LT3681B - N-acyl-alpha-amino acid derivatives, method for producting thereof,pharmaceutical compositions and preparing them - Google Patents

N-acyl-alpha-amino acid derivatives, method for producting thereof,pharmaceutical compositions and preparing them Download PDF

Info

Publication number: LT3681B
Authority: LT; Lithuania
Prior art keywords: group; acid; acetic acid; hydrogen; piperidinyl
Prior art date: 1991-03-26

Application number

LTIP861A

Other languages

English (en)

Lithuanian (lt)

Inventor

Leo Alig

Paul Hadvary

Marianne Huerzeler

Marcel Mueller

Beat Steiner

Thomas Weller

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.)

1991-03-26

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 LTIP861A publication Critical patent/LTIP861A/xx

1996-01-25 Publication of LT3681B publication Critical patent/LT3681B/lt

Links

238000000034 method Methods 0.000 title description 4
239000008194 pharmaceutical composition Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 50
238000011282 treatment Methods 0.000 claims abstract description 13
125000003368 amide group Chemical group 0.000 claims abstract description 5
102000004169 proteins and genes Human genes 0.000 claims abstract description 4
108090000623 proteins and genes Proteins 0.000 claims abstract description 4
239000000853 adhesive Substances 0.000 claims abstract description 3
230000001070 adhesive effect Effects 0.000 claims abstract description 3
-1 Ala Chemical compound 0.000 claims description 179
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 153
239000002253 acid Substances 0.000 claims description 44
229910052739 hydrogen Inorganic materials 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 31
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 21
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
125000000217 alkyl group Chemical group 0.000 claims description 18
150000001412 amines Chemical class 0.000 claims description 17
KSGBFAJYSBCOGG-UHFFFAOYSA-N 2-piperidin-1-ium-4-yloxyacetate Chemical compound OC(=O)COC1CCNCC1 KSGBFAJYSBCOGG-UHFFFAOYSA-N 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
150000001409 amidines Chemical group 0.000 claims description 12
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 10
HKMIWYWBIYCXFQ-UHFFFAOYSA-N 4-carbamimidoylbenzamide Chemical compound NC(=N)C1=CC=C(C(N)=O)C=C1 HKMIWYWBIYCXFQ-UHFFFAOYSA-N 0.000 claims description 9
125000003277 amino group Chemical group 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Chemical group CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 7
150000007513 acids Chemical class 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Chemical group CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims description 4
201000010099 disease Diseases 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000001033 ether group Chemical group 0.000 claims description 4
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125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
230000004962 physiological condition Effects 0.000 claims description 4
239000012453 solvate Substances 0.000 claims description 4
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 3
208000007536 Thrombosis Diseases 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000003435 aroyl group Chemical group 0.000 claims description 3
230000015572 biosynthetic process Effects 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 description 3
125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
206010003210 Arteriosclerosis Diseases 0.000 claims description 2
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 2
208000001132 Osteoporosis Diseases 0.000 claims description 2
239000002246 antineoplastic agent Substances 0.000 claims description 2
208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims description 2
150000004677 hydrates Chemical class 0.000 claims description 2
230000004054 inflammatory process Effects 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
230000007910 cell fusion Effects 0.000 claims 2
238000011321 prophylaxis Methods 0.000 claims 2
208000010110 spontaneous platelet aggregation Diseases 0.000 claims 2
208000032843 Hemorrhage Diseases 0.000 claims 1
206010061216 Infarction Diseases 0.000 claims 1
206010061218 Inflammation Diseases 0.000 claims 1
210000004556 brain Anatomy 0.000 claims 1
150000001732 carboxylic acid derivatives Chemical group 0.000 claims 1
239000000446 fuel Substances 0.000 claims 1
230000007574 infarction Effects 0.000 claims 1
210000004165 myocardium Anatomy 0.000 claims 1
239000003357 wound healing promoting agent Substances 0.000 claims 1
150000002825 nitriles Chemical class 0.000 abstract description 11
125000006239 protecting group Chemical group 0.000 abstract description 6
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 149
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 97
239000000047 product Substances 0.000 description 82
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
239000000741 silica gel Substances 0.000 description 68
229910002027 silica gel Inorganic materials 0.000 description 68
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 67
238000006243 chemical reaction Methods 0.000 description 59
238000004587 chromatography analysis Methods 0.000 description 59
238000002844 melting Methods 0.000 description 54
230000008018 melting Effects 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
239000000243 solution Substances 0.000 description 51
229960000583 acetic acid Drugs 0.000 description 49
235000019439 ethyl acetate Nutrition 0.000 description 49
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
239000007858 starting material Substances 0.000 description 39
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 35
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 33
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
WHNQTHDJEZTVHS-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)propanoic acid Chemical compound C1=CC=C2SC(CCC(=O)O)=NC2=C1 WHNQTHDJEZTVHS-UHFFFAOYSA-N 0.000 description 23
PCOKVBQRZCEGTJ-UHFFFAOYSA-N tert-butyl 2-piperidin-4-yloxyacetate Chemical compound CC(C)(C)OC(=O)COC1CCNCC1 PCOKVBQRZCEGTJ-UHFFFAOYSA-N 0.000 description 23
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 21
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
PAAZCQANMCYGAW-UHFFFAOYSA-N acetic acid;2,2,2-trifluoroacetic acid Chemical compound CC(O)=O.OC(=O)C(F)(F)F PAAZCQANMCYGAW-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
150000002148 esters Chemical class 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
238000007327 hydrogenolysis reaction Methods 0.000 description 12
VQMPDJWASLSMFZ-UHFFFAOYSA-N acetic acid;tert-butyl acetate Chemical compound CC(O)=O.CC(=O)OC(C)(C)C VQMPDJWASLSMFZ-UHFFFAOYSA-N 0.000 description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
239000007795 chemical reaction product Substances 0.000 description 11
238000005984 hydrogenation reaction Methods 0.000 description 11
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
238000003756 stirring Methods 0.000 description 11
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
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125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
KJBNWQLVMZQQSX-UHFFFAOYSA-N 4-carbamimidoylbenzoyl chloride;hydrochloride Chemical compound Cl.NC(=N)C1=CC=C(C(Cl)=O)C=C1 KJBNWQLVMZQQSX-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
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BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 8
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239000000463 material Substances 0.000 description 7
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238000001953 recrystallisation Methods 0.000 description 6
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125000003118 aryl group Chemical group 0.000 description 5
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VDKVPBCMAIZLLR-UHFFFAOYSA-N ethyl 2-piperidin-4-yloxyacetate Chemical compound CCOC(=O)COC1CCNCC1 VDKVPBCMAIZLLR-UHFFFAOYSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
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125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
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238000009835 boiling Methods 0.000 description 3
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WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
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OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 3
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125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000004651 carbonic acid esters Chemical group 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000008619 cell matrix interaction Effects 0.000 description 1
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
229910052906 cristobalite Inorganic materials 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
HDRXZJPWHTXQRI-BHDTVMLSSA-N diltiazem hydrochloride Chemical compound [Cl-].C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CC[NH+](C)C)C2=CC=CC=C2S1 HDRXZJPWHTXQRI-BHDTVMLSSA-N 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
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PFILESBKCPWBSF-KRWDZBQOSA-N ethyl 2-[1-[(2S)-2-amino-3-(4-methoxyphenyl)propanoyl]piperidin-4-yl]oxyacetate Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@@H](N)CC1=CC=C(OC)C=C1 PFILESBKCPWBSF-KRWDZBQOSA-N 0.000 description 1
YSPVHAUJXLGZHP-UHFFFAOYSA-N ethyl piperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCCC1 YSPVHAUJXLGZHP-UHFFFAOYSA-N 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
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125000000524 functional group Chemical group 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
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239000008103 glucose Substances 0.000 description 1
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230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000008011 inorganic excipient Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
238000004969 ion scattering spectroscopy Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
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HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000002523 lectin Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
SQRPEDUEGWFUKZ-UHFFFAOYSA-N methyl 2-(3-hydroxyphenoxy)acetate Chemical compound COC(=O)COC1=CC=CC(O)=C1 SQRPEDUEGWFUKZ-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 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
XQDBZKHPFFODOD-UHFFFAOYSA-N methyl 2-piperidin-4-yloxyacetate;hydrochloride Chemical compound Cl.COC(=O)COC1CCNCC1 XQDBZKHPFFODOD-UHFFFAOYSA-N 0.000 description 1
FNKLGGIAXFTGTF-UHFFFAOYSA-N methyl acetate;2,2,2-trifluoroacetic acid Chemical compound COC(C)=O.OC(=O)C(F)(F)F FNKLGGIAXFTGTF-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
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235000010755 mineral Nutrition 0.000 description 1
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230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
MVUFWOYGZNPKSO-UHFFFAOYSA-N n-[(2-methylpropan-2-yl)oxy]formamide Chemical compound CC(C)(C)> MVUFWOYGZNPKSO-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 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
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000008012 organic excipient Substances 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
ITDJKCJYYAQMRO-UHFFFAOYSA-L rhodium(2+);diacetate Chemical compound [Rh+2].CC([O-])=O.CC([O-])=O ITDJKCJYYAQMRO-UHFFFAOYSA-L 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
NVSZHSKKZDBLDS-VCSGRIEYSA-N tert-butyl 2-[(3R,4S)-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]-1-[2-(phenylmethoxycarbonylamino)propanoyl]pyrrolidin-3-yl]oxyacetate Chemical compound C([C@@H]([C@H](OCC(=O)OC(C)(C)C)C1)OCC(=O)OC(C)(C)C)N1C(=O)C(C)NC(=O)OCC1=CC=CC=C1 NVSZHSKKZDBLDS-VCSGRIEYSA-N 0.000 description 1
JECXIXOHQMBPCR-XGSMCBPESA-N tert-butyl 2-[(3s,4r)-1-[2-[(4-carbamimidoylbenzoyl)amino]propanoyl]-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]pyrrolidin-3-yl]oxyacetate Chemical compound C([C@@H]([C@H](OCC(=O)OC(C)(C)C)C1)OCC(=O)OC(C)(C)C)N1C(=O)C(C)NC(=O)C1=CC=C(C(N)=N)C=C1 JECXIXOHQMBPCR-XGSMCBPESA-N 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
230000007704 transition Effects 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
229960004441 tyrosine Drugs 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004474 valine Substances 0.000 description 1
125000002114 valyl group Chemical group 0.000 description 1
230000029663 wound healing Effects 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Classifications

- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

LTIP861A 1991-03-26 1993-08-16 N-acyl-alpha-amino acid derivatives, method for producting thereof,pharmaceutical compositions and preparing them LT3681B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CH91091		1991-03-26

Publications (2)

Publication Number	Publication Date
LTIP861A LTIP861A (en)	1995-03-27
LT3681B true LT3681B (en)	1996-01-25

Family

ID=4198024

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LTIP861A LT3681B (en)	1991-03-26	1993-08-16	N-acyl-alpha-amino acid derivatives, method for producting thereof,pharmaceutical compositions and preparing them

Country Status (6)

Country	Link
BR (2)	BR9201030A (pt)
LT (1)	LT3681B (pt)
MX (1)	MX9201169A (pt)
UY (1)	UY23389A1 (pt)
YU (2)	YU29492A (pt)
ZA (1)	ZA922022B (pt)

1992
- 1992-03-17 MX MX9201169A patent/MX9201169A/es not_active IP Right Cessation
- 1992-03-19 ZA ZA922022A patent/ZA922022B/xx unknown
- 1992-03-24 YU YU29492A patent/YU29492A/sh unknown
- 1992-03-24 YU YU29592A patent/YU48994B/sh unknown
- 1992-03-25 UY UY23389A patent/UY23389A1/es not_active IP Right Cessation
- 1992-03-25 BR BR929201030A patent/BR9201030A/pt not_active Application Discontinuation
1993
- 1993-08-16 LT LTIP861A patent/LT3681B/lt unknown
1996
- 1996-09-17 BR BR1100042-2A patent/BR1100042A/pt active IP Right Grant

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LAURENCE A. FITZGERALD, BETTY LEUNG, DAVID R.: "A method for purifying the platelet membrane glycoprotein IIb-IIIa complex", ANALYTICAL BIOCHEMISTRY, 1985, pages 169 - 177
PYTELA R ET AL.: "Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors", SCIENCE, 1986, pages 1559 - 1562

Also Published As

Publication number	Publication date
MX9201169A (es)	1992-10-01
YU48994B (sh)	2003-04-30
BR9201030A (pt)	1992-11-24
YU29492A (sh)	1994-09-09
BR1100042A (pt)	2000-04-11
YU29592A (sh)	1994-09-09
LTIP861A (en)	1995-03-27
UY23389A1 (es)	1992-09-15
ZA922022B (en)	1992-11-25

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CZ63994A3 (cs)	1995-10-18	Derivát heterocyklického sulfonamídu a farmaceutický prostředek, který ho obsahuje