127779-20-8 (沙喹那韦,Saquinavir)

沙喹那韦;沙奎那韦;N1-[(1S,2R)-3-[(3S,4aS,8aS)-3-[(叔丁基氨基)甲酰]八氢-2(1H)-异喹啉基]-2-羟基-1-苄基丙基]-2-[(2-喹啉甲酰)氨基]-丁二酰胺;沙奎那韦-D9;沙奎那维;拓扑替康;双喹纳韦;赛科纳瓦D9;沙奎那韦溶液,100PPM;

Saquinavir mesylate;Saquinavir;Ro 31-8959;SAGUINAVIR;(2S)-N-[(2S,3R)-4-[(3S)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediamide;000;2-[[2-METHYL-3-(TRIFLUOROMETHYL)PHENYL]AMINO]PYRIDINE-3-CARBOXYLIC ACID;FLUNIXIN;FLUNIXINE;SAQUINAVIRMESYLATE(SUBJECTTOPATENTFREE);N1-[(1S,2R)-3-[(3S,4aS,8aS)-3-[[(1,1-Dimethylethyl)amino]carbonyl]octahydro-2(1H)-isoquinolinyl]-2-hydroxy-1-(phenylmethyl)propyl]-2-[(2-quinolinylcarbonyl)amino]-butanediamide;Sch 52852;Saquinavir Solution, 100ppm;Saquinavir & Saquinavir Mesylate;003：Invirase;Ro-31-8959;SAQUINAVIR [EMA EPAR];BDBM50213021;(S)-N1-((2S,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-phenylbutan-2-yl)-2-(quinoline-2-carboxamido)succinamide;BIDD:GT0323;SAQUINAVIR [WHO-DD];MLS001304735;D00429;2fgv;MRF-0000273;SAQUINAVIR (MART.);BUTANEDIAMIDE, N(SUP 1)-(3-(3-(((1,1-DIMETHYLETHYL)AMINO)CARBONYL)OCTAHYDRO-2(1H)-ISOQUINOLINYL)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-2-((2-QUINOLINYLCARBONYL)AMINO)-, (3S-(2(1R*(R*),2S*),3.ALPHA.,4A.BETA.,8A.BETA.))-;SMR000469157;Saquinavir [USAN];DTXCID4024012;Saquinavir- Bio-X;N-tert.butyl-decahydro-2[2(R)-hydroxy-4-phenyl-3-(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide;(2S)-N-[(1S,2R)-3-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-1-benzyl-2-hydroxy-propyl]-2-(quinoline-2-carbonylamino)butanediamide;cis-N-tert-Butyldecahydro-2-((2R,3S)-2-hydroxy-4-phenyl-3-((N-(2-quinolylcarbonyl)-L-asparaginyl)amino)butyl)-(3S,4aS,8aS)-isoquinoline-3-carboxamide;Butanediamide, N1-(3-(3-(((1,1-dimethylethyl)amino)carbonyl)octahydro-2(1H)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)-, (3S-(2(1R*(R*),2S*),3alpha,4aalpha,8aalpha))-;SAQUINAVIR [WHO-IP];(S)-N-((.ALPHA.S)-.ALPHA.-((1R)-2-((3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)OCTAHYDRO-2(1H)-ISOQUINOLYL)-1-HYDROXYETHYL)PHENETHYL)-2-QUINALDAMIDOSUCCINAMIDE;N(1)-{(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-yl}-N(2)-(quinolin-2-ylcarbonyl)-L-aspartamide;SAQUINAVIR [USP IMPURITY];DTXSID6044012;CHEMBL114;1hxb;BRD-K09963420-066-03-4;N-tert.butyl-decahydro -2- [2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl) -L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide;AKOS000280831;PLCG-SQV;(S)-N-;SAQUINAVIR (USP IMPURITY);Fortovase;SAQUINAVIR [MART.];HSDB 7161;BIDD:PXR0010;(3S-(2(1R*(R*),2S*),3I,4athetav,8athetav))-N(sup 1)-(3-(3-(((1,1-Dimethylethyl)amino)carbonyl)octahydro-2(1H)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)butanediamide;Ro 31-8959/000;Saquinavir (JAN/USP/INN);NS00007140;DB01232;NSC722663;(S)-N-[(IS)-I-[(1R)-2-[(3S,4aS,8aS)-3-(tert-Butylcarbamoyl)octahydro-2(1H)-isoquinolyl]-1-hydroxyethyl]phenethyl]-2-quinaldamidosuccinamide;saquinaviri mesilas;Prestwick0_001114;Saquinivir;J05AE01;BS164390;SAQUINAVIR [HSDB];AB00514056;Ro 318959;MLS001195635;EN300-19767269;(S)-N-((alphaS)-alpha-((1R)-2-((3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)OCTAHYDRO-2(1H)-ISOQUINOLYL)-1-HYDROXYETHYL)PHENETHYL)-2-QUINALDAMIDOSUCCINAMIDE;Invirase;Ro 31 8959;(2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1;GTPL4813;Saquinavirum;SAQUINAVIR [ORANGE BOOK];CHEBI:63621;BUTANEDIAMIDE, N(SUP 1)-(3-(3-(((1,1-DIMETHYLETHYL)AMINO)CARBONYL)OCTAHYDRO-2(1H)-ISOQUINOLINYL)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-2-((2-QUINOLINYLCARBONYL)AMINO)-, (3S-(2(1R*(R*),2S*),3alpha,4Abeta,8Abeta))-;SAQUINAVIR [VANDF];Ro-31-8959/000;(2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediamide;(S)-N-((IS)-I-((1R)-2-((3S,4aS,8aS)-3-(tert-Butylcarbamoyl)octahydro-2(1H)-isoquinolyl)-1-hydroxyethyl)phenethyl)-2-quinaldamidosuccinamide;MFCD00866925;NCGC00091469-02;BDBM519;N~1~-{(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-yl}-N~2~-(quinolin-2-ylcarbonyl)-L-aspartamide;SCHEMBL6881;SAQUINAVIR [JAN];(2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide;Ro-318959000;HY-17007;SPBio_003114;UNII-L3JE09KZ2F;CS-1180;Prestwick1_001114;NP-SQV;Butanediamide, N1-((1S,2R)-3-((3S,4aS,8aS)-3-(((1,1-dimethylethyl)amino)carbonyl)octahydro-2(1H)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)-, (2S)-;ROC;Q422654;SAQUINAVIR [INN];Fortovase(TM);Prestwick2_001114;SAQUINAVIR [MI];Prestwick3_001114;Fortovase; SAQUINAVIR; RO 31-8959;Fortovase (TN);(2s)-N-[(2s,3r)-4-[(2s,3s,4as,8as)-3-(Tert-Butylcarbamoyl)-3,4,4a,5,6,7,8,8a-Octahydro-1h-Isoquinolin-2-Yl]-3-Hydroxy-1-Phenyl-Butan-2-Yl]-2-(Quinolin-2-Ylcarbonylamino)butanediamide;SQV;(2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide;N(1)-((2S,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-phenylbutan-2-yl)-N(2)-(quinolin-2-ylcarbonyl)-L-aspartamide;Butanediamide, N1-[(1S,2R)-3-[(3S,4aS,8aS)-3-[[(1,1-dimethylethyl)amino]carbonyl]octahydro-2(1H)-isoquinolinyl]-2-hydroxy-1-(phenylmethyl)propyl]-2-[(2-quinolinylcarbonyl)amino]-, (2S)-;SCH-52852;N-tert.butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide;127779-20-8;BPBio1_001373;BSPBio_001248;QWAXKHKRTORLEM-UGJKXSETSA-N;L3JE09KZ2F;AC-26377;SAQUINAVIRUM [WHO-IP LATIN];(2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide;Saquinavir [USAN:USP:INN:BAN];HMS2232L04;NCGC00091469-15;Saquinavir (USAN:USP:INN:BAN);-phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide;2fgu;Invirase(TM)(monomesylate);Ro-31-8959/003：Invirase;Saquinavir?;

MFCD00866925

QWAXKHKRTORLEM-UGJKXSETSA-N

1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1

O=C([C@@H]1C[C@@H]2CCCC[C@@H]2CN1C[C@H]([C@H](CC1C=CC=CC=1)NC([C@H](CC(N)=O)NC(C1C=CC2C=CC=CC=2N=1)=O)=O)O)NC(C)(C)C

抗病毒药。为选择性的Hiv蛋白酶抑制剂。

N-邻苯二甲酰基-(S)-苯丙氨酰氯(I)(31.35g，0.1mo1)和1，1，2-三[(三甲硅基)氧]乙烯(Ⅱ)(62.8g，0.215mo1)混合，在95～100℃下加热4h。冷至室温，加入40ml 0.6mol/L盐酸水溶液和100ml二氧六烷的混合液。形成的二相溶液在80～85℃下加热30min后，冷至室温。加入15g氯化钠，用乙醚提取(先100ml后50m1)。提取液合并，用饱和碳酸氢钠水溶液洗，无水硫酸钠干燥，浓缩。剩余物用50ml乙酸乙酯和90ml正己烷结晶，得19.5g米色的固体，即为1-羟基-4-苯基-3(S)-邻苯二甲酰亚氨基-2-丁酮(Ⅲ)，收率63%，熔点108～112℃，[α]D20-187.9°(C=0.876，乙醇)。化合物(Ⅲ)(34.09g，0.11mo1)溶于80ml二氯乙烷，在搅拌下，加入二氢吡咯(DHP)(10.16g，0.12mo1)和150mg对甲苯磺酸单水合物，在20℃下搅拌16h。反应液用饱和碳酸钠水溶液和盐水洗，然后浓缩。剩余物溶于220ml四氢呋喃，在冰盐浴冷却和搅拌下，滴加溶于水(20m1)的硼氢化钠(10.8g，0.29mo1)溶液，控制滴加的迅速以维持反应液的温度在0℃以下。加毕，在0℃继续搅拌15min，然后加水稀释。用2mol/L硫酸调至Ph=7，蒸出大部分四氢呋喃。产生的溶液用二氯甲烷提取，提取液用盐水洗后浓缩。剩下的粗品溶于110ml吡啶，在搅拌下滴加甲磺酰氯(15.11g，0.13mo1)。滴毕，在20℃下搅拌16h后浓缩。剩余物在乙酸乙酯和2mol/L硫酸水溶液之间进行分配。分出有机层，用盐水洗，浓缩。得到的产物溶于154ml乙醇，加入1.1g对甲苯磺酸单水合物，在20℃下搅拌1h，再在4℃下放置过夜。过滤收集析出的沉淀，用乙醇和乙醚洗，然后用乙醇重结晶，得12.62g白色固体，即为2?-(甲磺酰氧基)-4-苯基-3(S)-邻苯二甲酰亚胺基-l-丁醇(Ⅳ)，收率29%，熔点180～182℃，[α]D20-100.5°(C=0.4，甲醇)。化合物(Ⅳ)(150g，0.386mo1)溶于350ml二甲基甲酰胺中，在＜30℃下，加入叔丁醇钾(47．5g，0．424m01)在250ml二甲基甲酰胺中的溶液，在20℃下搅拌1h。将反应液倾入1L甲苯、50ml浓盐酸和500g冰所成的混合液中。分层，分出的水层用甲苯(2×500m1)提取。提取液和有机层合并，依次用水(2×500m1)、饱和碳酸氢钠水溶液(500m1)、水(2×500m1)和盐水(2×500m1)洗，干燥，浓缩。剩余物用250ml甲醇浸渍后过滤，滤饼用200ml甲醇洗，得78.4g奶油色固体，为2(S)-[2-苯基-1(S)-邻苯二甲酰亚胺基乙基]环氧乙烷(V)，收率69%，熔点180～182℃，[α]D20-155.2°(C=0.5，二氯甲烷)。化合物(Ⅵ)(14.52g，61mm01)和化合物(V)(17.87g，61mmo1)溶于120ml二甲基甲酰胺，在120℃下加热8.5h。蒸去溶剂，剩余物在乙酸乙酯和水之间进行分配。分出有机层，用盐水洗后浓缩，剩余物用硅胶柱层析，用乙醚-正己烷-甲醇(9.5：9.5：1)洗脱。得25.9g类白色化合物，即为N-叔丁基十氢-2-(2R)羟基-4-苯基3(S)-邻苯二甲酰亚胺基丁基-(4αS，8αS)-异喹啉-3(S)-甲酰胺(Ⅶ)，收率80%。用相同的溶剂结晶，可得用于分析的样品。化合物(Ⅶ)(26.55g，50mmo1)溶于100ml乙醇，加入25ml 33%甲胺的乙醇溶液，在室温下搅拌1h。浓缩，剩余物溶于250ml乙醇，加入250ml 4mol/L氯化氢的乙酸乙酯溶液，在室温下搅拌过夜。浓缩，剩余物溶于水，然后用乙酸乙酯洗，并用固体碳酸钠碱化，再用二氯甲烷提取。提取液用盐水洗，浓缩。剩下的棕色固体用乙醚浸渍，得17.48g白色固体，为2-(3(S)-氨基-2?-羟基-4-苯基丁基)-N-叔丁基十氢-(4αS，8αS)-异喹啉-3(S)-甲酰胺(Ⅷ)，收率87%，熔点173～175℃(乙腈重结晶)，[α] D20-104.9°(C=0.5，甲醇)。化合物(Ⅷ)(562mg，1.4mmo1)溶于20ml四氢呋喃，在冰浴冷却下，加入苯氧羰基-L-门冬酰胺(CbzAsnOH)(372mg，1.4mmo1)、1-羟基苯并三唑水合物(HOBT)(189mg，1.4mmo1)、二环己基碳化二亚胺(DCC)(317mg，1.54mmo1)和N-乙基**(161mg，1.4mmo1)。任反应液升至室温，并在室温下搅拌64h。用乙酸乙酯稀释，过滤。滤液用10%碳酸钠水溶液和盐水洗，浓缩。剩余物用硅胶柱层析，以二氯甲烷-甲醇(9：1)洗脱，得438mg产物，为2-[3(S)-[[N-(苯氧羰基)-L-门冬酰基]氨基]-2?-羟基-4-苯基丁基]-N-叔丁基十氢-(4αS，8αS)-异喹啉-3(S)-甲酰胺(Ⅸ)，收率48%。化合物(Ⅸ)(4.76g，7.3mmo1)溶于。73ml乙醇，在10%钯-炭催化剂存在下，室温和常压氢化16h。过滤除去催化剂，滤液浓缩。剩余物溶于甲苯，再浓缩。剩余物再溶于36.5ml四氢呋喃，在冰浴冷却和搅拌下，加入喹啉-2-羧酸(1.26g，7.3mmo1)、l-羟基苯三唑水合物(985mg，7.3mmo1)、二环己基碳化二亚胺(1.5g，7.3mmo1)和N-乙基吗啉(840mg，7.3mmo1)。任反应液升至生温，搅拌16h。过滤，滤液用水、10%碳酸钠水溶液和盐水洗。浓缩，剩余物月硅胶柱层析，用二氯甲烷-甲醇(92.5：7.5)洗脱。得3.09g沙奎那韦，收璋63%，D20-55.9°(C=0.5，甲醇)。