1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(indol-3-yl)propan-2-yl-amide]-3-phenylpropan-2-yl-amide]semicarbazide | 801297-79-0

• 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: 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(indol-3-yl)propan-2-yl-amide]-3-phenylpropan-2-yl-amide]semicarbazide
• 英文别名: N-{2-[(2S)-2-Aminobutanoyl]hydrazinecarbonyl}-L-phenylalanyl-L-tryptophanamide；(2S)-2-[[[(2S)-2-aminobutanoyl]amino]carbamoylamino]-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-3-phenylpropanamide
• CAS: 801297-79-0
• 化学式: C₂₅H₃₁N₇O₄
• 分子量: 493.566
• InChiKey: YWHLURKOQARNNG-JBACZVJFSA-N

物化性质

• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  184
• 氢给体数：
  7
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-色氨酸 、 N-芴甲氧羰基-L-2-氨基丁酸 以44%的产率得到1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(indol-3-yl)propan-2-yl-amide]-3-phenylpropan-2-yl-amide]semicarbazide
  参考文献：
  名称：

  Novel semicarbazide-derived inhibitors of human dipeptidyl peptidase I (hDPPI)

  摘要：

  Human dipeptidyl peptidase 1 (hDPPI, cathepsin C, EC 3.4.14.1) is a novel putative drug target for the treatment of inflammatory diseases. Using 1 as a starting point (IC50 > 10 mu M), we have improved potency by more than 500-fold and successfully identified novel inhibitors of DPPI via screening of a one-bead-two-compounds library of semicarbazide derivatives. Selected compounds were shown to inhibit intracellular DPPI in RBL-2H3 cells. These compounds were further characterized for adverse effects on HepG2 cells (cytotoxicity and viability) and their metabolic stability in rat liver microsomes was estimated. One of the most potent inhibitors, 8 (IC50 = 31 +/- 3 nM; K-i = 45 +/- 2 nM, competitive inhibition), is selective for DPPI over other cysteine and serine proteases, has a half-life of 24 min in rat liver microsomes, shows approximately 50% inhibition of intracellular DPPI at 20 mu M and is noncytotoxic. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.048

文献信息

• [EN] PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTEASE
  申请人：COMBIO AS

  公开号：WO2004106289A1

  公开（公告）日：2004-12-09

  A monoacyl semicarbazide of the general formula (I): (I), or a pharmaceutically acceptable salt or ester thereof, is capable of selectively inhibiting dipeptidyl-peptidase I (DPP-I), also known as cathepsin C. A compound of the invention is useful as an active substance for the treatment of inflammation, type 2 diabetes, asthma, severe influenza, respiratory syncytial virus infection, CD8 T cell inhibition, inflammatory bowel diseases, psoriasis, atopic dermatitis, Papillon Lefevre syndrome, Haim Munk syndrome, gum disease, periodontitis, rheumatoid arthritis, Huntington's disease, Chaga's disease, Alzheimer's disease, sepsis or for application in target cell apoptosis.

  通式（I）的单酰基半卡巴肼，或其药学上可接受的盐或酯，能够选择性地抑制二肽酶I（DPP-I），也称为猫hepsin C。发明中的化合物可用作治疗炎症、2型糖尿病、哮喘、严重流感、呼吸道合胞病毒感染、CD8 T细胞抑制、炎症性肠病、牛皮癣、特应性皮炎、Papillon Lefevre综合症、Haim Munk综合症、牙龈疾病、牙周炎、类风湿性关节炎、亨廷顿病、查加氏病、阿尔茨海默病、败血症或用于靶细胞凋亡的活性物质。
• Protease inhibitors
  申请人：Bondebjerg Jon

  公开号：US20070155803A1

  公开（公告）日：2007-07-05

  A monoacyl semicarbazide of the general formula (I): (I), or a pharmaceutically acceptable salt or ester thereof, is capable of selectively inhibiting dipeptidyl-peptidase I (DPP-I), also known as cathepsin C. A compound of the invention is useful as an active substance for the treatment of inflammation, type 2 diabetes, asthma, severe influenza, respiratory syncytial virus infection, CD8 T cell inhibition, inflammsatory bowel diseases, psoriasis, atopic dermatitis, Papillon Lefevre syndrome, Haim Munik syndrome, gum disease, periodontitis, rheumatoid arthritis, Huntington's disease, Chaga's disease, Alzheimer's disease, sepsis or for application in target cell apoptosis.

  一般式（I）的单酰基半卡巴肼（或其药学上可接受的盐或酯）能够选择性地抑制二肽酶I（DPP-I），也称为猫hepsin C。本发明的化合物可用作治疗炎症、2型糖尿病、哮喘、严重流感、呼吸道合胞病毒感染、CD8 T细胞抑制、炎症性肠病、牛皮癣、特应性皮炎、Papillon Lefevre综合症、Haim Munik综合症、牙龈疾病、牙周炎、类风湿性关节炎、亨廷顿病、查加病、阿尔茨海默病、败血症或用于目标细胞凋亡的活性物质。
• PROTEASE INHIBITORS
  申请人：Prozymex A/S

  公开号：EP1633702B1

  公开（公告）日：2008-07-02
• Novel semicarbazide-derived inhibitors of human dipeptidyl peptidase I (hDPPI)
  作者：Jon Bondebjerg、Henrik Fuglsang、Kirsten Rosendal Valeur、Dorte Wissing Kaznelson、Johnny Arnsdorf Hansen、René Orup Pedersen、Berit Olsen Krogh、Bo Skaaning Jensen、Conni Lauritzen、Gitte Petersen、John Pedersen、Lars Nærum

  DOI：10.1016/j.bmc.2005.04.048

  日期：2005.7

  Human dipeptidyl peptidase 1 (hDPPI, cathepsin C, EC 3.4.14.1) is a novel putative drug target for the treatment of inflammatory diseases. Using 1 as a starting point (IC50 > 10 mu M), we have improved potency by more than 500-fold and successfully identified novel inhibitors of DPPI via screening of a one-bead-two-compounds library of semicarbazide derivatives. Selected compounds were shown to inhibit intracellular DPPI in RBL-2H3 cells. These compounds were further characterized for adverse effects on HepG2 cells (cytotoxicity and viability) and their metabolic stability in rat liver microsomes was estimated. One of the most potent inhibitors, 8 (IC50 = 31 +/- 3 nM; K-i = 45 +/- 2 nM, competitive inhibition), is selective for DPPI over other cysteine and serine proteases, has a half-life of 24 min in rat liver microsomes, shows approximately 50% inhibition of intracellular DPPI at 20 mu M and is noncytotoxic. (c) 2005 Elsevier Ltd. All rights reserved.