH2—C(═O)—连接；一个—R11—Z4—R11—连接；或一个—L3—L4—L5—连接；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化合物（例如水合物）。 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：

  US20020173506A1

文献信息

• QUINAZOLINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1218357B1

  公开（公告）日：2005-04-06
• SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS AS INTEGRIN ANTAGONISTS
  申请人：Aventis Pharma Limited

  公开号：EP1183254A1

  公开（公告）日：2002-03-06
• US6706738B2
  申请人：——

  公开号：US6706738B2

  公开（公告）日：2004-03-16
• [EN] SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS AS INTEGRIN ANTAGONISTS<br/>[FR] COMPOSES D'HETEROARYLE BICYCLIQUE SUBSTITUE UTILISES COMME ANTAGONISTES DE L'INTEGRINE
  申请人：AVENTIS PHARMA LTD

  公开号：WO2000061580A1

  公开（公告）日：2000-10-19

  The invention is directed to physiologically active compounds of general formula (I) R?1Z1-Het-L1-Ar1-L2¿-Y wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring containing at least one heteroatom selected from O, S or N; R1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; Z1 represents a direct bond, an alkylene chain, NR4, O or S(O)¿n; L?1 is an a -R5-R6- linkage where R5 is alkylene, alkenylene or alkynylene and R6 is a direct bond, cycloalkylene, heterocycloalkylene, arylene, heteroaryldiyl, -C(=Z?3)-NR4-,-NR4-C(=Z3)-, -Z3¿-, -C(=O)-, -C(=NOR?4)-, -NR4-, -NR4-C(=Z3)-NR4¿-, -SO¿2?-NR?4-, -NR4-SO¿2-, -O-C(=O)-, -C(=O)-O-, -NR4-C(=O)-O- or -O-C(=O)-NR4-; L2 is a direct bond; an optionally substituted alkylene, alkenylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or arylene linkage; a -[C(=O)-N(R?9)-C(R4)(R10)]¿p- linkage; a -Z4-R11- linkage; a -C(=O)-CH¿2?-C(=O)- linkage; a -R?11-Z4-R11¿- linkage; or a -L3-L4-L5- linkage; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) 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 heteroaryl compounds and their use as integrin antagonists
  申请人：——

  公开号：US20020173506A1

  公开（公告）日：2002-11-21

  The invention is directed to physiologically active compounds of general formula (I): R 1 Z 1 —Het—L 1 —Ar 1 —L 2 —Y  (I) wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring containing at least one heteroatom selected from O, S or N; R 1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; Z 1 represents a direct bond, an alkylene chain, NR 4 , O or S(O) n ; L 1 is an a —R 5 —R 6 — linkage where R 5 is alkylene, alkenylene or alkynylene and R 6 is a direct bond, cycloalkylene, heterocycloalkylene, arylene, heteroaryldiyl, —C(═Z 3 )—NR 4 —, —NR 4 —C(═Z 3 )—, —Z 3 —, —C(═O)—, —C(═NOR 4 )—, —NR 4 —, —NR 4 —C(═Z 3 )—NR 4 —, —SO 2 —NR 4 —, —NR 4 —SO 2 —, —O—C(═O)—, —C(═O)—O—, —NR 4 —C(═O)—O— or —O—C(═O)—NR 4 —; L 2 is a direct bond; an optionally substituted alkylene, alkenylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or arylene linkage; a —[C(═O)—N(R 9 )—C(R 4 )(R 10 )] p — linkage; a —Z 4 —R 11 — linkage; a —C(═O)—CH 2 —C(═O)— linkage; a —R 11 —Z 4 —R 11 — linkage; or a —L 3 —L 4 —L 5 — linkage; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) 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： R1Z1—Het—L1—Ar1—L2—Y  (I) 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；R1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；Z1代表直链键、烷基链、NR4、O或S(O)n；L1是一个a—R5—R6—连接，其中R5是烷基、烯基或炔基，R6是直链、环烷基、杂环烷基、芳基、杂芳基二烷基、—C(═Z3)—NR4—、—NR4—C(═Z3)—、—Z3—、—C(═O)—、—C(═NOR4)—、—NR4—、—NR4—C(═Z3)—NR4—、—SO2—NR4—、—NR4—SO2—、—O—C(═O)—、—C(═O)—O—、—NR4—C(═O)—O—或—O—C(═O)—NR4—；L2是一个直链；一个可选择取代的烷基、烯基、炔基、环烯基、环烷基、杂芳基二烷基、杂环烷基或芳基连接；一个—[C(═O)—N(R9)—C(R4)(R10)]p—连接；一个—Z4—R11—连接；一个—C(═O)—CH2—C(═O)—连接；一个—R11—Z4—R11—连接；或一个—L3—L4—L5—连接；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化合物（例如水合物）。 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。