p-Methoxybenzyloxycarbonyl-L-histidine hydrazide | 42533-17-5

• 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: p-Methoxybenzyloxycarbonyl-L-histidine hydrazide
• 英文别名: Z(OMe)-His-NH-NH2；Z(OMe)-His-NH2NH2；Z(OMe)-His-NHNH2；N^α-(4-methoxy-benzyloxycarbonyl)-histidine hydrazide；N-(4-methoxybenzyloxycarbonyl)-L-histidine hydrazide；p-Methoxybenzyloxycarbonyl-His-NH-NH2；(4-methoxyphenyl)methyl N-[(2S)-1-hydrazinyl-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamate
• CAS: 42533-17-5
• 化学式: C₁₅H₁₉N₅O₄
• 分子量: 333.347
• InChiKey: KCCNZZDUJQFYMD-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  p-Methoxybenzyloxycarbonyl-L-histidine hydrazide 在 三乙胺 、 亚硝酸异戊酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 PMZ-His-L-leucinol
  参考文献：
  名称：

  Synthesis of human renin inhibitory peptides, angiotensinogen transition-state analogs containing a Retro-inverso amide bond.

  摘要：

  人肾素抑制剂的合成实验细节如下所述。为了防止过渡态类似物中Phe-His (P3-P2)酰胺键的代谢降解，抑制剂中融入了结构改良的酰基残基 (P4-P3)。化合物1a包含2-(1-萘甲基)-3-(N-苯乙基氨基甲酰)丙酰基残基 (P4-P3)，具有逆向内酰胺键，L-组氨酸和诺丝他汀异戊酰胺残基 (P1-P1') 作为过渡态模拟结构，显示出强大的人肾素抑制活性，并通过口服给药降低了普通狨猴的血压。

  DOI：

  10.1248/cpb.38.3042
• 作为产物：
  描述：

  Z(OMe)-His-OMe 生成 p-Methoxybenzyloxycarbonyl-L-histidine hydrazide
  参考文献：
  名称：

  INDZUKA, KINDZI;KAMIDZE, TEHSSEHJ;KUBOTA, TEHTSUXIRO;AKABA, KEHNDZI;UMEHY+

  摘要：

  DOI：

文献信息

• Studies on peptides. CXXXV. Preparation of seven peptide fragments for the synthesis of human calcitonin gene-related peptide (hCGRP).
  作者：NOBUTAKA FUJII、AKIRA OTAKA、SUSUMU FUNAKOSHI、MOTOYOSHI NOMIZU、KENICHI AKAJI、HARUAKI YAJIMA、KOUKI KITAGAWA、TADASHI AKITA、KENSHI ANDO、TATSUHIKO KAWAMOTO

  DOI：10.1248/cpb.34.603

  日期：——

  Seven peptide fragments were synthesized by known amide-forming reactions as building blocks for the solution-phase synthesis of the heptatriacontapeptide amide corresponding to the entire amino acid sequence of human calcitonin gene-related peptide (hCGRP). S-1-Adamantyl-cysteine [O. Nishimura, C. Kitada, and M. Fujino, Chem. Pharm. Bull., 26, 1576 (1978)] was employed, together with amino acid derivatives bearing protecting groups removable by 1 M trifluoromethanesulfonic acid-thioanisole in trifluoroacetic acid.

  七个肽片段通过已知的酰胺形成反应合成，作为溶液相合成与人类降钙素基因相关肽（hCGRP）完整氨基酸序列相对应的七十氨基肽酰胺的构建块。采用了S-1-亚当烷基半胱氨酸 [O. Nishimura, C. Kitada, 和 M. Fujino, Chem. Pharm. Bull., 26, 1576 (1978)]，同时使用了具有保护基团的氨基酸衍生物，这些保护基团可通过1 M三氟甲磺酸-硫醇醚在三氟乙酸中去除。
• Studies on peptides. CIX. Synthesis of the octatriacontapeptide corresponding to positions 1 to 38 of human parathyroid hormone.
  作者：SUSUMU FUNAKOSHI、NOBUTAKA FUJII、HARUAKI YAJIMA、CHOHEI SHIGENO、ITSUO YAMAMOTO、RIKUSHI MORITA、KANJI TORIZUKA

  DOI：10.1248/cpb.30.1706

  日期：——

  The octatriacontapeptide corresponding to positions 1 to 38 of human parathyroid hormone (hPTH), a half of the whole molecule, was synthesized by assembling 9 peptide fragments in a conventional manner. Arg (mesitylene-2-sulfonyl), a new arginine derivative bearing an acid-labile protecting group, was employed in combination with a new deprotecting procedure with 1 M trifluoromethanesulfonic acid-thioanisole in TFA. The synthetic peptide exhibited an activity of 1400 IU/mg when assayed by the mouse bone adenyl cyclase activity assay.

  合成人类甲状旁腺激素（hPTH）第1到第38位的八三十肽，通过传统方法组装9个肽片段合成。使用了一种新型的精氨酸衍生物Arg（美克辛烯-2-磺酸），该衍生物具有一种酸敏感的保护基团，并结合了使用1 M三氟甲烷磺酸-硫代苯醚在TFA中进行的新脱保护工艺。合成的肽在小鼠骨腺苷酸酰化酶活性测定中表现出1400 IU/mg的活性。
• Studies on peptides. CXLVII Synthesis of valosin, a novel 25-residue peptide from porcine intestine.
  作者：KENICHI AKAJI、MICHINORI TANAKA、SHOICHIRO SUMI、MASAFUMI KOGIRE、KYOICHI TAKAORI、RYUICHIRO DOI、KAZUTOMO INOUE、TAKAYOSHI TOBE、MOTOYUKI MORIGA、MITSURU AONO、HARUAKI YAJIMA

  DOI：10.1248/cpb.35.535

  日期：——

  A 25-residue peptide isolated from porcine intestine, designated valosin, was synthesized by assembling seven peptide fragments of established purity, followed by deprotection with 1 M trifluoromethanesulfonic acid in trifluoroacetic acid. γ-Cycloheptylglutamate, [Glu (OChp)], was employed to suppress pyrrolidone formation during fragment condensation. Before deprotection, Met (O) was reduced with phenylthiotrimethylsilane and trimethylsilyl trifluoromethanesulfonate. The effect of the synthetic peptide on arterial pressure, blood flow in the superior mesenteric artery, pancreatic capillary blood flow and pancreatic exocrine secretion was examined in dogs, but no significant dose-dependent response was observed. In rats, synthetic valosin stimulated pancreatic secretion, but showed no anti-gastric activity.

  通过组装七个已确定纯度的肽片段，然后用三氟乙酸中的 1 M 三氟甲磺酸去保护，合成了从猪肠中分离出的 25 个残基肽，命名为缬洛新。 γ-环庚基谷氨酸，[Glu (OChp)]，用于抑制片段缩合过程中吡咯烷酮的形成。在脱保护之前，用苯硫基三甲基硅烷和三氟甲磺酸三甲基甲硅烷基酯还原Met (O)。在狗身上检查了合成肽对动脉压、肠系膜上动脉血流、胰腺毛细血管血流和胰腺外分泌分泌的影响，但没有观察到明显的剂量依赖性反应。在大鼠中，合成的缬洛辛刺激胰腺分泌，但没有表现出抗胃活性。
• Histidine derivatives as renin inhibitors
  申请人：Kissei Pharmaceutical Co Ltd

  公开号：EP0181110A2

  公开（公告）日：1986-05-14

  @ Dipeptides are described which are represented by the formula wherein His represents an L-histidyl group, Ar, represents a phenyl group, a naphthyl group or an indolyl group, Ar2 represents a phenyl group or a naphthyl group, X represents a chemical bond, -NHCO-, -CONH-, -CO-, -CH2-, -NH-, -O- or -(CH=CH)P-wherein p is 1 or 2, Z represents an oxygen atom or in which R2 represents a hydrogen atom or combines with R, to form a chemical bond, m and n, which may be the same or different, each represents an integer of from 0 to 3, provided that when X is a chemical bond, the sum of n plus m is from 1 to 6 and when X is not a chemical bond, the sum of n plus m is from 1 to 4, Y represents a chemical bond when X is not a chemical bond, or, when X is a chemical bond, an alkylene group having 1 to 3 carbon atoms, R1 represents a hydrogen atom or combines with R2 to form a chemical bond, R3 represents a formyl group or a hydroxymethyl group, R4 represents an isobutyl group or a benzyl group, and C represents an L-configurational carbon atom; or the pharmaceutically acceptable salt thereof. These compounds have a strong inhibitory effect on human renin, and are useful as a therapeutically active agent for the treatment of hypertension, especially renin - associated hypertension.

  @ 描述了由式表示的二肽 其中 His 代表 L-组氨酰基，Ar 代表苯基、萘基或吲哚基，Ar2 代表苯基或萘基，X 代表化学键、-NHCO-、-CONH-、-CO-、-CH2-、-NH-、-O-或-(CH=CH)P-其中 p 为 1 或 2，Z 代表氧原子或 其中 R2 代表氢原子或与 R 结合形成化学键，m 和 n 可以相同或不同，各代表 0 至 3 的整数，但当 X 为化学键时，n 加 m 之和为 1 至 6，当 X 不是化学键时，n 加 m 之和为 1 至 4、当 X 不是化学键时，Y 代表化学键；当 X 是化学键时，Y 代表具有 1 至 3 个碳原子的亚烷基；R1 代表氢原子或与 R2 结合形成化学键；R3 代表甲酰基或羟甲基；R4 代表异丁基或苄基；C 代表 L 构型碳原子；或其药学上可接受的盐。 这些化合物对人体肾素有很强的抑制作用，可作为治疗高血压，特别是肾素相关性高血压的治疗活性剂。
• Novel amino acid derivatives
  申请人：Kissei Pharmaceutical Co Ltd

  公开号：EP0252727A1

  公开（公告）日：1988-01-13

  Novel amino acid derivatives useful as a therapeutic agent are disclosed. These amino acid derivatives and the pharmaceutically acceptable salts thereof have a human renin inhibitory effect when administered orally and are useful for treatment of hypertension, especially renin-associated hypertension.

  本研究公开了可用作治疗剂的新型氨基酸衍生物。 这些氨基酸衍生物及其药学上可接受的盐类在口服时具有人体肾素抑制作用，可用于治疗高血压，特别是肾素相关性高血压。