BG106636A - Съединения за лечението на исхемия - Google Patents

Съединения за лечението на исхемия Download PDF

Info

Publication number: BG106636A
Authority: BG; Bulgaria
Prior art keywords: alkyl; compound; pyrazole; guanidine; mono
Prior art date: 1999-09-30

Application number

BG106636A

Other languages

Bulgarian (bg)

English (en)

Inventor

Hiroko Masamune

Michael Deninno

Robert Scott

Original Assignee

Pfizer Products Inc.

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.)

1999-09-30

Filing date

2002-04-23

Publication date

2003-01-31

2002-04-23 Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.

2003-01-31 Publication of BG106636A publication Critical patent/BG106636A/bg

Links

208000028867 ischemia Diseases 0.000 title claims abstract description 28
239000000203 mixture Substances 0.000 title claims description 87
238000011282 treatment Methods 0.000 title claims description 17
150000001875 compounds Chemical class 0.000 claims abstract description 461
238000000034 method Methods 0.000 claims abstract description 103
206010021143 Hypoxia Diseases 0.000 claims abstract description 30
230000000451 tissue damage Effects 0.000 claims abstract description 24
231100000827 tissue damage Toxicity 0.000 claims abstract description 24
230000007954 hypoxia Effects 0.000 claims abstract description 16
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
-1 oxy, methylene Chemical group 0.000 claims description 310
229910052757 nitrogen Inorganic materials 0.000 claims description 135
150000003839 salts Chemical class 0.000 claims description 107
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 97
229920006395 saturated elastomer Polymers 0.000 claims description 91
239000000651 prodrug Substances 0.000 claims description 89
229940002612 prodrug Drugs 0.000 claims description 89
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 77
125000000217 alkyl group Chemical group 0.000 claims description 62
229910052760 oxygen Inorganic materials 0.000 claims description 61
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 58
239000001301 oxygen Substances 0.000 claims description 58
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 55
229910052736 halogen Inorganic materials 0.000 claims description 53
239000003112 inhibitor Substances 0.000 claims description 53
229910052717 sulfur Inorganic materials 0.000 claims description 50
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 49
239000011593 sulfur Chemical group 0.000 claims description 49
125000005842 heteroatom Chemical group 0.000 claims description 48
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 48
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 47
125000003545 alkoxy group Chemical group 0.000 claims description 47
150000002367 halogens Chemical class 0.000 claims description 45
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 44
239000002253 acid Substances 0.000 claims description 41
239000000460 chlorine Substances 0.000 claims description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
229910052801 chlorine Inorganic materials 0.000 claims description 33
241000124008 Mammalia Species 0.000 claims description 32
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 32
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 30
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 30
125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
125000003386 piperidinyl group Chemical group 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
125000004093 cyano group Chemical group *C#N 0.000 claims description 26
125000003226 pyrazolyl group Chemical group 0.000 claims description 26
125000003282 alkyl amino group Chemical group 0.000 claims description 25
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 23
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 22
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 22
125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 22
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 22
125000002757 morpholinyl group Chemical group 0.000 claims description 22
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 22
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 21
125000002619 bicyclic group Chemical group 0.000 claims description 21
239000003937 drug carrier Substances 0.000 claims description 20
125000004043 oxo group Chemical group O=* 0.000 claims description 19
230000000747 cardiac effect Effects 0.000 claims description 18
125000004076 pyridyl group Chemical group 0.000 claims description 18
239000002552 dosage form Substances 0.000 claims description 17
125000000842 isoxazolyl group Chemical group 0.000 claims description 17
125000002971 oxazolyl group Chemical group 0.000 claims description 17
125000000335 thiazolyl group Chemical group 0.000 claims description 17
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 16
125000000000 cycloalkoxy group Chemical group 0.000 claims description 16
125000002541 furyl group Chemical group 0.000 claims description 16
125000001786 isothiazolyl group Chemical group 0.000 claims description 16
125000004193 piperazinyl group Chemical group 0.000 claims description 16
125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 15
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 15
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 15
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 15
238000001356 surgical procedure Methods 0.000 claims description 15
230000001225 therapeutic effect Effects 0.000 claims description 15
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 15
239000012190 activator Substances 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 14
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 13
239000002126 C01EB10 - Adenosine Substances 0.000 claims description 13
229960005305 adenosine Drugs 0.000 claims description 13
239000003085 diluting agent Substances 0.000 claims description 13
125000000168 pyrrolyl group Chemical group 0.000 claims description 13
239000003981 vehicle Substances 0.000 claims description 13
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
239000002327 cardiovascular agent Substances 0.000 claims description 12
229940125692 cardiovascular agent Drugs 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
229910052731 fluorine Inorganic materials 0.000 claims description 12
239000011737 fluorine Substances 0.000 claims description 12
125000003373 pyrazinyl group Chemical group 0.000 claims description 12
239000011734 sodium Substances 0.000 claims description 11
125000001544 thienyl group Chemical group 0.000 claims description 11
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 10
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 claims description 10
108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 claims description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 9
125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 8
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 8
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 8
125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 8
125000002393 azetidinyl group Chemical group 0.000 claims description 8
239000011575 calcium Substances 0.000 claims description 8
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
239000003379 purinergic P1 receptor agonist Substances 0.000 claims description 7
102000048186 Endothelin-converting enzyme 1 Human genes 0.000 claims description 6
108030001679 Endothelin-converting enzyme 1 Proteins 0.000 claims description 6
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
230000002490 cerebral effect Effects 0.000 claims description 6
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
230000000968 intestinal effect Effects 0.000 claims description 6
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 5
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
230000036961 partial effect Effects 0.000 claims description 5
239000001103 potassium chloride Substances 0.000 claims description 5
235000011164 potassium chloride Nutrition 0.000 claims description 5
229960002816 potassium chloride Drugs 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
239000005541 ACE inhibitor Substances 0.000 claims description 4
102000005862 Angiotensin II Human genes 0.000 claims description 4
101800000733 Angiotensin-2 Proteins 0.000 claims description 4
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
229940123208 Biguanide Drugs 0.000 claims description 4
102000012751 Pyruvate Dehydrogenase Complex Human genes 0.000 claims description 4
108010090051 Pyruvate Dehydrogenase Complex Proteins 0.000 claims description 4
229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
229950006323 angiotensin ii Drugs 0.000 claims description 4
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 4
239000002876 beta blocker Substances 0.000 claims description 4
229940097320 beta blocking agent Drugs 0.000 claims description 4
150000004283 biguanides Chemical class 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims description 4
229960002768 dipyridamole Drugs 0.000 claims description 4
239000002934 diuretic Substances 0.000 claims description 4
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 4
229930182470 glycoside Natural products 0.000 claims description 4
150000002338 glycosides Chemical class 0.000 claims description 4
230000002440 hepatic effect Effects 0.000 claims description 4
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 4
229960003105 metformin Drugs 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
239000008024 pharmaceutical diluent Substances 0.000 claims description 4
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 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 3
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 3
ZJQFENWMXOATQM-UHFFFAOYSA-N 1-(2-chloro-4-methylsulfonylphenyl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound ClC1=CC(S(=O)(=O)C)=CC=C1N1C(C2CC2)=C(C(=O)NC(N)=N)C=N1 ZJQFENWMXOATQM-UHFFFAOYSA-N 0.000 claims description 3
DZXZXYVVTHIODU-UHFFFAOYSA-N 1-(2-chloro-5-methoxyphenyl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound COC1=CC=C(Cl)C(N2C(=C(C(=O)NC(N)=N)C=N2)C2CC2)=C1 DZXZXYVVTHIODU-UHFFFAOYSA-N 0.000 claims description 3
KTMBRLHJWLVWJN-UHFFFAOYSA-N 1-(2-chloro-5-methylsulfonylphenyl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound CS(=O)(=O)C1=CC=C(Cl)C(N2C(=C(C(=O)NC(N)=N)C=N2)C2CC2)=C1 KTMBRLHJWLVWJN-UHFFFAOYSA-N 0.000 claims description 3
BINSRSZWKJTYQD-UHFFFAOYSA-N 1-(2-chloro-5-sulfamoylphenyl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=C(C=2)S(N)(=O)=O)Cl)C=1C1CC1 BINSRSZWKJTYQD-UHFFFAOYSA-N 0.000 claims description 3
IRQHMLZBZSIPCM-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-(diaminomethylidene)-5-methylpyrazole-4-carboxamide Chemical compound CC1=C(C(=O)NC(N)=N)C=NN1C1=CC=CC=C1Cl IRQHMLZBZSIPCM-UHFFFAOYSA-N 0.000 claims description 3
FQKVIFIBQBRQEY-UHFFFAOYSA-N 1-(2h-benzotriazol-5-yl)-n-(diaminomethylidene)-5-ethylpyrazole-4-carboxamide Chemical compound CCC1=C(C(=O)NC(N)=N)C=NN1C1=CC=C(NN=N2)C2=C1 FQKVIFIBQBRQEY-UHFFFAOYSA-N 0.000 claims description 3
AWDVOIVMYCOEGE-UHFFFAOYSA-N 1-(3-chloro-2h-indazol-5-yl)-n-(diaminomethylidene)-5-ethylpyrazole-4-carboxamide Chemical compound CCC1=C(C(=O)NC(N)=N)C=NN1C1=CC=C(NN=C2Cl)C2=C1 AWDVOIVMYCOEGE-UHFFFAOYSA-N 0.000 claims description 3
XRJAKWJGDAHTMH-UHFFFAOYSA-N 1-(5-carbamoyl-2-chlorophenyl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=C(C=2)C(N)=O)Cl)C=1C1CC1 XRJAKWJGDAHTMH-UHFFFAOYSA-N 0.000 claims description 3
JMXVATATTWHXNZ-UHFFFAOYSA-N 1-(6-chloroquinolin-5-yl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2Cl)C=1C1CC1 JMXVATATTWHXNZ-UHFFFAOYSA-N 0.000 claims description 3
HQMDTNPGJUCYMV-UHFFFAOYSA-N 1-[2-chloro-4-(methylsulfamoyl)phenyl]-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound ClC1=CC(S(=O)(=O)NC)=CC=C1N1C(C2CC2)=C(C(=O)NC(N)=N)C=N1 HQMDTNPGJUCYMV-UHFFFAOYSA-N 0.000 claims description 3
RQGPHRVFYWHLQW-UHFFFAOYSA-N 1-[2-chloro-5-(dimethylsulfamoyl)phenyl]-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C(N2C(=C(C(=O)NC(N)=N)C=N2)C2CC2)=C1 RQGPHRVFYWHLQW-UHFFFAOYSA-N 0.000 claims description 3
QDEGSGKUDYTYJV-UHFFFAOYSA-N 1-[4-chloro-2-(trifluoromethyl)phenyl]-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC(Cl)=CC=2)C(F)(F)F)C=1C1CC1 QDEGSGKUDYTYJV-UHFFFAOYSA-N 0.000 claims description 3
NGHMKLRBKIPQRY-UHFFFAOYSA-N 5-butyl-n-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide Chemical compound CCCCC1=C(C(=O)NC(N)=N)C=NN1C1=CC=CC2=NC=CC=C12 NGHMKLRBKIPQRY-UHFFFAOYSA-N 0.000 claims description 3
ZWKXLNHOSNQZLS-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-(1h-indazol-7-yl)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C=3NN=CC=3C=CC=2)C=1C1CC1 ZWKXLNHOSNQZLS-UHFFFAOYSA-N 0.000 claims description 3
PTVBGVLITQPZTD-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-(2,6-dichlorophenyl)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=CC=2Cl)Cl)C=1C1CC1 PTVBGVLITQPZTD-UHFFFAOYSA-N 0.000 claims description 3
HMCQXPJNWHQROJ-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-(2-fluorophenyl)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=CC=2)F)C=1C1CC1 HMCQXPJNWHQROJ-UHFFFAOYSA-N 0.000 claims description 3
LFXTUZDNFLZCNR-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=CC=2)C(F)(F)F)C=1C1CC1 LFXTUZDNFLZCNR-UHFFFAOYSA-N 0.000 claims description 3
SSQWWXQZCXSTHE-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-[2-fluoro-6-(trifluoromethyl)phenyl]pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=CC=2F)C(F)(F)F)C=1C1CC1 SSQWWXQZCXSTHE-UHFFFAOYSA-N 0.000 claims description 3
DJEYTYIFAGYQSJ-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-[4-fluoro-2-(trifluoromethyl)phenyl]pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC(F)=CC=2)C(F)(F)F)C=1C1CC1 DJEYTYIFAGYQSJ-UHFFFAOYSA-N 0.000 claims description 3
NQDZNLKMTLAUGA-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-quinolin-4-ylpyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C3=CC=CC=C3N=CC=2)C=1C1CC1 NQDZNLKMTLAUGA-UHFFFAOYSA-N 0.000 claims description 3
GDXBRVCQGGKXJY-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide Chemical compound NC(N)=NC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 GDXBRVCQGGKXJY-UHFFFAOYSA-N 0.000 claims description 3
LFOAPSAWYUILCY-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-quinolin-8-ylpyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C3=NC=CC=C3C=CC=2)C=1C1CC1 LFOAPSAWYUILCY-UHFFFAOYSA-N 0.000 claims description 3
102000002045 Endothelin Human genes 0.000 claims description 3
108050009340 Endothelin Proteins 0.000 claims description 3
229940121931 Gluconeogenesis inhibitor Drugs 0.000 claims description 3
102000004877 Insulin Human genes 0.000 claims description 3
108090001061 Insulin Proteins 0.000 claims description 3
102000003960 Ligases Human genes 0.000 claims description 3
108090000364 Ligases Proteins 0.000 claims description 3
XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 claims description 3
108091000080 Phosphotransferase Proteins 0.000 claims description 3
108091026813 Poly(ADPribose) Proteins 0.000 claims description 3
229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 3
239000005557 antagonist Substances 0.000 claims description 3
230000002424 anti-apoptotic effect Effects 0.000 claims description 3
229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 claims description 3
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ZVGYIXBHESYHCE-UHFFFAOYSA-N spiro[6H-quinoline-5,4'-imidazolidine] Chemical compound N1=CC=CC2=C1C=CCC21NCNC1 ZVGYIXBHESYHCE-UHFFFAOYSA-N 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 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
BSADMUGZPVDELG-UHFFFAOYSA-N tert-butyl n-[5-(6-chloropurin-9-yl)-4-hydroxy-2-(methylcarbamoyl)oxolan-3-yl]carbamate Chemical compound OC1C(NC(=O)OC(C)(C)C)C(C(=O)NC)OC1N1C2=NC=NC(Cl)=C2N=C1 BSADMUGZPVDELG-UHFFFAOYSA-N 0.000 description 1
DKPKBWTVXUZRJC-UHFFFAOYSA-N tert-butyl n-[5-[6-[[5-chloro-2-[(3-methyl-1,2-oxazol-5-yl)methoxy]phenyl]methylamino]purin-9-yl]-4-hydroxy-2-(methylcarbamoyl)oxolan-3-yl]carbamate Chemical compound OC1C(NC(=O)OC(C)(C)C)C(C(=O)NC)OC1N1C2=NC=NC(NCC=3C(=CC=C(Cl)C=3)OCC=3ON=C(C)C=3)=C2N=C1 DKPKBWTVXUZRJC-UHFFFAOYSA-N 0.000 description 1
OPSAHHBIACQABD-UHFFFAOYSA-N tert-butyl n-[[5-chloro-2-(4,5-dihydro-1h-imidazol-2-ylmethoxy)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC(Cl)=CC=C1OCC1=NCCN1 OPSAHHBIACQABD-UHFFFAOYSA-N 0.000 description 1
XMZFHDMOAXSFDS-UHFFFAOYSA-N tert-butyl n-[[5-chloro-2-(cyanomethoxy)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC(Cl)=CC=C1OCC#N XMZFHDMOAXSFDS-UHFFFAOYSA-N 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000003777 thiepinyl group Chemical group 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
238000003354 tissue distribution assay Methods 0.000 description 1
LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
229960003069 tolrestat Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
239000006211 transdermal dosage form Substances 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000011277 treatment modality Methods 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
238000009423 ventilation Methods 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
229960001722 verapamil Drugs 0.000 description 1
MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 1
229960000537 xipamide Drugs 0.000 description 1
SXONDGSPUVNZLO-UHFFFAOYSA-N zenarestat Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SXONDGSPUVNZLO-UHFFFAOYSA-N 0.000 description 1
229950006343 zenarestat Drugs 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
229950005346 zopolrestat Drugs 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- 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
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Physical Education & Sports Medicine (AREA)
Urology & Nephrology (AREA)
Neurosurgery (AREA)
Genetics & Genomics (AREA)
Ophthalmology & Optometry (AREA)
Orthopedic Medicine & Surgery (AREA)
Vascular Medicine (AREA)
Gastroenterology & Hepatology (AREA)
Pulmonology (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
Biomedical Technology (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Saccharide Compounds (AREA)
Hydrogenated Pyridines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

BG106636A 1999-09-30 2002-04-23 Съединения за лечението на исхемия BG106636A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US15682899P	1999-09-30	1999-09-30
PCT/IB2000/001353 WO2001023399A1 (fr)	1999-09-30	2000-09-22	Composes destines au traitement d'ischemie

Publications (1)

Publication Number	Publication Date
BG106636A true BG106636A (bg)	2003-01-31

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ID=22561263

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Application Number	Title	Priority Date	Filing Date
BG106636A BG106636A (bg)	1999-09-30	2002-04-23	Съединения за лечението на исхемия

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EP (1)	EP1216257B1 (fr)
JP (1)	JP2003510331A (fr)
KR (1)	KR100481605B1 (fr)
CN (1)	CN1374967A (fr)
AP (1)	AP2002002458A0 (fr)
AR (1)	AR029887A1 (fr)
AT (1)	ATE312117T1 (fr)
AU (1)	AU778185B2 (fr)
BG (1)	BG106636A (fr)
BR (1)	BR0014384A (fr)
CA (1)	CA2386079A1 (fr)
CO (1)	CO5180581A1 (fr)
CR (1)	CR6592A (fr)
CZ (1)	CZ20021020A3 (fr)
DE (1)	DE60024649D1 (fr)
EA (1)	EA005422B1 (fr)
EC (1)	ECSP003682A (fr)
EE (1)	EE200200172A (fr)
GE (1)	GEP20043241B (fr)
GT (1)	GT200000161A (fr)
HK (1)	HK1049011A1 (fr)
HR (1)	HRP20020253A2 (fr)
HU (1)	HUP0202807A3 (fr)
IL (1)	IL148222A0 (fr)
IS (1)	IS6286A (fr)
MA (1)	MA26822A1 (fr)
MX (1)	MXPA02003308A (fr)
MY (1)	MY133996A (fr)
NO (1)	NO20021474L (fr)
NZ (1)	NZ517177A (fr)
OA (1)	OA12021A (fr)
PA (1)	PA8503301A1 (fr)
PE (1)	PE20010696A1 (fr)
PL (1)	PL357371A1 (fr)
SK (1)	SK4182002A3 (fr)
TN (1)	TNSN00191A1 (fr)
TR (1)	TR200200843T2 (fr)
UA (1)	UA73525C2 (fr)
WO (1)	WO2001023399A1 (fr)
YU (1)	YU23102A (fr)
ZA (1)	ZA200202461B (fr)

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GB0401334D0 (en)	2004-01-21	2004-02-25	Novartis Ag	Organic compounds
MXPA06010916A (es)	2004-03-24	2007-07-25	Fasgen Llc	Novedoso metodo de proteccion neurologica mediante inhibicion farmacologica de proteina quinasa activada por amp.
NZ551077A (en)	2004-05-07	2009-05-31	Janssen Pharmaceutica Nv	Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors
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MX2010007604A (es)	2008-01-11	2010-08-02	Novartis Ag	Pirimidinas como inhibidores de cinasa.
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WO2011010306A1 (fr)	2009-07-21	2011-01-27	Ramot At Tel-Aviv University Ltd.	Ligands du récepteur a3 de ladénosine modulant la pigmentation
US8389526B2 (en)	2009-08-07	2013-03-05	Novartis Ag	3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
JP5781510B2 (ja)	2009-08-12	2015-09-24	ノバルティスアーゲー	ヘテロ環式ヒドラゾン化合物および癌および炎症の処置のためのそれらの使用
PE20121148A1 (es)	2009-08-17	2012-09-07	Intellikine Llc	Compuestos heterociclicos y usos de los mismos
JP5775871B2 (ja)	2009-08-20	2015-09-09	ノバルティスアーゲー	ヘテロ環式オキシム化合物
WO2012034095A1 (fr)	2010-09-09	2012-03-15	Irm Llc	Composés et compositions comme inhibiteurs de trk
US8637516B2 (en)	2010-09-09	2014-01-28	Irm Llc	Compounds and compositions as TRK inhibitors
WO2012107500A1 (fr)	2011-02-10	2012-08-16	Novartis Ag	Composés de [1, 2, 4] triazolo [4, 3 -b] pyridazine en tant qu'inhibiteurs de la tyrosine kinase c-met
WO2012116237A2 (fr)	2011-02-23	2012-08-30	Intellikine, Llc	Composés hétérocycliques et leurs utilisations
WO2012116217A1 (fr)	2011-02-25	2012-08-30	Irm Llc	Composés et compositions en tant qu'inhibiteurs de trk
EA026655B1 (ru)	2011-09-15	2017-05-31	Новартис Аг	6-ЗАМЕЩЕННЫЕ 3-(ХИНОЛИН-6-ИЛТИО)[1,2,4]ТРИАЗОЛО[4,3-a]ПИРИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ c-MET ТИРОЗИНКИНАЗЫ
CA2856803A1 (fr)	2011-11-23	2013-05-30	Intellikine, Llc	Regimes de traitement ameliores utilisant des inhibiteurs de mtor
JP2015512425A (ja)	2012-04-03	2015-04-27	ノバルティスアーゲー	チロシンキナーゼ阻害剤との組合せ製品及びそれらの使用
JP6238969B2 (ja)	2012-05-08	2017-11-29	エアロミクス・インコーポレイテッドＡｅｒｏｍｉｃｓ，Ｉｎｃ．	新規方法
RU2559776C2 (ru) *	2012-08-20	2015-08-10	Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова"	Фармацевтические композиции для лечения цереброваскулярных расстройств и способы их изготовления
EP2968340A4 (fr)	2013-03-15	2016-08-10	Intellikine Llc	Combinaison d'inhibiteurs de kinase et ses utilisations
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RU2611339C2 (ru) *	2014-02-17	2017-02-21	Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова"	Фармацевтические композиции с пролонгированным высвобождением для лечения цереброваскулярных расстройств
WO2016011658A1 (fr)	2014-07-25	2016-01-28	Novartis Ag	Polythérapie
ES2831416T3 (es)	2014-07-31	2021-06-08	Novartis Ag	Terapia de combinación de un inhibidor de MET y un inhibidor de EGFR
RU2582961C1 (ru) *	2015-03-04	2016-04-27	Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова"	Фармацевтические композиции в жидких лекарственных формах для лечения цереброваскулярных расстройств и способы их изготовления
CN113194752A (zh)	2018-06-01	2021-07-30	康奈尔大学	Pi3k相关疾病或病症的组合疗法
RU2712150C1 (ru) *	2019-08-22	2020-01-24	Общество с ограниченной ответственностью "ЦЕНТР ТРАНСФЕРА БИОТЕХНОЛОГИЙ ОКА-Биотех"	ПРИМЕНЕНИЕ ТЕТРААЦЕТИЛИРОВАННОГО 5-АМИНО-4-КАРБАМОИЛИМИДАЗОЛИЛ-1-β-D-РИБОФУРАНОЗИДА В КАЧЕСТВЕ ИНГИБИТОРА ПРОТЕИНКИНАЗЫ Cδ
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TW336938B (en) *	1992-05-21	1998-07-21	Pfizer	Calcium channel blocking polypeptides from filistata hibernalis
DE69428536T2 (de) *	1993-07-13	2002-06-06	The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services	A3 -adenosin -rezeptor agonisten

2000
- 2000-09-05 CO CO00066880A patent/CO5180581A1/es not_active Application Discontinuation
- 2000-09-22 TR TR2002/00843T patent/TR200200843T2/xx unknown
- 2000-09-22 SK SK418-2002A patent/SK4182002A3/sk unknown
- 2000-09-22 PL PL00357371A patent/PL357371A1/xx not_active Application Discontinuation
- 2000-09-22 AU AU70352/00A patent/AU778185B2/en not_active Ceased
- 2000-09-22 HR HR20020253A patent/HRP20020253A2/xx not_active Application Discontinuation
- 2000-09-22 HU HU0202807A patent/HUP0202807A3/hu unknown
- 2000-09-22 OA OA1200200072A patent/OA12021A/en unknown
- 2000-09-22 WO PCT/IB2000/001353 patent/WO2001023399A1/fr not_active Ceased
- 2000-09-22 CZ CZ20021020A patent/CZ20021020A3/cs unknown
- 2000-09-22 AT AT00958949T patent/ATE312117T1/de not_active IP Right Cessation
- 2000-09-22 AP APAP/P/2002/002458A patent/AP2002002458A0/en unknown
- 2000-09-22 DE DE60024649T patent/DE60024649D1/de not_active Expired - Lifetime
- 2000-09-22 UA UA2002032515A patent/UA73525C2/uk unknown
- 2000-09-22 HK HK03101216.3A patent/HK1049011A1/zh unknown
- 2000-09-22 MX MXPA02003308A patent/MXPA02003308A/es unknown
- 2000-09-22 EE EEP200200172A patent/EE200200172A/xx unknown
- 2000-09-22 EP EP00958949A patent/EP1216257B1/fr not_active Expired - Lifetime
- 2000-09-22 CA CA002386079A patent/CA2386079A1/fr not_active Abandoned
- 2000-09-22 YU YU23102A patent/YU23102A/sh unknown
- 2000-09-22 CN CN00813154A patent/CN1374967A/zh active Pending
- 2000-09-22 JP JP2001526549A patent/JP2003510331A/ja active Pending
- 2000-09-22 GE GEAP20006392A patent/GEP20043241B/en unknown
- 2000-09-22 NZ NZ517177A patent/NZ517177A/en unknown
- 2000-09-22 EA EA200200316A patent/EA005422B1/ru not_active IP Right Cessation
- 2000-09-22 BR BR0014384-7A patent/BR0014384A/pt not_active IP Right Cessation
- 2000-09-22 KR KR10-2002-7004177A patent/KR100481605B1/ko not_active Expired - Fee Related
- 2000-09-25 PA PA20008503301A patent/PA8503301A1/es unknown
- 2000-09-27 PE PE2000001021A patent/PE20010696A1/es not_active Application Discontinuation
- 2000-09-28 EC EC2000003682A patent/ECSP003682A/es unknown
- 2000-09-28 AR ARP000105125A patent/AR029887A1/es unknown
- 2000-09-28 MY MYPI20004553 patent/MY133996A/en unknown
- 2000-09-28 GT GT200000161A patent/GT200000161A/es unknown
- 2000-09-29 TN TNTNSN00191A patent/TNSN00191A1/fr unknown
- 2000-09-29 IL IL14822200A patent/IL148222A0/xx unknown
2002
- 2002-02-18 CR CR6592A patent/CR6592A/es not_active Application Discontinuation
- 2002-02-26 IS IS6286A patent/IS6286A/is unknown
- 2002-03-15 MA MA26557A patent/MA26822A1/fr unknown
- 2002-03-25 NO NO20021474A patent/NO20021474L/no unknown
- 2002-03-27 ZA ZA200202461A patent/ZA200202461B/xx unknown
- 2002-04-23 BG BG106636A patent/BG106636A/bg unknown

Also Published As

Publication number	Publication date
ATE312117T1 (de)	2005-12-15
CZ20021020A3 (cs)	2003-04-16
HUP0202807A2 (hu)	2002-12-28
IS6286A (is)	2002-02-26
TR200200843T2 (tr)	2002-07-22
DE60024649D1 (de)	2006-01-12
EA200200316A1 (ru)	2002-08-29
OA12021A (en)	2006-04-19
TNSN00191A1 (fr)	2005-11-10
HK1049011A1 (zh)	2003-04-25
WO2001023399A1 (fr)	2001-04-05
EP1216257B1 (fr)	2005-12-07
NO20021474D0 (no)	2002-03-25
AU778185B2 (en)	2004-11-18
PA8503301A1 (es)	2003-06-30
GEP20043241B (en)	2004-05-25
CA2386079A1 (fr)	2001-04-05
AR029887A1 (es)	2003-07-23
AP2002002458A0 (en)	2002-06-30
PE20010696A1 (es)	2001-07-05
UA73525C2 (en)	2005-08-15
CO5180581A1 (es)	2002-07-30
IL148222A0 (en)	2002-09-12
KR20020034206A (ko)	2002-05-08
MY133996A (en)	2007-11-30
SK4182002A3 (en)	2003-04-01
EP1216257A1 (fr)	2002-06-26
EE200200172A (et)	2003-06-16
YU23102A (sh)	2006-01-16
JP2003510331A (ja)	2003-03-18
ZA200202461B (en)	2003-05-28
MA26822A1 (fr)	2004-12-20
ECSP003682A (es)	2002-04-23
GT200000161A (es)	2002-03-22
NO20021474L (no)	2002-05-22
CN1374967A (zh)	2002-10-16
KR100481605B1 (ko)	2005-04-08
BR0014384A (pt)	2002-07-02
MXPA02003308A (es)	2002-10-04
NZ517177A (en)	2003-10-31
CR6592A (es)	2004-02-23
HRP20020253A2 (en)	2004-04-30
EA005422B1 (ru)	2005-02-24
AU7035200A (en)	2001-04-30
HUP0202807A3 (en)	2005-02-28
PL357371A1 (en)	2004-07-26

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