HRP20000550A2 - N-/(substituted five-membered di- or triaza diunsaturated ring)carbonyl/ guanidine derivatives for the treatment of ischemia - Google Patents
N-/(substituted five-membered di- or triaza diunsaturated ring)carbonyl/ guanidine derivatives for the treatment of ischemiaInfo
- Publication number
- HRP20000550A2 HRP20000550A2 HR20000550A HRP20000550A HRP20000550A2 HR P20000550 A2 HRP20000550 A2 HR P20000550A2 HR 20000550 A HR20000550 A HR 20000550A HR P20000550 A HRP20000550 A HR P20000550A HR P20000550 A2 HRP20000550 A2 HR P20000550A2
- Authority
- HR
- Croatia
- Prior art keywords
- mono
- alkyl
- compound
- optionally
- pharmaceutically acceptable
- Prior art date
Links
- 208000028867 ischemia Diseases 0.000 title claims description 29
- 238000011282 treatment Methods 0.000 title description 13
- 150000002357 guanidines Chemical class 0.000 title description 4
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 603
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 330
- -1 cinolinyl Chemical group 0.000 claims description 257
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 225
- 150000003839 salts Chemical class 0.000 claims description 225
- 229910052757 nitrogen Chemical group 0.000 claims description 154
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 146
- 125000003282 alkyl amino group Chemical group 0.000 claims description 135
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 134
- 229940002612 prodrug Drugs 0.000 claims description 133
- 239000000651 prodrug Substances 0.000 claims description 133
- 125000004414 alkyl thio group Chemical group 0.000 claims description 132
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 129
- 229920006395 saturated elastomer Polymers 0.000 claims description 128
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 111
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 102
- 229910052760 oxygen Inorganic materials 0.000 claims description 101
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 100
- 239000001301 oxygen Substances 0.000 claims description 100
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 97
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 95
- 229910052717 sulfur Inorganic materials 0.000 claims description 94
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 93
- 125000005842 heteroatom Chemical group 0.000 claims description 93
- 239000011593 sulfur Chemical group 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 91
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 90
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 90
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 86
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 85
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 84
- 125000001424 substituent group Chemical group 0.000 claims description 84
- 235000019000 fluorine Nutrition 0.000 claims description 83
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 79
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 78
- 125000002619 bicyclic group Chemical group 0.000 claims description 77
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 76
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 74
- 125000005843 halogen group Chemical group 0.000 claims description 72
- 229910052799 carbon Inorganic materials 0.000 claims description 68
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 67
- 125000004423 acyloxy group Chemical group 0.000 claims description 66
- 125000001153 fluoro group Chemical group F* 0.000 claims description 65
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 55
- FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 claims description 53
- 210000001519 tissue Anatomy 0.000 claims description 52
- 241000124008 Mammalia Species 0.000 claims description 46
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 230000000302 ischemic effect Effects 0.000 claims description 37
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 35
- 229910052731 fluorine Inorganic materials 0.000 claims description 34
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 34
- 230000000451 tissue damage Effects 0.000 claims description 32
- 231100000827 tissue damage Toxicity 0.000 claims description 32
- 102000007390 Glycogen Phosphorylase Human genes 0.000 claims description 31
- 108010046163 Glycogen Phosphorylase Proteins 0.000 claims description 31
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 30
- 239000003937 drug carrier Substances 0.000 claims description 30
- 239000011737 fluorine Substances 0.000 claims description 30
- 210000002216 heart Anatomy 0.000 claims description 30
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 28
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 28
- 239000003085 diluting agent Substances 0.000 claims description 27
- 239000003288 aldose reductase inhibitor Substances 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- 230000001603 reducing effect Effects 0.000 claims description 25
- 239000003112 inhibitor Substances 0.000 claims description 23
- 230000001225 therapeutic effect Effects 0.000 claims description 22
- 230000002107 myocardial effect Effects 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 229940118148 Aldose reductase inhibitor Drugs 0.000 claims description 19
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims description 18
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 18
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 17
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 17
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 17
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 16
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 15
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 15
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 15
- 239000002327 cardiovascular agent Substances 0.000 claims description 14
- 229940125692 cardiovascular agent Drugs 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 238000007675 cardiac surgery Methods 0.000 claims description 13
- 208000037906 ischaemic injury Diseases 0.000 claims description 13
- 125000002950 monocyclic group Chemical group 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- 238000001356 surgical procedure Methods 0.000 claims description 13
- 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 12
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 10
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 10
- 210000004556 brain Anatomy 0.000 claims description 10
- 230000006378 damage Effects 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims description 10
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 210000000056 organ Anatomy 0.000 claims description 10
- 239000003379 purinergic P1 receptor agonist Substances 0.000 claims description 10
- 239000002552 dosage form Substances 0.000 claims description 9
- 210000004185 liver Anatomy 0.000 claims description 9
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000001103 potassium chloride Substances 0.000 claims description 9
- 235000011164 potassium chloride Nutrition 0.000 claims description 9
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 8
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 8
- 239000003981 vehicle Substances 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 238000002054 transplantation Methods 0.000 claims description 7
- NWYHYJVRSBVTGC-UHFFFAOYSA-N 5-ethyl-1-quinolin-5-ylpyrazole-4-carboxylic acid Chemical compound CCC1=C(C(O)=O)C=NN1C1=CC=CC2=NC=CC=C12 NWYHYJVRSBVTGC-UHFFFAOYSA-N 0.000 claims description 6
- HDPFDIUJHFATNN-UHFFFAOYSA-N 5-methyl-1-naphthalen-1-ylpyrazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)C=NN1C1=CC=CC2=CC=CC=C12 HDPFDIUJHFATNN-UHFFFAOYSA-N 0.000 claims description 6
- ZEDQLIICZORELY-UHFFFAOYSA-N 5-methyl-1-quinolin-6-ylpyrazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)C=NN1C1=CC=C(N=CC=C2)C2=C1 ZEDQLIICZORELY-UHFFFAOYSA-N 0.000 claims description 6
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 6
- 229960005305 adenosine Drugs 0.000 claims description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 210000005003 heart tissue Anatomy 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 230000002537 thrombolytic effect Effects 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 239000005541 ACE inhibitor Substances 0.000 claims description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 5
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims description 5
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 5
- 239000002593 adenosine A3 receptor agonist Substances 0.000 claims description 5
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 5
- 239000002876 beta blocker Substances 0.000 claims description 5
- 229940097320 beta blocking agent Drugs 0.000 claims description 5
- 229960002896 clonidine Drugs 0.000 claims description 5
- 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 5
- 229960002768 dipyridamole Drugs 0.000 claims description 5
- 239000002934 diuretic Substances 0.000 claims description 5
- 229930182470 glycoside Natural products 0.000 claims description 5
- 150000002338 glycosides Chemical class 0.000 claims description 5
- 229960002816 potassium chloride Drugs 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- IWLPHHUXVUATBQ-UHFFFAOYSA-N 2-isoquinolin-5-yl-5-methyltriazole-4-carboxylic acid Chemical compound N1=C(C(O)=O)C(C)=NN1C1=CC=CC2=CN=CC=C12 IWLPHHUXVUATBQ-UHFFFAOYSA-N 0.000 claims description 4
- KLLOIWZUJAJGPU-IBGZPJMESA-N 5-chloro-n-[(2s)-1-(3-hydroxyazetidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-1h-indole-2-carboxamide Chemical compound C1C(O)CN1C(=O)[C@@H](NC(=O)C=1NC2=CC=C(Cl)C=C2C=1)CC1=CC=CC=C1 KLLOIWZUJAJGPU-IBGZPJMESA-N 0.000 claims description 4
- WAAVFJWSRFFSSW-BETUJISGSA-N 5-chloro-n-[2-[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]-2-oxoethyl]-1h-indole-2-carboxamide Chemical compound C1[C@@H](O)[C@@H](O)CN1C(=O)CNC(=O)C1=CC2=CC(Cl)=CC=C2N1 WAAVFJWSRFFSSW-BETUJISGSA-N 0.000 claims description 4
- WSLKLYKPUZWAQW-UHFFFAOYSA-N 5-cyclopropyl-1-quinolin-5-ylpyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 WSLKLYKPUZWAQW-UHFFFAOYSA-N 0.000 claims description 4
- GOZINTPHLXUATQ-UHFFFAOYSA-N 5-cyclopropyl-1-quinolin-8-ylpyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C3=NC=CC=C3C=CC=2)C=1C1CC1 GOZINTPHLXUATQ-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- XAMARBFYCUIBJA-UHFFFAOYSA-N 5-methyl-2-naphthalen-1-yltriazole-4-carboxylic acid Chemical compound N1=C(C(O)=O)C(C)=NN1C1=CC=CC2=CC=CC=C12 XAMARBFYCUIBJA-UHFFFAOYSA-N 0.000 claims description 4
- ILKNSPWBNNHYMC-UHFFFAOYSA-N 5-methyl-2-quinolin-5-yltriazole-4-carboxylic acid Chemical compound N1=C(C(O)=O)C(C)=NN1C1=CC=CC2=NC=CC=C12 ILKNSPWBNNHYMC-UHFFFAOYSA-N 0.000 claims description 4
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 150000001805 chlorine compounds Chemical class 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 230000000968 intestinal effect Effects 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 claims description 4
- 229960001289 prazosin Drugs 0.000 claims description 4
- 210000000952 spleen Anatomy 0.000 claims description 4
- HYNXFOPOJQHNAI-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-methylpyrazole-4-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=NN1C1=CC=CC2=CN=CC=C12 HYNXFOPOJQHNAI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 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
- XXPUICQZACXXNY-UHFFFAOYSA-N butyl 1-isoquinolin-5-yl-3-methylpyrazole-4-carboxylate Chemical compound N1=C(C)C(C(=O)OCCCC)=CN1C1=CC=CC2=CN=CC=C12 XXPUICQZACXXNY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004537 indazol-5-yl group Chemical group N1N=CC2=CC(=CC=C12)* 0.000 claims description 3
- 210000000936 intestine Anatomy 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 230000002207 retinal effect Effects 0.000 claims description 3
- 210000002027 skeletal muscle Anatomy 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 2
- 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 2
- NHFITSUMYNECAK-UHFFFAOYSA-N 1-(3h-benzimidazol-5-yl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C=C3NC=NC3=CC=2)C=1C1CC1 NHFITSUMYNECAK-UHFFFAOYSA-N 0.000 claims description 2
- PJRZFTYVWGASFT-UHFFFAOYSA-N 1-(3h-benzimidazol-5-yl)-n-(diaminomethylidene)-5-ethylpyrazole-4-carboxamide Chemical compound CCC1=C(C(=O)NC(N)=N)C=NN1C1=CC=C(N=CN2)C2=C1 PJRZFTYVWGASFT-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- XLMUCHBVEFPSRM-UHFFFAOYSA-N 1-(8-bromoquinolin-5-yl)-5-cyclopropyl-n-(diaminomethylidene)pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C3=CC=CN=C3C(Br)=CC=2)C=1C1CC1 XLMUCHBVEFPSRM-UHFFFAOYSA-N 0.000 claims description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 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 2
- CNAUCBNUTUGRDC-UHFFFAOYSA-N 5-cyclopropyl-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C(=CC=CC=2)C(F)(F)F)C=1C1CC1 CNAUCBNUTUGRDC-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- PWCQUYVBQAFFPI-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-naphthalen-1-ylpyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C3=CC=CC=C3C=CC=2)C=1C1CC1 PWCQUYVBQAFFPI-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- NRQBHARHWSTOEU-UHFFFAOYSA-N ethyl 5-cyclopropyl-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C=2C(=CC=CC=2)C(F)(F)F)C=1C1CC1 NRQBHARHWSTOEU-UHFFFAOYSA-N 0.000 claims description 2
- KDRWXCMGMPBUFQ-UHFFFAOYSA-N ethyl 5-cyclopropyl-1-quinolin-5-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 KDRWXCMGMPBUFQ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
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- Obesity (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7636298P | 1998-02-27 | 1998-02-27 | |
PCT/IB1999/000206 WO1999043663A1 (en) | 1998-02-27 | 1999-02-05 | N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20000550A2 true HRP20000550A2 (en) | 2001-02-28 |
Family
ID=22131525
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20000550A HRP20000550A2 (en) | 1998-02-27 | 2000-08-24 | N-/(substituted five-membered di- or triaza diunsaturated ring)carbonyl/ guanidine derivatives for the treatment of ischemia |
HR20010666A HRP20010666A2 (en) | 1998-02-27 | 2001-08-29 | N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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HR20010666A HRP20010666A2 (en) | 1998-02-27 | 2001-08-29 | N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia |
Country Status (39)
Country | Link |
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US (2) | US6492401B1 (zh) |
EP (2) | EP1056729B1 (zh) |
JP (2) | JP2002504546A (zh) |
KR (4) | KR20030083004A (zh) |
CN (1) | CN1289326A (zh) |
AP (1) | AP9901478A0 (zh) |
AR (1) | AR015526A1 (zh) |
AT (1) | ATE286034T1 (zh) |
AU (1) | AU739403B2 (zh) |
BG (1) | BG104803A (zh) |
BR (1) | BR9908332A (zh) |
CA (1) | CA2321642A1 (zh) |
CO (1) | CO4980897A1 (zh) |
DE (1) | DE69922930T2 (zh) |
DK (1) | DK1056729T3 (zh) |
DZ (1) | DZ2729A1 (zh) |
EA (1) | EA003603B1 (zh) |
ES (1) | ES2237080T3 (zh) |
GT (1) | GT199900022A (zh) |
HR (2) | HRP20000550A2 (zh) |
HU (1) | HUP0204418A3 (zh) |
ID (1) | ID25505A (zh) |
IL (1) | IL136588A0 (zh) |
IS (1) | IS5548A (zh) |
NO (1) | NO20004192D0 (zh) |
NZ (1) | NZ504769A (zh) |
OA (1) | OA11450A (zh) |
PA (1) | PA8468401A1 (zh) |
PE (1) | PE20000334A1 (zh) |
PL (1) | PL342444A1 (zh) |
PT (1) | PT1056729E (zh) |
SI (1) | SI1056729T1 (zh) |
SK (1) | SK12342000A3 (zh) |
TN (1) | TNSN99028A1 (zh) |
TR (1) | TR200002480T2 (zh) |
TW (1) | TWI226329B (zh) |
WO (1) | WO1999043663A1 (zh) |
YU (1) | YU46200A (zh) |
ZA (1) | ZA991578B (zh) |
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-
1999
- 1999-02-05 EP EP99901083A patent/EP1056729B1/en not_active Expired - Lifetime
- 1999-02-05 KR KR10-2003-7012300A patent/KR20030083004A/ko not_active Application Discontinuation
- 1999-02-05 HU HU0204418A patent/HUP0204418A3/hu not_active Application Discontinuation
- 1999-02-05 KR KR10-2003-7009644A patent/KR20030078886A/ko not_active Application Discontinuation
- 1999-02-05 AU AU20706/99A patent/AU739403B2/en not_active Ceased
- 1999-02-05 IL IL13658899A patent/IL136588A0/xx unknown
- 1999-02-05 TR TR2000/02480T patent/TR200002480T2/xx unknown
- 1999-02-05 DE DE69922930T patent/DE69922930T2/de not_active Expired - Fee Related
- 1999-02-05 PT PT99901083T patent/PT1056729E/pt unknown
- 1999-02-05 EP EP04008203A patent/EP1454902A1/en not_active Withdrawn
- 1999-02-05 BR BR9908332-9A patent/BR9908332A/pt not_active IP Right Cessation
- 1999-02-05 CN CN99802628A patent/CN1289326A/zh active Pending
- 1999-02-05 SK SK1234-2000A patent/SK12342000A3/sk unknown
- 1999-02-05 SI SI9930743T patent/SI1056729T1/xx unknown
- 1999-02-05 YU YU46200A patent/YU46200A/sh unknown
- 1999-02-05 EA EA200000789A patent/EA003603B1/ru not_active IP Right Cessation
- 1999-02-05 AT AT99901083T patent/ATE286034T1/de not_active IP Right Cessation
- 1999-02-05 KR KR10-2000-7009529A patent/KR100449600B1/ko not_active IP Right Cessation
- 1999-02-05 JP JP2000533420A patent/JP2002504546A/ja active Pending
- 1999-02-05 WO PCT/IB1999/000206 patent/WO1999043663A1/en not_active Application Discontinuation
- 1999-02-05 ES ES99901083T patent/ES2237080T3/es not_active Expired - Lifetime
- 1999-02-05 DK DK99901083T patent/DK1056729T3/da active
- 1999-02-05 PL PL99342444A patent/PL342444A1/xx not_active Application Discontinuation
- 1999-02-05 US US09/367,731 patent/US6492401B1/en not_active Expired - Fee Related
- 1999-02-05 ID IDW20001633A patent/ID25505A/id unknown
- 1999-02-05 KR KR10-2002-7017553A patent/KR100407903B1/ko not_active IP Right Cessation
- 1999-02-05 CA CA002321642A patent/CA2321642A1/en not_active Abandoned
- 1999-02-05 NZ NZ504769A patent/NZ504769A/en unknown
- 1999-02-22 TW TW088102574A patent/TWI226329B/zh active
- 1999-02-22 GT GT199900022A patent/GT199900022A/es unknown
- 1999-02-23 PE PE1999000156A patent/PE20000334A1/es not_active Application Discontinuation
- 1999-02-24 DZ DZ990032A patent/DZ2729A1/xx active
- 1999-02-24 PA PA19998468401A patent/PA8468401A1/es unknown
- 1999-02-24 TN TNTNSN99028A patent/TNSN99028A1/fr unknown
- 1999-02-25 AR ARP990100791A patent/AR015526A1/es unknown
- 1999-02-25 AP APAP/P/1999/001478A patent/AP9901478A0/en unknown
- 1999-02-26 ZA ZA9901578A patent/ZA991578B/xx unknown
- 1999-03-01 CO CO99012526A patent/CO4980897A1/es unknown
-
2000
- 2000-06-27 IS IS5548A patent/IS5548A/is unknown
- 2000-08-18 OA OA1200000223A patent/OA11450A/en unknown
- 2000-08-22 NO NO20004192A patent/NO20004192D0/no not_active Application Discontinuation
- 2000-08-24 HR HR20000550A patent/HRP20000550A2/hr not_active Application Discontinuation
- 2000-09-27 BG BG104803A patent/BG104803A/bg unknown
-
2001
- 2001-08-29 HR HR20010666A patent/HRP20010666A2/hr not_active Application Discontinuation
-
2002
- 2002-12-09 US US10/315,369 patent/US6974813B2/en not_active Expired - Fee Related
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2004
- 2004-08-27 JP JP2004248129A patent/JP2005041879A/ja not_active Withdrawn
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