2-(4-甲氧基苯基)-4-甲基-1,3-噻唑-5-羧酸 | 54001-16-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(4-甲氧基苯基)-4-甲基-1,3-噻唑-5-羧酸
• 中文别名: 2-(4-甲氧苯基)-4-甲基-5-噻唑羧酸；2-(4-甲氧苯基)-4-甲基-噻唑-5-羧酸；2-(4-甲氧苯基)-4-甲基-1,3-噻吩-5-甲酸；2-(4-甲氧苯基)-4-甲基-1,3-噻唑-5-羧酸；2-(4-甲氧基苯基)-4-甲基噻唑-5-羧酸
• 英文名称: 4-methyl-2-[4-(methoxy)phenyl]-1,3-thiazole-5-carboxylic acid
• 英文别名: 2-(4-methoxy phenyl)-4-methyl-1,3-thiazol-5-carboxylic acid；2-(4-methoxyphenyl)-4-methyl-5-thiazolecarboxylic acid；2-(4-methoxy-phenyl)-4-methyl-thiazole-5-carboxylic acid；2-(4-methoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic Acid
• CAS: 54001-16-0
• 化学式: C₁₂H₁₁NO₃S
• mdl: MFCD06857928
• 分子量: 249.29
• InChiKey: HWHHZTHVYFDJNK-UHFFFAOYSA-N

物化性质

• 熔点：
  236-241℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  87.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  2-(4-甲氧基苯基)-4-甲基-1,3-噻唑-5-羧酸 在 氯化亚砜 、 氢溴酸 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 allyl-[2'-(4-methoxy-phenyl)-4'-methyl-[4,5']bithiazolyl-2-yl]-amine
  参考文献：
  名称：

  Csavassy,G.; Gyoerfi,Z.A., Justus Liebigs Annalen der Chemie, 1974, p. 1195 - 1205

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲氧基硫代苯甲胺 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 25.5h， 生成 2-(4-甲氧基苯基)-4-甲基-1,3-噻唑-5-羧酸
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• Decarboxylative Cross-Coupling of Azoyl Carboxylic Acids with Aryl Halides
  作者：Fengzhi Zhang、Michael F. Greaney

  DOI：10.1021/ol1019597

  日期：2010.11.5

  Decarboxylative cross-coupling of thiazole and oxazole-5-carboxylic acids with aryl halides is reported. Under a bimetallic system of catalytic palladium and a stoichiometric silver carbonate, a variety of (hetero)arylated azoles can be prepared in excellent yield.

  据报道噻唑和恶唑-5-羧酸与芳基卤的脱羧交叉偶联。在催化钯和化学计量的碳酸银的双金属体系下，可以以高收率制备各种（杂）芳基化的唑。
• Carboxamide derivatives having tetrazole and thiazole rings and their use
  申请人：Sawai Pharmaceutical Co., Ltd.

  公开号：US04946855A1

  公开（公告）日：1990-08-07

  A compound of the formula: ##STR1## wherein the free valency of the groups A-, R- and --X--Y-- is attached to any of 2-, 4- and 5- positions of the thiazol ring, A is a C.sub.1-6 alkyl group, an aryl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of hydroxy C.sub.1-6 alkoxy, aryl-(C.sub.1-6)alkoxy, halo-(C.sub.1-6)alkyl, halogen, and nitro, or 5- or 6-membered heterocyclic group containing at least one hetero atom selected from oxygen, nitrogen and sulfur, or a condensed heterocyclic group consisting of a heterocycle as defined above and a benzene nucleus, these two heterocyclic groups being unsubstituted or substituted with at least one substituent selected from halogen, R is hydrogen or a C.sub.1-6 alkyl group, X is --CO--or --NH--, and Y is --NH--or --CO--, with the proviso that (a) X and Y cannot be the same group, and (b) when X is --CO--and Y is --NH--, the group --X--Y--is attached to 2- or 5-position, or a pharmaceutically acceptable salt thereof are nobel and useful as antiallergic.

  该化合物的分子式为：##STR1##其中A-、R-和--X--Y--的自由价键附着在噻唑环的2-、4-和5-位置之一，A是C.sub.1-6烷基基团，是未取代或取代的芳基基团，其取代基选自羟基C.sub.1-6烷氧基、芳基-(C.sub.1-6)烷氧基、卤代-(C.sub.1-6)烷基、卤素和硝基，或者含有氧、氮和硫中的至少一个杂原子的5-或6-成员杂环基团，或者由上述定义的杂环和苯环核组成的缩合杂环基团，这两个杂环基团未取代或取代，取代基选自卤素，R是氢或C.sub.1-6烷基基团，X是--CO--或--NH--，Y是--NH--或--CO--，但是有以下限制：(a)X和Y不能是相同的基团，(b)当X是--CO--且Y是--NH--时，基团--X--Y--附着在2-或5-位置，或其药学上可接受的盐被用作抗过敏药物。
• Carboxylic acid derivative and medicine comprising salt or ester of the same
  申请人：——

  公开号：US20040214888A1

  公开（公告）日：2004-10-28

  The present invention provides novel carboxylic acid derivatives useful as an insulin sensitizer, a salt thereof or a hydrate of them, and a medicament comprising the derivative as the active ingredient. Specifically, it provides a carboxylic acid derivative represented by the following formula: 1 (wherein L represents a single bond, or a C1 to C6 alkylene group, a C2 to C6 alkenylene group or a C2 to C6 alkynylene group, each of which may have one or more substituent groups; M represents a single bond, or a C1 to C6 alkylene group, a C2 to C6 alkenylene group or a C2 to C6 alkynylene group, each of which may have one or more substituent groups; T represents a single bond, or a C1 to C3 alkylene group, a C2 to C3 alkenylene group or a C2 to C3 alkynylene group, each of which may have one or more substituent groups; W represents a carboxyl group; X represents a single bond, an oxygen atom, or a group represented by the various substituent groups including —NR X1 CQ 1 O— (wherein Q 1 represents an oxygen atom or a sulfur atom; R X1 represents a hydrogen atom, a cyano group, a formyl group, or various groups including a C1 to C6 alkyl group and a C1 to C6 hydroxyalkyl group, each of which may have one or more substituent groups), ONR X1 CQ 1 —, —NR X1 CQ 1 —, —CQ 1 NR X1 —, —NR X1a CQ 1 NR X1b —, —Q 2 SO 2 — and —SO 2 Q 2 —; Y represents a 5 to 14-membered aromatic group which may have one or more substituent groups and one or more hetero atoms, or a C3 to C7 alicyclic hydrocarbon group; and the rings Z and U may be the same as or different from each other and each represents a 5 to 14-membered aromatic group which may have 1 to 4 substituent groups and one or more hetero atoms, and the ring may be partially saturated.), a salt thereof, an ester thereof or a hydrate of them.

  本发明提供了一种新型羧酸衍生物，可用作胰岛素增敏剂，其盐或其水合物，以及包含该衍生物作为活性成分的药物。具体而言，本发明提供了一种由以下式子表示的羧酸衍生物：1（其中L表示单键，或C1至C6烷基，C2至C6烯基或C2至C6炔基，每个基团都可以有一个或多个取代基；M表示单键，或C1至C6烷基，C2至C6烯基或C2至C6炔基，每个基团都可以有一个或多个取代基；T表示单键，或C1至C3烷基，C2至C3烯基或C2至C3炔基，每个基团都可以有一个或多个取代基；W表示羧基；X表示单键，氧原子，或由各种取代基表示的基团，包括-NRX1CQ1O-（其中Q1表示氧原子或硫原子；RX1表示氢原子，氰基，甲酰基或各种基团，包括C1至C6烷基和C1至C6羟基烷基，每个基团都可以有一个或多个取代基），ONRX1CQ1-，-NRX1CQ1-，-CQ1NRX1-，-NRX1aCQ1NRX1b-，-Q2SO2-和-SO2Q2-；Y表示一个具有1个或多个取代基和1个或多个杂原子的5至14环芳基，或一个C3至C7脂环烃基；环Z和环U可以相同或不同，每个环表示一个具有1至4个取代基和1个或多个杂原子的5至14环芳基，环可能部分饱和），其盐，酯或其水合物。
• CARBOXYLIC ACID DERIVATIVE AND MEDICINE COMPRISING SALT OR ESTER OF THE SAME
  申请人：Eisai Co., Ltd.

  公开号：EP1394147A1

  公开（公告）日：2004-03-03

  The present invention provides novel carboxylic acid derivatives useful as an insulin sensitizer, a salt thereof or a hydrate of them, and a medicament comprising the derivative as the active ingredient. Specifically, it provides a carboxylic acid derivative represented by the following formula: (wherein L represents a single bond, or a C1 to C6 alkylene group, a C2 to C6 alkenylene group or a C2 to C6 alkynylene group, each of which may have one or more substituent groups; M represents a single bond, or a C1 to C6 alkylene group, a C2 to C6 alkenylene group or a C2 to C6 alkynylene group, each of which may have one or more substituent groups; T represents a single bond, or a C1 to C3 alkylene group, a C2 to C3 alkenylene group or a C2 to C3 alkynylene group, each of which may have one or more substituent groups; W represents a carboxyl group; X represents a single bond, an oxygen atom, or a group represented by the various substituent groups including -NRX1CQ1O- (wherein Q1 represents an oxygen atom or a sulfur atom; RX1 represents a hydrogen atom, a cyano group, a formyl group, or various groups including a C1 to C6 alkyl group and a C1 to C6 hydroxyalkyl group, each of which may have one or more substituent groups) , ONRX1CQ1-, -NRX1CQ1-, -CQ1NRX1-, -NRX1aCQ1NRX1b-, -Q2SO2- and -SO2Q2-; Y represents a 5 to 14-membered aromatic group which may have one or more substituent groups and one or more hetero atoms, or a C3 to C7 alicyclic hydrocarbon group; and the rings Z and U may be the same as or different from each other and each represents a 5 to 14-membered aromatic group which may have 1 to 4 substituent groups and one or more hetero atoms, and the ring may be partially saturated.), a salt thereof, an ester thereof or a hydrate of them.

  本发明提供了可用作胰岛素增敏剂的新型羧酸衍生物、其盐或水合物，以及以该衍生物为活性成分的药物。具体地说，它提供了由下式表示的羧酸衍生物： (其中 L 代表单键，或 C1 至 C6 亚烷基、C2 至 C6 烯基或 C2 至 C6 亚炔基，其中每个基团可具有一个或多个取代基；M 代表单键，或 C1 至 C6 亚烷基、C2 至 C6 烯基或 C2 至 C6 亚炔基，其中每个基团可具有一个或多个取代基；T 代表单键，或 C1 至 C3 亚烷基、C2 至 C3 烯基或 C2 至 C3 亚炔基，其中每个基团可带有一个或多个取代基； W 代表羧基； X 代表单键、氧原子或由各种取代基团代表的基团，包括 -NRX1CQ1O- （其中 Q1 代表氧原子或硫原子；RX1 代表氢原子、氰基、甲酰基或包括 C1 至 C6 烷基和 C1 至 C6 羟烷基在内的各种基团，其中每个基团可具有一个或多个取代基）、 ONRX1CQ1-、-NRX1CQ1-、-CQ1NRX1-、-NRX1aCQ1NRX1b-、-Q2SO2- 和 -SO2Q2-；Y 代表 5 至 14 元芳香基团，可带有一个或多个取代基团和一个或多个杂原子，或 C3 至 C7 脂环烃基团；且环 Z 和 U 可彼此相同或不同，且各自代表 5 至 14 元芳香基团，可带有 1 至 4 个取代基团和一个或多个杂原子，且环可为部分饱和。)、其盐、其酯或它们的水合物。
• Discovery of cyclic amine-substituted benzoic acids as PPARα agonists
  作者：Masahiro Nomura、Kazuhiro Yumoto、Takehiro Shinozaki、Shigeki Isogai、Yasuo Takano、Koji Murakami

  DOI：10.1016/j.bmcl.2011.11.002

  日期：2012.1

  A series of novel cyclic amine-substituted benzoic acid derivatives were synthesized and evaluated for their PPAR alpha agonist activity. Strucure-activity relationship studies led to the identification of (S)-3-[3[2-(4-chlorophenyl)-4-methylthyazole-5-carboxamido] piperidin-1-yl] benzoic acid (S)-4f (KRP-105) as a potent and high subtype-selective human PPARa agonist. (S)-4f showed excellent PK profile and oral administration of (S)-4f to high-fat diet dogs effectively lowered triglycerides. (C) 2011 Elsevier Ltd. All rights reserved.