(S)-N-(2-Amino-ethyl)-2-{(S)-3-[carbamoylmethyl-(6-chloro-naphthalene-2-sulfonyl)-amino]-2-oxo-pyrrolidin-1-yl}-N-isopropyl-propionamide | 713075-90-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-N-(2-Amino-ethyl)-2-{(S)-3-[carbamoylmethyl-(6-chloro-naphthalene-2-sulfonyl)-amino]-2-oxo-pyrrolidin-1-yl}-N-isopropyl-propionamide
• 英文别名: P4 alanylamide pyrrolidin-2-one 50；(2S)-N-(2-aminoethyl)-2-[(3S)-3-[(2-amino-2-oxoethyl)-(6-chloronaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-N-propan-2-ylpropanamide
• CAS: 713075-90-2
• 化学式: C₂₄H₃₂ClN₅O₅S
• 分子量: 538.068
• InChiKey: BANMLSXRXUYSKE-KKSFZXQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N-(2-Amino-ethyl)-2-{(S)-3-[carbamoylmethyl-(6-chloro-naphthalene-2-sulfonyl)-amino]-2-oxo-pyrrolidin-1-yl}-N-isopropyl-propionamide 、 氨基甲酸苯酯 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-{(S)-3-[Carbamoylmethyl-(6-chloro-naphthalene-2-sulfonyl)-amino]-2-oxo-pyrrolidin-1-yl}-N-isopropyl-N-(2-ureido-ethyl)-propionamide
  参考文献：
  名称：

  Structure- and property-based design of factor Xa inhibitors: Pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs

  摘要：

  Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

  DOI：

  10.1016/j.bmcl.2006.09.001
• 作为产物：
  描述：

  tert-butyl (2S)-2-((3S)-3-{[(benzyloxy)carbonyl]amino}-2-oxopyrrolidin-1-yl)propanoate 在 palladium on activated charcoal 吡啶 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-N-(2-Amino-ethyl)-2-{(S)-3-[carbamoylmethyl-(6-chloro-naphthalene-2-sulfonyl)-amino]-2-oxo-pyrrolidin-1-yl}-N-isopropyl-propionamide
  参考文献：
  名称：

  Structure- and property-based design of factor Xa inhibitors: Pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs

  摘要：

  Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

  DOI：

  10.1016/j.bmcl.2006.09.001

文献信息

• 2-(3-SULFONYLAMINO-2-OXOPYRROLIDIN-1-YL)PROPANAMIDES AS FACTOR XA INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1444201A1

  公开（公告）日：2004-08-11
• [EN] 2-(3-SULFONYLAMINO-2-OXOPYRROLIDIN-1-YL)PROPANAMIDES AS FACTOR XA INHIBITORS<br/>[FR] 2-(3-SULFONYLAMINO-2-OXOPYRROLIDIN-1-YL)PROPANAMIDES EN TANT QU'INHIBITEURS DU FACTEUR XA
  申请人：GLAXO GROUP LTD

  公开号：WO2003043981A1

  公开（公告）日：2003-05-30

  The invention relates to compounds of formula (I), wherein: R1 represents hydrogen or -C¿1-3?alkylCONR?aRb¿; One of R?2 and R3¿ represents -C¿1-3?alkyl and the other represents hydrogen; R?4¿ represents hydrogen, -C¿1-4?alkyl, -C3-4alkenyl, -C2-4alkylOH, -C2-4alkylOC1-4alkyl, -C1-4alkylCN or -C0-4alkylC3-6cycloalkyl; R?5¿ represents -C¿2-4?alkylOH, -C1-4alkyl, -C2-4alkylOC1-4alkyl, -C1-4alkylCN, -C1-4alkylCONR?cRd¿, -C¿2-4?alkylNR?aRb¿, -C¿2-4?alkylNHCOC1-3alkyl, -C2-4alkylNHCONR?aRb¿, -C2-4alkylNHSO¿2R?e, -C¿2-4?alkylSO2NR?aRb¿, -C¿2-4?alkylNHCO2C1-4alkyl, -C2-4alkylNHC(NH2)=NR?f¿, or a group X-Y; X represents -C¿1-4?alkylene- optionally substitued by -OH, or a direct link, with the proviso that when X is substituted by -OH, X represents C2-4alkylene and the -OH group is not alpha with respect to the amide N atom to which the group X is attached; Y represents -C3-6cycloalkyl, phenyl, or an aromatic or non-aromatic 5-, 6- or 7-membered heterocyclic group containing at least one heteroatom selected from O, N or S and optionally substituted at C and/or N atoms by -C1-3alkyl, C1-3alkoxy, C1-3alkylOH, halogen, -CN, -CF3, -NH2, -CO2H and -OH; R?a and Rb¿ independently represent hydrogen or -C¿1-4?alkyl; R?c and Rd¿ independently represent hydrogen or -C¿1-4?alkyl or together with the N atom to which they are attached form a non-aromatic 5-, 6- or 7- membered heterocyclic group optionally substituted by a heteroatom selected from O, N or S; R?e¿ represents -C¿1-4?alkyl or -CF3; R?f¿ represents NO¿2? or CN; R?6¿ represents a group selected from: (i), (ii), (iii), (iv), (v), Z represents an optional substituent halogen, alk represents alkylene or alkenylene, T represents a heteroatom selected from S or N; and pharmaceutically acceptable derivatives thereof. The invention also relates to processes for the preparation of compounds of formula (I), pharmaceutical compositions containing compounds of formula (I) and to the use of compounds of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.
• Structure- and property-based design of factor Xa inhibitors: Pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs
  作者：Robert J. Young、Matthew Campbell、Alan D. Borthwick、David Brown、Cynthia L. Burns-Kurtis、Chuen Chan、Máire A. Convery、Miriam C. Crowe、Satish Dayal、Hawa Diallo、Henry A. Kelly、N. Paul King、Savvas Kleanthous、Andrew M. Mason、Jackie E. Mordaunt、Champa Patel、Anthony J. Pateman、Stefan Senger、Gita P. Shah、Paul W. Smith、Nigel S. Watson、Helen E. Weston、Ping Zhou

  DOI：10.1016/j.bmcl.2006.09.001

  日期：2006.12

  Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.