FI120494B - Tekijän Xa inhibiittoreita - Google Patents

Info

Publication number

FI120494B

FI120494B FI964317A FI964317A FI120494B FI 120494 B FI120494 B FI 120494B FI 964317 A FI964317 A FI 964317A FI 964317 A FI964317 A FI 964317A FI 120494 B FI120494 B FI 120494B

Authority

FI

Finland

Prior art keywords

chg

arg

paph

leu

pro

Prior art date

1994-04-26

Links

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• 229940123583 Factor Xa inhibitor Drugs 0.000 title description 12
• 150000001875 compounds Chemical class 0.000 claims abstract description 170
• 108010074860 Factor Xa Proteins 0.000 claims abstract description 70
• -1 respectively Substances 0.000 claims abstract description 66
• 230000000694 effects Effects 0.000 claims abstract description 59
• 150000001413 amino acids Chemical class 0.000 claims abstract description 42
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 29
• 125000001424 substituent group Chemical group 0.000 claims abstract description 27
• 230000005764 inhibitory process Effects 0.000 claims abstract description 21
• 210000004899 c-terminal region Anatomy 0.000 claims abstract description 16
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 14
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
• 125000002252 acyl group Chemical group 0.000 claims abstract description 7
• 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 38
• 125000006239 protecting group Chemical group 0.000 claims description 35
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
• 150000003839 salts Chemical class 0.000 claims description 23
• 125000003277 amino group Chemical group 0.000 claims description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
• 239000002253 acid Substances 0.000 claims description 13
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
• 150000002148 esters Chemical class 0.000 claims description 11
• 238000011282 treatment Methods 0.000 claims description 10
• 239000003146 anticoagulant agent Substances 0.000 claims description 9
• 229940127219 anticoagulant drug Drugs 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
• 210000003462 vein Anatomy 0.000 claims description 7
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 238000001356 surgical procedure Methods 0.000 claims description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
• 238000002360 preparation method Methods 0.000 claims description 5
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 239000001630 malic acid Substances 0.000 claims description 4
• 235000011090 malic acid Nutrition 0.000 claims description 4
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
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• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
• PJWCWGXAVIVXQC-STECZYCISA-N Tyr-Ile-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PJWCWGXAVIVXQC-STECZYCISA-N 0.000 claims description 2
• 125000005042 acyloxymethyl group Chemical group 0.000 claims description 2
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 2
• 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 claims description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 2
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 125000006351 ethylthiomethyl group Chemical group [H]C([H])([H])C([H])([H])SC([H])([H])* 0.000 claims description 2
• 229910001959 inorganic nitrate Inorganic materials 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
• 239000011976 maleic acid Substances 0.000 claims description 2
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 2
• 150000007522 mineralic acids Chemical class 0.000 claims description 2
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 150000007524 organic acids Chemical class 0.000 claims description 2
• 235000006408 oxalic acid Nutrition 0.000 claims description 2
• 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
• 229940095064 tartrate Drugs 0.000 claims description 2
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
• DZWHFXYOHKJJJA-IUCAKERBSA-N (2s)-1-[(2s)-2-amino-4-methylpentanoyl]pyrrolidine-2-carboxamide Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(N)=O DZWHFXYOHKJJJA-IUCAKERBSA-N 0.000 claims 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 2
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims 1
• 125000005916 2-methylpentyl group Chemical group 0.000 claims 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
• 125000004848 alkoxyethyl group Chemical group 0.000 claims 1
• 238000002399 angioplasty Methods 0.000 claims 1
• 230000036770 blood supply Effects 0.000 claims 1
• 150000001735 carboxylic acids Chemical group 0.000 claims 1
• 235000015165 citric acid Nutrition 0.000 claims 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims 1
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• 229940049920 malate Drugs 0.000 claims 1
• 210000000056 organ Anatomy 0.000 claims 1
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• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
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• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 abstract description 17
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