(S)-N-[(tert-butyloxy)carbonyl]-[3-N-(benzyloxy)carbonylaminophenyl]glycine | 227778-60-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-N-[(tert-butyloxy)carbonyl]-[3-N-(benzyloxy)carbonylaminophenyl]glycine
• 英文别名: (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[3-(phenylmethoxycarbonylamino)phenyl]acetic acid
• CAS: 227778-60-1
• 化学式: C₂₁H₂₄N₂O₆
• 分子量: 400.431
• InChiKey: OMWIQHFADIGRRV-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-N-[(tert-butyloxy)carbonyl]-[3-N-(benzyloxy)carbonylaminophenyl]glycine 在 palladium on activated charcoal 氢气 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 12.0h， 生成 (S)-methyl 2-(3-aminophenyl)-2-(tert-butoxycarbonylamino)acetate
  参考文献：
  名称：

  Asymmetric Synthesis of Conformationally Restricted l-Arginine Analogues as Active Site Probes of Nitric Oxide Synthase

  摘要：

  Using the catalytic asymmetric Sharpless carbamate aminohydroxylation, conformationally restricted L-arginine and L-homoarginine derivatives (5-8) were prepared in good enantiomeric excess to investigate the binding requirements of L-arginine-based compounds with nitric oxide synthase. The L-arginine derivatives (5 and 6) inhibited both the inducible and neuronal isoforms of nitric oxide synthase with little isoform selectivity (5, IC50 = 42 and 144 mu M, 6, 8 and 12 mu M, respectively). The guanidine-containing compound (5) did not act as a nitric oxide producing substrate for nitric oxide synthase. The ability of these compounds to interact with the enzyme supports the idea that L-arginine-based inhibitors bind to the enzyme in a folded conformation. The L-homoarginine derivatives (7 and 8) did not interact with the enzyme as either substrates or inhibitors. The two-carbon L-arginine homologue (9), prepared from L-phenylalanine, demonstrated the greatest isoform selective inhibition of the compounds examined (IC50(iNOS) = 19 and IC50- (nNOS) = 147 mu M, IC50(nNOS)/IC(50)i(NOS) = 7.7). These results suggest isoform selective inhibition may be related to the folded conformations required for binding of these higher L-arginine homologues.

  DOI：

  10.1021/jo982161f
• 作为产物：
  描述：

  3-硝基苯乙烯 在 2,6-二甲基吡啶 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 四氧化锇 、 sodium dithionite 、 (DHQ)2-PHAL 、 次氯酸叔丁酯 、 potassium carbonate 、 1,1'-dioctyl-4,4'-bipyridinium dibromide 、 potassium bromide 作用下， 以 丙醇 、 sodium hydroxide 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 9.0h， 生成 (S)-N-[(tert-butyloxy)carbonyl]-[3-N-(benzyloxy)carbonylaminophenyl]glycine
  参考文献：
  名称：

  Asymmetric Synthesis of Conformationally Restricted l-Arginine Analogues as Active Site Probes of Nitric Oxide Synthase

  摘要：

  Using the catalytic asymmetric Sharpless carbamate aminohydroxylation, conformationally restricted L-arginine and L-homoarginine derivatives (5-8) were prepared in good enantiomeric excess to investigate the binding requirements of L-arginine-based compounds with nitric oxide synthase. The L-arginine derivatives (5 and 6) inhibited both the inducible and neuronal isoforms of nitric oxide synthase with little isoform selectivity (5, IC50 = 42 and 144 mu M, 6, 8 and 12 mu M, respectively). The guanidine-containing compound (5) did not act as a nitric oxide producing substrate for nitric oxide synthase. The ability of these compounds to interact with the enzyme supports the idea that L-arginine-based inhibitors bind to the enzyme in a folded conformation. The L-homoarginine derivatives (7 and 8) did not interact with the enzyme as either substrates or inhibitors. The two-carbon L-arginine homologue (9), prepared from L-phenylalanine, demonstrated the greatest isoform selective inhibition of the compounds examined (IC50(iNOS) = 19 and IC50- (nNOS) = 147 mu M, IC50(nNOS)/IC(50)i(NOS) = 7.7). These results suggest isoform selective inhibition may be related to the folded conformations required for binding of these higher L-arginine homologues.

  DOI：

  10.1021/jo982161f

文献信息

• Use of amino acid transporter atbo,+ as a delivery system for drugs and prodrugs
  申请人：——

  公开号：US20040142317A1

  公开（公告）日：2004-07-22

  The present invention has revealed the compounds transportable by ATB 0+ . Based on the information about these compounds, drugs transportable by ATB 0,+ may be designed, produced and screened. Such drugs may serve to treat and/or prevent the diseases in which NOS, phenylglycine, carnitine, D-amino NOS, phenylglycine, carnivolved. The ATB 0,+ gene may be administered to patients to be used for gene therapy of the diseases as described above.

  本发明揭示了可通过 ATB 0&plus； .根据这些化合物的信息，可通过 ATB 0,&plus； 可以设计、生产和筛选。这些药物可用于治疗和/或预防由 NOS、苯甘氨酸、肉碱、D-氨基 NOS、苯甘氨酸、肉碱引起的疾病。ATB 0,&plus； 基因可施用给患者，用于上述疾病的基因治疗。
• USE OF AMINO ACID TRANSPORTER ATB0,+ AS A DELIVERY SYSTEM FOR DRUGS AND PRODRUGS
  申请人：Medical College Of Georgia Research Institute, Inc.

  公开号：EP1384081A2

  公开（公告）日：2004-01-28
• [EN] USE OF AMINO ACID TRANSPORTER ATB<0,+> AS A DELIVERY SYSTEM FOR DRUGS AND PRODRUGS<br/>[FR] UTILISATION DU TRANSPORTEUR ATB<0,+> D'ACIDES AMINES COMME SYSTEME D'ADMINISTRATION DE MEDICAMENTS ET PROMEDICAMENTS
  申请人：MED COLLEGE GEORGIA RES INST

  公开号：WO2002083060A2

  公开（公告）日：2002-10-24

  The present invention has revealed the compounds transportable by ATB0,+. Based on the information about these compounds, drugs transportable by ATB0,+ may be designed, producedand screened. Such drugs may serve to treat and/or prevent the diseases in which NOS, phenylglycine, carnitine, D-amino NOS, phenylglycine, carnivolved. The ATB0,+ gene may be administered to patients to be used for gene therapy of the diseases as described above.
• Asymmetric Synthesis of Conformationally Restricted <scp>l</scp>-Arginine Analogues as Active Site Probes of Nitric Oxide Synthase
  作者：Robert N. Atkinson、Lisa Moore、Joseph Tobin、S. Bruce King

  DOI：10.1021/jo982161f

  日期：1999.5.1

  Using the catalytic asymmetric Sharpless carbamate aminohydroxylation, conformationally restricted L-arginine and L-homoarginine derivatives (5-8) were prepared in good enantiomeric excess to investigate the binding requirements of L-arginine-based compounds with nitric oxide synthase. The L-arginine derivatives (5 and 6) inhibited both the inducible and neuronal isoforms of nitric oxide synthase with little isoform selectivity (5, IC50 = 42 and 144 mu M, 6, 8 and 12 mu M, respectively). The guanidine-containing compound (5) did not act as a nitric oxide producing substrate for nitric oxide synthase. The ability of these compounds to interact with the enzyme supports the idea that L-arginine-based inhibitors bind to the enzyme in a folded conformation. The L-homoarginine derivatives (7 and 8) did not interact with the enzyme as either substrates or inhibitors. The two-carbon L-arginine homologue (9), prepared from L-phenylalanine, demonstrated the greatest isoform selective inhibition of the compounds examined (IC50(iNOS) = 19 and IC50- (nNOS) = 147 mu M, IC50(nNOS)/IC(50)i(NOS) = 7.7). These results suggest isoform selective inhibition may be related to the folded conformations required for binding of these higher L-arginine homologues.