Boc-Phe-His-OH | 63648-87-3

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

中文名称

——

中文别名

——

英文名称

Boc-Phe-His-OH

英文别名

Boc-Phe-His；N-[N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanyl]-L-histidine；(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoic acid

CAS

63648-87-3

化学式

C₂₀H₂₆N₄O₅

mdl

——

分子量

402.45

InChiKey

HDNXGFGVFDEIJW-HOTGVXAUSA-N

BEILSTEIN

——

EINECS

——

物化性质

熔点：

197-198 °C
沸点：

743.8±60.0 °C(Predicted)
密度：

1.270±0.06 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

1.3
重原子数：

29
可旋转键数：

10
环数：

2.0
sp3杂化的碳原子比例：

0.4
拓扑面积：

133
氢给体数：

4
氢受体数：

6

上下游信息

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	{(S)-1-[(S)-1-((1S,2S)-2-Hydroxy-1-isobutyl-5-methyl-hexylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	——	C₃₁H₄₉N₅O₅	571.761
——	{(S)-1-[(S)-1-{(S)-1-[(S)-1-Hydroxy-2-(3-methyl-butyrylamino)-ethyl]-3-methyl-butylcarbamoyl}-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	108868-64-0	C₃₂H₅₀N₆O₆	614.786
——	{1-[1-[1-Cyclohexylmethyl-2-hydroxy-4-(3-methyl-butyrylamino)-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	108868-67-3	C₃₆H₅₆N₆O₆	668.877
——	{1-[1-[1-Cyclohexylmethyl-2-hydroxy-3-(3-methyl-butyrylamino)-propylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	108868-65-1	C₃₅H₅₄N₆O₆	654.85
——	{1-[1-[1-Cyclohexylmethyl-4-(2-dimethylamino-acetylamino)-2-hydroxy-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	108868-77-5	C₃₅H₅₅N₇O₆	669.865
——	{(S)-1-[(S)-1-[(1S,2S)-1-Cyclohexylmethyl-2-hydroxy-4-(4-methyl-pentanoylamino)-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	108868-70-8	C₃₇H₅₈N₆O₆	682.904
——	{(S)-1-[(S)-1-[(1S,2S)-1-Cyclohexylmethyl-2-hydroxy-3-(4-methyl-pentanoylamino)-propylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	108868-66-2	C₃₆H₅₆N₆O₆	668.877
——	{(S)-1-[(S)-1-[(S)-1-((R)-1-Hydroxy-2-isopropylsulfanyl-ethyl)-3-methyl-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	109996-44-3	C₃₀H₄₇N₅O₅S	589.8
——	{1-[1-(1-Benzyl-3-cyclohexylsulfanyl-2-hydroxy-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110269-24-4	C₃₆H₄₉N₅O₅S	663.882
——	{1-[1-(1-Cyclohexylmethyl-2-hydroxy-3-methylsulfanyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110205-78-2	C₃₁H₄₇N₅O₅S	601.811
——	{1-[1-(1-Cyclohexylmethyl-2-hydroxy-3-isopropylsulfanyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110269-26-6	C₃₃H₅₁N₅O₅S	629.864
——	{1-[1-(1-Cyclohexylmethyl-2-hydroxy-3-isobutylsulfanyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110205-77-1	C₃₄H₅₃N₅O₅S	643.891
——	{(S)-1-[(S)-1-((1S,2R)-1-Cyclohexylmethyl-3-cyclohexylsulfanyl-2-hydroxy-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110269-25-5	C₃₆H₅₅N₅O₅S	669.929
——	{1-[1-(1-Cyclohexylmethyl-2-hydroxy-3-methanesulfonyl-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110205-81-7	C₃₁H₄₇N₅O₇S	633.809
——	{1-[1-[1-Cyclohexylmethyl-2-hydroxy-4-(3-methyl-butylcarbamoyl)-pent-4-enylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110613-42-8	C₃₈H₅₈N₆O₆	694.915
——	{1-[1-(1-Cyclohexylmethyl-2-hydroxy-4-isobutylcarbamoyl-pent-4-enylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110613-45-1	C₃₇H₅₆N₆O₆	680.888
——	{(2R,3S)-3-[(S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-3-(1H-imidazol-4-yl)-propionylamino]-2-hydroxy-5-methyl-hexyl}-phosphonic acid dimethyl ester	123381-36-2	C₂₉H₄₆N₅O₈P	623.687
——	{1-[1-[1-Cyclohexylmethyl-2,4-dihydroxy-4-(3-methyl-butylcarbamoyl)-pentylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110613-62-2	C₃₈H₆₀N₆O₇	712.93
——	tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S,3S,5R)-1-cyclohexyl-3,5-dihydroxy-5-methyl-6-(3-methylbutylamino)-6-oxohexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	110613-62-2	C₃₈H₆₀N₆O₇	712.93
——	{1-[1-(1-Cyclohexylmethyl-2,4-dihydroxy-4-isobutylcarbamoyl-6-methyl-heptylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110613-64-4	C₄₀H₆₄N₆O₇	740.984
——	{1-[1-[1-Cyclohexylmethyl-2-hydroxy-3-(propane-2-sulfonyl)-propylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110205-80-6	C₃₃H₅₁N₅O₇S	661.863
——	(2S,3S)-dimethyl <3-<<<(tert-butyloxycarbonyl)phenylalaninyl>histidyl>amino>-4-cyclohexyl-2-hydroxybutyl>phosphonate	123482-53-1	C₃₂H₅₀N₅O₈P	663.751
——	(2R,3S)-dimethyl <3-<<<(tert-butyloxycarbonyl)phenylalaninyl>histidyl>amino>-4-cyclohexyl-2-hydroxybutyl>phosphonate	123381-39-5	C₃₂H₅₀N₅O₈P	663.751
——	{(S)-1-[(S)-1-((1S,2R)-3-Cyclohexanesulfonyl-1-cyclohexylmethyl-2-hydroxy-propylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester	110205-79-3	C₃₆H₅₅N₅O₇S	701.928
——	tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S,3S,5S)-5-(chloromethyl)-1-cyclohexyl-3,5-dihydroxy-6-(2-methylpropylamino)-6-oxohexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	110613-65-5	C₃₇H₅₇ClN₆O₇	733.349
——	tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S,3S,5R)-5-(chloromethyl)-1-cyclohexyl-3,5-dihydroxy-6-(2-methylpropylamino)-6-oxohexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	110613-65-5	C₃₇H₅₇ClN₆O₇	733.349
——	N--L-phenylalanyl-L-histidyl>-5(S)-amino-1-azido-6-cyclohexyl-2(R),4(S)-dihydroxy-2-(isobutylcarbamoyl)hexane	——	C₃₇H₅₇N₉O₇	739.916

反应信息

作为反应物：

描述：

Boc-Phe-His-OH 生成 tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-5-(2-methylpropylsulfonylamino)pentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate

参考文献：

名称：

ROSENBERG, SAUL H.;LULY, JAY R.;PLATTNER, JACOB J.

摘要：

DOI：
作为产物：

描述：

(2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-[1-(phenylmethoxymethyl)imidazol-4-yl]propanoic acid 、甲醇生成 Boc-Phe-His-OH

参考文献：

名称：

NATARAJAN, SESHA I.;RYONO, DENIS E.;PETRILLO, EDWARD W. (JR)

摘要：

DOI：

点击查看最新优质反应信息

文献信息

Amino acid derivatives which have renin inhibiting activity

申请人：Hoffmann-La Roche, Inc.

公开号：US05140011A1

公开（公告）日：1992-08-18

The compounds of the formula ##STR1## wherein A, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the significance given in claim 1, in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates as well as pharmaceutically usable salts thereof inhibit the activity of the natural enzyme renin and can accordingly be used in the form of pharmaceutical preparations in the control or prevention of high blood pressure and cardiac insufficiency.

公式##STR1##的化合物，其中A、R.sup.1、R.sup.2、R.sup.3和R.sup.4的含义如权利要求1所述，以光学纯对映异构体、对映异构体混合物、对映异构体外消旋混合物或对映异构体外消旋混合物的形式，以及它们的药用盐，能够抑制天然酶肾素的活性，因此可以以药物制剂的形式用于控制或预防高血压和心脏衰竭。
New inhibitors of human renin that contain novel Leu-Val replacements

作者：Jay R. Luly、Nwe Yi、Jeff Soderquist、Herman Stein、Jerome Cohen、Thomas J. Perun、Jacob J. Plattner

DOI：10.1021/jm00392a015

日期：1987.9

than phenyl greater than substituted phenyl. Sulfur is the best X group; oxidation leads to slight (X = SO2) and significant (X = SO) decreases in inhibitory potency. One such inhibitor, 60, has an IC50 of 13 nM when tested with purified human renin at pH 6.0. The significant activity of these small inhibitors is thought to be due in part to the hydroxyl group of the fragment functioning as a transition-state

提出了一些非肽片段的立体选择性合成，这些片段在人类血管紧张素原中起Leu10-Val11易断裂键替代的作用。用各种硫，氧，氮和碳亲核试剂打开N保护的氨基烷基环氧化物3是制备这些新片段4-8的关键反应。这些片段与模拟血管紧张素原中位置8和9的受保护二肽的偶联产生了人肾素的抑制剂，即使该分子不包含超出血管紧张素原的Val11侧链的功能。优选与Val侧链的R基团非常相似的R基团。因此，异丙基大于或等于高级烷基大于苯基大于取代苯基。硫是最好的X基团；氧化导致抑制力轻微（X = SO2）和明显（X = SO）降低。当用纯化的人肾素在pH 6.0下测试时，一种这样的抑制剂60的IC50为13 nM。这些小抑制剂的显着活性被认为部分是由于片段的羟基起过渡状态类似物的作用。其中，含有组氨酸的抑制剂相对于相关的天冬氨酸蛋白酶胃蛋白酶对肾素表现出明显的选择性。
New inhibitors of human renin that contain novel Leu-Val replacements. Examination of the P1 site

作者：Jay R. Luly、Giorgio Bolis、Nwe BaMaung、Jeff Soderquist、Joseph F. Dellaria、Herman Stein、Jerome Cohen、Thomas J. Perun、Jonathan Greer、Jacob J. Plattner

DOI：10.1021/jm00398a008

日期：1988.3

replacements in human angiotensinogen are presented. These fragments are prepared from a variety of amino acids with formal P1 side chains varying in size and lipophilicity by converting them to their corresponding N-protected aminoalkyl epoxide 5 followed by ring opening with isopropyl mercaptan. The coupling of these fragments to either Boc-Phe-Ala-OH or Boc-Phe-His-OH produces inhibitors of human renin, 6 and

介绍了在人血管紧张素原中用作Leu10-Val11（P1-P1'）易断裂键替代物的几个非肽硫代乙醇片段的立体选择性合成。这些片段是通过将各种形式的P1侧链的大小和亲脂性不同的氨基酸制成的，方法是将其转化为相应的N保护的氨基烷基环氧化物5，然后用异丙硫醇开环。这些片段与Boc-Phe-Ala-OH或Boc-Phe-His-OH偶联分别产生人肾素抑制剂6和7，通过分子比较将其与一系列二肽醛抑制剂4进行比较。建模和生化方法。定性地，含组氨酸的（P2）抑制剂7具有比其相应的丙氨酸（P2）类似物6更大的抑制能力，它们比系列4中相应的醛类抑制剂更有效。在给定的系列中，具有环己基甲基P1侧链的抑制剂比苄基类似物更有效，而苄基类似物又比环己基或异丁基衍生物更有效。具有Parger P1侧链的抑制剂（例如金刚烷基甲基和二苯甲基）的活性要低得多。根据与酶的特异性相互作用，讨论了这些化合物对人肾素的抑制作用。
Renin inhibitors based on novel dipeptide analogs. Incorporation of the dehydrohydroxyethylene isostere at the scissile bond

作者：Dale J. Kempf、Ed De Lara、Herman H. Stein、Jerome Cohen、Jacob J. Plattner

DOI：10.1021/jm00394a008

日期：1987.11

The design and synthesis of renin inhibitors that incorporate the novel dipeptide isostere (4S,5S)-5-amino-6-cyclohexyl-4-hydroxyhex-1-ene-2-carboxylic acid as a transition-state analogue are described. Titanium-promoted condensation of dilithiated N-alkylmethacrylamides with protected amino aldehydes results in efficient preparation of protected dipeptide analogues 7 and 8. Incorporation of 7 into

描述了肾素抑制剂的设计和合成，该抑制剂结合了新型二肽等排物（4S，5S）-5-氨基-6-环己基-4-羟基己基-1-烯-2-羧酸作为过渡态类似物。钛促进的二锂化N-烷基甲基丙烯酰胺与受保护的氨基醛缩合，可有效制备受保护的二肽类似物7和8。将7掺入血管紧张素原的部分序列可提供有效的人肾素体外抑制剂。对不饱和酰胺部分的进一步化学处理允许研究P1'和P2'位点的结构-活性关系。介绍了合成，立体化学测定和体外肾素抑制的详细信息。
Renin inhibitors. Dipeptide analogs of angiotensinogen utilizing a dihydroxyethylene transition-state mimic at the scissile bond to impart greater inhibitory potency

作者：Jay R. Luly、Nwe BaMaung、Jeff Soderquist、Anthony K. L. Fung、Herman Stein、Hollis D. Kleinert、Patrick A. Marcotte、David A. Egan、Barbara Bopp

DOI：10.1021/jm00120a005

日期：1988.12

extremely selective for human renin over the related enzymes cathepsin D, pepsin, and gastricsin. At high concentrations, compounds containing a leucine or phenylalanine rather than a histidine at the P2 position gave only minor amounts of inhibition of the other enzymes. Inhibitor 43 suppressed plasma renin activity completely and lowered mean blood pressure in monkeys after both intravenous and intraduodenal

含二醇的肾素抑制剂的合成表明，与人血管紧张素原中易裂的Leu-Val键相对应的简单邻位二醇官能团能够以与相应的醛或羟甲基官能团相当或更高的水平赋予抑制活性（比较抑制剂2a-c或3a-c）。这一发现通过在Leu-Val替代物中包含第二个羟基，从而在200-700-pM范围内抑制人肾素的化合物（例如43）进一步优化了一系列小型过渡态类似物抑制剂。，45，63，66）。第二羟基对效能的影响大小不仅由二醇的绝对立体化学决定，而且由P1残基的侧链决定。含二醇抑制剂的分子模型表明，一个羟基氢键与Asp 32和Asp 215，而另一个氢键与Asp215。这些二醇抑制剂对人肾素的选择性超过相关的组织蛋白酶D，胃蛋白酶和胃蛋白酶。在高浓度下，在P2位上含有亮氨酸或苯丙氨酸而不是组氨酸的化合物对其他酶的抑制作用很小。在静脉内和十二指肠内给药后，抑制剂43完全抑制了血浆血浆肾素活性，并降低了猴子的平均血压，但