tert.-Butoxycarbonyl-L-norvalyl-L-methionine methyl ester | 78664-54-7

• 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: tert.-Butoxycarbonyl-L-norvalyl-L-methionine methyl ester
• 英文别名: BOC-Nva-Met-OMe；methyl (2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]-4-methylsulfanylbutanoate
• CAS: 78664-54-7
• 化学式: C₁₆H₃₀N₂O₅S
• 分子量: 362.491
• InChiKey: KFOHTSDMKDVVAN-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert.-Butoxycarbonyl-L-norvalyl-L-methionine methyl ester 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 {(S)-1-[(S)-1-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-{(S)-2-methyl-1-[(pyridin-4-ylmethyl)-carbamoyl]-propylcarbamoyl}-pentylcarbamoyl)-3-methylsulfanyl-propylcarbamoyl]-butyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR

  摘要：

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.084
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-L-norvaline 、 L-蛋氨酸甲酯盐酸盐 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 tert.-Butoxycarbonyl-L-norvalyl-L-methionine methyl ester
  参考文献：
  名称：

  Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR

  摘要：

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.084

文献信息

• Tripeptides acting on the central nervous system and a process for the
  申请人：Patentbureau DANUBIA

  公开号：US04386073A1

  公开（公告）日：1983-05-31

  The invention relates to new peptide derivatives which act on the central nervous system and correspond to the general formula (I), X--Y--W--NH.sub.2 (I) wherein X is L-pyroglutamyl, D-pyroglutamyl, L-2-keto-imidazolidine-4-carbonyl, L-6-keto-pipecolyl, L-thiazolidine-4-carbonyl, L-prolyl or orotyl group, Y is L-leucyl, L-norvalyl or L-histidyl group, and W is L-prolyl, D-prolyl, L-thiazolidine-4-carbonyl, L-pipecolyl, L-homoprolyl, L-leucyl, L-isoleucyl, L-methionyl or D-pipecolyl group, or the W-NH.sub.2 group stands for pyrrolidyl or piperidyl group, with the proviso that if X is L-pyroglutamyl and Y is L-histidyl group, W is other than L-prolyl group, and pharmaceutically acceptable complexes thereof. These compounds are prepared by methods commonly applied in the peptide chemistry.

  本发明涉及一种新的肽衍生物，其作用于中枢神经系统，符合通式（I），X-Y-W-NH.sub.2（I），其中X为L-吡咯糜酰基，D-吡咯糜酰基，L-2-酮咪唑啉-4-羧酰基，L-6-酮-哌嗪基，L-噻唑啉-4-羧酰基，L-脯氨酰基或乌洛替基，Y为L-亮氨酰基，L-异戊氨酰基或L-组氨酰基，W为L-脯氨酰基，D-脯氨酰基，L-噻唑啉-4-羧酰基，L-哌嗪基，L-同型脯氨酰基，L-亮氨酰基，L-异亮氨酰基，L-甲硫氨酰基或D-哌嗪基，或W-NH.sub.2基团代表吡咯烷基或哌啶基，但如果X为L-吡咯糜酰基且Y为L-组氨酰基，则W为除L-脯氨酰基以外的其他基团，以及其药学上可接受的复合物。这些化合物是通过肽化学中常用的方法制备的。
• US4386073A
  申请人：——

  公开号：US4386073A

  公开（公告）日：1983-05-31
• Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR
  作者：Jason Lamar、Jingdan Hu、Ana Belen Bueno、Hsiu-Chiung Yang、Deqi Guo、James D. Copp、James McGee、Bruce Gitter、David Timm、Patrick May、James McCarthy、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.084

  日期：2004.1

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.