2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxylic acid | 148672-68-8

• 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)[1,1'-biphenyl]-4-carboxylic acid
• 英文别名: 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid；2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-biphenyl-4-carboxylic acid；4-(2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)benzoic acid；2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) biphenyl-4-carboxylic acid；4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]benzoic Acid
• CAS: 148672-68-8
• 化学式: C₁₇H₁₄N₂O₃
• 分子量: 294.31
• InChiKey: NCYAKOVWIQBPGN-UHFFFAOYSA-N

物化性质

• 沸点：
  493.8±55.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  76.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  室温、密封、干燥

反应信息

• 作为反应物：
  描述：

  2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxylic acid 在 sodium hydroxide 、 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 N-[3-[2-(二甲基氨基)乙氧基]-4-甲氧基苯基]-2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)-[1,1'-联苯]-4-甲酰胺
  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
• 作为产物：
  描述：

  4-溴-3-甲基苯甲腈 在 四(三苯基膦)钯 、 羟胺 、 sodium carbonate 作用下， 以 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 生成 2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-carboxylic acid
  参考文献：
  名称：

  Identification of a potent and selective 5-HT1B receptor antagonist

  摘要：

  An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.085

文献信息

• Tetracyclic spiro compounds, process for their preparation and their use
  申请人：SmithKline Beecham plc

  公开号：US05972951A1

  公开（公告）日：1999-10-26

  Novel piperidine derivatives of formula (I), processes for their preparation, pharmaceutical compositions containing them and their use as medicaments for the treatment of CNS disorders are disclosed.

  披露了公式(I)的新哌啶衍生物，它们的制备过程，含有它们的药物组合物以及它们作为治疗中枢神经系统疾病的药物的应用。
• Dihydrobenzofuranyl-biphenyl carboxamides having 5HT.sub.1D antagonistic
  申请人：SmithKline Beecham p.l.c.

  公开号：US05700818A1

  公开（公告）日：1997-12-23

  This invention discloses dyhydrobenzofuranyl-biphenyl carboxamides having 5HT.sub.1D antagonistic activity.

  本发明公开了具有5HT.sub.1D拮抗活性的二氢苯并呋喃基-联苯甲酰胺。
• Heterocyclic biphenylylamides useful as 5HT1D antagonists
  申请人：SmithKline Beecham plc

  公开号：US05801170A1

  公开（公告）日：1998-09-01

  A compound of formula (I) or a salt thereof: ##STR1## wherein P is a 5 to 7 membered heterocyclic ring selected from the group consisting of thienyl, furyl, pyrrolyl, triazolyl, diazolyl, tetrazolyl, imidazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimdyl and pyrazinyl; R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, alkanoyl, optionally substituted phenyl, alkanoyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.9,CONR.sup.10 R.sup.11 where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl; R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl; R.sup.6 is hydrogen, halogen, hydroxy, C.sub.1-6 alkyl or C.sub.1-6 alkoxy R.sup.7 and R.sup.8 are independently hydrogen, C.sub.1-6 alkyl, a optionally substituted phenylalkyl or together with the nitrogen atom to which they are attached form an optionally substituted 5- to 7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur; A is CONH or NHCO; B is oxygen, S(O)p where p is 0, 1 or 2, NR.sup.12 where R.sup.12 is hydrogen, C.sub.1-6 alkyl or phenylC.sub.1-6 alkyl, or B is CR.sup.4 .dbd.CR.sup.5 or CR.sup.4 R.sup.5 where R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl; m is 1 to 4; and n is 1 or 2.

  式（I）的化合物或其盐：##STR1##其中P是从噻吩基，呋喃基，吡咯基，三唑基，二唑基，四唑基，咪唑基，噁二唑基，异噻唑基，异噁唑基，噻二唑基，吡啶基，吡啶二基和吡啶基中选择的5至7成员杂环环；R.sup.1，R.sup.2和R.sup.3分别是氢，卤素，C.sub.1-6烷基，C.sub.3-6环烷基，C.sub.3-6环烯基，C.sub.1-6烷氧基，羟基C.sub.1-6烷基，C.sub.1-6烷氧基C.sub.1-6烷基，烷酰基，可选择地取代的苯基，烷酰氧基，羟基，硝基，三氟甲基，氰基，CO.sub.2R.sup.9，CONR.sup.10R.sup.11其中R.sup.9，R.sup.10和R.sup.11分别是氢或C.sub.1-6烷基；R.sup.4和R.sup.5分别是氢或C.sub.1-6烷基；R.sup.6是氢，卤素，羟基，C.sub.1-6烷基或C.sub.1-6烷氧基R.sup.7和R.sup.8分别是氢，C.sub.1-6烷基，可选择地取代的苯基烷基或与它们连接的氮原子一起形成一个可选择地取代的5-至7成员杂环环，其中含有一个或两个从氧，氮或硫中选择的杂原子；A是CONH或NHCO；B是氧，S（O）p其中p为0，1或2，NR.sup.12其中R.sup.12是氢，C.sub.1-6烷基或苯基C.sub.1-6烷基，或B是CR.sup.4.dbd.CR.sup.5或CR.sup.4R.sup.5其中R.sup.4和R.sup.5分别是氢或C.sub.1-6烷基；m为1至4；n为1或2。
• Indole, indoline and quinoline derivatives with 5HT.sub.1D
  申请人：SmithKline Beecham, p.l.c.

  公开号：US05889022A1

  公开（公告）日：1999-03-30

  Novel indole, indoline and quinoline derivatives of formula (I) processes for their preparation, pharmaceutical compositions containing them, and their use in medicine is disclosed. A structurally distinct class of compounds have now been discovered and have been found to exhibit 5HT.sub.1-D antagonist activity. In a first aspect, the present invention therefore provides a compound of formula (I) or a salt thereof, in which P is a 5-7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, A, B, m, R.sup.1 -R.sup.8 are defined in the application.

  披露了公式(I)的吲哚、吲哚啉和喹啉衍生物及其制备过程，含有它们的药物组合物及其在医学上的用途。现已发现了一个结构上明显不同的化合物类别，并发现这些化合物具有5HT.sub.1-D拮抗剂活性。因此，在一个方面，本发明提供了一种公式(I)的化合物或其盐，其中P是一个含有1到3个氧、氮或硫杂原子的5-7成员杂环，A、B、m、R.sup.1 -R.sup.8在申请中定义。
• Biphenylamide derivatives as 5HT.sub.1D antagonists
  申请人：SmithKline Beecham p.l.c.

  公开号：US05919932A1

  公开（公告）日：1999-07-06

  Biphenyl amide derivatives as 5HT.sub.1D antagonists, processes for their preparation, pharmaceutical compositions containing them and their use for the treatment of CNS disorders.

  联苯酰胺衍生物作为5HT.sub.1D拮抗剂，它们的制备方法，包含它们的药物组合物及其用于治疗CNS疾病的应用。