2-amino-3-(2-chlorobenzoyl)-5-(2-(4-isobutylphenyl)ethyl)thiophene | 117280-04-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-3-(2-chlorobenzoyl)-5-(2-(4-isobutylphenyl)ethyl)thiophene
• 英文别名: 2-Amino-5-(2-(4-isobutylphenyl)ethyl)-3-(2-chlorobenzoyl)thiophene；[2-Amino-5-[2-[4-(2-methylpropyl)phenyl]ethyl]thiophen-3-yl]-(2-chlorophenyl)methanone
• CAS: 117280-04-3
• 化学式: C₂₃H₂₄ClNOS
• 分子量: 397.969
• InChiKey: ODVOIOMIVLAKAN-UHFFFAOYSA-N

物化性质

• 沸点：
  557.3±50.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  71.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-3-(2-chlorobenzoyl)-5-(2-(4-isobutylphenyl)ethyl)thiophene 在 盐酸 、 一水合肼 、 溶剂黄146 作用下， 以 氯仿 、 异丙醇 为溶剂， 反应 27.5h， 生成 5-(2-Chloro-phenyl)-7-[2-(4-isobutyl-phenyl)-ethyl]-3-methyl-1,3-dihydro-thieno[2,3-e][1,4]diazepin-2-one
  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
• 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 、 Celite 、 三氟化硼乙醚 、 sulfur 、 一水合肼 、 三乙胺 作用下， 以 二氯甲烷 、 乙二醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 2-amino-3-(2-chlorobenzoyl)-5-(2-(4-isobutylphenyl)ethyl)thiophene
  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

• PAF-antagonistic thienotriazolodiazepine compounds and pharmaceutical
  申请人：Yoshitomi Pharmaceutical Industries Ltd.

  公开号：US04820703A1

  公开（公告）日：1989-04-11

  A thienotriazolodiazepine compound of the formula: ##STR1## wherein A is alkylene or substituted alkylene and each other 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.

  一种噻唑三氮杂环化合物，化学式为：##STR1## 其中A是烷基或取代烷基，其它符号如规范中所定义，并且是一种药学上可接受的酸加成盐，以及其药学用途。该化合物表现出PAF-拮抗活性，可用于预防或治疗各种PAF引起的疾病。
• 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。
• Verfahren zur Herstellung von 4-(4-Isobutylphenyl)-butyraldehyd
  申请人：BOEHRINGER INGELHEIM KG

  公开号：EP0428854A2

  公开（公告）日：1991-05-29

  Die Erfindung betrifft eine einfache, wirtschaftliche Synthese von 4-(4-Isobutylphenyl)-butyraldehyd und seine Verwendung zur Herstellung von (-)-4-(2-Chlorphenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-­thieno[3,2-f][1,2,4]triazolo[4,3-a]-1,4-diazepin.

  本发明涉及一种简单、经济的 4-(4-异丁基苯基)-丁醛合成方法及其在制备 (-)-4-(2-氯苯基)-2-[2-(4-异丁基苯基)乙基]-6,9-二甲基-6H-噻吩并[3,2-f][1,2,4]三唑并[4,3-a]-1,4-二氮杂卓中的应用。
• Optically active thienotriazolodiazepine compounds
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0480455A1

  公开（公告）日：1992-04-15

  Stable crystals of an acid addition salt of an optically active thienotriazolodiazepine compound or its hydrate of the formula wherein R1 is hydrogen, R2 is 2-phenylethyl substituted by alkyl having 1 to 5 carbon atoms, 2-morpholinocar- bonylethyl or alkyl having 6 to 12 carbon atoms, or R1 and R2 may combinedly form a saturated 5-membered ring having one substituent selected from the group consisting of morpholinomethyl, morpholinocarbonyl and N,N-dipropylcarbamoyl, R3 is halogen, alkyl having 1 to 5 carbon atoms or alkoxy having 1 to 5 carbon atoms, R4 is trifluoromethyl or alkyl having 1 to 5 carbon atoms, R5 is hydrogen or methyl, m is 1-2, and n is 0-2. The present invention provides optically active thienotriazolodiazepine compounds having strong PAF-antagonistic activity as markedly stable crystals which are excellent in crystalline property, permit purification by recrystallization, and have high chemical purity and optical purity, thereby rendering industrial large-scale synthesis attainable. In addition, crystallization thereof facilitates medicinal standardization and pharmaceutical formulation.

  具有光学活性的噻吩三唑并二氮杂卓化合物的酸加成盐或其水合物的稳定晶体，其式为 其中 R1 为氢，R2 为被 1 至 5 个碳原子的烷基、2-吗啉羰基或 6 至 12 个碳原子的烷基取代的 2-苯基乙基，或 R1 和 R2 可结合形成一个饱和 5 元环，该环具有一个选自吗啉甲基、吗啉羰基和 N,N-二丙基氨基甲酰基的取代基、R3为卤素、具有 1 至 5 个碳原子的烷基或具有 1 至 5 个碳原子的烷氧基，R4 为三氟甲基或具有 1 至 5 个碳原子的烷基，R5 为氢或甲基，m 为 1-2，n 为 0-2。本发明提供的光学活性噻吩三唑并二氮杂卓化合物具有很强的 PAF 拮抗活性，其结晶明显稳定，结晶性质优良，可通过重结晶纯化，化学纯度和光学纯度高，因此可实现工业化大规模合成。此外，其结晶还有助于药物标准化和药物配方。
• REMEDY FOR OSTEOPOROSIS AND DIAZEPINE COMPOUND
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0638560A1

  公开（公告）日：1995-02-15

  A remedy for osteoporosis containing a diazepine compound represented by general formula (I) or a pharmaceutically acceptable salt thereof as the active ingredient; a method of treating osteoporosis by administering the above compound; and the use of the compound for preparing a remedy for osteoporosis in formula (I) Ar represents aryl or heteroaryl; X represents oxygen or sulfur; W represents -N(R³⁶)-, -O- or -S-; Q represents a ring selected among (a), (b), (c) and (d), X and Y may be combined together to form =N-N=C(R⁶)-, =N-C(R⁵)=C(R⁶)-, =C(R⁵)-N=C(R⁶)-, =N-O-CO- or =N-N(R⁵)-CO-.

  一种治疗骨质疏松症的药物，含有通式(I)代表的二氮杂卓化合物或其药学上可接受的盐作为活性成分；一种通过施用上述化合物治疗骨质疏松症的方法；以及该化合物用于制备骨质疏松症药物的用途，在式(I)中 Ar 代表芳基或杂芳基；X代表氧或硫； W代表-N(R³⁶)-、-O-或-S-；Q 代表选自(a)、(b)、(c)和(d)的环，X 和 Y 可结合在一起形成 =N-N=C(R⁶)-、=N-C(R⁵)=C(R⁶)-、=C(R⁵)-N=C(R⁶)-、=N-O-CO- 或 =N-N(R⁵)-CO-。