3,7-dithiaPGE₁ methyl ester 11,15-bis(tert-butyldimethylsilyl ether) | 210819-04-8

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 3,7-dithiaPGE₁ methyl ester 11,15-bis(tert-butyldimethylsilyl ether)
• 英文别名: (3{(1R,2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-[(S)-(E)-3-(tert-butyldimethylsilanoxy)oct-1-enyl]-5-oxocyclopentylsulfanyl} propylsulfanyl)acetic acid methyl ester；(3-{(1R,2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-[(S)-(E)-3-(tert-butyldimethylsilanoxy)oct-1-enyl]-5-oxocyclopentylsulfanyl} propylsulfanyl)acetic acid methyl ester；methyl 2-[3-[(1R,2S,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-[(E,3S)-3-[tert-butyl(dimethyl)silyl]oxyoct-1-enyl]-5-oxocyclopentyl]sulfanylpropylsulfanyl]acetate
• CAS: 210819-04-8
• 化学式: C₃₁H₆₀O₅S₂Si₂
• 分子量: 633.117
• InChiKey: ZXWQZONUDKUNEA-VXOUFEQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.89
• 重原子数：
  40
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3,7-dithiaPGE₁ methyl ester 11,15-bis(tert-butyldimethylsilyl ether) 在 (HF)n*pyridine 作用下， 以 吡啶 、 乙腈 为溶剂， 反应 0.5h， 以92%的产率得到3,7-dithiaprostaglandin E₁ methyl ester
  参考文献：
  名称：

  Design and synthesis of a selective EP4-Receptor agonist. Part 1: discovery of 3,7-DithiaPGE1 derivatives and identification of Their ω chains

  摘要：

  Improvement of EP4-receptor selectivity and the agonist activity by introduction of heteroatoms into the a chain of PGE(1) was investigated. Among the compounds tested, 3,7-dithiaPGE(1) 4a exhibited good EP4-receptor selectivity and agonist activity. Further modification of the omega chain of 3,7-dithiaPGE(1) was performed to improve EP4-receptor selectivity and agonist activity. Of the compounds produced, 16-phenyl-omega-tetranor-3.7-dithiaPGE(1) 4p possessing moderate EP4-receptor selectivity and agonist activity. was identified as a new chemical lead for further optimization by modification of the aromatic moiety. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00351-0
• 作为产物：
  描述：

  methyl 6-mercapto-3-thiahexanoate 在 aluminum oxide 、 叔丁基锂 作用下， 以 乙醚 、 二氯甲烷 、 正戊烷 为溶剂， 反应 14.0h， 生成 3,7-dithiaPGE₁ methyl ester 11,15-bis(tert-butyldimethylsilyl ether)
  参考文献：
  名称：

  Design and synthesis of a selective EP4-Receptor agonist. Part 1: discovery of 3,7-DithiaPGE1 derivatives and identification of Their ω chains

  摘要：

  Improvement of EP4-receptor selectivity and the agonist activity by introduction of heteroatoms into the a chain of PGE(1) was investigated. Among the compounds tested, 3,7-dithiaPGE(1) 4a exhibited good EP4-receptor selectivity and agonist activity. Further modification of the omega chain of 3,7-dithiaPGE(1) was performed to improve EP4-receptor selectivity and agonist activity. Of the compounds produced, 16-phenyl-omega-tetranor-3.7-dithiaPGE(1) 4p possessing moderate EP4-receptor selectivity and agonist activity. was identified as a new chemical lead for further optimization by modification of the aromatic moiety. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00351-0

文献信息

• 3, 7 or 3 and 7 thia or oxa prostanoic acid derivatives as agents for lowering intraocular pressure
  申请人：Allergan, Inc.

  公开号：US06538018B1

  公开（公告）日：2003-03-25

  The present invention provides a method of treating ocular hypertension or glaucoma which comprises administering to an animal having ocular hypertension or glaucoma therapeutically effective amount of a compound represented by the general formula I; where in A, B, D, X, Y, Z, R1, R3 and R4 are as defined in the specification.

  本发明提供了一种治疗眼压增高或青光眼的方法，包括向患有眼压增高或青光眼的动物施用一定治疗剂量的一种化合物，该化合物由一般式I表示；其中A、B、D、X、Y、Z、R1、R3和R4如规范中定义。
• Combination therapy for glaucoma treatment
  申请人：Burk M. Robert

  公开号：US20050209194A1

  公开（公告）日：2005-09-22

  A method is disclosed herein comprising administering a compound and a second drug to an eye of a mammal for the treatment of glaucoma or the reduction of intraocular pressure, said compound represented by the general formula I; wherein A, B, D, X, Y, Z, R 1 , R 3 and R 4 are as defined in the specification.

  本方法包括向哺乳动物的眼睛内给予化合物和第二种药物，用于治疗青光眼或降低眼内压，所述化合物由一般式I表示；其中A、B、D、X、Y、Z、R1、R3和R4如规范中所定义。
• 3,7 or 3 and 7 thia or oxa prostanoic acid derivatives as agents for lowering intraocular pressure
  申请人：Allergan Sales, Inc.

  公开号：US06410591B1

  公开（公告）日：2002-06-25

  The present invention provides a method of treating ocular hypertension or glaucoma which comprises administering to an animal having ocular hypertension or glaucoma a therapeutically effective amount of a 3, 7 or 3 and 7 thia or oxa prostanoic acid derivative.

  本发明提供了一种治疗眼压升高或青光眼的方法，包括向患有眼压升高或青光眼的动物施用治疗有效量的3、7或3和7硫或氧代前列腺酸衍生物。
• Treatment of inflammatory bowel disease
  申请人：Burk M. Robert

  公开号：US20050222094A1

  公开（公告）日：2005-10-06

  A method is disclosed herein comprising administering a compound to a mammal suffering from an inflammatory bowel disease for the treatment of said disease, said compound represented by the general formula I; wherein A, B, D, X, Y, Z, R 1 , R 3 and R 4 are as defined in the specification.

  本文公开了一种方法，包括向患有炎症性肠病的哺乳动物施用一种化合物以治疗该疾病，所述化合物由一般式I表示；其中A、B、D、X、Y、Z、R1、R3和R4如规范中定义。
• 3, 7or3 and 7 thia or oxa prostanoic acid derivatives as agents for lowering intraocular pressure
  申请人：Allergan Sales, Inc.

  公开号：US20030027853A1

  公开（公告）日：2003-02-06

  The present invention provides a method of treating ocular hypertension or glaucoma which comprises administering to an animal having ocular hypertension or glaucoma therapeutically effective amount of a compound represented by the general formula I; 1 wherein hatched lines represent the &agr; configuration, a triangle represents the &bgr; configuration, a wavy line represents the &agr; configuration or the &bgr; configuration and a dotted line represents the presence or absence of a double bond; A and B are independently selected from the group consisting of O, S and CH 2 ; provided that at least one of A or B is S; D represents a covalent bond or CH 2 , O, S or NH; X is CO 2 R, CONR 2 , CH 2 OR, P(O)(OR) 2 , CONRSO 2 R SONR 2 or 2 Y is O, OH, OCOR 2 , halogen or cyano; Z is CH 2 or a covalent bond; R is H, or R 2 ; R 1 is H, R 2 , phenyl, or COR 2 ; R 2 is C 1 -C 5 lower alkyl or alkenyl and R 3 is benzothienyl, benzofuranyl, naphthyl or substituted derivatives thereof, wherein the substituents maybe selected from the group consisting of C 1 -C 5 alkyl, halogen, CF 3 , CN, NO 2 , NR 2 , CO 2 R and OR.

  本发明提供了一种治疗眼压或青光眼的方法，该方法包括向患有眼压或青光眼的动物给予一种由一般式I表示的化合物的治疗有效量；其中，虚线表示α构型，三角形表示β构型，波浪线表示α构型或β构型，点线表示双键的存在或不存在；A和B分别选自O、S和CH2组成的群体中，但至少其中一个是S；D表示共价键或CH2、O、S或NH；X是CO2R、CONR2、CH2OR、P（O）（OR）2、CONRSO2R、SONR2或2Y是O、OH、OCOR2、卤素或氰基；Z是CH2或共价键；R是H或R2；R1是H、R2、苯基或COR2；R2是C1-C5低碳基或烯基，R3是苯并噻吩基、苯并呋喃基、萘基或其取代衍生物，其中取代基可以选自C1-C5烷基、卤素、CF3、CN、NO2、NR2、CO2R和OR组成的群体。