N-Benzyloxycarbonyl-5-fluoro-RS-tryptophan | 1881-79-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-Benzyloxycarbonyl-5-fluoro-RS-tryptophan
• 英文别名: 2-(((Benzyloxy)carbonyl)amino)-3-(5-fluoro-1h-indol-3-yl)propanoic acid；3-(5-fluoro-1H-indol-3-yl)-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 1881-79-4
• 化学式: C₁₉H₁₇FN₂O₄
• 分子量: 356.353
• InChiKey: KRCKGUZDYXRPIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  621.4±55.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  91.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-Benzyloxycarbonyl-5-fluoro-RS-tryptophan 、 (3-bromo-4,5-dihydroisoxazol-5-yl)methanamine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以25 mg的产率得到[1-[(3-Bromo-4,5-dihydro-isoxazol-5-ylmethyl)-carbamoyl]-2-(5-fluoro-1H-indol-3-yl)-ethyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of the Selective Inhibition of Transglutaminase 2 by Dihydroisoxazoles

  摘要：

  Human transglutaminase 2 (TG2) is believed to play an important role in the pathogenesis of various human disorders including celiac sprue, certain neurological diseases, and some types of cancer. Selective inhibition of TG2 should therefore enable further investigation of its role in physiology and disease and may lead to effective clinical treatment. Recently we showed that certain 3-halo-4-,5-dihydroisoxazole containing compounds are selective inhibitors of human TG2 with promising pharmacological activities. Here, we present definitive evidence that this class of compounds targets the active site of human TG2. Structure-activity relationship studies have provided insights into the structural prerequisites for selectivity and have led to the discovery of an inhibitor with about 50-fold higher activity than a prototypical dihydroisoxazole inhibitor with good in vivo activity. A method for preparing enantiomerically enriched analogues was also developed. Our studies show that the 5-(S)-dihydroisoxazole is a markedly better inhibitor of human TG2 than its 5-(R) stereoisomer.

  DOI：

  10.1021/jm060839a
• 作为产物：
  描述：

  5-氟-DL-色氨酸 、 氯甲酸苄酯 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-Benzyloxycarbonyl-5-fluoro-RS-tryptophan
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of the Selective Inhibition of Transglutaminase 2 by Dihydroisoxazoles

  摘要：

  Human transglutaminase 2 (TG2) is believed to play an important role in the pathogenesis of various human disorders including celiac sprue, certain neurological diseases, and some types of cancer. Selective inhibition of TG2 should therefore enable further investigation of its role in physiology and disease and may lead to effective clinical treatment. Recently we showed that certain 3-halo-4-,5-dihydroisoxazole containing compounds are selective inhibitors of human TG2 with promising pharmacological activities. Here, we present definitive evidence that this class of compounds targets the active site of human TG2. Structure-activity relationship studies have provided insights into the structural prerequisites for selectivity and have led to the discovery of an inhibitor with about 50-fold higher activity than a prototypical dihydroisoxazole inhibitor with good in vivo activity. A method for preparing enantiomerically enriched analogues was also developed. Our studies show that the 5-(S)-dihydroisoxazole is a markedly better inhibitor of human TG2 than its 5-(R) stereoisomer.

  DOI：

  10.1021/jm060839a

文献信息

• Tachykinin antagonists
  申请人：Warner-Lambert Company

  公开号：US05594022A1

  公开（公告）日：1997-01-14

  The invention concerns tachykinin antagonists. The compounds are nonpeptides which have utility in treating disorders mediated by tachykinins. Such disorders are respiratory, inflammatory, gastrointestinal, ophthalmic, allergies, pain, vascular, diseases of the central nervous system, and migraine. Methods of preparing compounds and novel intermediates are also included. The compounds are expected to be especially useful in asthma and rheumatoid arthritis.

  这项发明涉及缓激肽拮抗剂。这些化合物是非肽类化合物，对治疗由缓激肽介导的疾病具有用途。这些疾病包括呼吸系统、炎症、消化系统、眼科、过敏、疼痛、血管、中枢神经系统疾病和偏头痛。还包括制备化合物和新颖中间体的方法。这些化合物预计在哮喘和类风湿关节炎方面特别有用。
• [EN] TACHYKININ ANTAGONISTS<br/>[FR] ANTAGONISTES DE TACHYKININE
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1994004494A1

  公开（公告）日：1994-03-03

  (EN) Compounds of formula (I) wherein R, R8 and R6 are possibly substituted phenyl, pyridine, thiophene, furan, naphthalene, etc.; R1 and R2 are each independently hydrogen or alkyl of from 1 to 4 atoms; R and R2, when joined by a bond, can form a ring; X is $g(a) wherein R11 is hydrogen or alkyl of from 1 to 3 carbon atoms; R3 is hydrogen or (CH2)mR13 where m is an integer of from 1 to 6 and R13 is H, CN, NH2, N(CH3)2, or NHCOCH3; n is an integer of from 1 to 2; Y is $g(b) wherein R4 is hydrogen or alkyl of from 1 to 3 carbon atoms, -CO2-, etc.; R5 and R7 are each independently hydrogen or alkyl of from 1 to 4 carbon atoms; q is an integer of from 0 to 1. The compounds are nonpeptide tachykinin antagonists and are expected to be especially useful in asthma and rheumatoid arthritis.(FR) L'invention concerne des composés ayant la formule (I), dans laquelle R, R8 et R6 représentent phenyle substitué, pyridine, thiophène, furane, napthtalène, etc. R1 et R2 représentent indépendamment hydrogène ou alkyle ayant de 1 à 4 atomes; R et R2, lorsqu'ils sont joint par une liaison, peuvent former un cycle; X est représenté par la formule $g(a) dans laquelle R11 est hydrogène ou alkyle ayant de 1 à 3 atomes de carbone; R3 représente hydrogène ou (CH2)mR13 dans laquelle m est un nombre entier compris entre 1 et 6 et R13 représente H, CN, NH2, N(CH3)2, ou NHCOCH3; n est un nombre entier égal à 1 ou 2; Y est représenté par la formule $g(b) dans laquelle R4 est hydrogène ou alkyle ayant de 1 à 3 atomes de carbone, -CO2-, etc. R5 et R7 représentent indépendamment hydrogène ou alkyle ayant de 1 à 4 atomes de carbone; q est un nombre entier de 0 à 1; les composés sont des antagonistes de tachykinine non peptides et peuvent être particulièremet utiles pour traiter l'asthme et le rhumatisme articulaire.

  (中) 公式（I）中的化合物，其中R，R8和R6可能是取代的苯基，吡啶，噻吩，呋喃，萘等；R1和R2分别独立地为氢或1至4个原子的烷基；当R和R2通过键结合时，可以形成环；X是$ g（a），其中R11为1至3个碳原子的氢或烷基；R3为氢或（CH2）mR13，其中m为1至6的整数，R13为H，CN，NH2，N（CH3）2或NHCOCH3；n为1至2的整数；Y是$ g（b），其中R4为氢或1至3个碳原子的烷基，-CO2-等；R5和R7各自独立地为氢或1至4个碳原子的烷基；q为0至1的整数。这些化合物是非肽类缩氨酸拮抗剂，预计在哮喘和类风湿性关节炎等方面特别有用。
• TACHYKININ ANTAGONISTS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0655055A1

  公开（公告）日：1995-05-31
• US5594022A
  申请人：——

  公开号：US5594022A

  公开（公告）日：1997-01-14
• US5716979A
  申请人：——

  公开号：US5716979A

  公开（公告）日：1998-02-10