(R)-2-[1-(2-Hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (R)-2-[1-(2-Hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid
• 英文别名: (R)-2-((1-((2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)carbamoyl)cyclopentyl)methyl)pentanoic acid；(2R)-2-[[1-[[2-(hydroxymethyl)-1,3-dihydroinden-2-yl]carbamoyl]cyclopentyl]methyl]pentanoic acid
• 化学式: C₂₂H₃₁NO₄
• 分子量: 373.492
• InChiKey: WRLJDWUKTUNXCU-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (+)-2-{[1-({[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]amino}carbonyl)cyclopentyl]-methyl}pentanoic acid 以83 mg的产率得到(R)-2-[1-(2-Hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid
  参考文献：
  名称：

  Novel Selective Inhibitors of Neutral Endopeptidase for the Treatment of Female Sexual Arousal Disorder. Synthesis and Activity of Functionalized Glutaramides

  摘要：

  Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemistry strategy, lead compounds, and SAR investigations are detailed. In particular, the strategy of starting with the clinically precedented selective NEP inhibitor, Candoxatrilat, and targeting low molecular weight and relatively polar mono-carboxylic acids is described. This led ultimately to the prototype development candidate R-13, for which detailed pharmacology and pharmacokinetic parameters are presented.(1)

  DOI：

  10.1021/jm060133g

文献信息

• Treatment of male sexual dysfunction
  申请人：——

  公开号：US20020028799A1

  公开（公告）日：2002-03-07

  The present invention relates to the use of neutral endopeptidase inhibitors (NEPi) and a combination of NEPi and phosphodiesterase type 5 (PDE5) inhibitor for the treatment of male sexual dysfunction, in particular MED.

  本发明涉及使用中性内肽酶抑制剂（NEPi）和NEPi与磷酸二酯酶5型（PDE5）抑制剂的组合物治疗男性性功能障碍，特别是MED。
• Cyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
  申请人：——

  公开号：US20020052370A1

  公开（公告）日：2002-05-02

  The invention provides compounds of formula I wherein R 1 is optionally substituted C 1-6 alkyl, optionally substituted C 3-7 cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl; n is 0, 1 or 2; and Y is —NR 18 S(O) u R 19 or a group shown below. 1

  本发明提供了式I的化合物，其中R1是可选取代的C1-6烷基，可选取代的C3-7环烷基，可选取代的芳基或可选取代的杂环基；n为0、1或2；Y为—NR18S(O)uR19或下图所示的基团1。
• [EN] CYCLOALKYL-SUBSTITUTED GLUTARAMIDE DIURETIC AGENTS
  申请人：PFIZER LIMITED

  公开号：WO1991010644A1

  公开（公告）日：1991-07-25

  (EN) Compounds of formula (I), wherein A completes a 4 to 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further saturated or unsaturated 5 or 6 membered carbocyclic ring; R is H, C1-C6 alkyl, benzyl or an alternative biolabile ester-forming group; R1 is H or C1-C4 alkyl; R2 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, halo or CF3; R3 is CH2OH or CO2R4 where R4 is as defined for R; and R5 is defined to include a range of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and substituted alkyl groups including in particular methoxyethyl, S-lysylamino-methyl, N2-acetyl-S-lysylaminomethyl and N2-methanesulphonyl-S-lysyl-aminomethyl, are atriopeptidase inhibitors of utility in the treatment of hypertension, heart failure, renal insufficiency and other disorders(FR) L'invention se rapporte à des composés représentés par la formule: (I); où: A complète une chaîne fermée carbocyclique à 4-7 éléments, qui peut être saturée ou mono-insaturée et qui peut éventuellement être fusionnée à une autre chaîne fermée carbocyclique à 5 ou 6 éléments saturée ou insaturée; R représente H, un alkyl C1-C6, un benzyle ou un groupe formant ester biolabile alternatif; R1 représente H ou un alkyl C1-C4; R2 représente H, OH, un alkyl C1-C4, un alkoxy C1-C4, un halo ou CF3; R3 représente CH2 OH ou CO2R4, où R4 est identique à R défini ci-dessus; et R5 est défini comme pouvant comporter une gamme de groupes alkyle, alkényle, alkynyle, cycloalkyle, cycloalkényle et alkyle substitué contenant en particulier un méthoxyéthyle, un S-lysylaminométhyle, un N2-acétyle-S-lysylaminométhyle et un N2-méthanesulphonyle-S-lysylaminométhyle. Ces composés constituent des inhibiteurs de l'atriopeptidase, utiles dans le traitement de l'hypertension, des défaillances cardiaques, de l'insuffisance rénale et d'autres troubles.
• Novel Selective Inhibitors of Neutral Endopeptidase for the Treatment of Female Sexual Arousal Disorder. Synthesis and Activity of Functionalized Glutaramides
  作者：David C. Pryde、Graham N. Maw、Simon Planken、Michelle Y. Platts、Vivienne Sanderson、Martin Corless、Alan Stobie、Christopher G. Barber、Rachel Russell、Laura Foster、Laura Barker、Christopher Wayman、Piet Van Der Graaf、Peter Stacey、Debbie Morren、Christopher Kohl、Kevin Beaumont、Sara Coggon、Michael Tute

  DOI：10.1021/jm060133g

  日期：2006.7.1

  Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemistry strategy, lead compounds, and SAR investigations are detailed. In particular, the strategy of starting with the clinically precedented selective NEP inhibitor, Candoxatrilat, and targeting low molecular weight and relatively polar mono-carboxylic acids is described. This led ultimately to the prototype development candidate R-13, for which detailed pharmacology and pharmacokinetic parameters are presented.(1)