(3β,5α)-3-羟基-3-(三氟甲基)孕烷-20-酮 | 177080-77-2

• 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
• 中文名称: (3β,5α)-3-羟基-3-(三氟甲基)孕烷-20-酮
• 英文名称: 1-((3S,5S,8R,9S,10S,13S,14S,17S)-3-Hydroxy-10,13-dimethyl-3-trifluoromethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-ethanone
• 英文别名: Pregnan-20-one, 3-hydroxy-3-(trifluoromethyl)-, (3alpha,5alpha)-；1-[(3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-3-(trifluoromethyl)-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 177080-77-2
• 化学式: C₂₂H₃₃F₃O₂
• 分子量: 386.498
• InChiKey: BLMOPJSSNJGYSZ-PECKBWEZSA-N

物化性质

• 沸点：
  430.5±40.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (三氟甲基)三甲基硅烷 、 20,20-(ethylenedioxy)-5α-pregnan-3-one 在 盐酸 、 四丁基氟化铵 作用下， 生成 (3β,5α)-3-羟基-3-(三氟甲基)孕烷-20-酮 、 Co 2-1970
  参考文献：
  名称：

  Synthesis and in Vitro Activity of 3β-Substituted-3α-hydroxypregnan-20-ones:  Allosteric Modulators of the GABA_A Receptor

  摘要：

  Two naturally occurring metabolites of progesterone, 3 alpha-hydroxy-5 alpha- and 5 beta-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABA(A) receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and sedative/hypnotics is limited by rapid metabolism. To avoid these shortcomings, a series of 3 beta-substituted derivatives of 1 and 2 was prepared. Small lipophilic groups generally maintain potency in both the 5 alpha- and 5 beta-series as determined by inhibition of [S-35]TBPS binding. In the 5 alpha-series, 3 beta-ethyl, -propyl, -trifluoromethyl and -(benzyloxy)methyl, as well as substituents of the form 3 beta-XCH(2), where X is Cl, Br, or I or contains unsaturation, show limited efficacy in inhibiting [S-35]TBPS binding. In the 5 beta-series, the unsubstituted parent 2 is a two-component inhibitor, whereas all of the 3 beta-substituted derivatives of 2 inhibit TBPS via a single class of binding sites. In addition, all of the 3-substituted 5 beta-sterols tested are full inhibitors of [S-35]TBPS binding. Electrophysiological measurements using alpha 1 beta 2 gamma 2L receptors expressed in oocytes show that 3 beta-methyl- and 3 beta-(azidomethyl)-3 alpha-hydroxy-5 alpha-pregnan-20-one (6 and 22, respectively) are potent full efficacy modulators and that 3 alpha-hydroxy-3 beta-(trifluoromethyl)-5 alpha-pregnan-20-one (24) is a low-efficacy modulator, confirming the results obtained from [S-35]TBPS binding. These results indicate that modification of the 3 beta-position in 1 and 2 maintains activity at the neuroactive steroid site on the GABA(A) receptor. In animal studies, compound 6 (CCD 1042) is an orally active anticonvulsant, while the naturally occurring progesterone metabolites I and 2 are inactive when administered orally, suggesting that 3 beta-substitution slows metabolism of the S-hydroxyl, resulting in orally bioavailable steroid modulators of the GABA(A) receptor.

  DOI：

  10.1021/jm960021x

文献信息

• [EN] ANDROSTANE AND PREGNANE SERIES FOR ALLOSTERIC MODULATION OF GABA RECEPTOR<br/>[FR] SERIES DE L'ANDROSTANE ET DE LA PREGNANE PRODUISANT UNE MODULATION ALLOSTERIQUE DU RECEPTEUR DU GABA
  申请人：COCENSYS, INC.

  公开号：WO1996016076A1

  公开（公告）日：1996-05-30

  (EN) Methods, compositions, and compounds for modulating the GABAA receptor-chloride ionophore complex to alleviate stress, anxiety, seizures, mood disorders, PMS and PND and to induce anesthesia.(FR) Procédés, compositions et composés servant à moduler le complexe ionophore de chlorure et récepteur du GABAA, permettant ainsi d'atténuer le stress, l'anxiété, les crise d'épilepsie, les troubles de l'humeur, la dépression post natale et le syndrome prémenstruel, et de provoquer l'anesthésie.

  (中文) 用于调节GABAA受体-氯离子复合物以缓解压力、焦虑、癫痫、情绪障碍、PMS和PND并诱导麻醉的方法、组合物和化合物。
• ANDROSTANE AND PREGNANE SERIES FOR ALLOSTERIC MODULATION OF GABA RECEPTOR
  申请人：COCENSYS, INC.

  公开号：EP0808325B1

  公开（公告）日：2001-01-17
• EP0808325A4
  申请人：——

  公开号：EP0808325A4

  公开（公告）日：1997-12-17