TW442452B - Serine protease inhibitors having an alkynylamino side chain - Google Patents
Serine protease inhibitors having an alkynylamino side chain Download PDFInfo
- Publication number
- TW442452B TW442452B TW086102261A TW86102261A TW442452B TW 442452 B TW442452 B TW 442452B TW 086102261 A TW086102261 A TW 086102261A TW 86102261 A TW86102261 A TW 86102261A TW 442452 B TW442452 B TW 442452B
- Authority
- TW
- Taiwan
- Prior art keywords
- lysamine
- alkyl
- cns
- tert
- cha
- Prior art date
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- 125000006319 alkynyl amino group Chemical group 0.000 title claims description 5
- 239000003001 serine protease inhibitor Substances 0.000 title claims description 5
- -1 cyclic amino acid Chemical class 0.000 claims abstract description 137
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 45
- 150000002148 esters Chemical class 0.000 claims abstract description 20
- 108090000190 Thrombin Proteins 0.000 claims abstract description 18
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 18
- 229960004072 thrombin Drugs 0.000 claims abstract description 18
- 150000001413 amino acids Chemical class 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 17
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 12
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
- 150000008574 D-amino acids Chemical class 0.000 claims abstract description 7
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 273
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 120
- 239000000203 mixture Substances 0.000 claims description 85
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 82
- 238000011049 filling Methods 0.000 claims description 82
- 150000007857 hydrazones Chemical class 0.000 claims description 78
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 68
- 229910052796 boron Inorganic materials 0.000 claims description 62
- 229910052799 carbon Inorganic materials 0.000 claims description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 59
- 239000011541 reaction mixture Substances 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 45
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- 230000002079 cooperative effect Effects 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- 150000001336 alkenes Chemical class 0.000 claims description 17
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 17
- 235000001014 amino acid Nutrition 0.000 claims description 17
- 230000008878 coupling Effects 0.000 claims description 15
- 238000010168 coupling process Methods 0.000 claims description 15
- 238000005859 coupling reaction Methods 0.000 claims description 15
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 13
- 238000000746 purification Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 9
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 238000010511 deprotection reaction Methods 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 6
- 150000008064 anhydrides Chemical class 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 5
- 239000008363 phosphate buffer Substances 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 235000004279 alanine Nutrition 0.000 claims description 4
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical group OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 125000006267 biphenyl group Chemical group 0.000 claims description 3
- 239000001273 butane Substances 0.000 claims description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical compound OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 claims description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- HZVTZSFWPLLBRF-UHFFFAOYSA-N 4-chlorobut-2-ynylazanium;chloride Chemical compound Cl.NCC#CCCl HZVTZSFWPLLBRF-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000012937 correction Methods 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 229920001971 elastomer Polymers 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000004312 hexamethylene tetramine Substances 0.000 claims description 2
- 235000010299 hexamethylene tetramine Nutrition 0.000 claims description 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 238000007639 printing Methods 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000004576 sand Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229940098465 tincture Drugs 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 5
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 claims 4
- 101100335897 Caenorhabditis elegans gly-9 gene Proteins 0.000 claims 1
- 241000233855 Orchidaceae Species 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims 1
- 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 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 235000002020 sage Nutrition 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 6
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 5
- 230000007935 neutral effect Effects 0.000 abstract description 5
- 150000003839 salts Chemical class 0.000 abstract description 5
- 239000012634 fragment Substances 0.000 abstract description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract description 3
- 150000008575 L-amino acids Chemical group 0.000 abstract description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract description 3
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- 239000004473 Threonine Substances 0.000 abstract description 3
- 125000001931 aliphatic group Chemical group 0.000 abstract description 3
- 239000000651 prodrug Substances 0.000 abstract description 3
- 229940002612 prodrug Drugs 0.000 abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 abstract description 3
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 abstract description 2
- 125000004043 oxo group Chemical group O=* 0.000 abstract 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 2
- 230000014508 negative regulation of coagulation Effects 0.000 abstract 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 169
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- 239000000243 solution Substances 0.000 description 111
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- 235000011152 sodium sulphate Nutrition 0.000 description 32
- 239000012044 organic layer Substances 0.000 description 24
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07K5/0202—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-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- 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
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
-
- 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
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96200543 | 1996-03-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW442452B true TW442452B (en) | 2001-06-23 |
Family
ID=8223736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW086102261A TW442452B (en) | 1996-03-01 | 1997-02-25 | Serine protease inhibitors having an alkynylamino side chain |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6410684B1 (enExample) |
| EP (1) | EP0886647B1 (enExample) |
| JP (1) | JP2000506837A (enExample) |
| KR (1) | KR19990087415A (enExample) |
| CN (1) | CN1212704A (enExample) |
| AR (1) | AR006310A1 (enExample) |
| AT (1) | ATE221080T1 (enExample) |
| AU (1) | AU709330B2 (enExample) |
| BR (1) | BR9707808A (enExample) |
| CA (1) | CA2246246A1 (enExample) |
| CZ (1) | CZ277898A3 (enExample) |
| DE (1) | DE69714222T2 (enExample) |
| DK (1) | DK0886647T3 (enExample) |
| ES (1) | ES2180933T3 (enExample) |
| HU (1) | HUP9900390A3 (enExample) |
| IL (1) | IL120310A (enExample) |
| NO (1) | NO983991L (enExample) |
| NZ (1) | NZ331484A (enExample) |
| PL (1) | PL328875A1 (enExample) |
| PT (1) | PT886647E (enExample) |
| RU (1) | RU2178419C2 (enExample) |
| TR (1) | TR199801704T2 (enExample) |
| TW (1) | TW442452B (enExample) |
| WO (1) | WO1997031937A1 (enExample) |
| ZA (1) | ZA971667B (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2246256A1 (en) * | 1996-02-13 | 1997-08-21 | Akzo Nobel Nv | Serine protease inhibitors |
| US6214841B1 (en) | 1997-05-15 | 2001-04-10 | Eli Lilly And Company | Antithrombotic compound |
| TR200003159T2 (tr) | 1998-04-30 | 2001-09-21 | Agouron Pharmaceuticals,Inc. | Antipicornaviral bileşikler, hazırlanışları ve kullanımları |
| EP1105412A1 (en) * | 1998-08-17 | 2001-06-13 | Cortech, Inc. | Serine protease inhibitors comprising alpha-keto heterocycles |
| AU3731400A (en) | 1999-03-05 | 2000-09-21 | Trustees Of University Technology Corporation, The | Methods and compositions useful in inhibiting apoptosis |
| WO2000051623A2 (en) | 1999-03-05 | 2000-09-08 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide-induced clinical conditions |
| US6849605B1 (en) | 1999-03-05 | 2005-02-01 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of viral infections |
| JP2003506457A (ja) | 1999-08-04 | 2003-02-18 | アグロン・ファーマシュウティカルズ・インコーポレーテッド | 抗ピコルナウィルス化合物及び組成物、その医薬的使用、並びにその合成のための物質 |
| WO2001096297A2 (en) | 2000-06-14 | 2001-12-20 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis |
| SK742003A3 (en) | 2000-07-21 | 2003-06-03 | Schering Corp | Novel peptides as NS3-serine protease inhibitors of hepatitis C virus |
| US7012066B2 (en) | 2000-07-21 | 2006-03-14 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| US7244721B2 (en) | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| HUP0304058A2 (hu) | 2001-01-30 | 2004-04-28 | Bristol-Myers Squibb Company | Xa faktor szulfonamid-laktám inhibitorok és alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények |
| US7405210B2 (en) * | 2003-05-21 | 2008-07-29 | Osi Pharmaceuticals, Inc. | Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase |
| ATE483708T1 (de) | 2004-03-08 | 2010-10-15 | Prosidion Ltd | Pyrrolopyridin-2-carbonsäurehydrazide als inhibitoren von glykogenphosphorylase |
| ATE424821T1 (de) | 2004-12-02 | 2009-03-15 | Prosidion Ltd | Pyrrolopyridin-2-karbonsäureamide |
| CA2740197A1 (en) * | 2008-10-15 | 2010-04-22 | Danisco Us Inc. | Modified variant bowman birk protease inhibitors |
| JP7164521B2 (ja) | 2016-06-21 | 2022-11-01 | オリオン・オフサルモロジー・エルエルシー | 炭素環式プロリンアミド誘導体 |
| JP7179721B2 (ja) | 2016-06-21 | 2022-11-29 | オリオン・オフサルモロジー・エルエルシー | 複素環式プロリンアミド誘導体 |
| EP4178955A1 (en) | 2020-07-11 | 2023-05-17 | Pfizer Inc. | Antiviral heteroaryl ketone derivatives |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4556655A (en) * | 1984-09-24 | 1985-12-03 | Schering Corporation | Antihypertensive compounds having both diuretic and angiotensin converting enzyme inhibitory activity |
| CA2008116C (en) * | 1989-02-23 | 2001-11-20 | Thomas Weller | Glycine derivatives |
| ZW11290A1 (en) * | 1989-07-14 | 1990-10-31 | Smithkline Beecham Corp | Hemoregulatory peptides |
| EP0699074B1 (en) | 1993-04-30 | 2002-11-13 | Merck & Co. Inc. | Thrombin inhibitors |
| US5672582A (en) * | 1993-04-30 | 1997-09-30 | Merck & Co., Inc. | Thrombin inhibitors |
| SE9301916D0 (sv) * | 1993-06-03 | 1993-06-03 | Ab Astra | New peptides derivatives |
| ZA951618B (en) | 1994-03-04 | 1996-08-27 | Lilly Co Eli | Antithrombotic agents |
| ZA951617B (en) | 1994-03-04 | 1997-02-27 | Lilly Co Eli | Antithrombotic agents. |
| US5561146A (en) | 1994-06-10 | 1996-10-01 | Bristol-Myers Squibb Company | Modified guanidino and amidino thrombin inhibitors |
| JPH10503176A (ja) * | 1994-06-17 | 1998-03-24 | コーバス インターナショナル， インコーポレイテッド | 酵素インヒビターとしての３−アミノ−２−オキソ−１−ピペリジン酢酸誘導体 |
| JPH0820597A (ja) * | 1994-07-07 | 1996-01-23 | Meiji Seika Kaisha Ltd | トロンビン阻害作用を有する複素環カルボニル化合物 |
| CN1175259A (zh) | 1994-12-22 | 1998-03-04 | 生化制药有限公司 | 低分子量双环凝血酶抑制剂 |
-
1997
- 1997-02-25 IL IL12031097A patent/IL120310A/en not_active IP Right Cessation
- 1997-02-25 TW TW086102261A patent/TW442452B/zh not_active IP Right Cessation
- 1997-02-26 KR KR1019980706833A patent/KR19990087415A/ko not_active Ceased
- 1997-02-26 ZA ZA9701667A patent/ZA971667B/xx unknown
- 1997-02-26 JP JP9530600A patent/JP2000506837A/ja not_active Ceased
- 1997-02-26 CN CN97192682A patent/CN1212704A/zh active Pending
- 1997-02-26 CZ CZ982778A patent/CZ277898A3/cs unknown
- 1997-02-26 DK DK97905099T patent/DK0886647T3/da active
- 1997-02-26 CA CA002246246A patent/CA2246246A1/en not_active Abandoned
- 1997-02-26 WO PCT/EP1997/000938 patent/WO1997031937A1/en not_active Ceased
- 1997-02-26 ES ES97905099T patent/ES2180933T3/es not_active Expired - Lifetime
- 1997-02-26 PT PT97905099T patent/PT886647E/pt unknown
- 1997-02-26 TR TR1998/01704T patent/TR199801704T2/xx unknown
- 1997-02-26 AU AU18775/97A patent/AU709330B2/en not_active Ceased
- 1997-02-26 HU HU9900390A patent/HUP9900390A3/hu unknown
- 1997-02-26 RU RU98117949/04A patent/RU2178419C2/ru active
- 1997-02-26 EP EP97905099A patent/EP0886647B1/en not_active Expired - Lifetime
- 1997-02-26 US US09/142,110 patent/US6410684B1/en not_active Expired - Fee Related
- 1997-02-26 DE DE69714222T patent/DE69714222T2/de not_active Expired - Fee Related
- 1997-02-26 PL PL97328875A patent/PL328875A1/xx unknown
- 1997-02-26 AT AT97905099T patent/ATE221080T1/de not_active IP Right Cessation
- 1997-02-26 NZ NZ331484A patent/NZ331484A/xx unknown
- 1997-02-26 BR BR9707808A patent/BR9707808A/pt not_active Application Discontinuation
- 1997-03-03 AR ARP970100833A patent/AR006310A1/es unknown
-
1998
- 1998-08-31 NO NO983991A patent/NO983991L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ES2180933T3 (es) | 2003-02-16 |
| EP0886647A1 (en) | 1998-12-30 |
| KR19990087415A (ko) | 1999-12-27 |
| ATE221080T1 (de) | 2002-08-15 |
| IL120310A (en) | 2002-02-10 |
| HUP9900390A2 (hu) | 1999-06-28 |
| EP0886647B1 (en) | 2002-07-24 |
| HUP9900390A3 (en) | 2000-11-28 |
| CN1212704A (zh) | 1999-03-31 |
| ZA971667B (en) | 1997-09-10 |
| AR006310A1 (es) | 1999-08-25 |
| DE69714222T2 (de) | 2003-02-20 |
| AU709330B2 (en) | 1999-08-26 |
| JP2000506837A (ja) | 2000-06-06 |
| PL328875A1 (en) | 1999-03-01 |
| IL120310A0 (en) | 1997-06-10 |
| NZ331484A (en) | 2000-01-28 |
| DE69714222D1 (de) | 2002-08-29 |
| NO983991L (no) | 1998-10-30 |
| NO983991D0 (no) | 1998-08-31 |
| HK1021541A1 (en) | 2000-06-16 |
| CA2246246A1 (en) | 1997-09-04 |
| US6410684B1 (en) | 2002-06-25 |
| PT886647E (pt) | 2002-12-31 |
| TR199801704T2 (xx) | 1998-12-21 |
| AU1877597A (en) | 1997-09-16 |
| CZ277898A3 (cs) | 1999-06-16 |
| RU2178419C2 (ru) | 2002-01-20 |
| DK0886647T3 (da) | 2002-11-04 |
| BR9707808A (pt) | 1999-07-27 |
| WO1997031937A1 (en) | 1997-09-04 |
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Legal Events
| Date | Code | Title | Description |
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| GD4A | Issue of patent certificate for granted invention patent | ||
| MM4A | Annulment or lapse of patent due to non-payment of fees |