4-氯-5-噻唑羧酸 | 444909-59-5

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-氯-5-噻唑羧酸
• 中文别名: 4-氯-1,3-噻唑-5-羧酸
• 英文名称: 4-chlorothiazole-5-carboxylic acid
• 英文别名: 4-Chloro-1,3-thiazole-5-carboxylic acid
• CAS: 444909-59-5
• 化学式: C₄H₂ClNO₂S
• mdl: MFCD09837290
• 分子量: 163.584
• InChiKey: PIORVFYHSPLLLG-UHFFFAOYSA-N

物化性质

• 沸点：
  336.3±22.0 °C(Predicted)
• 密度：
  1.693±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氯-5-噻唑羧酸 、 (1S,3R,4S,5S,7S)-4-amino-adamantan-1-ol hydrochloride 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以79%的产率得到4-chloro-N-(5-hydroxy-2-adamantyl)thiazole-5-carboxamide
  参考文献：
  名称：

  Optimization of Brain Penetrant 11β-Hydroxysteroid Dehydrogenase Type I Inhibitors and in Vivo Testing in Diet-Induced Obese Mice

  摘要：

  11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11 beta-HSD1 activity alleviates metabolic syndrome.

  DOI：

  10.1021/jm4016729
• 作为产物：
  描述：

  4-氯噻唑-5-甲醛 、 2-甲基-2-丁烯 、 叔丁醇 、 、 以 水 为溶剂， 反应 17.33h， 以to give 10.6 g of white solid的产率得到4-氯-5-噻唑羧酸
  参考文献：
  名称：

  Oxazolyl-acid amide derivatives useful as inhibitors of PDE4 isozymes

  摘要：

  本申请涉及的化合物可用作PDE4的抑制剂，用于治疗由嗜酸性粒细胞的激活和脱颗粒调节的疾病，特别是哮喘、慢性支气管炎和慢性阻塞性肺疾病，其化学式为：其中Y为═C（R1a）-或-[N（O）k]-，其中k为0或1；G1为饱和或不饱和的碳环系统，是3-至7-成员的单环，或是7-至12-成员的融合多环；但要求G1不是根据G2定义的不连续或受限的双芳基基团；其中可选地，一个碳原子可以被来自N、O和S的杂原子所取代；其中可选地，第二个碳原子和进一步可选地第三个碳原子可以被N所取代；-G2为饱和或不饱和的碳环系统，是3-至7-成员的单环，或是7-至12-成员的融合多环；或是7-至18-成员的不连续或受限的双芳基基团；对于所述的每个碳环系统，可选地，其中一个碳原子可以被N、O和S中选择的杂原子所取代；其中可选地，第二个碳原子和进一步可选地第三个碳原子可以被N所取代；E选自：以及上述所有其他取代基在说明书中定义。

  公开号：

  US06894041B2

文献信息

• Substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：——

  公开号：US20030045546A1

  公开（公告）日：2003-03-06

  The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: 1 wherein Ar 1 , Ar 3 , A, B and D are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及取代的3-芳基-5-芳基-[1,2,4]-噁二唑及其类似物，由以下式I表示： 1 其中Ar1，Ar3，A，B和D在此处定义。本发明还涉及发现具有式I的化合物是caspase的激活剂和凋亡诱导剂。因此，本发明的caspase激活剂和凋亡诱导剂可用于诱导在各种临床病况中发生未受控制的异常细胞生长和扩散的细胞死亡。
• Pyrrolyl-and imidazolyl-acid amide derivatives useful as inhibitors of PDE4 isozymes
  申请人：Marfat Anthony

  公开号：US06869945B2

  公开（公告）日：2005-03-22

  This application is directed to compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructuive pulmonary disease, of the formula: where Y is ═C(R 1 a )— or —[N→(O) k ]— where k is 0 or 1; G 1 is a saturated or unsaturated carbon ring system that is a 3- to 7-membered monocyclic, or that is a 7- to 12-membered, fused polycyclic; provided that G 1 is not a discontinuous or restricted biaryl moiety as defined under G 2 ; where optionally one carbon atom may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; -G 2 is a saturated or unsaturated carbon ring system that is a 3- to 7-membered monocyclic; or that is a 7- to 12-membered, fused polycyclic; or that is a 7- to 18-membered discontinuous or restricted biaryl moiety; wherein for each of the carbon ring systems recited, optionally one carbon atom of said carbon ring system may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; E is selected from: and all other substituents shown above are as defined in the specification.

  本申请涉及一种化合物，其可用作PDE4的抑制剂，用于治疗由嗜酸性粒细胞的激活和脱颗粒调节的疾病，特别是哮喘、慢性支气管炎和慢性阻塞性肺疾病，其化学式为：其中Y为═C（R1a）—或—[N→（O）k]—，其中k为0或1；G1为饱和或不饱和的碳环系统，是一个3-至7-成员的单环，或是一个7-至12-成员的融合多环；前提是G1不是根据G2下定义的不连续或受限制的双芳基基团；其中可选地，一个碳原子可被N、O和S中选择的一个杂原子所替换；其中可选地，其第二个碳原子，进一步可选地，其第三个碳原子可被N所替换；-G2为饱和或不饱和的碳环系统，是一个3-至7-成员的单环；或是一个7-至12-成员的融合多环；或是一个7-至18-成员的不连续或受限制的双芳基基团；其中对于所述的每个碳环系统，可选地，其一个碳原子可被N、O和S中选择的一个杂原子所替换；其中可选地，其第二个碳原子，进一步可选地，其第三个碳原子可被N所替换；E选择自：以及上述所有其他取代基在规范中定义。
• Thiazolyl-acid amide derivatives useful as inhibitors of PDE4 isozymes
  申请人：Pfizer Inc

  公开号：US06559168B2

  公开（公告）日：2003-05-06

  This application is directed to compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructuive pulmonary disease, of the formula: where Y is ═C(R1a)— or —[N□(O)k]— where k is 0 or 1; G1 is a saturated or unsaturated carbon ring system that is a 3- to 7-membered monocyclic, or that is a 7- to 12-membered, fused polycyclic; provided that G1 is not a discontinuous or restricted biaryl moiety as defined under G2; where optionally one carbon atom may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; —G2 is a saturated or unsaturated carbon ring system that is a 3- to 7-membered monocyclic; or that is a 7- to 12-membered, fused polycyclic; or that is a 7- to 18-membered discontinuous or restricted biaryl moiety; wherein for each of the carbon ring systems recited, optionally one carbon atom of said carbon ring system may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; E is selected from: and all other substituents shown above are as defined in the specification.

  本申请涉及的化合物可用作PDE4抑制剂，用于治疗由嗜酸性粒细胞的激活和脱颗粒调节的疾病，特别是哮喘，慢性支气管炎和慢性阻塞性肺疾病，其化学式为：其中Y为═C（R1a）—或—[N□(O)k]—，其中k为0或1；G1是饱和或不饱和的碳环系统，是3-至7-成员的单环，或是7-至12-成员的融合多环；但要求G1不是根据G2定义的不连续或受限的双芳基基团；其中可以用N，O和S中选择的杂原子替换其中一个碳原子；其中第二个碳原子和进一步选择的第三个碳原子可以用N替换；—G2是饱和或不饱和的碳环系统，是3-至7-成员的单环；或是7-至12-成员的融合多环；或是7-至18-成员的不连续或受限的双芳基基团；其中对于所述的每个碳环系统，可以选择用N，O和S中的杂原子替换其中一个碳原子；其中第二个碳原子和进一步选择的第三个碳原子可以用N替换；E选择自：所有上述其他取代基如说明书所定义。