1-(4-Cyano-3-methylbenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine | 335155-20-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 1-(4-Cyano-3-methylbenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine
• 英文别名: 2-methyl-4-(2,3,4,5-tetrahydro-1H-1-benzazepin-1-ylcarbonyl)-benzonitrile；2-Methyl-4-((2,3,4,5-tetrahydro-1H-benzo[b]azepine)-1-carbonyl)-benzonitrile；2-methyl-4-(2,3,4,5-tetrahydrobenzo[b]azepine-1-carbonyl)benzonitrile；2-Methyl-4-(2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carbonyl)benzonitrile；2-methyl-4-(2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)benzonitrile
• CAS: 335155-20-9
• 化学式: C₁₉H₁₈N₂O
• 分子量: 290.365
• InChiKey: VDFGCBODBVCSRU-UHFFFAOYSA-N

物化性质

• 熔点：
  126-128 °C
• 沸点：
  508.1±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  1-(4-Cyano-3-methylbenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine 以98的产率得到1-(4-(Aminomethyl)-3-methylbenzoyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepine hydrochloride
  参考文献：
  名称：

  Fused azepine derivatives and their use as antidiuretic agents

  摘要：

  根据通式（1和2），其中G1是一种氮杂七环衍生物，G2是根据通式（9-11）的一种基团，所形成的化合物是新的。本发明的化合物是加压素V2受体激动剂。该化合物的药物组成物作为抗利尿剂是有用的。

  公开号：

  US20040038962A1
• 作为产物：
  描述：

  2,3,4,5-四氢-1H-苯并[b]氮杂卓 、 4-cyano-3-methylbenzoyl chloride 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以76%的产率得到1-(4-Cyano-3-methylbenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepine
  参考文献：
  名称：

  Subtlety of the Structure−Affinity and Structure−Efficacy Relationships around a Nonpeptide Oxytocin Receptor Agonist

  摘要：

  Very Few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In all attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of representative ligands of the V-1a, V-2, and OT receptor subtypes. Despite apparently obvious similarity between the ligand structures on one hand, and between the receptor subtypes on the other hand, the binding affinity and the functional activity profiles of truncated and hybrid ligands highlight the subtlety of ligand-receptor interactions for obtaining nonpeptide OT receptor agonists.

  DOI：

  10.1021/jm901084f

文献信息

• [EN] HETEROCYCLIC CONDENSED COMPOUNDS USEFUL AS ANTIDIURETIC AGENTS<br/>[FR] COMPOSES CONDENSES HETEROCYCLIQUES UTILISES EN TANT QU'ANTIDIURETIQUES
  申请人：FERRING BV

  公开号：WO2006018443A1

  公开（公告）日：2006-02-23

  The invention concerns compounds according to general formulae 1, wherein G1 is an amine. Compounds according to the invention are vasopressin V2 receptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents.

  这项发明涉及通式1中的化合物，其中G1是胺基。根据该发明的化合物是抗利尿激素V2受体激动剂。这些化合物的药物组合物可用作抗利尿剂。
• New Benzylureas as a Novel Series of Potent, Nonpeptidic Vasopressin V2 Receptor Agonists
  作者：Christopher M. Yea、Christine E. Allan、Doreen M. Ashworth、James Barnett、Andy J. Baxter、Janice D. Broadbridge、Richard J. Franklin、Sally L. Hampton、Peter Hudson、John A. Horton、Paul D. Jenkins、Andy M. Penson、Gary R. W. Pitt、Pierre Rivière、Peter A. Robson、David P. Rooker、Graeme Semple、Andy Sheppard、Robert M. Haigh、Michael B. Roe

  DOI：10.1021/jm8008162

  日期：2008.12.25

  proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements

  加压素（AVP）是一种激素，可通过激活肾脏中的V2受体来刺激水渗透性的增加。AVP的去氨加压素类似物已被证明可有效治疗需要减少尿量的疾病。但是，其肽性质限制了其生物利用度。我们在此报告了加压素V2受体有效，非肽类，苄脲衍生的激动剂的发现。我们描述了苄基上的取代，以提高效力，随后对尿素端基进行了修饰，从而在利尿大鼠模型中提高了溶解度并提高了口服功效。首次报道了铅化合物20e（VA106483），已被选择用于临床开发。
• Condensed azepines as vasopressin agonists
  申请人：——

  公开号：US20030087892A1

  公开（公告）日：2003-05-08

  This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V 1 and V 2 are both H, OMe or F, or one of V 1 and V 2 is Br, Cl, F, OH, OMe, OBn, OPh, O-acyl, N 3 , NH 2 , NHBn or NH-acyl and the other is H, or V 1 and V 2 together are ═O, —O(CH 2 ) p O— or —S(CH 2 ) p S—; W 1 is either O or S; X 1 and X 2 are both H, or together are ═O or ═S; Y is OR 5 or NR 6 R 7 ; R 1 , R 2 , R 3 and R 4 are independently selected from H, lower alkyl, lower alkyloxy, F, Cl and Br; R 5 is selected from H and lower alkyl; R 6 and R 7 are independently selected from H and lower alkyl, or together are —(CH 2 ) n ; n=3, 4, 5, 6; and p is 2 or 3. The compounds are agonists at the vasopressin V2 receptor and are useful as antidiuretics and procoagulants. The invention further comprises pharmaceutical compositions incorporating these vasopressin agonists, which compositions are particularly useful in the treatment of central diabetes insipidus, nocturnal enuresis and nocturia.

  该发明提供了根据一般式（1）的新化合物，其中A是具有双环或三环氮杂丙烷衍生物，V1和V2均为H、OMe或F，或者V1和V2中的一个为Br、Cl、F、OH、OMe、OBn、OPh、O-酰基、N3、NH2、NHBn或NH-酰基，另一个为H，或者V1和V2一起是═O、—O(CH2)pO—或—S(CH2)pS—；W1为O或S；X1和X2均为H，或者一起为═O或═S；Y为OR5或NR6R7；R1、R2、R3和R4独立地选自H、低碳烷基、低烷氧基、F、Cl和Br；R5选自H和低碳烷基；R6和R7独立地选自H和低碳烷基，或者一起为—(CH2)n；n=3、4、5、6；p为2或3。这些化合物是抗利尿素和促凝剂，在抗利尿素和促凝剂方面具有用途。该发明还包括包含这些抗利尿素激动剂的药物组合物，这些组合物在治疗中枢尿崩症、夜尿症和夜尿症方面特别有用。
• Bicyclic vasopressin agonists
  申请人：Ferring BV

  公开号：US06664249B1

  公开（公告）日：2003-12-16

  Compounds according to general formula (1), and pharmaceutically acceptable salts thereof, wherein V is a covalent bond or NH, X is selected from CH2, O and N-alkyl, Z is either S or —CH═CH—, R1 and R2 are independently selected from H, F, Cl, Br and alkyl, R3 is selected from OH, O-alkyl and NR4R5, R4 and R5 are each independently H or alkyl, or together are —(CH2)q—, p is 0, 1, 2, 3 or 4, and q is 4 or 5, are new. They are agonists at the asopressin V2 receptor and are useful as antidiuretics and pro-coagulants.

  根据一般式（1）及其药用可接受的盐，其中V是共价键或NH，X从CH2、O和N-烷基中选择，Z是S或—CH2CH—，R1和R2分别选择自H、F、Cl、Br和烷基，R3从OH、O-烷基和NR4R5中选择，R4和R5各自独立地选择H或烷基，或者一起是—（CH2）q—，p为0、1、2、3或4，q为4或5，这些化合物是新的。它们是抗利尿激素V2受体的激动剂，可用作抗利尿剂和促凝剂。
• [EN] FUSED AZEPINE DERIVATIVES AND THEIR USE AS ANTIDIURETIC AGENTS<br/>[FR] DERIVES D'AZEPINE FUSIONNES ET LEURS UTILISATIONS COMME ANTI-DIURETIQUES
  申请人：FERRING BV

  公开号：WO2002000626A1

  公开（公告）日：2002-01-03

  Compounds according to general formulae (1 and 2), wherein G1 is an azepine derivative and G2 is a group according to general formulae (9 - 11) are new. Compounds according to the invention are vasopressin V¿2? receptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents.

  通式（1和2）所示的化合物，其中G1是一种氮杂七环衍生物，G2是根据通式（9-11）的一种基团，是新的。根据本发明的化合物是加压素V2受体激动剂。化合物的制药组合物可用作抗利尿剂。