3a-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester | 193274-12-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3a-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester
• 英文别名: 3a-(R,S)-Benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester；tert-butyl 3a-benzyl-2-ethyl-3-oxo-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate
• CAS: 193274-12-3
• 化学式: C₂₀H₂₇N₃O₃
• 分子量: 357.453
• InChiKey: CRYFAKQSVHLJID-UHFFFAOYSA-N

物化性质

• 沸点：
  465.6±55.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3a-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 2-amino-N-[2-(3a-(R)-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1-(R)-benzyloxymethyl-2-oxo-ethyl]-isobutyramide hydrochloride
  参考文献：
  名称：

  Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs)

  摘要：

  Novel pyrazolinone-piperidine dipeptide derivatives were synthesized and evaluated as growth hormone secretagogues (GHSs). Two analogues, capromorelin (5, CP-424391-18, hGHS-R1a K-i=7 nM, rat pituicyte EC50=3 nM) and the des-methyl analogue 5c (hGHS-R1a K-i=17 nM, rat pituicyte EC50 = 3 nM), increased plasma GH levels in an anesthesized rat model, with ED50 values less than 0.05 mg/kg iv. Capromorelin showed enhanced intestinal absorption in rodent models and exhibited superior pharmacokinetic properties, including high bioavailabilities in two animal species [F(rat) = 65%, F(dog) = 44%]. This short-duration GHS was orally active in canine models and was selected as a development candidate for the treatment of musculoskeletal frailty in elderly adults. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00433-9
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 sodium hydride 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.25h， 生成 3a-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs)

  摘要：

  Novel pyrazolinone-piperidine dipeptide derivatives were synthesized and evaluated as growth hormone secretagogues (GHSs). Two analogues, capromorelin (5, CP-424391-18, hGHS-R1a K-i=7 nM, rat pituicyte EC50=3 nM) and the des-methyl analogue 5c (hGHS-R1a K-i=17 nM, rat pituicyte EC50 = 3 nM), increased plasma GH levels in an anesthesized rat model, with ED50 values less than 0.05 mg/kg iv. Capromorelin showed enhanced intestinal absorption in rodent models and exhibited superior pharmacokinetic properties, including high bioavailabilities in two animal species [F(rat) = 65%, F(dog) = 44%]. This short-duration GHS was orally active in canine models and was selected as a development candidate for the treatment of musculoskeletal frailty in elderly adults. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00433-9

文献信息

• Treatment of insulin resistance with growth hormone secretagogues
  申请人：——

  公开号：US20030100561A1

  公开（公告）日：2003-05-29

  This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, 1 where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and the compounds of formula I. This invention is further directed to methods comprising administering to a human or other animal a combination of a functional somatostatin antagonist such as an alpha-2 adrenergic agonist and a compound of formula I.

  本发明涉及治疗哺乳动物胰岛素抵抗的方法，包括向该哺乳动物施用公式I，其中变量在说明书中定义的化合物的有效量，或其立体异构混合物、对映异构体富集物、对映异构体纯物、对映异构体纯物或其药学上可接受的盐和前药。公式I的化合物是生长激素分泌素，因此对于增加内源性生长激素水平非常有用。在另一个方面，本发明提供了某些中间体，这些中间体在合成上述化合物中非常有用，并且提供了某些合成上述中间体和公式I化合物的方法。本发明还涉及向人类或其他动物施用功能性生长抑素拮抗剂（如α-2肾上腺素受体激动剂）和公式I化合物的组合的方法。
• GROWTH-HORMONE SECRETAGOGUES
  申请人：PFIZER INC.

  公开号：EP0869968B1

  公开（公告）日：2007-05-02
• TREATMENT OF INSULIN RESISTANCE WITH GROWTH HORMONE SECRETAGOGUES
  申请人：Pfizer Products Inc.

  公开号：EP1000085B1

  公开（公告）日：2005-09-28
• US6107306A
  申请人：——

  公开号：US6107306A

  公开（公告）日：2000-08-22
• US6124264A
  申请人：——

  公开号：US6124264A

  公开（公告）日：2000-09-26