HRP20030252A2 - Aminopyridinyl-, aminoguanidinyl- and alkoxiguanidinyl- substituted phenyl acetamides as protease inhibitors - Google Patents
Aminopyridinyl-, aminoguanidinyl- and alkoxiguanidinyl- substituted phenyl acetamides as protease inhibitors Download PDFInfo
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- HRP20030252A2 HRP20030252A2 HR20030252A HRP20030252A HRP20030252A2 HR P20030252 A2 HRP20030252 A2 HR P20030252A2 HR 20030252 A HR20030252 A HR 20030252A HR P20030252 A HRP20030252 A HR P20030252A HR P20030252 A2 HRP20030252 A2 HR P20030252A2
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- Prior art keywords
- alkyl
- amino
- aryl
- mmol
- methyl
- Prior art date
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- -1 Aminopyridinyl- Chemical group 0.000 title claims description 68
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical class CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 title abstract description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 254
- 239000000203 mixture Substances 0.000 claims abstract description 85
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 33
- 108090000190 Thrombin Proteins 0.000 claims abstract description 27
- 229960004072 thrombin Drugs 0.000 claims abstract description 23
- 210000004369 blood Anatomy 0.000 claims abstract description 20
- 239000008280 blood Substances 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 108091005804 Peptidases Proteins 0.000 claims abstract description 14
- 102000035195 Peptidases Human genes 0.000 claims abstract description 14
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 10
- 108010074860 Factor Xa Proteins 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 229940127219 anticoagulant drug Drugs 0.000 claims abstract description 6
- 230000017531 blood circulation Effects 0.000 claims abstract description 5
- 238000000502 dialysis Methods 0.000 claims abstract description 5
- 238000003860 storage Methods 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
- 241000124008 Mammalia Species 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 19
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 108090000790 Enzymes Proteins 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 13
- 229940088598 enzyme Drugs 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 108090000317 Chymotrypsin Proteins 0.000 claims description 12
- 229960002376 chymotrypsin Drugs 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 108090000631 Trypsin Proteins 0.000 claims description 11
- 102000004142 Trypsin Human genes 0.000 claims description 11
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 11
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 239000012588 trypsin Substances 0.000 claims description 11
- 229960001322 trypsin Drugs 0.000 claims description 11
- 229960005356 urokinase Drugs 0.000 claims description 11
- 102100033174 Neutrophil elastase Human genes 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 claims description 9
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
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- 125000005914 C6-C14 aryloxy group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
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- 230000004054 inflammatory process Effects 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
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- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
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- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- UPQFJBYLYJVPDV-UHFFFAOYSA-N 2-[3-(benzylsulfonylamino)phenyl]-n-[2-(diaminomethylideneamino)oxyethyl]acetamide Chemical compound NC(N)=NOCCNC(=O)CC1=CC=CC(NS(=O)(=O)CC=2C=CC=CC=2)=C1 UPQFJBYLYJVPDV-UHFFFAOYSA-N 0.000 claims description 3
- VMXOHYQKOLDOBL-UHFFFAOYSA-N 2-[5-(benzylsulfonylamino)-2-methylphenyl]-n-[2-(diaminomethylideneamino)oxyethyl]acetamide Chemical compound C1=C(CC(=O)NCCONC(N)=N)C(C)=CC=C1NS(=O)(=O)CC1=CC=CC=C1 VMXOHYQKOLDOBL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 3
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 239000003527 fibrinolytic agent Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- PTZXMCCDZKPNFR-UHFFFAOYSA-N n-[(6-amino-2-methylpyridin-3-yl)methyl]-2-[6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl]acetamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)CC1=C(Cl)C=CC(NCC(F)(F)C=2C=CC=CC=2)=C1F PTZXMCCDZKPNFR-UHFFFAOYSA-N 0.000 claims description 3
- DZEJHPMTDNDECN-UHFFFAOYSA-N n-[2-({[amino(imino)methyl]amino}oxy)ethyl]-2-{6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl}acetamide Chemical compound NC(=N)NOCCNC(=O)CC1=C(Cl)C=CC(NCC(F)(F)C=2C=CC=CC=2)=C1F DZEJHPMTDNDECN-UHFFFAOYSA-N 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 229960000103 thrombolytic agent Drugs 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 claims description 2
- YAVLSJOHHRYFQV-UHFFFAOYSA-N 2-[5-(benzylsulfonylamino)-2-chlorophenyl]-n-[2-(diaminomethylideneamino)oxyethyl]acetamide Chemical compound C1=C(Cl)C(CC(=O)NCCONC(=N)N)=CC(NS(=O)(=O)CC=2C=CC=CC=2)=C1 YAVLSJOHHRYFQV-UHFFFAOYSA-N 0.000 claims description 2
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- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
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- LSSPSEWHOYRDFX-UHFFFAOYSA-N 2-[6-chloro-3-[[2,2-difluoro-2-(4-fluoronaphthalen-1-yl)ethyl]amino]-2-fluorophenyl]-n-[2-(diaminomethylideneamino)oxyethyl]acetamide Chemical compound NC(=N)NOCCNC(=O)CC1=C(Cl)C=CC(NCC(F)(F)C=2C3=CC=CC=C3C(F)=CC=2)=C1F LSSPSEWHOYRDFX-UHFFFAOYSA-N 0.000 claims 1
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- LFSUMGISHQANRR-UHFFFAOYSA-N n-[(6-amino-2-methylpyridin-3-yl)methyl]-2-[2-hydroxy-6-methyl-3-[(3-methylphenyl)sulfonylamino]phenyl]acetamide Chemical compound CC1=CC=CC(S(=O)(=O)NC=2C(=C(CC(=O)NCC=3C(=NC(N)=CC=3)C)C(C)=CC=2)O)=C1 LFSUMGISHQANRR-UHFFFAOYSA-N 0.000 claims 1
- GPJIYMVTTVFTEO-UHFFFAOYSA-N n-[(6-amino-2-methylpyridin-3-yl)methyl]-2-[6-chloro-3-[[2,2-difluoro-2-(4-fluoronaphthalen-1-yl)ethyl]amino]-2-fluorophenyl]acetamide Chemical compound CC1=NC(N)=CC=C1CNC(=O)CC1=C(Cl)C=CC(NCC(F)(F)C=2C3=CC=CC=C3C(F)=CC=2)=C1F GPJIYMVTTVFTEO-UHFFFAOYSA-N 0.000 claims 1
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- HKZDMSDQWBPUPK-UHFFFAOYSA-N tert-butyl n-[2-[[2-[5-(benzylsulfonylamino)-2-methylphenyl]acetyl]amino]ethoxy]-n-[n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate Chemical compound C1=C(CC(=O)NCCON(C(=O)OC(C)(C)C)C(N)=NC(=O)OC(C)(C)C)C(C)=CC=C1NS(=O)(=O)CC1=CC=CC=C1 HKZDMSDQWBPUPK-UHFFFAOYSA-N 0.000 description 1
- PENVOJCQDOJXST-UHFFFAOYSA-N tert-butyl n-[2-[[2-[6-methyl-3-[(3-methylphenyl)sulfonylamino]-2-phenylmethoxyphenyl]acetyl]amino]ethoxy]-n-[n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate Chemical compound CC1=CC=CC(S(=O)(=O)NC=2C(=C(CC(=O)NCCON(C(=O)OC(C)(C)C)C(N)=NC(=O)OC(C)(C)C)C(C)=CC=2)OCC=2C=CC=CC=2)=C1 PENVOJCQDOJXST-UHFFFAOYSA-N 0.000 description 1
- YRNOEWNXOPEOAB-UHFFFAOYSA-N tert-butyl n-[5-[[[2-[6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl]acetyl]amino]methyl]-6-methylpyridin-2-yl]carbamate Chemical compound CC1=NC(NC(=O)OC(C)(C)C)=CC=C1CNC(=O)CC1=C(Cl)C=CC(NCC(F)(F)C=2C=CC=CC=2)=C1F YRNOEWNXOPEOAB-UHFFFAOYSA-N 0.000 description 1
- LEQABXYTMOJPSP-UHFFFAOYSA-N tert-butyl n-[[2-[[2-[6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl]acetyl]amino]ethoxyamino]-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(=NC(=O)OC(C)(C)C)NOCCNC(=O)CC1=C(Cl)C=CC(NCC(F)(F)C=2C=CC=CC=2)=C1F LEQABXYTMOJPSP-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 201000005665 thrombophilia Diseases 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- AWSFICBXMUKWSK-UHFFFAOYSA-N ytterbium(3+) Chemical compound [Yb+3] AWSFICBXMUKWSK-UHFFFAOYSA-N 0.000 description 1
- 150000004799 α-ketoamides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US23813200P | 2000-10-06 | 2000-10-06 | |
PCT/US2001/031249 WO2002028825A2 (en) | 2000-10-06 | 2001-10-05 | Aminopyridinyl-, aminoguanidinyl- and alkoxyguanidinyl- substituted phenyl acetamides as protease inhibitors |
Publications (1)
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HRP20030252A2 true HRP20030252A2 (en) | 2005-10-31 |
Family
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HR20030252A HRP20030252A2 (en) | 2000-10-06 | 2003-04-03 | Aminopyridinyl-, aminoguanidinyl- and alkoxiguanidinyl- substituted phenyl acetamides as protease inhibitors |
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US (3) | US6521663B2 (no) |
EP (1) | EP1324981B1 (no) |
JP (1) | JP4256160B2 (no) |
KR (1) | KR20030045103A (no) |
CN (1) | CN1315803C (no) |
AT (1) | ATE337299T1 (no) |
AU (2) | AU2002211464B2 (no) |
BR (1) | BR0114263A (no) |
CA (1) | CA2423883A1 (no) |
CY (1) | CY1106243T1 (no) |
DE (1) | DE60122546T2 (no) |
DK (1) | DK1324981T3 (no) |
ES (1) | ES2269474T3 (no) |
HK (1) | HK1058032A1 (no) |
HR (1) | HRP20030252A2 (no) |
HU (1) | HUP0303149A3 (no) |
IL (1) | IL155160A0 (no) |
MX (1) | MXPA03002998A (no) |
NO (1) | NO20031390L (no) |
NZ (1) | NZ525438A (no) |
PL (1) | PL361185A1 (no) |
PT (1) | PT1324981E (no) |
RU (1) | RU2003113205A (no) |
UA (1) | UA75093C2 (no) |
WO (1) | WO2002028825A2 (no) |
ZA (1) | ZA200303091B (no) |
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UA75093C2 (en) * | 2000-10-06 | 2006-03-15 | Dimensional Pharm Inc | Aminopyridinyl-,aminoguanidinyl-, and alkoxyguanidinesubstituted phenylsubstituted phenylacetamides as protease inhibitors |
US6610701B2 (en) * | 2001-02-09 | 2003-08-26 | Merck & Co., Inc. | Thrombin inhibitors |
WO2003043624A1 (en) * | 2001-11-16 | 2003-05-30 | Bristol-Myers Squibb Company | Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein |
US7759513B2 (en) * | 2003-02-21 | 2010-07-20 | Nigu Chemie Gmbh | Photolabile protective groups for improved processes to prepare oligonucleotide arrays |
US7550474B2 (en) * | 2003-04-10 | 2009-06-23 | Johnson & Johnson Pharmaceuticals Research & Development, L.L.C. | Substituted phenyl acetamides and their use as protease inhibitors |
JP2007525460A (ja) | 2003-04-25 | 2007-09-06 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | c−fmsキナーゼ阻害剤 |
US7427683B2 (en) * | 2003-04-25 | 2008-09-23 | Ortho-Mcneil Pharmaceutical, Inc. | c-fms kinase inhibitors |
US7790724B2 (en) | 2003-04-25 | 2010-09-07 | Janssen Pharmaceutica N.V. | c-fms kinase inhibitors |
US7914705B2 (en) * | 2005-01-10 | 2011-03-29 | Robert Eliot Sisson | Flowable electrical conductive liquid |
HU0500126D0 (en) * | 2005-01-26 | 2005-04-28 | Sanofi Aventis | New compounds and process for their preparation |
EP1893601A1 (en) * | 2005-06-17 | 2008-03-05 | AstraZeneca AB | Thrombin inhibiting 2-oxo-1, 2, 5, 6-tetrahydropyridine derivatives |
WO2007120729A2 (en) * | 2006-04-12 | 2007-10-25 | Merck & Co., Inc. | Pyridyl amide t-type calcium channel antagonists |
RU2353619C2 (ru) * | 2007-06-28 | 2009-04-27 | Общество С Ограниченной Ответственностью "Бионика" | Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции |
RU2354647C2 (ru) * | 2007-06-28 | 2009-05-10 | Общество С Ограниченной Ответственностью "Бионика" | Новые соединения, обладающие функцией ингибиторов тромбина, и фармацевтические композиции на их основе |
CN101665465B (zh) * | 2007-09-19 | 2011-09-07 | 复旦大学 | 一种含胍基杂环化合物凝血酶抑制剂及其制备方法 |
AU2008317353B2 (en) * | 2007-10-24 | 2014-08-07 | Merck Sharp & Dohme Llc | Heterocycle phenyl amide T-type calcium channel antagonists |
CA2818522C (en) * | 2010-12-02 | 2016-05-17 | Becton, Dickinson And Company | Blood collection devices containing blood stabilization agent |
RU2019121905A (ru) | 2010-12-31 | 2019-09-03 | Астразенека Юкей Лимитед | Ингибиторы аргиназы и способы их применения |
AU2012255137A1 (en) | 2011-05-17 | 2013-12-12 | The Brigham And Women's Hospital, Inc. | Improved platelet storage using a sialidase inhibitor |
US9788539B2 (en) | 2011-05-17 | 2017-10-17 | Velico Medical, Inc. | Platelet protection solution having beta-galactosidase and sialidase inhibitors |
EP2903430A1 (en) | 2012-10-05 | 2015-08-12 | Velico Medical, Inc. | Platelet additive solution having a beta-galactosidase inhibitor |
RU2524647C1 (ru) * | 2012-12-25 | 2014-07-27 | Государственное Бюджетное Учреждение Санкт-Петербургский Научно-Исследовательский Институт Скорой Помощи Им. И.И. Джанелидзе" | Способ лечения синдрома эндогенной интоксикации, обусловленного гиперпротеолизом |
WO2014120886A1 (en) | 2013-01-30 | 2014-08-07 | Velico Medical, Inc. | Platelet additive solution having a self-assembling hydrogel-forming peptide |
WO2015143376A1 (en) * | 2014-03-21 | 2015-09-24 | Nivalis Therapeutics, Inc. | Novel compounds for the treatment of cystic fibrosis |
PL3325482T3 (pl) | 2015-07-21 | 2021-01-11 | Immunogen, Inc. | Sposoby otrzymywania cytotoksycznych pochodnych benzodiazepiny |
WO2018216012A1 (en) * | 2017-05-24 | 2018-11-29 | Ramot At Tel-Aviv University Ltd. | Chemiluminescent probes for imaging/detection of proteases |
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