2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carbonyl chloride | 165381-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carbonyl chloride
• 英文别名: 4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]benzoyl chloride
• CAS: 165381-86-2
• 化学式: C₁₇H₁₃ClN₂O₂
• 分子量: 312.755
• InChiKey: PCCNAGJFZPBIHP-UHFFFAOYSA-N

物化性质

• 沸点：
  462.8±55.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carbonyl chloride 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 N-[2-(Dimethylaminomethyl)1,4-benzodioxan-7-yl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide
  参考文献：
  名称：

  Substituted benzanilides as CCR5 receptors ligands, antiinflammatory agents and antiviral agents

  摘要：

  本发明涉及作为CCR5受体的配体、激动剂或拮抗剂的取代苯甲酰亚胺。此外，本发明还涉及通过使用作为CCR5受体拮抗剂的取代苯甲酰亚胺，治疗和预防由CCR5介导的疾病状态，包括但不限于哮喘和变应性疾病（例如，特应性皮炎和过敏症）、类风湿性关节炎、结节病和其他纤维化疾病、动脉粥样硬化、银屑病、自身免疫性疾病如多发性硬化症和炎症性肠病，所有这些疾病都发生在哺乳动物中。此外，由于CD8+ T细胞与慢性阻塞性肺病（COPD）有关，CCR5可能在其招募中发挥作用，因此CCR5的拮抗剂可能为COPD的治疗提供潜在的治疗方法。另外，由于CCR5是HIV进入细胞的共受体，选择性的受体配体可能在治疗HIV感染中是有用的。

  公开号：

  US06515027B1
• 作为产物：
  描述：

  2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxylic acid 在 氯化亚砜 作用下， 反应 1.0h， 生成 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carbonyl chloride
  参考文献：
  名称：

  The Selective 5-HT_1B Receptor Inverse Agonist 1‘-Methyl-5-[[2‘-methyl-4‘- (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4‘-piperidine] (SB-224289) Potently Blocks Terminal 5-HT Autoreceptor Function Both in Vitro and in Vivo

  摘要：

  5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively Linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1D beta and 5-HT1D alpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

  DOI：

  10.1021/jm970457s

文献信息

• Indole and indoline derivatives as 5HT.sub.1D receptor antagonists
  申请人：SmithKline Beecham p.l.c.

  公开号：US05696122A1

  公开（公告）日：1997-12-09

  The present invention provides novel indole and indoline derivatives according to formula (I) below, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments. The present indole and indoline derivatives are compounds of formula (I) or a salt thereof: ##STR1## in which R is a group of formula (i): ##STR2## in which P.sup.1 is a phenyl or a 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; and R.sup.1 and R.sup.2 are independently hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxyC.sub.1-6 alkyl, acyl, nitro, trifluoromethyl, cyano, SR.sup.5, SOR.sup.5, SO.sub.2 R.sup.5, SO.sub.2 NR.sup.5 R.sup.6, CO.sub.2 R.sup.5, CONR.sup.5 R.sup.6, CONR.sup.5 (CH.sub.2).sub.x CO.sub.2 R.sup.6, NR.sup.5 R.sup.6, NR.sup.5 CO.sub.2 R.sup.6, CR.sup.5 =NOR.sup.6, where R.sup.5 and R.sup.6 are independently hydrogen or C.sub.1-6 alkyl and x is 1 to 3; or R is a group of formula (ii): ##STR3## in which P.sup.2 is phenyl or biphenyl; P.sub.3 is phenyl or a 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; A is a bond or a group (CH.sub.2).sub.p --R.sup.8 --(CH.sub.2).sub.q where R.sup.8 is oxygen, S(O).sub.m where m is 0 to 2, carbonyl, CO.sub.2 or CH.sub.2 and p and q are independently 0 to 3; and R.sup.1 and R.sup.2 are as defined above in formula (i); R.sup.3 is hydrogen, halogen, hydroxy, C.sub.1-6 alkyl or C.sub.1-6 alkoxy; n is 1 or 2; R.sup.4 is hydrogen or C.sub.1-6 alkyl; and B is --CHR.sup.9 CHR.sup.10 -- or --CR.sup.9 .dbd.CR.sup.10 -- where R.sup.9 and R.sup.10 are independently hydrogen or C.sub.1-6 alkyl. C.sub.1-6 alkyl groups, whether alone or as part of another group, may be straight chain or branched. The groups P.sub.1, P.sub.2, and P.sub.3 can be aromatic or saturated heterocyclic rings.

  本发明提供了新型吲哚和吲哚啉衍生物，其化学式如下（I），以及它们的制备方法，含有它们的药物组合物和它们作为药物的用途。本发明的吲哚和吲哚啉衍生物是化合物式（I）或其盐：##STR1## 其中R是式（i）的基团：##STR2## 其中P.sup.1是苯基或含有1至3个氧、氮或硫杂原子的5至7元杂环；R.sup.1和R.sup.2分别是氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基、羟基C.sub.1-6烷基、酰基、硝基、三氟甲基、氰基、SR.sup.5、SOR.sup.5、SO.sub.2R.sup.5、SO.sub.2NR.sup.5R.sup.6、CO.sub.2R.sup.5、CONR.sup.5R.sup.6、CONR.sup.5(CH.sub.2).sub.xCO.sub.2R.sup.6、NR.sup.5R.sup.6、NR.sup.5CO.sub.2R.sup.6、CR.sup.5=NOR.sup.6，其中R.sup.5和R.sup.6分别是氢或C.sub.1-6烷基，x为1至3；或R是式（ii）的基团：##STR3## 其中P.sup.2是苯基或联苯基；P.sub.3是苯基或含有1至3个氧、氮或硫杂原子的5至7元杂环；A是键或(CH.sub.2).sub.p--R.sup.8--(CH.sub.2).sub.q的基团，其中R.sup.8是氧、S（O）.sub.m（m为0至2）、羰基、CO.sub.2或CH.sub.2，p和q独立地为0至3；R.sup.1和R.sup.2如上述式（i）中定义；R.sup.3是氢、卤素、羟基、C.sub.1-6烷基或C.sub.1-6烷氧基；n为1或2；R.sup.4是氢或C.sub.1-6烷基；B是--CHR.sup.9CHR.sup.10--或--CR.sup.9.dbd.CR.sup.10--，其中R.sup.9和R.sup.10独立地为氢或C.sub.1-6烷基。C.sub.1-6烷基，无论是单独存在还是作为另一基团的一部分，可以是直链或支链。基团P.sub.1、P.sub.2和P.sub.3可以是芳香环或饱和杂环。
• INDOLE AND INDOLINE DERIVATIVES AS 5HT1D RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0716650B1

  公开（公告）日：1999-03-24
• AZASPIRODERIVATIVES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0889893A1

  公开（公告）日：1999-01-13
• COMPOUNDS FOR THE TREATMENT OF CCR5-MEDIATED DISEASES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1001766B1

  公开（公告）日：2003-04-09
• PIPERAZINE DERIVATIVES, THEIR PREPARATION AND USES IN THERAPY (5HT1B RECEPTOR ACTIVITY)
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1368344A1

  公开（公告）日：2003-12-10