5-methyl-2-(S)-proline methyl ester | 947281-39-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-methyl-2-(S)-proline methyl ester
• 英文别名: (2S)-Methyl 5-methylpyrrolidine-2-carboxylate；methyl (2S)-5-methylpyrrolidine-2-carboxylate
• CAS: 947281-39-2
• 化学式: C₇H₁₃NO₂
• 分子量: 143.186
• InChiKey: FZBQCOBVXDOWIT-GDVGLLTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methyl-2-(S)-proline methyl ester 在 吡啶 、 咪唑 、 盐酸 、 氨 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (2S,5S)-1-[2-(Adamantan-1-ylamino)-acetyl]-5-methyl-pyrrolidine-2-carbonitrile
  参考文献：
  名称：

  cis-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization

  摘要：

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0600085
• 作为产物：
  描述：

  重氮甲烷 、 (2S)-5-methylpyrrolidine-2-carboxylic acid 以 四氢呋喃 、 乙醚 为溶剂， 生成 5-methyl-2-(S)-proline methyl ester
  参考文献：
  名称：

  cis-2,5-Dicyanopyrrolidine Inhibitors of Dipeptidyl Peptidase IV:  Synthesis and in Vitro, in Vivo, and X-ray Crystallographic Characterization

  摘要：

  Inhibitors of the glucagon-like peptide-1 (GLP-1) degrading enzyme dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes in animal models and in human subjects. A novel series of cis-2,5-dicyanopyrrolidine alpha-amino amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. 1-({[1-(Hydroxymethyl) cyclopentyl] amino}acetyl) pyrrolidine-2,5-cis-dicarbonitrile (1c) is an achiral, slow-binding (time-dependent) inhibitor of DPP-IV that is selective for DPP-IV over other DPP isozymes and proline specific serine proteases, and which has oral bioavailability in preclinical species and in vivo efficacy in animal models. The mode of binding of the cis-2,5-dicyanopyrrolidine moiety was determined by X-ray crystallography. The hydrochloride salt of 1c was further profiled for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0600085

文献信息

• 7a-alkoxy-4H-pyrano [3,2-d] -oxazol-2 (3H) -one and process for producing the same
  申请人：——

  公开号：US20020072612A1

  公开（公告）日：2002-06-13

  The present invention provides a novel 7a-alkoxy-4H-pyrano-[3,2-d]-oxazol-2(3H)-one represented by the formula (I): 1 wherein R 1 and R 2 each represent a hydrogen atom, an alkyl group, an alkenyl group, an aryl group or an aralkyl group; R 3 represents an alkyl group, a cycloalkyl group, an alkenyl group, an aryl group or an aralkyl group, provided that a 2-alkenyl group is excluded from the alkenyl group of R 3 ; and R 4 represents an alkyl group, an aryl group, an alkoxycarbonyl group or a cyano group, and a process for producing the same which comprises reacting 5-alkoxy-2(3H)-oxazolone with an &agr;,&bgr;-unsaturated ketone in the presence of a Lewis acid in a solvent.

  本发明提供了一种新型的7a-烷氧基-4H-吡喃-[3,2-d]-噁唑-2(3H)-酮，其化学式表示为(I)：其中R1和R2分别代表氢原子、烷基、烯基、芳基或芳基烷基；R3代表烷基、环烷基、烯基、芳基或芳基烷基，但要求R3的烯基中排除2-烯基；R4代表烷基、芳基、烷氧羰基或氰基；以及一种制备该化合物的方法，包括在溶剂存在下，将5-烷氧基-2(3H)-噁唑酮与α,β-不饱和酮在Lewis酸存在下反应。
• THIOPHENE DERIVATIVES AS PPAR AGONISTS I
  申请人：Ayscough Andrew

  公开号：US20100063065A1

  公开（公告）日：2010-03-11

  The invention discloses compounds of formula (I); wherein: R is a carboxylic acid or a derivative thereof; R 1 is alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkylthio, halo or trihalomethyl; R 2 is aryl, heteroaryl, arylalkyl or heteroarylalkyl; R 3 is H or F; and L is a linking group comprising a chain of from 2 to 8 atoms linking R and the carbonyl group (A); and pharmaceutically acceptable derivatives thereof, useful for treating disorders mediated by peroxisome-proliferator-activated receptor (PPAR) subtype δ (PPARδ). The compounds of the invention are therefore useful in the treatment of metabolic syndrome, obesity, type-II diabetes, dyslipidemia, wound healing, inflammation, neurodegenerative disorders and multiple sclerosis.

  本发明揭示了式(I)的化合物;其中：R是羧酸或其衍生物; R1是烷基，烯基，炔基，环烷基，烷氧基，烷硫基，卤素或三卤甲基; R2是芳基，杂环芳基，芳基烷基或杂环芳基烷基; R3是H或F; L是一个链接基团，包括从2到8个原子的链连接R和羰基(A);以及其药学上可接受的衍生物，用于治疗通过过氧化物酶体增殖物激活受体(PPAR)亚型δ (PPARδ)介导的疾病。因此，本发明的化合物在代谢综合征、肥胖症、2型糖尿病、脂质代谢异常、伤口愈合、炎症、神经退行性疾病和多发性硬化症的治疗中有用。
• PYRROLIDINE OR THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS AS AGONISTS OF G-PROTEIN COUPLED RECEPTOR 43 (GPR43)
  申请人：Hoveyda Hamid R.

  公开号：US20130023539A1

  公开（公告）日：2013-01-24

  The present invention is directed to novel compounds of formula (I) and their use in treating and/or preventing metabolic diseases.

  本发明涉及式（I）的新化合物及其在治疗和/或预防代谢性疾病方面的应用。
• Substituted pyrrolidines as G-protein coupled receptor 43 agonists
  申请人：Ogeda SA

  公开号：US10017468B2

  公开（公告）日：2018-07-10

  The present invention is directed to a process for the preparation of aryl-pyrrolidine carboxylic acid derivative compounds which are useful in treating metabolic diseases, said process consisting of coupling an aryl-pyrrolidine compound with an aryl carboxylic acid compound followed by alkaline or acidic treatment, hydrogenolysis or treatment with a fluoride of the ester intermediate to afford novel aryl-pyrrolidine carboxylic acid derivative compounds.

  本发明涉及一种用于制备治疗代谢性疾病的芳基吡咯烷羧酸衍生物化合物的工艺，所述工艺包括将芳基吡咯烷化合物与芳基羧酸化合物偶联，然后对酯类中间体进行碱性或酸性处理、氢解或用氟化物处理，以得到新型芳基吡咯烷羧酸衍生物化合物。
• SAR study of bicyclo[4.1.0]heptanes as melanin-concentrating hormone receptor R1 antagonists: Taming hERG
  作者：Jing Su、Brian A. McKittrick、Haiqun Tang、Duane A. Burnett、John W. Clader、William J. Greenlee、Brian E. Hawes、Kim O’Neill、Brian Spar、Blair Weig、Timothy Kowalski、Steve Sorota、Cheng Li、Tongtong Liu

  DOI：10.1016/j.bmc.2007.05.068

  日期：2007.8

  To improve the ex vivo potency of MCH inhibitor la and to address its hERG liability, a structure-activity study was carried out, focusing on three regions of the lead structure. Introduction of new side chains with basic nitrogen improved in vitro and ex vivo bindings. Many potent compounds with K-i < 10 nM were discovered (compounds 6a-j) and several Compounds (14-17) had excellent ex vivo binding at 6 h and 24 h. Attenuating the basicity of nitrogen on the side chain, and in particular, introduction of a polar group such as aminomethyl on the distal phenyl ring significantly lowered the hERG activity. Further replacement of the distal phenyl group with heteroaryl groups in the cyclohexene series provided compounds such as 281 with excellent ex vivo activity with much reduced hERG liability. (c) 2007 Elsevier Ltd. All rights reserved.