LT3682B - Method for preparing amino acid derivatives and pharmaceuthical compositions thereof - Google Patents

Method for preparing amino acid derivatives and pharmaceuthical compositions thereof Download PDF

Info

Publication number: LT3682B
Authority: LT; Lithuania
Prior art keywords: formula; compound; acid; hydroxy; isoquinoline
Prior art date: 1989-12-11

Application number

LTIP862A

Other languages

English (en)

Lithuanian (lt)

Inventor

Joseph Armstrong Martin

Sally Redshaw

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-12-11

Filing date

1993-08-16

Publication date

1996-01-25

1993-08-16 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1995-03-27 Publication of LTIP862A publication Critical patent/LTIP862A/xx

1996-01-25 Publication of LT3682B publication Critical patent/LT3682B/lt

Links

239000000203 mixture Substances 0.000 title claims description 24
238000000034 method Methods 0.000 title claims description 19
150000003862 amino acid derivatives Chemical class 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 57
150000003839 salts Chemical class 0.000 claims abstract description 26
239000002253 acid Substances 0.000 claims abstract description 23
-1 2-quinolylcarbonyl Chemical group 0.000 claims abstract description 22
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 14
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims abstract description 12
238000011282 treatment Methods 0.000 claims abstract description 10
208000036142 Viral infection Diseases 0.000 claims abstract description 8
230000009385 viral infection Effects 0.000 claims abstract description 8
239000003814 drug Substances 0.000 claims abstract description 6
238000011321 prophylaxis Methods 0.000 claims abstract description 5
239000003795 chemical substances by application Substances 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
NVJKKZFIMURKNZ-DVZKKUMJSA-N (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-aminobutanediamide Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@@H](N)CC(N)=O)C1=CC=CC=C1 NVJKKZFIMURKNZ-DVZKKUMJSA-N 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
108091005804 Peptidases Proteins 0.000 abstract description 3
239000004365 Protease Substances 0.000 abstract description 3
102000035195 Peptidases Human genes 0.000 abstract 1
230000003612 virological effect Effects 0.000 abstract 1
239000000243 solution Substances 0.000 description 31
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
239000000706 filtrate Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
229920000159 gelatin Polymers 0.000 description 6
235000019322 gelatine Nutrition 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
238000003556 assay Methods 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
230000007017 scission Effects 0.000 description 5
OJDLZOUHAPYVTA-XHSDSOJGSA-N (3s,4as,8as)-2-phenylmethoxycarbonyl-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinoline-3-carboxylic acid Chemical compound C([C@H]1CCCC[C@H]1C[C@H]1C(=O)O)N1C(=O)OCC1=CC=CC=C1 OJDLZOUHAPYVTA-XHSDSOJGSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
239000001828 Gelatine Substances 0.000 description 4
241000725303 Human immunodeficiency virus Species 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
235000011167 hydrochloric acid Nutrition 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000000758 substrate Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
VSHYTRKWRSIOEV-NSHDSACASA-N (2s)-4-amino-4-oxo-2-(quinoline-2-carbonylamino)butanoic acid Chemical compound C1=CC=CC2=NC(C(=O)N[C@@H](CC(=O)N)C(O)=O)=CC=C21 VSHYTRKWRSIOEV-NSHDSACASA-N 0.000 description 3
UPZBXVBPICTBDP-TUAOUCFPSA-N (3s,4as,8as)-n-tert-butyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxamide Chemical compound C1CCC[C@@H]2CN[C@H](C(=O)NC(C)(C)C)C[C@@H]21 UPZBXVBPICTBDP-TUAOUCFPSA-N 0.000 description 3
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
108010010369 HIV Protease Proteins 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000008298 dragée Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 3
NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 description 2
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
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OCYROESYHWUPBP-CIUDSAMLSA-N Pro-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)[C@@H]1CCC[NH2+]1 OCYROESYHWUPBP-CIUDSAMLSA-N 0.000 description 2
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150000008065 acid anhydrides Chemical class 0.000 description 2
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
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150000008064 anhydrides Chemical class 0.000 description 2
230000000840 anti-viral effect Effects 0.000 description 2
YLHIITUTRCZRRB-OTWHNJEPSA-N benzyl (3s,4as,8as)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinoline-2-carboxylate Chemical compound C([C@H]1CCCC[C@H]1C[C@H]1C(=O)NC(C)(C)C)N1C(=O)OCC1=CC=CC=C1 YLHIITUTRCZRRB-OTWHNJEPSA-N 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
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ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
102100038239 Protein Churchill Human genes 0.000 description 1
101150085390 RPM1 gene Proteins 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
108010067390 Viral Proteins Proteins 0.000 description 1
241000700605 Viruses Species 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000002421 anti-septic effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
239000002585 base Substances 0.000 description 1
239000012267 brine Substances 0.000 description 1
SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229910052801 chlorine Chemical group 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
IFYLVUHLOOCYBG-UHFFFAOYSA-N eticyclidine Chemical compound C=1C=CC=CC=1C1(NCC)CCCCC1 IFYLVUHLOOCYBG-UHFFFAOYSA-N 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
239000008103 glucose Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000011256 inorganic filler Substances 0.000 description 1
229910003475 inorganic filler Inorganic materials 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
210000001161 mammalian embryo Anatomy 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012766 organic filler Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
229940079877 pyrogallol Drugs 0.000 description 1
LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
230000007484 viral process Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Virology (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Genetics & Genomics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Oncology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Communicable Diseases (AREA)
Crystallography & Structural Chemistry (AREA)
Biochemistry (AREA)
Biophysics (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)
Peptides Or Proteins (AREA)
Confectionery (AREA)
Cleaning Or Clearing Of The Surface Of Open Water (AREA)
Measurement Of Force In General (AREA)

LTIP862A 1989-12-11 1993-08-16 Method for preparing amino acid derivatives and pharmaceuthical compositions thereof LT3682B (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB898927913A GB8927913D0 (en)	1989-12-11	1989-12-11	Amino acid derivatives
SG120493A SG120493G (en)	1989-12-11	1993-11-02	N-tert-Butyl-decahydro-2(3-amino-2-hydroxy-4-phenyl-butyl) isoquinoline-3-carboxamide and asparaginyl derivatives thereof

Publications (2)

Publication Number	Publication Date
LTIP862A LTIP862A (en)	1995-03-27
LT3682B true LT3682B (en)	1996-01-25

Family

ID=26296345

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LTIP862A LT3682B (en)	1989-12-11	1993-08-16	Method for preparing amino acid derivatives and pharmaceuthical compositions thereof

Country Status (48)

Country	Link
US (1)	US5196438A (lv)
EP (1)	EP0432695B1 (lv)
JP (1)	JP2807093B2 (lv)
KR (1)	KR970005912B1 (lv)
CN (2)	CN1066329C (lv)
AT (1)	ATE122661T1 (lv)
AU (1)	AU634319B2 (lv)
BG (1)	BG51452A3 (lv)
BR (1)	BR9006264A (lv)
CA (1)	CA2030433C (lv)
CU (1)	CU22305A3 (lv)
CZ (1)	CZ280558B6 (lv)
DE (2)	DE19675051I2 (lv)
DK (1)	DK0432695T3 (lv)
DZ (1)	DZ1467A1 (lv)
EG (1)	EG19722A (lv)
ES (1)	ES2072959T3 (lv)
FI (2)	FI100883B (lv)
GB (2)	GB8927913D0 (lv)
GR (1)	GR3017114T3 (lv)
HK (1)	HK129093A (lv)
HR (1)	HRP930341B1 (lv)
HU (2)	HU207298B (lv)
ID (1)	ID1018B (lv)
IE (1)	IE67523B1 (lv)
IL (1)	IL96550A (lv)
IN (1)	IN172553B (lv)
IS (1)	IS1803B (lv)
LT (1)	LT3682B (lv)
LU (1)	LU90014I2 (lv)
LV (1)	LV5738B4 (lv)
MA (1)	MA22014A1 (lv)
MC (1)	MC2195A1 (lv)
MT (1)	MTP1075B (lv)
MW (1)	MW8890A1 (lv)
MX (1)	MX173630B (lv)
NL (1)	NL970013I2 (lv)
NO (1)	NO176566C (lv)
OA (1)	OA09334A (lv)
PL (1)	PL165225B1 (lv)
PT (1)	PT96145B (lv)
RO (1)	RO107942B1 (lv)
RU (1)	RU2071470C1 (lv)
SG (1)	SG120493G (lv)
SI (1)	SI9012315B (lv)
SK (1)	SK576590A3 (lv)
ZA (1)	ZA909743B (lv)
ZW (1)	ZW17490A1 (lv)

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- 1989-12-11 GB GB898927913A patent/GB8927913D0/en active Pending
1990
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1991
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1993
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- 1993-11-25 HK HK1290/93A patent/HK129093A/xx not_active IP Right Cessation
1995
- 1995-06-16 HU HU95P/P00230P patent/HU211342A9/hu unknown
- 1995-08-11 GR GR950402228T patent/GR3017114T3/el unknown
1996
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Publication number	Publication date
LTIP862A (en)	1995-03-27
PT96145B (pt)	1998-04-30
DZ1467A1 (fr)	2004-09-13
EP0432695B1 (en)	1995-05-17
US5196438A (en)	1993-03-23
EP0432695A2 (en)	1991-06-19
OA09334A (fr)	1992-09-15
PL288201A1 (en)	1991-09-09
GB2239016A (en)	1991-06-19
ID1018B (id)	1996-10-18
IS3651A7 (is)	1991-06-12
HU211342A9 (en)	1995-11-28
DE69019481T2 (de)	1995-11-09
ATE122661T1 (de)	1995-06-15
GB8927913D0 (en)	1990-02-14
AU634319B2 (en)	1993-02-18
CA2030433A1 (en)	1991-06-12
LU90014I2 (fr)	1997-01-31
NO176566C (no)	1995-04-26
BG51452A3 (bg)	1993-05-14
NO905322D0 (no)	1990-12-10
FI100883B (fi)	1998-03-13
MW8890A1 (en)	1991-03-13
PL165225B1 (pl)	1994-11-30
JP2807093B2 (ja)	1998-09-30
CN1034805C (zh)	1997-05-07
SK280249B6 (sk)	1999-10-08
LV5738A4 (lv)	1996-08-20
DE19675051I2 (de)	2001-04-12
NL970013I1 (nl)	1997-05-01
DE69019481D1 (de)	1995-06-22
SI9012315B (sl)	1998-06-30
DK0432695T3 (da)	1995-09-11
MX173630B (es)	1994-03-18
CN1052482A (zh)	1991-06-26
SG120493G (en)	1994-01-21
FI973895A0 (fi)	1997-10-06
EG19722A (en)	1996-01-31
RU2071470C1 (ru)	1997-01-10
MA22014A1 (fr)	1991-07-01
GR3017114T3 (en)	1995-11-30
FI973895L (fi)	1997-10-06
HU207298B (en)	1993-03-29
MC2195A1 (fr)	1992-10-05
BR9006264A (pt)	1991-09-24
HRP930341B1 (en)	1998-12-31
HU908076D0 (en)	1991-06-28
NL970013I2 (nl)	1997-09-01
ES2072959T3 (es)	1995-08-01
FI905983L (fi)	1991-06-12
EP0432695A3 (en)	1991-12-18
MTP1075B (en)	1991-07-31
CN1066329C (zh)	2001-05-30
CZ576590A3 (en)	1995-11-15
IS1803B (is)	2002-02-26
NO176566B (no)	1995-01-16
CN1138983A (zh)	1997-01-01
GB2239016B (en)	1993-08-04
FI905983A0 (fi)	1990-12-04
ZW17490A1 (en)	1992-06-17
IL96550A (en)	1995-03-15
HRP930341A2 (en)	1994-10-31
IE904453A1 (en)	1991-06-19
KR970005912B1 (en)	1997-04-22
KR910011894A (ko)	1991-08-07
IN172553B (lv)	1993-09-25
NO905322L (no)	1991-06-12
CU22305A3 (es)	1995-01-31
ZA909743B (en)	1991-08-28
JPH03255076A (ja)	1991-11-13
IL96550A0 (en)	1991-09-16
AU6787690A (en)	1991-06-13
PT96145A (pt)	1991-09-30
LV5738B4 (lv)	1996-12-20
SI9012315A (en)	1997-10-31
RO107942B1 (ro)	1994-01-31
IE67523B1 (en)	1996-04-03
CA2030433C (en)	1997-10-21
GB9026776D0 (en)	1991-01-30
HK129093A (en)	1993-12-03
SK576590A3 (en)	1999-10-08
CZ280558B6 (cs)	1996-02-14
MX23619A (es)	1993-10-01
HUT56073A (en)	1991-07-29

Publication	Publication Date	Title
LT3682B (en)	1996-01-25	Method for preparing amino acid derivatives and pharmaceuthical compositions thereof
JP2515019B2 (ja)	1996-07-10	アミノ酸誘導体
US4294832A (en)	1981-10-13	Tetrahydroisoquinoline compounds and a pharmaceutical composition thereof
AU606901B2 (en)	1991-02-21	Novel phosphinic acid derivatives
EP0643072B1 (en)	1999-02-24	2-Piperazinone compounds and their use
RU2232760C2 (ru)	2004-07-20	Ингибитор сериновых протеаз и фармацевтическая композиция на его основе
DE60221508T2 (de)	2008-04-24	Aminosäurederivate als hiv-protease-inhibitoren
KR20000016700A (ko)	2000-03-25	뎁시 펩티드 및 이를 유효 성분으로 하는 의약
US4216209A (en)	1980-08-05	Tripeptide angiotensin converting enzyme inhibitors
US4587250A (en)	1986-05-06	Thiazaspirane derivatives, process for their preparation, and medicaments
KR870001239B1 (ko)	1987-06-26	테트라하이드로-β-카르보린 유도체의 제조방법
FR2594831A1 (fr)	1987-08-28	Derives de proline, leur procede de preparation, composition pharmaceutique en comportant et procede d'inhibition de l'enzyme transformant l'angiotensine
JPH07126286A (ja)	1995-05-16	新規なペプチド誘導体
BG60367B2 (bg)	1995-01-30	Аминокиселинни производни
JPH075633B2 (ja)	1995-01-25	アミノ酸誘導体その製造方法及び血圧降下剤
RU2109731C1 (ru)	1998-04-27	Производные аминокислоты и их фармацевтически приемлемые соли, которые являются основными, способы получения производных аминокислоты и фармацевтическая композиция, обладающая антивирусной активностью
SA90110168B1 (ar)	2003-09-02	مشتقات الاحماض الامينية.
EP0279750A2 (en)	1988-08-24	Aminoacid derivatives as antihypertensives
JPH07157472A (ja)	1995-06-20	２−ピペラジノン−１−酢酸誘導体およびその用途

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