1-[2-(tert-butoxycarbonyl)-4-phenylbutyl]cyclopentane-1-carboxylic acid | 168081-19-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 1-[2-(tert-butoxycarbonyl)-4-phenylbutyl]cyclopentane-1-carboxylic acid
• 英文别名: 1-(2-t-Butoxycarbonyl-4-phenylbutyl)cyclopentanecarboxylic acid；1-[2-[(2-methylpropan-2-yl)oxycarbonyl]-4-phenylbutyl]cyclopentane-1-carboxylic acid
• CAS: 168081-19-4
• 化学式: C₂₁H₃₀O₄
• 分子量: 346.467
• InChiKey: WZASJDMMNNYDET-UHFFFAOYSA-N

物化性质

• 沸点：
  479.1±28.0 °C(Predicted)
• 密度：
  1.092±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[2-(tert-butoxycarbonyl)-4-phenylbutyl]cyclopentane-1-carboxylic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 2-((1-((5-Ethyl-1,3,4-thiadiazol-2-yl)carbamoyl)cyclopentyl)methyl)-4-phenylbutanoic 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
• 作为产物：
  描述：

  3-溴丙酸叔丁酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 11.25h， 生成 1-[2-(tert-butoxycarbonyl)-4-phenylbutyl]cyclopentane-1-carboxylic 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

• Carboxyalkylcarbonyl aminoacid endopeptidase inhibitors
  申请人：Schering Corporation

  公开号：US05389610A1

  公开（公告）日：1995-02-14

  Carboxyalkylcarbonyl aminoacid inhibitors of endopeptidases of the formula: ##STR1## or pharmaceutically acceptable salt thereof, wherein R.sup.1 is H, alkyl, arylalkyl, aryl or aryloxyalkyl; R.sup.2 is alkyl, alkenyl, alkynyl, alkoxy or alkylthio, wherein the alkyl portion is substituted with 0-3 substituents independently selected from the group consisting of hydroxy, alkoxy, alkoxyalkoxy, alkylthio, aryl, alkoxyalkylthio, arylalkoxy and arylalkylthio; R.sup.3 and R.sup.4 are independently alkyl or arylalkyl; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form an optionally substituted 5-, 6- or 7-membered ring wherein said ring comprises 0 to 1 heteroatoms selected from the group consisting of sulfur and oxygen; R.sup.5 is H, alkyl, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylalkoxyalkyl or arylalkylthioalkyl; R.sup.6 is H, hydroxy, alkoxy, alkyl, arylalkoxy, alkoxyalkyl, alkylthioalkyl, arylalkoxyalkyl, arylalkylthioalkyl, aryl or heteroaryl; R.sup.7 is hydroxy, alkoxy, aryloxy, arylalkoxy, amino, alkylamino or dialkylamino; m is 0 or 1; and n is 0, 1, 2 or 3, use of the compounds, alone or in combination with an ACE inhibitor or an ANF, in the treatment of cardiovascular disorders such as hypertension, congestive heart failure, edema and renal insufficiency, use of the compounds in the treatment of nephrotoxicity and pain conditions, and pharmaceutical compositions containing said compounds are disclosed.

  公开了以下式子的内切蛋白酶的羧基烷基羧酰基氨基酸抑制剂：##STR1##或其药学上可接受的盐，其中R.sup.1为H，烷基，芳基烷基，芳基或芳氧基烷基; R.sup.2为烷基，烯基，炔基，烷氧基或烷硫基，其中烷基部分被0-3个取自羟基，烷氧基，烷氧基烷氧基，烷硫基，芳基，烷氧基烷硫基，芳基烷氧基和芳基烷硫基的基团独立取代; R.sup.3和R.sup.4独立地为烷基或芳基烷基; 或R.sup.3和R.sup.4与它们连接的碳一起形成一个可选取代的5-，6-或7-成员环，其中所述环包括0到1个取自硫和氧的杂原子; R.sup.5为H，烷基，烷氧基烷基，烷硫基烷基，芳基，芳基烷基，杂芳基，杂芳基烷基，芳基烷氧基烷基或芳基烷硫基烷基; R.sup.6为H，羟基，烷氧基，烷基，芳基烷氧基，烷氧基烷基，烷硫基烷基，芳基烷氧基烷基，芳基烷硫基烷基，芳基或杂芳基; R.sup.7为羟基，烷氧基，芳氧基，芳基烷氧基，氨基，烷基氨基或二烷基氨基; m为0或1; n为0, 1, 2或3，本发明公开了这些化合物的使用，单独或与ACE抑制剂或ANF组合使用，用于治疗心血管疾病，如高血压，充血性心力衰竭，水肿和肾功能不全，用于治疗肾毒性和疼痛症状的化合物的使用，以及含有所述化合物的制药组合物。
• CARBOXYALKYLCARBONYL AMINOACID ENDOPEPTIDASE INHIBITORS
  申请人：SCHERING CORPORATION

  公开号：EP0502075A1

  公开（公告）日：1992-09-09
• US5389610A
  申请人：——

  公开号：US5389610A

  公开（公告）日：1995-02-14
• US5677297A
  申请人：——

  公开号：US5677297A

  公开（公告）日：1997-10-14
• [EN] CARBOXYALKYLCARBONYL AMINOACID ENDOPEPTIDASE INHIBITORS
  申请人：SCHERING CORPORATION

  公开号：WO1991007386A1

  公开（公告）日：1991-05-30

  (EN) Carboxyalkylcarbonyl aminoacid inhibitors of endopeptidases of formula (I), or pharmaceutically acceptable salt thereof, wherein R1 is H, alkyl, arylalkyl, aryl or aryloxyalkyl; R2 is alkyl, alkenyl, alkynyl, alkoxy or alkylthio, wherein the alkyl portion is substituted with 0-3 substituents independently selected from the group consisting of hydroxy, alkoxy, alkoxyalkoxy, alkylthio, aryl, alkoxyalkylthio, arylalkoxy and arylalkylthio; R3 and R4 are independently alkyl or arylalkyl; or R3 and R4 together with the carbon to which they are attached form an optionally substituted 5-, 6- or 7-membered ring wherein said ring comprises 0 to 1 heteroatoms selected from the group consisting of sulfur and oxygen; R5 is H, alkyl, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylalkoxyalkyl or arylalkylthioalkyl; R6 is H, hydroxy, alkoxy, alkyl, arylalkoxy, alkoxyalkyl, alkylthioalkyl, arylalkoxyalkyl, arylalkylthioalkyl, aryl or heteroaryl; R7 is hydroxy, alkoxy, aryloxy, arylalkoxy, amino, alkylamino or dialkylamino; m is 0 or 1; and n is 0, 1, 2 or 3, use of the compounds, alone or in combination with an ACE inhibitor or an ANF, in the treatment of cardiovascular disorders such as hypertension, congestive heart failure, edema and renal insufficiency, use of the compounds in the treatment of nephrotoxicity and pain conditions, and pharmaceutical compositions containing said compounds are disclosed.(FR) Sont décrits des acides aminés de carboxyalkylcarbonyle inhibiteurs d'endopeptidases de la formule (I), ou un de leurs sels pharmaceutiquement acceptables, dans laquelle R1 représente H, alkyle, arylalkyle, aryle ou aryloxyalkyle; R2 représente alkyle, alcényle, alkynyle, alkoxy ou alkylthio, où la partie alkyle est remplacée par 0 à 3 substituants indépendamment sélectionnés dans le groupe composé de hydroxy, alkoxy, alkoxyalkoxy, alkylthio, aryle, alkoxyalkylthio, arylalkoxy et arylalkylthio; R3 et R4 représentent indépendamment alkyle ou arylalkyle; ou R3 et R4, avec l'atome de carbone auquel ils sont fixés, forment un anneau à 5, 6 ou 7 éléments à substitution facultative, ledit anneau comprenant 0 à 1 hétéroatome séléctionné dans le groupe composé de soufre et d'oxygène; R5 représente H, alkyle, alkoxyalkyle, alkylthioalkyle, aryle, arylakyl, hétéroaryle, hétéroarylalkyle, arylalkoxyalkyle ou arylalkylthioalkyle; R6 représente H, hydroxy, alkoxy, alkyle, arylalkoxy, alkoxyalkyle, alkylthioalkyle, arylalkoxyalkyle, arylalkylthioalyle, aryle ou hétéroaryle; R7 représente hydroxy, alkoxy, aryloxy, arylalkoxy, amino, alkylamino ou dialkylamino; m représente 0 ou 1; et n représente 0, 1, 2 ou 3; l'emploi des composés, seuls ou en combinaison avec un inhibiteur d'ACE ou un ANF, dans le traitement de troubles cardiovasculaires tels que l'hypertension, l'insuffisance cardiaque, l'÷dème et l'insuffisance rénale; l'emploi des composés dans le traitement de néphrotoxicité ainsi que d'états douloureux, et des compositions pharmaceutiques contenant lesdits composés.