(1S,3aS,3bS,9aR,9bS,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid diethylamide | 151519-73-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (1S,3aS,3bS,9aR,9bS,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid diethylamide
• 英文别名: 17beta-N,N-diethylcarbamoyl-6-azaandrost-4-en-3-one；(1S,3aS,3bS,9aR,9bS,11aS)-N,N-diethyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide
• CAS: 151519-73-2
• 化学式: C₂₃H₃₆N₂O₂
• 分子量: 372.551
• InChiKey: PSUDAQNIQNWLHN-XEAGOBSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,3aS,3bS,9aR,9bS,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid diethylamide 在 N-碘代丁二酰亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (1S,3aS,3bS,9aR,9bS,11aS)-6-Iodo-9a,11a-dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid diethylamide
  参考文献：
  名称：

  6-Azasteroids: Structure-Activity Relationships for Inhibition of Type 1 and 2 Human 5.alpha.-Reductase and Human Adrenal 3.beta.-Hydroxy-.DELTA.5-steroid Dehydrogenase/3-Keto-.DELTA.5-steroid Isomerase

  摘要：

  6-Azaandrost-4-en-3-ones were synthesized and tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human adrenal 3 beta-hydroxy-Delta(5)-steroid dehydrogenase/3-keto-Delta(5)-steroid isomerase (3BHSD) to explore the structure-activity relationship of this novel series in order to optimize potency versus both isozymes of 5AR and selectivity versus 3BHSD. Compounds with picomolar IC50's versus human type 2 5AR and low nanomolar K-i's versus human type 1 5AR with 100-fold selectivity versus 3BHSD were identified (70). Preliminary in vivo evaluation of some optimal compounds from this series in a chronic castrated rat model of 5AR inhibitor-induced prostate involution and dog pharmacokinetic measurements identified a series of 17 beta-[N-(diphenylmethyl)carbamoyl]-6-azaandrost-4-en-3-ones (compounds 54, 66, and 67) with good in vivo efficacy and half-life in the dog. Inhibitors with, at the minimum, low nanomolar potency toward both human 5AR's and selectivity versus 3BHSD may show advantages over previously known 5AR inhibitors in the treatment of disease states which depend upon dihydrotestosterone, such as benign prostatic hyperplasia.

  DOI：

  10.1021/jm00041a014
• 作为产物：
  描述：

  17β-carboxy-6-(tert-butylcarboxy)-6-azaandrost-4-en-3-one 在 吡啶 、 氯化亚砜 、 三氟乙酸 作用下， 生成 (1S,3aS,3bS,9aR,9bS,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid diethylamide
  参考文献：
  名称：

  6-氮杂类固醇：人1型和2型类固醇5α-还原酶的有效双重抑制剂。

  摘要：

  DOI：

  10.1021/jm00078a022

文献信息

• Inhibitors of 5-.alpha.-testosterone reductase
  申请人：Glaxo Wellcome, Inc.

  公开号：US05543406A1

  公开（公告）日：1996-08-06

  The present invention relates to certain substituted 17.beta.-substituted carbonyl-6-azaandrost-4-en-3-ones of formula (I), especially those of formula (IG) ##STR1## wherein R.sup.1 and R.sup.2 are i) independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, or ii) taken together are a --CH.sub.2 -- group to form a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond; R.sup.3c is hydrogen; R.sup.4c is hydrogen, lower alkyl, lower cycloalkyl, lower alkenyl, alkanoyl of 2-6 carbons, --(CH.sub.2).sub.m CO.sub.2 R.sup.16, --(CH.sub.2).sub.m Ar.sup.a, --(CH.sub.2).sub.n 'CONR.sup.17 R.sup.18, --(CH.sub.2).sub.n 'NR.sup.17 R.sup.18 or --(CH.sub.2).sub.n 'OR.sup.16, wherein R.sup.16 is hydrogen, lower alkyl or lower alkenyl; R.sup.17 and R.sup.18 are independently hydrogen, lower alkyl lower cycloalkyl or lower alkenyl; Ar.sup.a is an aromatic group of 6 to 12 carbons; n' is 0 or an integer from 1 to 5; m is an integer from 1 to 5; R.sup.19 and R.sup.20 are independently hydrogen or lower alkyl, or taken together R.sup.19 and R.sup.20 form a carbonyl group (.dbd.O); R.sup.5c is lower alkyl, lower alkenyl, lower cycloalkyl, lower alkoxy, or NR.sup.21 R.sup.22, wherein R.sup.21 and R.sup.22 are independently hydrogen, lower alkyl or lower alkenyl; and pharmaceutically acceptable salts thereof, their preparation, medical use and pharmaceutical formulations.

  本发明涉及某些置换的17β-取代的羰基-6-azaandrost-4-en-3-酮化合物，其化学式为(I)，特别是化学式(IG)的化合物：其中，R1和R2分别为i)独立的氢或较低的烷基，并且带有R1和R2的碳之间的键是单键或双键，或ii)一起取代为-CH2-基团以形成环丙烷环，并且带有R1和R2的碳之间的键是单键；R3c为氢；R4c为氢、较低的烷基、较低的环烷基、较低的烯基、2-6个碳的脂肪酰基、-(CH2)mCO2R16、-(CH2)mAr a、-(CH2)n'CONR17R18、-(CH2)n'NR17R18或-(CH2)n'OR16，其中，R16为氢、较低的烷基或较低的烯基；R17和R18分别为氢、较低的烷基、较低的环烷基或较低的烯基；Ar a是6至12个碳的芳基；n'为0或1至5的整数；m为1至5的整数；R19和R20独立地为氢或较低的烷基，或一起形成羰基(.dbd.O)；R5c为较低的烷基、较低的烯基、较低的环烷基、较低的烷氧基或NR21R22，其中，R21和R22独立地为氢、较低的烷基或较低的烯基；以及它们的药学上可接受的盐、制备方法、医疗用途和制药配方。
• 6-Azasteroids: potent dual inhibitors of human type 1 and 2 steroid 5.alpha.-reductase
  作者：Stephen V. Frye、Curt D. Haffner、Patrick R. Maloney、Robert A. Mook、G. F. Dorsey、Roger N. Hiner、Kenneth W. Batchelor、H. Neal Bramson、J. Darren Stuart

  DOI：10.1021/jm00078a022

  日期：1993.12
• INHIBITORS OF 5-ALPHA-TESTOSTERONE REDUCTASE
  申请人：GLAXO WELLCOME INC.

  公开号：EP0641356B1

  公开（公告）日：1998-04-22
• US5302589A
  申请人：——

  公开号：US5302589A

  公开（公告）日：1994-04-12
• US5457098A
  申请人：——

  公开号：US5457098A

  公开（公告）日：1995-10-10