4-(4'-fluoro-4-biphenylyl)-butyric acid | 40096-29-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(4'-fluoro-4-biphenylyl)-butyric acid
• 英文别名: 4-[4-(4-fluorophenyl)phenyl]butanoic acid
• CAS: 40096-29-5
• 化学式: C₁₆H₁₅FO₂
• 分子量: 258.292
• InChiKey: QJXYFMHMLHXAGW-UHFFFAOYSA-N

物化性质

• 沸点：
  412.1±33.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4'-fluoro-4-biphenylyl)-butyric acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 4-[4-(4-Fluorophenyl)phenyl]butanoyl chloride
  参考文献：
  名称：

  Inhibition of Stromelysin-1 (MMP-3) by P₁‘-Biphenylylethyl Carboxyalkyl Dipeptides

  摘要：

  Carboxyalkyl peptides containing a biphenylylethyl group at the P-1' position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10-50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P-1', a tert-butyl group at P-2', and a methyl group at P-3' produced orally bioavailable inhibitors as measured by an in vivo model of MMP-3 degradation of radiolabeled transferrin in the mouse pleural cavity. The X-ray structure of a complex of a P-1'-biphenyl inhibitor and the catalytic domain of MMP-3 is described. Inhibitors that contained halogenated biphenylylethyl residues at P-1' proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4'-fluoro-4-biphenylyl)ethyl]-4(S)-n-butyl -1,5-pentanedioic acid 1-(alpha(S)-tert-butylglycine methylamide) amide (L-758,354, 26) having a K-i of 10 nM against MMP-3 and an ED(50) of 11 mg/kg po in the mouse pleural cavity assay. This compound was evaluated in acute (MMP-3 and IL-1 beta injection in the rabbit) and chronic (rat adjuvant-induced arthritis and mouse collagen-induced arthritis) models of cartilage destruction but showed activity only in the MMP-3 injection model (ED(50) = 6 mg/kg iv).

  DOI：

  10.1021/jm960465t
• 作为产物：
  描述：

  4-氟联苯 在 palladium dihydroxide 三氯化铝 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 4-(4'-fluoro-4-biphenylyl)-butyric acid
  参考文献：
  名称：

  Inhibition of Stromelysin-1 (MMP-3) by P₁‘-Biphenylylethyl Carboxyalkyl Dipeptides

  摘要：

  Carboxyalkyl peptides containing a biphenylylethyl group at the P-1' position were found to be potent inhibitors of stromelysin-1 (MMP-3) and gelatinase A (MMP-2), in the range of 10-50 nM, but poor inhibitors of collagenase (MMP-1). Combination of a biphenylylethyl moiety at P-1', a tert-butyl group at P-2', and a methyl group at P-3' produced orally bioavailable inhibitors as measured by an in vivo model of MMP-3 degradation of radiolabeled transferrin in the mouse pleural cavity. The X-ray structure of a complex of a P-1'-biphenyl inhibitor and the catalytic domain of MMP-3 is described. Inhibitors that contained halogenated biphenylylethyl residues at P-1' proved to be superior in terms of enzyme potency and oral activity with 2(R)-[2-(4'-fluoro-4-biphenylyl)ethyl]-4(S)-n-butyl -1,5-pentanedioic acid 1-(alpha(S)-tert-butylglycine methylamide) amide (L-758,354, 26) having a K-i of 10 nM against MMP-3 and an ED(50) of 11 mg/kg po in the mouse pleural cavity assay. This compound was evaluated in acute (MMP-3 and IL-1 beta injection in the rabbit) and chronic (rat adjuvant-induced arthritis and mouse collagen-induced arthritis) models of cartilage destruction but showed activity only in the MMP-3 injection model (ED(50) = 6 mg/kg iv).

  DOI：

  10.1021/jm960465t

文献信息

• Derivatives of 4-(4-biphenylyl)-butyric acid
  申请人：Boehringer Ingelheim GmbH

  公开号：US04021479A1

  公开（公告）日：1977-05-03

  Compounds of the formulas ##STR1## and ##STR2## wherein A is --CH.sub.2 -- or --CH(OH)--, R.sub.1 is hydrogen, halogen or, when R.sub.2 and R.sub.3 are other than both hydrogen, also methyl, R.sub.2 is hydrogen, halogen, cyano, nitro, amino or (alkanoyl of 1 to 4 carbon atoms)-amino, R.sub.3 is hydrogen or halogen, Provided, however, that at least one of R.sub.1, R.sub.2 and R.sub.3 is other than hydrogen, and R.sub.4 is hydrogen or alkyl of 1 to 4 carbon atoms, and non-toxic salts of the free acids (R.sub.4 = H) formed with inorganic or organic bases; the compounds as well as their salts are useful as antiphlogistics and antiproliferatives.

  ##STR1##和##STR2##的化合物，其中A为--CH.sub.2--或--CH(OH)--，R.sub.1为氢、卤素或者当R.sub.2和R.sub.3不同时为氢时，也可以是甲基，R.sub.2为氢、卤素、氰基、硝基、氨基或(1到4个碳原子的酰基)-氨基，R.sub.3为氢或卤素，但至少R.sub.1、R.sub.2和R.sub.3中的一个不是氢，R.sub.4为氢或1到4个碳原子的烷基，以及与无机或有机碱形成的游离酸(R.sub.4 = H)的无毒盐；这些化合物及其盐可用作抗炎和抗增殖剂。
• Chiral synthesis of C-carboxyalkyl dipeptide inhibitors of stromelysin-1 (MMP-3)
  作者：Mitree M. Ponpipom、William K. Hagmann

  DOI：10.1016/s0040-4020(99)00334-8

  日期：1999.5

  Enantioselective alkylation of chiral amide enolates derived From L-prolinol with beta-branched chiral iodides afforded good yields of hydroxy amide adducts. which were elaborated in four steps to give C-carboxyalkyl dipeptide inhibitors of stromelysin-1 (MMP-3). (C) 1999 Elsevier Science Ltd. All rights reserved.
• US4021479A
  申请人：——

  公开号：US4021479A

  公开（公告）日：1977-05-03
• US5684152A
  申请人：——

  公开号：US5684152A

  公开（公告）日：1997-11-04
• [EN] PREPARATION OF CARBOXYALKYL DERIVATIVES<br/>[FR] PREPARATION DE DERIVES DE CARBOXYALKYLE
  申请人：MERCK & CO., INC.

  公开号：WO1997011936A1

  公开（公告）日：1997-04-03

  (EN) Carboxy-peptidyl compounds of formula (I) are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, coronary thrombosis associated with atherosclerotic plaque rupture, and aneurysmal aortic disease. This invention relates to a process of making the carboxy-peptidyl compounds of formula (I).(FR) On a découvert que les composés carboxy-peptidyle de la formule (I) sont des inhibiteurs utiles de maladies induites par des métalloendoprotéinases matricielles, en particulier de l'ostétoarthrite, de la polyarthite rhumatoïde, de l'arthrite aigue suppurée, des tumeurs invasives dans certains cancers, des paradontolyses, des ulcérations de la cornée, de la protéinurie, de l'épidermolyse bulleuse dystrophique, des thromboses coronaires associées à la rupture des plaques athéroscléreuses et des anévrismes de l'aorte. L'invention concerne un procédé de production de composés carboxy-peptidyle de la formule (I).