N-(azepan-1-yl)-5-(5-bromothiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide | 869891-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(azepan-1-yl)-5-(5-bromothiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
• 英文别名: N-homopiperidinyl-5-(5-bromo-thiophen-2-yl)-1-(2',4'-dichlorophenyl)-4-methyl-1H-pyrazol-3-carboxamide；N-(azepan-1-yl)-5-(5-bromothiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide
• CAS: 869891-73-6
• 化学式: C₂₁H₂₁BrCl₂N₄OS
• 分子量: 528.3
• InChiKey: XKHUPGMHSOHXQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  、 1-氨基高哌啶 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以86 mg的产率得到N-(azepan-1-yl)-5-(5-bromothiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Bioisosteric Replacement of the Pyrazole 5-Aryl Moiety of N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A Novel Series of Alkynylthiophenes as Potent and Selective Cannabinoid-1 Receptor Antagonists

  摘要：

  Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl rnoiety appended with ail appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, its typified by compound 18, showed significant weight reduction in diet-indUced obese Mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship Studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB I-receptor homology model might exist in the binding site.

  DOI：

  10.1021/jm800066v

文献信息

• Pharmaceutical compounds
  申请人：Lazzari Paolo

  公开号：US20050261281A1

  公开（公告）日：2005-11-24

  Pyrazole derivatives of the following formula (I), having affinity for the cannabinoidergic CB1 and/or CB2 receptors: wherein: R is a group selected from: C 1 -C 10 alkyl; aryl, arylalkyl or arylalkenyl, not substituted or having from one to four substituents, equal to or different from each other; A is a group selected from the following: an ether group of formula —(CH 2 )—O—(CH 2 ) v —R″ wherein v is equal to 1 or 2; R″ is as defined in the present application; a ketone group of formula —C(O)-Z′, wherein Z′ is as defined in the present application; a substituent having an hydroxyl function of formula —CH(OH)-Z′, Z′ being as defined in the present application; Description of the industrial invention in the name of: NEUROSCIENZE S.c. a r.l., of Italian nationality, with head office in Cagliari, via Palabanda 9.

  以下式子（I）的吡唑衍生物具有对大麻素受体CB1和/或CB2的亲和力：其中：R是以下组中选择的一组：C1-C10烷基；芳基，芳基烷基或芳基烯基，未取代或具有一个到四个取代基，相互相同或不同；A是以下组中选择的一组：化学式为—（CH2）-O-（ ）v-R″的醚基，其中v等于1或2；R″如本申请所定义；化学式为—C（O）-Z′的酮基，其中Z′如本申请所定义；具有羟基功能的取代基，化学式为—CH（OH）-Z′，其中Z′如本申请所定义；该工业发明的描述以NEUROSCIENZE S.c. a r.l.的名义进行，该公司是意大利国籍，总部位于卡利亚里，Palabanda 9号。
• PYRAZOLE DERIVATIVES HAVING AFFINITY FOR CB1 AND/OR CB2 RECEPTORS
  申请人：NEUROSCIENZE PHARMANESS S.C. a R.L.

  公开号：EP1602656A1

  公开（公告）日：2005-12-07

  Pyrazole derivatives of the following formula (I), having affinity for the cannabinoidergic CB1 and/or CB2 receptors:    wherein: R is a group selected from: C1-C10 alkyl; aryl, arylalkyl or arylalkenyl, not substituted or having from one to four substituents, equal to or different from each other; A is a group selected from the following: an ether group of formula -(CH2)-O-(CH2)v-R" wherein    - v is equal to 1 or 2;    - R" is as defined in the present application; a ketone group of formula -C(O)-Z', wherein Z' is as defined in the present application; a substituent having an hydroxyl function of formula -CH(OH)-Z', Z' being as defined in the present application; an amide substituent of formula -C(O)-NH-T', T' being as defined in the present application; B is a group as defined in the present application; D is an heteroaryl optionally substituted.

  对大麻素能 CB1 和/或 CB2 受体具有亲和力的下式 (I) 吡唑衍生物： 其中 R 是选自以下各项的基团 C1-C10 烷基 芳基、芳烷基或芳烯基，未被取代或具有一至四个相互等同或不同的取代基； A 是选自以下的基团 式中的醚基-(CH2)-O-( )v-R" 其中 - v 等于 1 或 2； - R "如本申请中所定义； 式-C(O)-Z'的酮基，其中 Z'如本申请中所定义； 式-CH(OH)-Z'的具有羟基官能团的取代基，其中 Z'定义如本申请所 述； 式-C(O)-NH-T'的酰胺取代基，T'如本申请中所定义； B 是本申请中所定义的基团； D 是任选取代的杂芳基。
• EP1602656B1
  申请人：——

  公开号：EP1602656B1

  公开（公告）日：2011-06-29
• PHARMACEUTICAL COMPOUNDS
  申请人：Lazzari Paolo

  公开号：US20100105896A1

  公开（公告）日：2010-04-29

  Pyrazole derivatives of the following formula (I), having affinity for the cannabinoidergic CB1 and/or CB2 receptors: wherein: R is a group selected from C 1 -C 10 alkyl; aryl, arylalkyl or arylalkenyl, not substituted or having from one to four substituents, equal to or different from each other; A is a group selected from the following: an ether group of formula —(CH 2 )—O—(CH 2 ) v —R″ wherein v is equal to 1 or 2; R″ is as defined in the present application; a ketone group of formula —C(O)—Z′, wherein Z′ is as defined in the present application; a substituent having an hydroxyl function of formula —CH(OH)—Z′, being as defined in the present application; an amide substituent of formula —C(O)—NH-T′, T′ being as defined in the present application; B is a group as defined in the present application; D is an heteroaryl optionally substituted.
• US7659407B2
  申请人：——

  公开号：US7659407B2

  公开（公告）日：2010-02-09