N-Boc-cyclohexylnorstatin | 105116-44-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-Boc-cyclohexylnorstatin
• 英文别名: Boc-Chns-OH；N-t-butyloxycarbonyl-2(R)-hydroxy-3(S)-amino-4-cyclohexylbutanoic acid；(2R,3S)-4-cyclohexyl-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 105116-44-7
• 化学式: C₁₅H₂₇NO₅
• 分子量: 301.383
• InChiKey: OGIFVSFQVHLIDP-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-Boc-cyclohexylnorstatin 以 异丙醇 为溶剂， 生成 2(R)-Hydroxy-3(S)-amino-4-cyclohexylbutanoic acid, 2-propanol ester, hydrochloride
  参考文献：
  名称：

  Nor-statine and nor-cyclostatine polypeptides

  摘要：

  多肽及其衍生物中含有诺斯他汀和诺环斯他汀，对抑制酶肾素的血管紧张素原裂解作用是有用的。

  公开号：

  US04814342A1
• 作为产物：
  描述：

  (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutyric acid 生成 N-Boc-cyclohexylnorstatin
  参考文献：
  名称：

  HOOVER, DENNIS J.

  摘要：

  DOI：

文献信息

• Synthesis and structure-activity relationships of human renin inhibitors designed from angiotensinogen transition state.
  作者：Kinji IIZUKA、Tetsuhide KAMIJO、Hiromu HARADA、Kenji AKAHANE、Tetsuhiro KUBOTA、Yasuo ETOH、Iwao SHIMAOKA、Atsushi TSUBAKI、Makoto MURAKAMI、Toshiaki YAMAGUCHI、Akira IYOBE、Hideaki UMEYAMA、Yoshiaki KISO

  DOI：10.1248/cpb.38.2487

  日期：——

  The synthesis and the structure-activity relationships of renin inhibitors designed from the angiotensinogen transition state are described. These inhibitors contained residues modified at P1-P1, , P2, and P4-P3. Decrease in the size of side chain alkyl group in norstatine analog at P1 diminished the inhibitory activities of the compounds. Compound 5j, which contained valine residue instead of histidine residue at P2, inhibited potently cathepsin D (IC50=6.0×10-9 M) and pepsin (IC50=3.5×10-7 M) to the same extent as renin (IC50=8.5×10-10 M), and thus was not specific for renin. The reduction of the β-carbonyl group to methylene group in β-carbonylpropionyl residue at P4-P3 decreased the potency about 2 orders against human renin (5i : IC50=1.1×10-7 M vs. 1 : IC50=2.4 ×10-9 M). These results confirmed the rationality of our analysis of the interaction between an orally potent human renin inhibitor 1 and the active site of human renin using modeling techniques, showing that 1 fits the active site of renin favorably. The experimental details of the synthesis are presented.

  描述了基于血管紧张素原过渡态设计的肾素抑制剂的合成及其构效关系。这些抑制剂在P1-P1、P2和P4-P3位点含有修饰的残基。在P1位点，诺斯他酮类似物侧链烷基基团的尺寸减小，降低了化合物的抑制活性。化合物5j在P2位点含有缬氨酸残基而非组氨酸残基，能有效抑制猫hepsin D（IC50=6.0×10⁻⁹ M）和胃蛋白酶（IC50=3.5×10⁻⁷ M），其抑制活性与肾素相当（IC50=8.5×10⁻¹⁰ M），因此并非特异性针对肾素。P4-P3处β-羰基基团减少为亚甲基基团，使其对人肾素的效能下降了约两个数量级（5i: IC50=1.1×10⁻⁷ M vs. 1: IC50=2.4×10⁻⁹ M）。这些结果证实了我们对口服有效的人肾素抑制剂1与人肾素活性位点间相互作用的分析合理性，显示出1与肾素活性位点的适配良好。合成的实验细节也已呈现。
• Renin inhibiting polypeptides and intermediates therefor
  申请人：PFIZER INC.

  公开号：EP0211580A2

  公开（公告）日：1987-02-25

  Polypeptides and derivatives thereof containing oxa- and azahomocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.

  含有oxa-和azahomocyclostatine的多肽及其衍生物可用于抑制肾素酶的血管紧张素原分解作用。
• Analysis of Amide Bond Formation with an α-Hydroxy-β-amino Acid Derivative, 3-Amino-2-hydroxy-4-phenylbutanoic Acid, as an Acyl Component:  Byproduction of Homobislactone
  作者：Yoshio Hayashi、Yuko Kinoshita、Koushi Hidaka、Aiko Kiso、Hirokazu Uchibori、Tooru Kimura、Yoshiaki Kiso

  DOI：10.1021/jo010233o

  日期：2001.8.1

  In the synthesis of peptidomimetics containing alpha -hydroxy-beta -amino acid, the coupling of this N-beta-protected beta -amino acid with amine components was generally performed without the protection of its alpha -hydroxyl group. However, the formation of dipeptides in low yield was often observed when sterically hindered amine components were used. Boc-Apns-OH [Apns: (2S,3S)-3-amino-2-hydroxy4-phenylbutanoic acid, allophenylnorstatine] (6), which is one of such beta -amino acid derivatives, is intensively employed as a core structure in the development of HIV-1 protease inhibitors. There have been no precise studies, to date, that have examined amide bond formation with alpha -hydroxy-beta -amino acid derivatives as an acyl component. To determine the cause of this low-yield reaction, we studied the amide bond formation focusing on the activation step of N-beta-protected alpha -hydroxy-beta -amino acid by using a model coupling reaction between 6 and H-Dmt-OR [Dmt: (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid] (7). A significant amount of homobislactone 9 was formed through the activation of the carboxyl group of 6 to the benzotriazole-type active esters such as OBt and OAt. In addition, this homobislactone formation was markedly increased in the presence of a catalytic amount of a base, which exhibited good correlation with the low yield of the amide bond formation, suggesting that homobislactone formation is one major reason for the low yield of the amide bond formation. Moreover, homobislactones were also formed in other derivatives of the N-beta-protected alpha -hydroxy-beta -amino acid, suggesting a common feature of this type of amino acids. The use of a strong activation method like EDC-HOAt without base addition enhanced amide bond formation, although a small amount of homobislactone may be formed during the coupling reaction.
• HOOVER, DENNIS J.
  作者：HOOVER, DENNIS J.

  DOI：——

  日期：——
• US4599198A
  申请人：——

  公开号：US4599198A

  公开（公告）日：1986-07-08