desmethyl-Y-24180

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烯杂卓类
• 英文名称: desmethyl-Y-24180
• 英文别名: 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine；4-(2-Chloro-phenyl)-2-[2-(4-isobutyl-phenyl)-ethyl]-9-methyl-6H-1-thia-5,7,8,9a-tetraaza-cyclopenta[e]azulene；7-(2-chlorophenyl)-13-methyl-4-[2-[4-(2-methylpropyl)phenyl]ethyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene
• 化学式: C₂₇H₂₇ClN₄S
• 分子量: 475.057
• InChiKey: UNRYNEUZUOGHCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  desmethyl-Y-24180 生成 (2-chlorophenyl)-[2-[3-[(dimethylamino)methyl]-5-methyl-1,2,4-triazol-4-yl]-5-[2-[4-(2-methylpropyl)phenyl]ethyl]thiophen-3-yl]methanone
  参考文献：
  名称：

  MORIVAKI, MINORU;NAKADZIMA, TORU;TEHRASAVA, MITIO;TAXARA, TEHTSUXARU

  摘要：

  DOI：
• 作为产物：
  描述：

  异丁基苯 在 吡啶 、 chromium(VI) oxide 、 氢氧化钾 、 sodium tetrahydroborate 、 三氯化铝 、 tetraphosphorus decasulfide 、 Celite 、 三氟化硼乙醚 、 氨 、 sulfur 、 一水合肼 、 溶剂黄146 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 乙二醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 44.5h， 生成 desmethyl-Y-24180
  参考文献：
  名称：

  Structural optimization of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepines as antagonists for platelet activating factor: pharmacological contribution of substituents at the 2- and 6-positions of a condensed ring system

  摘要：

  A series of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine derivatives bearing substituents at the 2- and 6-positions were synthesized, and evaluated in vitro for their inhibitory activity on rabbit platelet aggregation induced by platelet activating factor (PAF) and in vivo for their preventing effect on PAF-induced mortality in mice. The length of alkyl or arylalkyl side chain at the 2-position was responsible for enhancing the affinity for the PAF receptor. The simultaneous substitution at both the 2- and 6-positions resulted in a successful separation of the affinity for the PAF receptor from that for the benzodiazepine (BZ) receptor. Thus, (+/-)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180) was confirmed to be a specific antagonist for the PAF receptor and is currently under clinical trials.

  DOI：

  10.1016/0223-5234(96)85877-6

文献信息

• Thienylazole compound and thienotriazolodiazepine compound
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US05760032A1

  公开（公告）日：1998-06-02

  Thienylazole compounds (I) and thienotriazolodiazepine compounds (II) of the formulas ##STR1## wherein R.sup.1 and R.sup.2 are hydrogen, halogen, C.sub.1 -C.sub.5 alkyl and the like; --A.dbd.B-- is --N.dbd.N-- and the like; R.sup.3 and R.sup.19 are hydrogen, C.sub.1 -C.sub.5 alkyl and the like; Y is --NHCO--, --NHCONH--, --NHCOO-- and the like; Z.sup.1 and Z.sup.2 are aryl, heteroaryl and the like; Ar is halogen-substituted phenyl and the like; and m is 0 or an integer of 1-5. The compounds of the present invention have CCK antagonistic action and gastrin antagonistic action, particularly potent antagonistic action against CCK-A receptor, and are useful as agents for the prophylaxis and treatment of central and peripheral nervous system diseases (e.g., anxiety, schizophrenia, and the like) and digestive diseases (e.g., pancreatitis, gastric ulcer, enterelcosis, irritable bowel syndrome, constipation, and the like).

  本发明提供了Thienylazole化合物（I）和thienotriazolodiazepine化合物（II），其化学式为##STR1##其中R.sup.1和R.sup.2是氢，卤素，C.sub.1-C.sub.5烷基等；--A.dbd.B--是--N.dbd.N--等；R.sup.3和R.sup.19是氢，C.sub.1-C.sub.5烷基等；Y是--NHCO--，--NHCONH--，--NHCOO--等；Z.sup.1和Z.sup.2是芳基，杂芳基等；Ar是卤素取代的苯基等；m为0或1-5的整数。本发明的化合物具有CCK拮抗作用和胃泌素拮抗作用，特别是对CCK-A受体具有强烈的拮抗作用，可用作中枢和外周神经系统疾病（如焦虑，精神分裂症等）和消化系统疾病（如胰腺炎，胃溃疡，肠炎，肠易激综合征，便秘等）的预防和治疗剂。
• PAF-antagonistic thienotriazolodiazepine compounds and pharmaceutical uses thereof
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0268242A1

  公开（公告）日：1988-05-25

  A thienotriazolodiazepine compound of the general formula (I): wherein each symbol is as defined in the specification and a pharmaceutically acceptable acid addition salt thereof, and pharmaceutical uses thereof. Said compounds exhibit PAF-antagonistic activity and are useful for the prevention or treatment of various PAF-induced diseases.

  通式(I)的噻吩三唑二氮杂卓化合物： 其中各符号如说明书中所定义及其药学上可接受的酸加成盐，以及它们的药物用途。 所述化合物具有 PAF 拮抗活性，可用于预防或治疗各种 PAF 引起的疾病。
• 3S,7S-3-(Morpholinocarbonyl)-5-(2-chlorphenyl)-7,10-dimethyl-3,4-dihydro-2H,7H-cyclopenta[4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin.
  申请人：BOEHRINGER INGELHEIM KG

  公开号：EP0368175A1

  公开（公告）日：1990-05-16

  Die Erfindung betrifft neue Hetrazepine, Verfahren zu deren Herstellung sowie ihre Verwendung als Arzneimittel mit PAF-antagonistischer Wirkung.

  本发明涉及新的三氮杂卓、其制备工艺及其作为具有 PAF 拮抗作用的药物的用途。
• PAF-Antagonisten zur Herstellung eines Arzneimittels, welches zur Behandlung der durch verminderte beta-Rezeptorstimulation verursachten Herzkrankheiten geeignet ist
  申请人：Dr. Karl Thomae GmbH

  公开号：EP0416604A2

  公开（公告）日：1991-03-13

  Die vorliegende Erfindung betrifft die neue Verwendung der PAF-Antagonisten zur Behandlung des durch verminderte β-Re­zeptorstimulation am Herzen verursachten Krankheiten und deren Verwendung zur Herstellung eines entsprechenden Arzneimittels.

  本发明涉及 PAF 拮抗剂用于治疗因心脏中 β 受体刺激减少而引起的疾病的新用途，以及它们在制造相应药物中的用途。
• THIENYLAZOLE COMPOUND AND THIENOTRIAZOLODIAZEPINE COMPOUND
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0776892A1

  公开（公告）日：1997-06-04

  Thienylazole compounds (I) and thienotriazolodiazepine compounds (II) of the formulas wherein R1 and R2 are hydrogen, halogen, C1-C5 alkyl and the like; -A=B-is -N=N- and the like; R3 and R19 are hydrogen, C1-C5 alkyl and the like; Y is -NHCO, -NHCONH-, -NHCOO- and the like; Z1 and Z2 are aryl, heteroaryl and the like; Ar is halogen-substituted phenyl and the like; and m is 0 or an integer of 1-5. The compounds of the present invention have CCK antagonistic action and gastrin antagonistic action, particularly potent antagonistic action against CCK-A receptor, and are useful as agents for the prophylaxis and treatment of central and peripheral nervous system diseases (e.g., anxiety, schizophrenia, and the like) and digestive diseases (e.g., pancreatitis, gastric ulcer, enterelcosis, irritable bowel syndrome, constipation, and the like).

  噻吩基氮唑化合物(I)和噻吩三唑并二氮杂卓化合物(II)，其式如下 其中 R1 和 R2 是氢、卤素、C1-C5 烷基和类似物；-A=B- 是-N=N- 和类似物；R3 和 R19 是氢、C1-C5 烷基和类似物；Y 是-NHCO、-NHCONH-、-NHCOO- 和类似物；Z1 和 Z2 是芳基、杂芳基和类似物；Ar 是卤素取代的苯基和类似物；m 是 0 或 1-5 的整数。 本发明的化合物具有 CCK 拮抗作用和胃泌素拮抗作用，特别是对 CCK-A 受体具有强效的拮抗作用，可作为预防和治疗中枢和周围神经系统疾病（如焦虑症、精神分裂症等）和消化系统疾病（如胰腺炎、胃溃疡、肠梗阻、肠易激综合征、便秘等）的药物。