ethyl 2-methyl-4-(4-methylphenyl)thiazole-5-carboxylate | 159448-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-methyl-4-(4-methylphenyl)thiazole-5-carboxylate
• 英文别名: 2-methyl-4-p-tolyl-thiazole-5-carboxylic acid ethyl ester；2-Methyl-4-(4-methylphenyl)-5-ethoxycarbonylthiazole；ethyl 2-methyl-4-(4-methylphenyl)-1,3-thiazole-5-carboxylate
• CAS: 159448-57-4
• 化学式: C₁₄H₁₅NO₂S
• 分子量: 261.345
• InChiKey: UKDMJXJPDOXXMX-UHFFFAOYSA-N

物化性质

• 沸点：
  402.6±33.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-methyl-4-(4-methylphenyl)thiazole-5-carboxylate 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 水 、 sodium hydride 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 为溶剂， 反应 23.0h， 生成 2-butyl-5-chloro-4-(hydroxymethyl)-1-<<1-(5-carboxy-2-methylthiazol-4-yl)-4-phenyl>methyl>-1H-imidazole
  参考文献：
  名称：

  Nonpeptide Angiotensin II Receptor Antagonists. Synthesis, in vitro Activity, and Molecular Modeling Studies of N-[(Heterobiaryl)methyl]imidazoles

  摘要：

  With the aim of explaining the influence of the structural changes on the biphenylic moiety on the activity, a series of N-[(heterobiaryl)methyl]imidazoles (I), constructed on the model of DuPont compounds by replacing either the central or terminal phenyl ring with a heteroaromatic one, such as furan, thiophene, thiazole, and pyridine, was synthesized. Compared to the reference DuPont compound (EXP-7711), all the heterobiaryl derivatives showed a reduced potency both in receptor binding (rat adrenal capsular membranes) and in the functional assay (angiotensin II-induced contraction of rabbit aorta strips). The lower activity was justified by the extensive molecular modeling studies, which took into consideration the conformational and electrostatic features of several heterobiaryl derivatives. On the basis of the results obtained, it was hypothesized that the central aromatic ring of the biarylic portion works as a spacer, orienting in the right way the terminal phenyl ring, whose electronic distribution is, instead, crucial to its fitting well with a lipophilic pocket at the receptor site.

  DOI：

  10.1021/jm00049a012
• 作为产物：
  描述：

  (4-甲基苯甲酰基)乙酸乙酯 在 溴 作用下， 以 四氯化碳 、 乙醇 为溶剂， 反应 4.5h， 生成 ethyl 2-methyl-4-(4-methylphenyl)thiazole-5-carboxylate
  参考文献：
  名称：

  Nonpeptide Angiotensin II Receptor Antagonists. Synthesis, in vitro Activity, and Molecular Modeling Studies of N-[(Heterobiaryl)methyl]imidazoles

  摘要：

  With the aim of explaining the influence of the structural changes on the biphenylic moiety on the activity, a series of N-[(heterobiaryl)methyl]imidazoles (I), constructed on the model of DuPont compounds by replacing either the central or terminal phenyl ring with a heteroaromatic one, such as furan, thiophene, thiazole, and pyridine, was synthesized. Compared to the reference DuPont compound (EXP-7711), all the heterobiaryl derivatives showed a reduced potency both in receptor binding (rat adrenal capsular membranes) and in the functional assay (angiotensin II-induced contraction of rabbit aorta strips). The lower activity was justified by the extensive molecular modeling studies, which took into consideration the conformational and electrostatic features of several heterobiaryl derivatives. On the basis of the results obtained, it was hypothesized that the central aromatic ring of the biarylic portion works as a spacer, orienting in the right way the terminal phenyl ring, whose electronic distribution is, instead, crucial to its fitting well with a lipophilic pocket at the receptor site.

  DOI：

  10.1021/jm00049a012

文献信息

• [EN] THIAZOLIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS THIAZOLIDINES EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010004507A1

  公开（公告）日：2010-01-14

  The invention relates to thiazolidine derivatives of the formula (I) wherein A, B, and R1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to their use as medicaments, especially as orexin receptor antagonists.

  这项发明涉及式(I)的噻唑啉衍生物，其中A、B和R1如描述中所述，以及这些化合物的盐，特别是药学上可接受的盐，以及它们作为药物的用途，特别是作为促进睡眠的药物受体拮抗剂。
• [EN] PHENETHYLAMIDE DERIVATIVES AND THEIR HETEROCYCLIC ANALOGUES<br/>[FR] DÉRIVÉS DE PHÉNÉTHYLAMIDE ET LEURS ANALOGUES HÉTÉROCYCLIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010044054A1

  公开（公告）日：2010-04-22

  The invention relates to novel phenethylamide derivatives and their heterocyclic analogues of formula (I), wherein A, B, R1, R2 and R3 are as described in the application, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.

  这项发明涉及新型苯乙酰胺衍生物及其异环类似物，其化学式为(I)，其中A、B、R1、R2和R3如申请中所述，并且涉及将这种化合物或这种化合物的药用可接受盐用作药物，特别是促进睡眠的药物受体拮抗剂。
• THIAZOLIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS
  申请人：Aissaoui Hamed

  公开号：US20110105491A1

  公开（公告）日：2011-05-05

  The invention relates to thiazolidine derivatives of the formula (I) wherein A, B, and R 1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to their use as medicaments, especially as orexin receptor antagonists.

  这项发明涉及式(I)的噻唑啉衍生物，其中A、B和R1如描述中所述，以及这些化合物的盐，特别是药用可接受的盐，以及它们作为药物的用途，特别是作为促进睡眠的药物受体拮抗剂。
• Imidazole ethers having a II antagonist activity
  申请人：Istituto Luso Farmaco D'Italia S.p.A.

  公开号：US05538987A1

  公开（公告）日：1996-07-23

  Compounds of general formula (I) ##STR1## wherein E is O or S; R is C.sub.1 -C.sub.5 straight, branched or cyclic alkyl or C.sub.2 -C.sub.5 alkenyl; X can be H, F, Cl, Br, I, CF.sub.3 ; n is an integer 1 to 4; m is an integer 0 to 4; A and B are 5- or 6- membered aromatic carbocyclic rings optionally containing one or more heteroatoms selected from N, O, S and carrying the substituents R.sub.1, R.sub.2 and R.sub.3, respectively; R.sub.1 can be hydrogen, halogen, C.sub.1 -C.sub.4 alkoxycarbonyl, a sulfonic group or a tetrazole group of formula ##STR2## wherein R.sub.4 can be hydrogen or C.sub.1 -C.sub.5 alkyl; R.sub.2 can be hydrogen or a COOR.sub.4 group (wherein R.sub.4 is hydrogen or C.sub.1 -C.sub.5 alkyl), CN, SO.sub.3 H, PO.sub.3 H or a tetrazole group R.sub.3 ; can be a hydrogen or a moiety of formula (II) B'(R'.sub.2,R'.sub.3) (II) wherein: B.sup.1, R.sup.1.sub.2 have the same meanings reported above for B and R.sub.2, R'.sub.3 is H; with the proviso that when A is phenyl, R.sub.1 is different from H, and the pharmaceutically acceptable salts thereof.

  通式（I）的化合物##STR1##其中E为O或S；R为C.sub.1-C.sub.5直链、支链或环烷基或C.sub.2-C.sub.5烯基；X可以是H、F、Cl、Br、I、CF.sub.3；n为1到4的整数；m为0到4的整数；A和B为5-或6-成员芳香碳环，可选地含有来自N、O、S的一个或多个杂原子，并携带取代基R.sub.1、R.sub.2和R.sub.3，分别；R.sub.1可以是氢、卤素、C.sub.1-C.sub.4烷氧羰基、磺酰基或式的四唑基团##STR2##其中R.sub.4可以是氢或C.sub.1-C.sub.5烷基；R.sub.2可以是氢或COOR.sub.4基团（其中R.sub.4为氢或C.sub.1-C.sub.5烷基）、CN、SO.sub.3 H、PO.sub.3 H或四唑基团R.sub.3；可以是氢或式的一个基团（II）B'(R'.sub.2,R'.sub.3)（II）其中：B.sup.1，R.sup.1.sub.2具有上述B和R.sub.2的相同含义，R'.sub.3为H；但条件是当A为苯时，R.sub.1不同于H，及其药学上可接受的盐。
• PHENETHYLAMIDE DERIVATIVES AND THEIR HETEROCYCLIC ANALOGUES
  申请人：Aissaoui Hamed

  公开号：US20110212968A1

  公开（公告）日：2011-09-01

  The invention relates to novel phenethylamide derivatives and their wherein A, B, R 1 , R 2 and R 3 are as described in the application, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.

  本发明涉及新型苯乙酰胺衍生物及其其中A、B、R1、R2和R3如本申请中所述的衍生物的药物学上可接受的盐的使用，特别是作为药物，尤其是作为促进睡眠的药物，如促进睡眠的药物。