6-azasteroid | 151520-28-4

• 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: 6-azasteroid
• 英文别名: (1S,3aS,3bS,9aR,9bS,11aS)-N-benzhydryl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide
• CAS: 151520-28-4
• 化学式: C₃₂H₃₈N₂O₂
• 分子量: 482.666
• InChiKey: WOJPQMHAJQJQJK-JPFNMMHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-azasteroid 、 碘甲烷 在 sodium hydride 作用下， 生成 (1S,3aS,3bS,9aR,9bS,11aS)-5,9a,11a-Trimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid benzhydryl-amide
  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 6-azasteroid
  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

• 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
• PROCESS FOR PREPARING STEROIDS HAVING A CARBOXAMIDE SIDE-CHAIN
  申请人：PHARMACIA & UPJOHN S.p.A.

  公开号：EP0902790A1

  公开（公告）日：1999-03-24
• [EN] PROCESS FOR PREPARING STEROIDS HAVING A CARBOXAMIDE SIDE-CHAIN<br/>[FR] PROCEDE DE PREPARATION DE STEROIDES A CHAINE LATERALE CARBOXAMIDE
  申请人：PHARMACIA & UPJOHN S.P.A.

  公开号：WO1997040062A1

  公开（公告）日：1997-10-30

  (EN) Process for preparing steroids having a carboxamide side-chain of formula (I) wherein: the formula - - - are each independently, single or double bonds; z is a single bond, or a straight or branched C1-C5 alkylene; the moiety represents the A and B rings of a steroid; R18 is hydrogen or C1-C4 alkyl; R22, R23, and R24 are, each independently, selected from: hydrogen, optionally substituted C1-C10 alkyl, C5-C7 cycloalkyl, C6-C10 alkylcycloalkyl or cycloalkylakyl, C6-C10 aryl, C7-C14 arylalkyl or alkylarly, heterocyclyl, heteroaryl, heterocyclylalkyl, and heteroarylalkyl. The process comprises reacting the corresponding 17-cyanosteroids with an alcohol, and alkene or a halide. The compounds of formula (I) are useful as testosterone 5$g(a)-reductase inhibitors.(FR) L'invention se rapporte à un procédé de préparation de stéroïdes à chaîne latérale carboxamide de la formule (I) dans laquelle les symboles - - - représentent chacun, indépendamment, des liaisons simples ou doubles, Z représente une liaison simple ou un alkylène en C1-C5 à chaîne droite ou ramifiée; la traction (a) représente les noyaux A et B d'un stéroïde; R18 représente hydrogène ou alkyle en C1-C4; R22, R23, R24 sont chacun indépendamment, sélectionnés parmi: hydrogène; alkyle en C1-C10 éventuellement substitué, cylcoalkyle en C5-C7, alkylcycloalkyle ou cycloalkylalkyle en C6-C10, aryle en C6-C10, arylalkyle ou alkylaryle en C7-C14, hétérocyclyle, hétéroaryle, hétérocyclylalkyle et hétéroalkylalkyle. Le procédé consiste à faire réagir les 17-cyanostéroïdes correspondant avec un alcool, un alcène ou un halogénure. Les composés de la formule (I) sont utilisés comme inhibiteurs de la testostérone 5$g(a)-réductase.
• 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
  作者：Stephen V. Frye、Curt D. Haffner、Patrick R. Maloney、Robert A. Mook、George F. Dorsey、Roger N. Hiner、Cindy M. Cribbs、Thomas N. Wheeler、John A. Ray

  DOI：10.1021/jm00041a014

  日期：1994.7

  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.