2-[(4-benzylbenzyl)methoxyphosphinoylmethyl]-4-methylpentanoic acid benzyl ester | 202975-47-1

• 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: 2-[(4-benzylbenzyl)methoxyphosphinoylmethyl]-4-methylpentanoic acid benzyl ester
• 英文别名: Benzyl 2-[[(4-benzylphenyl)methyl-methoxyphosphoryl]methyl]-4-methylpentanoate
• CAS: 202975-47-1
• 化学式: C₂₉H₃₅O₄P
• 分子量: 478.568
• InChiKey: AKFDRVPBZLBWDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(4-benzylbenzyl)methoxyphosphinoylmethyl]-4-methylpentanoic acid benzyl ester 在 palladium on barium sulfate 水 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket

  摘要：

  Through the use of empirical and computational methods, phosphinate-based inhibitors of MMP-1 and MMP-13 that bind into the S-2 pocket of these enzymes were designed. The synthesis and testing of 2 suggested that binding was occurring as hypothesized. Structure determination of a co-crystal of 2 bound to the catalytic domain of MMP-1 confirmed the binding mode. Substituents binding into S-2, S-1', S-2' and S-3', were optimized yielding compounds with low double-digit nM IC50's against these enzymes. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00729-x
• 作为产物：
  描述：

  benzyl 4-methyl-2-methylenepentanoate 在 N,O-双三甲硅基乙酰胺 、 双(三甲基硅基)亚磷酸盐 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 18.5h， 生成 2-[(4-benzylbenzyl)methoxyphosphinoylmethyl]-4-methylpentanoic acid benzyl ester
  参考文献：
  名称：

  Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket

  摘要：

  Through the use of empirical and computational methods, phosphinate-based inhibitors of MMP-1 and MMP-13 that bind into the S-2 pocket of these enzymes were designed. The synthesis and testing of 2 suggested that binding was occurring as hypothesized. Structure determination of a co-crystal of 2 bound to the catalytic domain of MMP-1 confirmed the binding mode. Substituents binding into S-2, S-1', S-2' and S-3', were optimized yielding compounds with low double-digit nM IC50's against these enzymes. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00729-x

文献信息

• Phosphinate based inhibitors of matrix metalloproteases
  申请人：Pfizer Inc.

  公开号：US06147061A1

  公开（公告）日：2000-11-14

  A compound of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, synergy with cytotoxic anticancer agents, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, in combination with standard NSAID'S and analgesics and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S) and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinim, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.

  一种化合物的化学式为##STR1##其中R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5、R.sup.6和Ar如上所定义，用于治疗从以下疾病组中选择的疾病：关节炎、癌症、与细胞毒性抗癌药物的协同作用、组织溃疡、黄斑变性、再狭窄、牙周病、表皮溃疡性水疱病、巩膜炎、与标准NSAID'S和止痛药联合使用以及其他以基质金属蛋白酶活性为特征的疾病、艾滋病、败血症、感染性休克和其他涉及TNF产生的疾病。此外，本发明的化合物可与标准非甾体类抗炎药（NSAID'S）和止痛药联合用于组合疗法，并与顺铂、多柔比星、顺铂、依托泊苷、紫杉醇、多西他赛和其他生物碱（如长春碱）等细胞毒性药物联合用于癌症治疗。
• [EN] PHOSPHINATE BASED INHIBITORS OF MATRIX METALLOPROTEASES<br/>[FR] COMPOSES A BASE DE PHOSPHINATE INHIBITEURS DES METALLOPROTEASES MATRICIELLES
  申请人：PFIZER INC.

  公开号：WO1998003516A1

  公开（公告）日：1998-01-29

  (EN) A compound of the formula (I) wherein R1, R2, R3, R4, R5, R6 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, synergy with cytotoxic anticancer agents, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, in combination with standard NSAID'S and analgesics and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of TNF. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S) and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinim, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.(FR) Cette invention se rapporte à un composé représenté par la formule (I), où R1, R2, R3, R4, R5, R6 et Ar sont définis dans les pièces descriptives de la demande, ce composé étant utile dans le traitement des états choisis dans le groupe des affections comprenant l'arthrite, le cancer, les synergies avec des agents anticancéreux cytotoxiques, les ulcérations de tissus, la dégénérescence maculaire, la resténose, les parodontopathies, l'épidermolyse bulleuse, les sclérites, en combinaison avec des anti-inflammatoires non stéréoïdiens et des analgésiques, ainsi que d'autres maladies caractérisées par une activité des métalloprotéases matricielles, le SIDA, les infections, les chocs septiques et d'autres maladies impliquant la production du facteur de nécrose tumorale (TNF). En outre, ces composés peuvent être utilisés dans des thérapies associées avec anti-inflammatoires non stéroïdiens standards et analgésiques, ou en combinaison avec des médicaments cytotoxiques tels que adriamycine, daunomycine, cis-platinim, étoposide, taxol, taxotère et autres alcaloïdes, par exemple vincristine, dans le traitement du cancer.

  一种具有公式（I）的化合物，其中R1、R2、R3、R4、R5、R6和Ar如上所定义，在治疗以下病症方面有用：关节炎、癌症、与细胞毒性抗癌药物的协同作用、组织溃疡、黄斑变性、再狭窄、牙周病、表皮溃疡性病变、巩膜炎、与标准非甾体类抗炎药和镇痛药联合使用以及其他以基质金属蛋白酶活性为特征的疾病、艾滋病、败血症、败血性休克和其他涉及TNF产生的疾病。此外，本发明的化合物可以与标准非甾体类抗炎药（NSAID'S）和镇痛药联合使用，并与细胞毒性药物如阿霉素、多柔比星、顺铂、依托泊苷、紫杉醇、多西他赛和其他生物碱如长春碱联合使用，在癌症治疗中使用。
• PHOSPHINATE BASED INHIBITORS OF MATRIX METALLOPROTEASES
  申请人：PFIZER INC.

  公开号：EP0923585B1

  公开（公告）日：2002-05-08
• US6147061A
  申请人：——

  公开号：US6147061A

  公开（公告）日：2000-11-14
• Inhibition of MMP-1 and MMP-13 with phosphinic acids that exploit binding in the S2 pocket
  作者：Lawrence A. Reiter、James P. Rizzi、Jayvardan Pandit、Michael J. Lasut、Shunda M. McGahee、Vinod D. Parikh、James F. Blake、Dennis E. Danley、Ellen R. Laird、Arturo Lopez-Anaya、Lori L. Lopresti-Morrow、Mahmoud N. Mansour、Gary J. Martinelli、Peter G. Mitchell、Brian S. Owens、Thomas A. Pauly、Lisa M. Reeves、Gayle K. Schulte、Sue A. Yocum

  DOI：10.1016/s0960-894x(98)00729-x

  日期：1999.1

  Through the use of empirical and computational methods, phosphinate-based inhibitors of MMP-1 and MMP-13 that bind into the S-2 pocket of these enzymes were designed. The synthesis and testing of 2 suggested that binding was occurring as hypothesized. Structure determination of a co-crystal of 2 bound to the catalytic domain of MMP-1 confirmed the binding mode. Substituents binding into S-2, S-1', S-2' and S-3', were optimized yielding compounds with low double-digit nM IC50's against these enzymes. (C) 1999 Elsevier Science Ltd. All rights reserved.