7-溴-5-(2-氯苯基)-2,3-二氢-2-(甲氧基甲基)-1-甲基-1H-1,4-苯并二氮杂卓 | 84031-17-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 7-溴-5-(2-氯苯基)-2,3-二氢-2-(甲氧基甲基)-1-甲基-1H-1,4-苯并二氮杂卓
• 中文别名: 美他西泮
• 英文名称: Metaclazepam
• 英文别名: 7-bromo-1-methyl-2-methoxymethyl-5-(2'-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin；Brometazepam；7-bromo-5-(2-chlorophenyl)-2-(methoxymethyl)-1-methyl-2,3-dihydro-1,4-benzodiazepine
• CAS: 84031-17-4
• 化学式: C₁₈H₁₈BrClN₂O
• 分子量: 393.711
• InChiKey: WABYCCJHARSRBH-UHFFFAOYSA-N

物化性质

• 沸点：
  472.4±45.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)
• 保留指数：
  2690;2640
• 稳定性/保质期：
  盐酸美他西泮（Metaclazepam Hydrochloride）的化学式为C18H18BrClN2O·HCl， CAS号为61802-93-5。从乙醇结晶得到，熔点为193-196℃。急性毒性实验中，小白鼠口服剂量为1578 mg/kg时表现为半数致死量。

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  24.8
• 氢给体数：
  0
• 氢受体数：
  3

制备方法与用途

化学性质
盐酸美他西泮（Metaclazepam Hydrochloride）：C₁₈H₁₈BrClN₂O·HCI，[61802-93-5]。从乙醇结晶，熔点为193-196℃。急性毒性LD₅₀小白鼠（mg/kg）：1578口服。

用途
盐酸美他西泮是一种苯并二氮杂卓类药物，主要用于抗抑郁。

生产方法
化合物(I)用邻氯苯甲酰氯进行酰化反应，得到化合物(Ⅱ)。随后与三氯氧磷一起回流，生成化合物(Ⅲ)和化合物(IV)的混合物。该混合物在甲醇钠存在下于甲醇中回流，转化为化合物(V)。最终，在二氯甲烷中回流并进行溴化反应，得到盐酸美他西泮。

反应信息

• 作为反应物：
  描述：

  7-溴-5-(2-氯苯基)-2,3-二氢-2-(甲氧基甲基)-1-甲基-1H-1,4-苯并二氮杂卓 在 N-溴代丁二酰亚胺(NBS) 、 氢氟酸 作用下， 生成 7,9-dibromo-1-methyl-2-methoxymethyl-5-(2'-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine
  参考文献：
  名称：

  Milkowski; Liepman; Zeugner, European Journal of Medicinal Chemistry, 1985, vol. 20, # 4, p. 345 - 358

  摘要：

  DOI：
• 作为产物：
  描述：

  2-chloro-N-[3-(N-methylanilino)propyl]benzamide 生成 7-溴-5-(2-氯苯基)-2,3-二氢-2-(甲氧基甲基)-1-甲基-1H-1,4-苯并二氮杂卓
  参考文献：
  名称：

  ROEMER, D.;RUHLAND, M.;ZEUGNER, H.;MILKOWSKI, W.;LIEPMANN, H.

  摘要：

  DOI：

文献信息

• [EN] COT MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE COT ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：GILEAD SCIENCES INC

  公开号：WO2017007689A1

  公开（公告）日：2017-01-12

  The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.

  本公开涉及通常与Cot（大阪甲状腺癌）调节剂及其使用和制造方法。
• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• [EN] PESTICIDE COMPOUNDS<br/>[FR] COMPOSÉS PESTICIDES
  申请人：BASF SE

  公开号：WO2015007682A1

  公开（公告）日：2015-01-22

  The present invention relates to novel compounds of the formula I and the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof wherein C1 is C or CH; C2 is C or CH; A1 is N or C; A2 is N, C(R2), N(R3), O, S or C(R4,R5); and A3 is N, O, S, N(R6), C(R7) or C(R8,R9); where one or two non-adjacent bonds in the 5-membered ring formed by C1, C2, A1, A2 and A3 are double bonds, while the others are single bonds, provided that the bond between A1 and A2 or the bond between A1 and C1 or the bond between A2 and A3 or the bond between C1 and C2 or the bond between A3 and C2 is a double bond further provided that at least one of A1, A2 and A3 is N, N(R3) or N(R6), and where Ar, R1, R2, R3, R4,R5, R6, R7, R8, R9 and (R)k are as defined in the claims and in the description, which are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及公式I的新化合物及其N-氧化物、立体异构体、互变异构体和农业或兽医可接受的盐，其中C1为C或CH；C2为C或CH；A1为N或C；A2为N、C(R2)、N(R3)、O、S或C(R4,R5)；A3为N、O、S、N(R6)、C(R7)或C(R8,R9)；其中由C1、C2、A1、A2和A3形成的5元环中的一个或两个非相邻键为双键，而其他键为单键，前提是A1和A2之间的键或A1和C1之间的键或A2和A3之间的键或C1和C2之间的键或A3和C2之间的键为双键，进一步前提是A1、A2和A3中至少有一个为N、N(R3)或N(R6)，其中Ar、R1、R2、R3、R4、R5、R6、R7、R8、R9和(R)k的定义如权利要求和说明书中所述，用于对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫。该发明还涉及一种利用这些化合物控制无脊椎动物害虫的方法，以及包括所述化合物的植物繁殖材料和农业和兽医组合物。
• [EN] DEUTERATED ANALOGS OF ETIFOXINE, THEIR DERIVATIVES AND USES THEROF<br/>[FR] ANALOGUES DEUTÉRÉS D'ÉTIFOXINE, LEURS DÉRIVÉS ET LEURS UTILISATIONS
  申请人：ANVYL LLC

  公开号：WO2016154039A1

  公开（公告）日：2016-09-29

  This invention relates to deuterated analogs of etifoxine of Formula 1, solvates, prodrugs, and pharmaceutically acceptable salts thereof, as well as to methods for their preparation and use, and to pharmaceutical compositions. Briefly, this invention is generally directed to deuterated analogs of etifoxine as well as to methods for their preparation and use, and to pharmaceutical compositions containing the same.

  这项发明涉及到公式1的依托氟辛的氘代物、溶剂化合物、前药以及其药用盐，以及它们的制备和使用方法，以及药物组合物。简而言之，这项发明通常涉及到依托氟辛的氘代物，以及它们的制备和使用方法，以及含有它们的药物组合物。
• [EN] N-ACYLIMINO HETEROCYCLIC COMPOUNDS FOR COMBATING INVERTEBRATE PESTS<br/>[FR] COMPOSES N-ACYLIMINO HETEROCYCLIQUES POUR LUTTER CONTRE LES NUISIBLES INVERTEBRES
  申请人：BASF SE

  公开号：WO2015124706A1

  公开（公告）日：2015-08-27

  The present invention relates to N-acylimino compound of formula (I): wherein X is O or S, in particular O;Cyc is a radical Cyc-1 or Cyc-2 (II) (III) D is CH2 or CH2 -CH2, where 1 or 2 of the hydrogen atoms may be replaced by R4, Y is O, S, CR5a R5b or N-R5; Het is a 5 or 6 membered carbon-bound or nitrogen-bound heterocyclic ring, W1 -W2 -W3 -W4 represents a carbon chain group connected to N and C=N, and thus forming a saturated, unsaturated, or partially unsaturated 5 or 6 membered nitrogen containing heterocycle, wherein W1, W2, W3 and W4 each individually represent 1 CRvRw; R1, R2 may be hydrogen, halogen, C1-C6 -alkyl etc.; R3 hydrogen, C1-C6 -alkyl, C2-C6 -alkenyl, C2 -C6 -alkynyl, C3 -C8 -cycloalkyl, C3 -C8 - cycloalkyl-C1-C4 -alkyl, etc.; R4, R5, R5a, R5b hydrogen, halogen, C1-C6 -alkyl, C2-C6-alkenyl, C2 -C6 -alkynyl, C3 -C8 -cycloalkyl, C3 -C8 -cycloalkyl-C1-C4-alkyl, etc.; The invention also relates to the use of the N-acylimino heterocyclic compounds, their stereoisomers, their tautomers and their salts,for combating invertebrate pests. Furthermore the invention relates also to methods of combating invertebrate pests, which comprises applying such compounds.

  本发明涉及式(I)的N-酰基亚胺化合物：其中X为O或S，特别是O；Cyc为基团Cyc-1或Cyc-2（II）（III）D为CH2或CH2-CH2，其中氢原子的1或2个可被R4取代，Y为O、S、CR5aR5b或N-R5；Het为5或6个成员的碳键合或氮键合杂环环，W1-W2-W3-W4代表连接到N和C=N的碳链基团，从而形成饱和的、不饱和的或部分不饱和的5或6个成员的含氮杂环，其中W1、W2、W3和W4分别代表1个CRvRw；R1、R2可以是氢、卤素、C1-C6-烷基等；R3为氢、C1-C6-烷基、C2-C6-烯基、C2-C6-炔基、C3-C8-环烷基、C3-C8-环烷基-C1-C4-烷基等；R4、R5、R5a、R5b为氢、卤素、C1-C6-烷基、C2-C6-烯基、C2-C6-炔基、C3-C8-环烷基、C3-C8-环烷基-C1-C4-烷基等；该发明还涉及N-酰基亚胺杂环化合物及其立体异构体、互变异构体和盐的用途，用于对抗无脊椎动物害虫。此外，该发明还涉及对抗无脊椎动物害虫的方法，包括应用这些化合物。