2,5-dichloro-N-methoxy-N-methylthiophene-3-carboxamide | 210097-99-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2,5-dichloro-N-methoxy-N-methylthiophene-3-carboxamide
• CAS: 210097-99-7
• 化学式: C₇H₇Cl₂NO₂S
• mdl: MFCD28165933
• 分子量: 240.11
• InChiKey: CNAVXLVFOGTNLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  57.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,5-dichloro-N-methoxy-N-methylthiophene-3-carboxamide 在 sodium tetrahydroborate 、 三氟乙酸 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 2.0h， 生成 5-[(2,5-dichlorothiophen-3-yl)methyl]-1H-imidazole
  参考文献：
  名称：

  α₂ Adrenoceptor Agonists as Potential Analgesic Agents. 3. Imidazolylmethylthiophenes

  摘要：

  A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the at adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the alpha (2D) adrenoceptor, the 4-bromo analogues 20e and 21e were very active in the rat abdominal irritant test (RAIT) with ED50 doses of 0.38 and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the biological activity of the present series, dexmedetomidine (1), and conformationally restrained analogues 3 and 4.

  DOI：

  10.1021/jm0003891
• 作为产物：
  描述：

  2,5-二氯-3-噻吩甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 2.0h， 生成 2,5-dichloro-N-methoxy-N-methylthiophene-3-carboxamide
  参考文献：
  名称：

  α₂ Adrenoceptor Agonists as Potential Analgesic Agents. 3. Imidazolylmethylthiophenes

  摘要：

  A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the at adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the alpha (2D) adrenoceptor, the 4-bromo analogues 20e and 21e were very active in the rat abdominal irritant test (RAIT) with ED50 doses of 0.38 and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the biological activity of the present series, dexmedetomidine (1), and conformationally restrained analogues 3 and 4.

  DOI：

  10.1021/jm0003891

文献信息

• Pyridylfuran and pyridylthiophene compounds
  申请人：——

  公开号：US20020022729A1

  公开（公告）日：2002-02-21

  A compound of the formula: 1 and its pharmaceutically effective salts, wherein R 1 and R 2 are independently selected from the following: (a) hydrogen, halo, R 5 —, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy-R 5 —, R 5 —O—R 5 —, or the like; (b) Ar—, Ar—R 5 —, Ar—C 2-6 alkenyl, Ar—C 2-6 alkynyl, Ar—O—, Ar—O—R 5 — or the like; (c) R 5 —C(O)—, —NO 2 , cyano, NH 2 —C(O)—, R 5 —NH—C(O)—, (R 5 ) 2 —N—C(O)—, Ar—C(O)— or the like; and (d) R 5 —C(O)—NH—, Ar—C(O)—NH— or the like; wherein Ar is optionally substituted aryl or heteroaryl such as phenyl and pyridyl; and wherein R 5 is optionally halo-substituted C 1-6 alkyl; R 3 is selected from the following: (e) cyano, formyl, tetrazolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, R 5 —C(O)—, C 2-6 alkenyl-C(O)—, C 2-6 alkynyl—C(O)—, R 5 —C(O)—R 5 —, or the like; (f) R 5 —C(O)—NH—, Ar—C(O)—NH—, or the like; (g) R 5 —S—, R 5 —S(O)—, R 5 —NH—S(O) 2 —, or the like; and (h) Ar—C(O)—, Ar—R 5 —C(O)—, Ar—C 2-6 alkenylene-C(O)— or the like; or two of R 1 , R 2 and R 3 together form a group of the formula —A 1 —B 1 —A 2 — or —A 1 —B 1 —A 3 —B 2 —A 2 — such as cyclic alkyl optionally substitued with oxo; R 4 is hydrogen, halo, R 5 —C(O)— and the like; X is O, S, S(O) or S(O) 2 ; m is 0, 1, 2, 3 or 4. The present invention also provides processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and/or cell adhesion molecule (CAM) mediated diseases and pharmaceutical compositions for use in such therapy.

  该化合物的分子式为1，以及其药效盐，其中R1和R2独立地选自以下选项：（a）氢，卤素，R5—，C2-6烯基，C2-6炔基，羟基-R5—，R5—O—R5—或类似物;（b）Ar—，Ar—R5—，Ar—C2-6烯基，Ar—C2-6炔基，Ar—O—，Ar—O—R5—或类似物;（c）R5—C（O）—，—NO2，氰基，NH2—C（O）—，R5—NH—C（O）—，（R5）2—N—C（O）—，Ar—C（O）—或类似物;（d）R5—C（O）—NH—，Ar—C（O）—NH—或类似物;其中Ar是可选取代芳基或杂环芳基，例如苯基和吡啶基; R5是可选取代卤素的C1-6烷基; R3选自以下选项：（e）氰基，甲酰基，四唑基，三唑基，咪唑基，噁唑基，噻唑基，R5—C（O）—，C2-6烯基-C（O）—，C2-6炔基-C（O）—，R5—C（O）—R5—或类似物;（f）R5—C（O）—NH—，Ar—C（O）—NH—或类似物;（g）R5—S—，R5—S（O）—，R5—NH—S（O）2—或类似物;以及（h）Ar—C（O）—，Ar—R5—C（O）—，Ar—C2-6烯基-C（O）—或类似物;或者R1、R2和R3中的两个组成公式—A1—B1—A2—或—A1—B1—A3—B2—A2—的基团，例如可选取代氧杂环的环烷基; R4为氢，卤素，R5—C（O）—等; X为O，S，S（O）或S（O）2; m为0、1、2、3或4。本发明还提供了其制备方法，在治疗细胞因子介导的疾病和/或细胞黏附分子（CAM）介导的疾病中使用以及用于此类治疗的制药组合物。
• Pyridylthiophene compounds
  申请人：Pfizer Inc.

  公开号：US06696470B2

  公开（公告）日：2004-02-24

  A compound of the formula: and its pharmaceutically effective salts, wherein R1 and R2 are independently selected from the following: (a) hydrogen, halo, R5—, C2-6 alkenyl, C2-6 alkynyl, hydroxy-R5—, R5—O—R5—, or the like; (b) Ar—, Ar—R5—, Ar—C2-6 alkenyl, Ar—C2-6 alkynyl, Ar—O—, Ar—O—R5— or the like; (c) R5—C(O)—, —NO2, cyano, NH2—C(O)—, R5—NH—C(O)—, (R5)2—N—C(O)—, Ar—C(O)— or the like; and (d) R5—C(O)—NH—, Ar—C(O)—NH— or the like; wherein Ar is optionally substituted aryl or heteroaryl such as phenyl and pyridyl; and wherein R5 is optionally halo-substituted C1-6 alkyl; R3 is selected from the following: (e) cyano, formyl, tetrazolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, R5—C(O)—, C2-6 alkenyl-C(O)—, C2-6 alkynyl-C(O)—, R5—C(O)—R5—, or the like; (f) R5—C(O)—NH—, Ar—C(O)—NH—, or the like; (g) R5—S—, R5—S(O)—, R5—NH—S(O)2—, or the like; and (h) Ar—C(O)—, Ar—R5—C(O)—, Ar—C2-6 alkenylene-C(O)— or the like; or two of R1, R2 and R3 together form a group of the formula —A1—B1—A2— or —A1—B1—A3—B2—A2— such as cyclic alkyl optionally substitued with oxo; R4 is hydrogen, halo, R5—C(O)— and the like; X is O, S, S(O) or S(O)2; m is 0, 1, 2, 3 or 4. The present invention also provides processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and/or cell adhesion molecule (CAM) mediated diseases and pharmaceutical compositions for use in such therapy.

  该化合物的公式为：及其药效盐，其中R1和R2分别选自以下：（a）氢，卤素，R5—，C2-6烯基，C2-6炔基，羟基-R5—，R5—O—R5—或类似物；（b）Ar—，Ar—R5—，Ar—C2-6烯基，Ar—C2-6炔基，Ar—O—，Ar—O—R5—或类似物；（c）R5—C（O）—，—NO2，氰基，NH2—C（O）—，R5—NH—C（O）—，（R5）2—N—C（O）—，Ar—C（O）—或类似物；和（d）R5—C（O）—NH—，Ar—C（O）—NH—或类似物；其中Ar是可选取代芳基或杂环芳基，例如苯基和吡啶基；而R5是可选取代卤素的C1-6烷基；R3选自以下：（e）氰基，甲酰基，四唑基，三唑基，咪唑基，噁唑基，噻唑基，R5—C（O）—，C2-6烯基-C（O）—，C2-6炔基-C（O）—，R5—C（O）—R5—或类似物；（f）R5—C（O）—NH—，Ar—C（O）—NH—或类似物；（g）R5—S—，R5—S（O）—，R5—NH—S（O）2—或类似物；和（h）Ar—C（O）—，Ar—R5—C（O）—，Ar—C2-6烯基-C（O）—或类似物；或者R1、R2和R3中的两个形成公式—A1—B1—A2—或—A1—B1—A3—B2—A2—的基团，例如可选取代氧杂环的环烷基；R4为氢，卤素，R5—C（O）—等；X为O，S，S（O）或S（O）2；m为0、1、2、3或4。本发明还提供了其制备方法，以及在治疗细胞因子介导疾病和/或细胞黏附分子（CAM）介导疾病中使用的制药组合物。
• Pyridylfuran and pyridylthiophene compounds and pharmaceutical use thereof
  申请人：PFIZER INC.

  公开号：EP0853083A1

  公开（公告）日：1998-07-15

  This invention relates to pyridylfuran and pyridylthiophene compounds, their pharmaceutically effective salts, processes for the preparation thereof, and pharmaceutical compositions for use in treating cytokine mediated diseases and/or cell adhesion molecule (CAM) mediated diseases. The ability of the compounds of the formula (I) to inhibit TNFα biosynthesis and CAMs expression has been demonstrated in vitro.

  本发明涉及用于治疗细胞因子介导的疾病和/或细胞粘附分子（CAM）介导的疾病的吡啶基呋喃和吡啶基噻吩化合物、它们的药用有效盐、其制备工艺和药物组合物。 式 (I) 化合物抑制 TNFα 生物素的能力 抑制 TNFα 生物合成和 CAMs 表达的能力已在体外得到证实。
• US6048880A
  申请人：——

  公开号：US6048880A

  公开（公告）日：2000-04-11
• US6696470B2
  申请人：——

  公开号：US6696470B2

  公开（公告）日：2004-02-24