N-(benzyloxycarbonyl)-cis-3'-hydroxyproline | 166383-72-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(benzyloxycarbonyl)-cis-3'-hydroxyproline
• 英文别名: (3S)-1-t-butoxycarbonyl-N-t-butyl-3-hydroxy-L-prolinamide；(3S)-1-t-Butoxycarbonyl-3-hydroxy-N-t-butyl-L-prolinamide；tert-butyl (2S,3S)-2-(tert-butylcarbamoyl)-3-hydroxypyrrolidine-1-carboxylate
• CAS: 166383-72-8
• 化学式: C₁₄H₂₆N₂O₄
• 分子量: 286.371
• InChiKey: CHSWFMDAHSVIOA-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(benzyloxycarbonyl)-cis-3'-hydroxyproline 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 0.5h， 生成 (3S)-N-t-butyl-3-hydroxy-L-prolinamide
  参考文献：
  名称：

  Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA—II. Modification of pyrrolidine ring at P1′ proline

  摘要：

  Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a C1 atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K-i = 4.5 nM against HIV PR and IC(50)s 0.58 mu M and 0.06 mu M in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00130-7
• 作为产物：
  描述：

  (2R,3R)-1-t-Butoxycarbonyl-2-benzyloxymethyl-3-hydroxypyrrolidine 在 钯 sodium hydroxide 、 甲酸 、 jones reagent 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 33.83h， 生成 N-(benzyloxycarbonyl)-cis-3'-hydroxyproline
  参考文献：
  名称：

  Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA—II. Modification of pyrrolidine ring at P1′ proline

  摘要：

  Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a C1 atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K-i = 4.5 nM against HIV PR and IC(50)s 0.58 mu M and 0.06 mu M in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00130-7

文献信息

• HIV protease inhibitors
  申请人：Wong Chi-Huey

  公开号：US06900238B1

  公开（公告）日：2005-05-31

  Combinatorial libraries of HIV and FIV protease inhibitors are characterized by α-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.

  HIV和FIV蛋白酶抑制剂的组合库以α-酮酰胺或羟乙基胺核心结构为特征，一侧为取代吡咯烷、哌啶或氮代糖，另一侧为苯丙氨酸、酪氨酸或取代酪氨酸。这些库是通过一步偶联反应合成的。通过筛选这些库，识别出对HIV和FIV蛋白酶的结合和抑制活性高效的药物候选化合物。对HIV和FIV蛋白酶都显示出临床有用活性的药物候选化合物被确定为潜在对抗由于HIV耐药株的发展而导致的抑制活性丧失。
• Inhibitors of HIV protease
  申请人：Sankyo Company, Limited

  公开号：US05629406A1

  公开（公告）日：1997-05-13

  Compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen, alkyl, aralkyl, --COR.sup.a, --COR.sup.b, --CSR.sup.a, --CSR.sup.b, --SO.sub.2 R.sup.b, --CONHR.sup.b, --CSNHR.sup.b, --CONR.sup.b R.sup.b or --CSNR.sup.b R.sup.b ; R.sup.2 is hydrogen or alkyl; R.sup.3 is hydrogen, alkylidene, substituted alkyl, or R.sup.b ; R.sup.4 is optionally substituted alkyl, cycloalkyl, or aryl; R.sup.5 is R.sup.b O--, R.sup.b R.sup.b N--, R.sup.b HN--, aralkyloxycarbonyloxy or aralkyloxycarbonylamino, or R.sup.5 is --(CH.sub.2).sub.p --D--(CH.sub.2).sub.r --, where D is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH.sub.2 .dbd.CH.sub.2)-- or --NHCO--; and p and r are each 0 or an integer from 1 to 5; A is --(CH.sub.2).sub.m --B--(CH.sub.2).sub.n -- where B is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH.sub.2 .dbd.CH.sub.2)-- or --NHCO--; and m and n are each 0 or an integer from 1 to 5; R.sup.a is alkoxy, aralkyloxy, aryloxy or alkoxycarbonyl; R.sup.b is optionally substituted alkyl, cycloalkyl, heterocyclic, aryl or arylalkenyl; and pharmaceutically acceptable salts and esters thereof and pro-drugs therefor, have the ability to inhibit the activity of HIV protease and may thus be used for the treatment and prophylaxis of AIDS.

  式(I)的化合物：其中：R.sup.1为氢，烷基，芳基甲基，-COR.sup.a，-COR.sup.b，-CSR.sup.a，-CSR.sup.b，-SO.sub.2R.sup.b，-CONHR.sup.b，-CSNHR.sup.b，-CONR.sup.b R.sup.b或-CSNR.sup.b R.sup.b；R.sup.2为氢或烷基；R.sup.3为氢，烷基亚烷基，取代烷基，或R.sup.b；R.sup.4为可选择取代的烷基，环烷基，或芳基；R.sup.5为R.sup.b O--，R.sup.b R.sup.b N--，R.sup.b HN--，芳基氧羰氧基或芳基氧羰氨基，或R.sup.5为--(CH.sub.2).sub.p--D--(CH.sub.2).sub.r--，其中D为单键，羰基，氧，硫，-NH--，-(CH.sub.2.dbd.CH.sub.2)-或-NHCO--；p和r分别为0或1至5的整数；A为-(CH.sub.2).sub.m--B--(CH.sub.2).sub.n--，其中B为单键，羰基，氧，硫，-NH--，-(CH.sub.2.dbd.CH.sub.2)-或-NHCO--；m和n分别为0或1至5的整数；R.sup.a为烷氧基，芳基甲氧基，芳氧基或烷氧羰基；R.sup.b为可选择取代的烷基，环烷基，杂环烷基，芳基或芳基烯基；其药学上可接受的盐和酯以及其前药，具有抑制HIV蛋白酶活性的能力，因此可用于治疗和预防艾滋病。
• Peptides capable of inhibiting the activity of HIV protease, their preparation and their therapeutic use
  申请人：SANKYO COMPANY LIMITED

  公开号：EP0587311A1

  公开（公告）日：1994-03-16

  Compounds of formula (I) : [wherein: R¹ is hydrogen, alkyl, aralkyl, -CORa, -CORb, -CSRa, -CSRb, -SO₂Rb, -CONHRb, -CSNHRb, -CONRbRb or -CSNRbRb; R² is hydrogen or alkyl; R³ is hydrogen, alkylidene, substituted alkyl, or Rb; R⁴ is optionally substituted alkyl, cycloalkyl, or aryl; R⁵ is RbO-, RbRbN-, RbHN-, aralkyloxycarbonyloxy or aralkyloxycarbonylamino, or R⁵ is -(CH₂)p-D-(CH₂)r- [where D is a single bond, carbonyl, oxygen, sulphur, -NH-, -(CH₂=CH₂)- or -NHCO-; and p and r are each 0 or an integer from 1 to 5]; A is -(CH₂)m-B-(CH₂)n- [where B is a single bond, carbonyl, oxygen, sulphur, -NH-, -(CH₂=CH₂)- or -NHCO-; and m and n are each 0 or an integer from 1 to 5]; Ra is alkoxy, aralkyloxy, aryloxy or alkoxycarbonyl; Rb is optionally substituted alkyl, cycloalkyl, heterocyclic, aryl or arylalkenyl]; and pharmaceutically acceptable salts and esters thereof and pro-drugs therefor, have the ability to inhibit the activity of HIV protease and may thus be used for the treatment and prophylaxis of AIDS.

  化合物的化学式为(I)：[其中：R¹为氢，烷基，芳基烷基，-CORa，-CORb，-CSRa，-CSRb，-SO₂Rb，-CONHRb，-CSNHRb，-CONRbRb或-CSNRbRb；R²为氢或烷基；R³为氢，烷基亚甲基，取代烷基或Rb；R⁴为可选取代的烷基，环烷基或芳基；R⁵为RbO-，RbRbN-，RbHN-，芳基烷氧羰氧基氧或芳基烷氧羰氨基，或R⁵为-(CH₂)p-D-(CH₂)r- [其中D为单键，酰基，氧，硫，-NH-，-(CH₂=CH₂)-或-NHCO-；p和r分别为0或1到5的整数]；A为-(CH₂)m-B-(CH₂)n- [其中B为单键，酰基，氧，硫，-NH-，-(CH₂=CH₂)-或-NHCO-；m和n分别为0或1到5的整数]；Ra为烷氧基，芳基烷氧基，芳氧基或烷氧羰基；Rb为可选取代的烷基，环烷基，杂环，芳基或芳基烷烯基]；以及其药学上可接受的盐和酯以及其前药，具有抑制HIV蛋白酶活性的能力，因此可用于治疗和预防艾滋病。
• US5629406A
  申请人：——

  公开号：US5629406A

  公开（公告）日：1997-05-13
• Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA—II. Modification of pyrrolidine ring at P1′ proline
  作者：Tomoaki Komai、Susumu Higashida、Mitsuya Sakurai、Tamayo Nitta、Atsushi Kasuya、Shuichi Miyamaoto、Ryuichi Yagi、Yuji Ozawa、Hiroshi Handa、Hiroshi Mohri、Akira Yasuoka、Shinichi Oka、Takashi Nishigaki、Satoshi Kimura、Kaoru Shimada、Yuichiro Yabe

  DOI：10.1016/0968-0896(96)00130-7

  日期：1996.8

  Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a C1 atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K-i = 4.5 nM against HIV PR and IC(50)s 0.58 mu M and 0.06 mu M in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration. Copyright (C) 1996 Elsevier Science Ltd