DE69635135T2 - Benzimidazolderivate - Google Patents
Benzimidazolderivate Download PDFInfo
- Publication number
- DE69635135T2 DE69635135T2 DE69635135T DE69635135T DE69635135T2 DE 69635135 T2 DE69635135 T2 DE 69635135T2 DE 69635135 T DE69635135 T DE 69635135T DE 69635135 T DE69635135 T DE 69635135T DE 69635135 T2 DE69635135 T2 DE 69635135T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- lower alkyl
- compound
- aryl
- chlorobenzyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims abstract description 30
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 298
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 208000035475 disorder Diseases 0.000 claims abstract description 23
- 206010020772 Hypertension Diseases 0.000 claims abstract description 13
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
- 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 12
- 206010012655 Diabetic complications Diseases 0.000 claims abstract description 12
- 125000003277 amino group Chemical group 0.000 claims abstract description 12
- 206010019280 Heart failures Diseases 0.000 claims abstract description 11
- 201000001881 impotence Diseases 0.000 claims abstract description 11
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 9
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 7
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 7
- 208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 7
- 201000006370 kidney failure Diseases 0.000 claims abstract description 7
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 206010059245 Angiopathy Diseases 0.000 claims abstract description 6
- 206010006895 Cachexia Diseases 0.000 claims abstract description 6
- 208000022461 Glomerular disease Diseases 0.000 claims abstract description 6
- 208000002705 Glucose Intolerance Diseases 0.000 claims abstract description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 6
- 208000024780 Urticaria Diseases 0.000 claims abstract description 6
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 6
- 230000001684 chronic effect Effects 0.000 claims abstract description 6
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 6
- 201000008383 nephritis Diseases 0.000 claims abstract description 6
- 201000009104 prediabetes syndrome Diseases 0.000 claims abstract description 6
- 208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 6
- 208000037803 restenosis Diseases 0.000 claims abstract description 6
- 230000002441 reversible effect Effects 0.000 claims abstract description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 5
- -1 alkenylene radical Chemical class 0.000 claims description 543
- 125000000217 alkyl group Chemical group 0.000 claims description 110
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 108
- 238000002360 preparation method Methods 0.000 claims description 87
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- LBATZZNFAPQUDG-UHFFFAOYSA-N n-(benzenesulfonyl)-3-[(2-chlorophenyl)methyl]-2-methylbenzimidazole-5-carboxamide Chemical group CC1=NC2=CC=C(C(=O)NS(=O)(=O)C=3C=CC=CC=3)C=C2N1CC1=CC=CC=C1Cl LBATZZNFAPQUDG-UHFFFAOYSA-N 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- RWDQSTJLUVKOJI-UHFFFAOYSA-N n-butylsulfonyl-2-ethyl-3-[(4-phenylphenyl)methyl]benzimidazole-5-carboxamide Chemical compound C12=CC(C(=O)NS(=O)(=O)CCCC)=CC=C2N=C(CC)N1CC(C=C1)=CC=C1C1=CC=CC=C1 RWDQSTJLUVKOJI-UHFFFAOYSA-N 0.000 claims description 8
- 150000005840 aryl radicals Chemical class 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 150000003254 radicals Chemical class 0.000 claims description 7
- 229940124530 sulfonamide Drugs 0.000 claims description 7
- 150000003456 sulfonamides Chemical class 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 6
- FAUSRGUYSULHPP-UHFFFAOYSA-N n-(benzenesulfonyl)-3-[(2,4-dichlorophenyl)methyl]-2-methylbenzimidazole-5-carboxamide Chemical compound CC1=NC2=CC=C(C(=O)NS(=O)(=O)C=3C=CC=CC=3)C=C2N1CC1=CC=C(Cl)C=C1Cl FAUSRGUYSULHPP-UHFFFAOYSA-N 0.000 claims description 6
- WPAAFQPHODWODI-UHFFFAOYSA-N n-butylsulfonyl-2-methyl-3-[(4-phenylphenyl)methyl]benzimidazole-5-carboxamide Chemical compound C12=CC(C(=O)NS(=O)(=O)CCCC)=CC=C2N=C(C)N1CC(C=C1)=CC=C1C1=CC=CC=C1 WPAAFQPHODWODI-UHFFFAOYSA-N 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 5
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 5
- 125000002944 cyanoaryl group Chemical group 0.000 claims description 5
- 125000003106 haloaryl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 230000036210 malignancy Effects 0.000 claims description 5
- NGJFMFMTNCABET-UHFFFAOYSA-N n-(benzenesulfonyl)-2-cyclopropyl-3-[(2-fluorophenyl)methyl]benzimidazole-5-carboxamide Chemical compound FC1=CC=CC=C1CN1C2=CC(C(=O)NS(=O)(=O)C=3C=CC=CC=3)=CC=C2N=C1C1CC1 NGJFMFMTNCABET-UHFFFAOYSA-N 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
- 150000008065 acid anhydrides Chemical class 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000004927 thianaphthalenyl group Chemical group S1C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
- 125000004997 halocarbonyl group Chemical group 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- CXZVMCRXDOHXQU-UHFFFAOYSA-N n-(benzenesulfonyl)-3-[(2,4-difluorophenyl)methyl]-2-methylbenzimidazole-5-carboxamide Chemical compound CC1=NC2=CC=C(C(=O)NS(=O)(=O)C=3C=CC=CC=3)C=C2N1CC1=CC=C(F)C=C1F CXZVMCRXDOHXQU-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 150000001556 benzimidazoles Chemical class 0.000 claims 13
- UYGZODVVDUIDDQ-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-2-methyl-n-pentylsulfonylbenzimidazole-5-carboxamide Chemical compound C12=CC(C(=O)NS(=O)(=O)CCCCC)=CC=C2N=C(C)N1CC1=CC=C(Cl)C=C1Cl UYGZODVVDUIDDQ-UHFFFAOYSA-N 0.000 claims 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- AFRXMQTUBOBDBP-UHFFFAOYSA-N n-butylsulfonyl-3-[(2-fluoro-4-phenylphenyl)methyl]-2-methylbenzimidazole-5-carboxamide Chemical compound C12=CC(C(=O)NS(=O)(=O)CCCC)=CC=C2N=C(C)N1CC(C(=C1)F)=CC=C1C1=CC=CC=C1 AFRXMQTUBOBDBP-UHFFFAOYSA-N 0.000 claims 1
- 238000006798 ring closing metathesis reaction Methods 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 abstract 1
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 abstract 1
- 206010061876 Obstruction Diseases 0.000 abstract 1
- 101150098694 PDE5A gene Proteins 0.000 abstract 1
- 208000006011 Stroke Diseases 0.000 abstract 1
- 125000003368 amide group Chemical group 0.000 abstract 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 abstract 1
- 230000002490 cerebral effect Effects 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 312
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 308
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 240
- 230000015572 biosynthetic process Effects 0.000 description 231
- 238000003786 synthesis reaction Methods 0.000 description 231
- 239000000243 solution Substances 0.000 description 211
- 239000000203 mixture Substances 0.000 description 205
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 177
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 162
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 135
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 118
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 116
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 106
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 88
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 88
- 239000013078 crystal Substances 0.000 description 85
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 238000004519 manufacturing process Methods 0.000 description 66
- 238000001914 filtration Methods 0.000 description 64
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 60
- 239000000126 substance Substances 0.000 description 59
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 58
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 56
- WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000012044 organic layer Substances 0.000 description 51
- 239000002904 solvent Substances 0.000 description 42
- VXBLDUOHSHPNKR-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-2-methylbenzimidazole-5-carboxylic acid Chemical compound CC1=NC2=CC=C(C(O)=O)C=C2N1CC1=CC=CC=C1Cl VXBLDUOHSHPNKR-UHFFFAOYSA-N 0.000 description 41
- 239000003480 eluent Substances 0.000 description 41
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 39
- 238000010898 silica gel chromatography Methods 0.000 description 36
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 235000017557 sodium bicarbonate Nutrition 0.000 description 28
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 28
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 26
- 229910052739 hydrogen Inorganic materials 0.000 description 25
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 24
- 239000011343 solid material Substances 0.000 description 22
- 239000011736 potassium bicarbonate Substances 0.000 description 21
- 235000015497 potassium bicarbonate Nutrition 0.000 description 21
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 21
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 21
- CBDHQIOQTZNJKO-UHFFFAOYSA-N ethyl 3-acetamido-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(C)=O)=C1 CBDHQIOQTZNJKO-UHFFFAOYSA-N 0.000 description 20
- 239000011259 mixed solution Substances 0.000 description 20
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 235000011121 sodium hydroxide Nutrition 0.000 description 18
- 239000010410 layer Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000007864 aqueous solution Substances 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- OVIZSQRQYWEGON-UHFFFAOYSA-N butane-1-sulfonamide Chemical compound CCCCS(N)(=O)=O OVIZSQRQYWEGON-UHFFFAOYSA-N 0.000 description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- ACRMYCWODJZYOX-UHFFFAOYSA-N 4-amino-n-(benzenesulfonyl)-3-[(4-phenylphenyl)methylamino]benzamide Chemical compound NC1=CC=C(C(=O)NS(=O)(=O)C=2C=CC=CC=2)C=C1NCC(C=C1)=CC=C1C1=CC=CC=C1 ACRMYCWODJZYOX-UHFFFAOYSA-N 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- GUIKFCJYHASTDO-UHFFFAOYSA-N ethyl 3-[(2-chlorophenyl)methyl]-2-methylbenzimidazole-5-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2N=C(C)N1CC1=CC=CC=C1Cl GUIKFCJYHASTDO-UHFFFAOYSA-N 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 10
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- HWPMTUWWESZFAI-UHFFFAOYSA-N ethyl 3-(butanoylamino)-4-nitrobenzoate Chemical compound CCCC(=O)NC1=CC(C(=O)OCC)=CC=C1[N+]([O-])=O HWPMTUWWESZFAI-UHFFFAOYSA-N 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- 229910052697 platinum Inorganic materials 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229910052707 ruthenium Inorganic materials 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- 229910052723 transition metal Inorganic materials 0.000 description 10
- 150000003624 transition metals Chemical class 0.000 description 10
- WZVJKXJRWSRGNA-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-2-methylbenzimidazole-5-carboxylic acid Chemical compound CC1=NC2=CC=C(C(O)=O)C=C2N1CC1=CC=C(Cl)C=C1Cl WZVJKXJRWSRGNA-UHFFFAOYSA-N 0.000 description 9
- SMUPCXIVIMRZES-UHFFFAOYSA-N 4-acetamido-3-amino-n-(benzenesulfonyl)benzamide Chemical compound C1=C(N)C(NC(=O)C)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 SMUPCXIVIMRZES-UHFFFAOYSA-N 0.000 description 9
- 125000005907 alkyl ester group Chemical group 0.000 description 9
- 229910052759 nickel Inorganic materials 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- JQTXXVRYHZLCRM-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-2-methyl-n-(pyridin-2-ylmethyl)benzimidazole-5-carboxamide Chemical compound CC1=NC2=CC=C(C(=O)NCC=3N=CC=CC=3)C=C2N1CC1=CC=C(Cl)C=C1Cl JQTXXVRYHZLCRM-UHFFFAOYSA-N 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 8
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- 229910000032 lithium hydrogen carbonate Inorganic materials 0.000 description 5
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- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
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- 210000001367 artery Anatomy 0.000 description 3
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- KKGWBHMAFQGPKF-UHFFFAOYSA-N ethyl 3-[3-(2-methylphenyl)propanoylamino]-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(=O)CCC=2C(=CC=CC=2)C)=C1 KKGWBHMAFQGPKF-UHFFFAOYSA-N 0.000 description 1
- KUHVKYHBLNLOQI-UHFFFAOYSA-N ethyl 3-[3-(3,4-dichlorophenyl)propanoylamino]-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(=O)CCC=2C=C(Cl)C(Cl)=CC=2)=C1 KUHVKYHBLNLOQI-UHFFFAOYSA-N 0.000 description 1
- MNHWCLAUWKILQW-UHFFFAOYSA-N ethyl 3-[3-(4-methoxyphenyl)propanoylamino]-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(=O)CCC=2C=CC(OC)=CC=2)=C1 MNHWCLAUWKILQW-UHFFFAOYSA-N 0.000 description 1
- ZNNJHZRLSBDYFI-UHFFFAOYSA-N ethyl 3-[3-(4-tert-butylphenyl)propanoylamino]-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(=O)CCC=2C=CC(=CC=2)C(C)(C)C)=C1 ZNNJHZRLSBDYFI-UHFFFAOYSA-N 0.000 description 1
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- RXZUGYLINMJKBH-UHFFFAOYSA-N ethyl 3-[4-(3-methylphenyl)butanoylamino]-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(=O)CCCC=2C=C(C)C=CC=2)=C1 RXZUGYLINMJKBH-UHFFFAOYSA-N 0.000 description 1
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- VOBAONRDJXETCN-UHFFFAOYSA-N ethyl 3-[5-(4-chlorophenyl)pentanoylamino]-4-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C([N+]([O-])=O)C(NC(=O)CCCCC=2C=CC(Cl)=CC=2)=C1 VOBAONRDJXETCN-UHFFFAOYSA-N 0.000 description 1
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- 125000005003 perfluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 125000005804 perfluoroheptyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 125000005005 perfluorohexyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 125000005008 perfluoropentyl group Chemical group FC(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical compound NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 description 1
- 125000004346 phenylpentyl group Chemical group C1(=CC=CC=C1)CCCCC* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- WKFBZNUBXWCCHG-UHFFFAOYSA-N phosphorus trifluoride Chemical compound FP(F)F WKFBZNUBXWCCHG-UHFFFAOYSA-N 0.000 description 1
- 229920003199 poly(diethylsiloxane) Polymers 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 description 1
- SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical compound CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- ZTYZEUXZHGOXRT-UHFFFAOYSA-N quinoline-8-sulfonamide Chemical compound C1=CN=C2C(S(=O)(=O)N)=CC=CC2=C1 ZTYZEUXZHGOXRT-UHFFFAOYSA-N 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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- 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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- C07—ORGANIC CHEMISTRY
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- 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
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- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
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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
- C07D417/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- 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
- C07D417/10—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 linked by a carbon chain containing aromatic rings
-
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- 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
- C07D417/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34342595 | 1995-12-28 | ||
| JP34342595 | 1995-12-28 | ||
| JP28767696 | 1996-10-08 | ||
| JP28767696 | 1996-10-08 | ||
| PCT/JP1996/003858 WO1997024334A1 (en) | 1995-12-28 | 1996-12-27 | Benzimidazole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69635135D1 DE69635135D1 (en) | 2005-10-06 |
| DE69635135T2 true DE69635135T2 (de) | 2006-07-06 |
Family
ID=26556834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69635135T Expired - Lifetime DE69635135T2 (de) | 1995-12-28 | 1996-12-27 | Benzimidazolderivate |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US6166219A (enExample) |
| EP (1) | EP0882718B1 (enExample) |
| JP (2) | JP3063162B2 (enExample) |
| CN (1) | CN1211238A (enExample) |
| AT (1) | ATE303365T1 (enExample) |
| AU (1) | AU722514B2 (enExample) |
| BR (1) | BR9612434A (enExample) |
| DE (1) | DE69635135T2 (enExample) |
| DK (1) | DK0882718T3 (enExample) |
| EA (1) | EA002357B1 (enExample) |
| ES (1) | ES2244979T3 (enExample) |
| HU (1) | HUP9900625A3 (enExample) |
| IL (1) | IL124969A (enExample) |
| NZ (1) | NZ324834A (enExample) |
| TR (1) | TR199801249T2 (enExample) |
| WO (1) | WO1997024334A1 (enExample) |
Families Citing this family (134)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997048697A1 (en) | 1996-06-19 | 1997-12-24 | Rhone-Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
| TW453999B (en) * | 1997-06-27 | 2001-09-11 | Fujisawa Pharmaceutical Co | Benzimidazole derivatives |
| DE69826286T2 (de) | 1997-06-27 | 2005-11-24 | Fujisawa Pharmaceutical Co., Ltd. | Derivate mit einem aromatischen ring |
| EP0995742A4 (en) * | 1997-06-27 | 2004-08-25 | Fujisawa Pharmaceutical Co | SULPHONAMIDE COMPOUNDS AND THEIR MEDICAL USE |
| ES2222613T3 (es) * | 1997-09-12 | 2005-02-01 | Pharis Biotec Gmbh | Composicion para la terapia de diabetes mellitus y de la obesidad. |
| US6410584B1 (en) | 1998-01-14 | 2002-06-25 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells with indole derivatives |
| BR9909440A (pt) * | 1998-04-06 | 2000-12-26 | Fujisawa Pharmaceutical Co | Derivados de indol |
| US6200771B1 (en) | 1998-10-15 | 2001-03-13 | Cell Pathways, Inc. | Method of using a novel phosphodiesterase in pharmaceutical screeing to identify compounds for treatment of neoplasia |
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| US5196444A (en) * | 1990-04-27 | 1993-03-23 | Takeda Chemical Industries, Ltd. | 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof |
| US5703110A (en) * | 1990-04-27 | 1997-12-30 | Takeda Chemical Industries, Ltd. | Benzimidazole derivatives, their production and use |
| RU1836357C (ru) * | 1990-07-23 | 1993-08-23 | Др.Карл Томэ ГмбХ | Производные бензимидазола, их изомеры, смеси изомеров, гидраты или их физиологически переносимые соли, обладающие антагонистическими в отношении ангиотензина свойствами |
| DE4224133A1 (de) * | 1992-07-22 | 1994-01-27 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5594003A (en) * | 1991-02-06 | 1997-01-14 | Dr. Karl Thomae Gmbh | Tetrahydroimidazo[1,2-a]pyridin-2-yl-(benzimidazol-1-yl)-methyl-biphenyls useful as angiotensin-II antagonists |
| US5602127A (en) * | 1991-02-06 | 1997-02-11 | Karl Thomae Gmbh | (Alkanesultam-1-yl)-benzimidazol-1-yl)-1yl)-methyl-biphenyls useful as angiotensin-II antagonists |
| US5614519A (en) * | 1991-02-06 | 1997-03-25 | Karl Thomae Gmbh | (1-(2,3 or 4-N-morpholinoalkyl)-imidazol-4-yl)-benizimidazol-1-yl-methyl]-biphenyls useful as angiotensin-II antagonists |
| GB9121776D0 (en) * | 1991-10-14 | 1991-11-27 | Fujisawa Pharmaceutical Co | Benzimidazole derivatives and process for preparation thereof |
| DE4237557A1 (de) * | 1992-11-06 | 1994-05-11 | Bayer Ag | Substituierte Benzimidazole |
| JPH0853424A (ja) * | 1994-08-11 | 1996-02-27 | Kureha Chem Ind Co Ltd | ベンズイミダゾールスルホン酸アミド誘導体 |
| GB9423910D0 (en) * | 1994-11-26 | 1995-01-11 | Pfizer Ltd | Therapeutic agents |
| JPH11154208A (ja) | 1997-11-21 | 1999-06-08 | Mitsubishi Electric Corp | Icカード及びその製造方法 |
-
1996
- 1996-12-27 WO PCT/JP1996/003858 patent/WO1997024334A1/ja not_active Ceased
- 1996-12-27 EA EA199800609A patent/EA002357B1/ru not_active IP Right Cessation
- 1996-12-27 ES ES96943331T patent/ES2244979T3/es not_active Expired - Lifetime
- 1996-12-27 HU HU9900625A patent/HUP9900625A3/hu unknown
- 1996-12-27 BR BR9612434-2A patent/BR9612434A/pt not_active Application Discontinuation
- 1996-12-27 NZ NZ324834A patent/NZ324834A/en unknown
- 1996-12-27 US US09/091,997 patent/US6166219A/en not_active Expired - Lifetime
- 1996-12-27 TR TR1998/01249T patent/TR199801249T2/xx unknown
- 1996-12-27 JP JP9524201A patent/JP3063162B2/ja not_active Expired - Fee Related
- 1996-12-27 IL IL12496996A patent/IL124969A/en not_active IP Right Cessation
- 1996-12-27 AT AT96943331T patent/ATE303365T1/de not_active IP Right Cessation
- 1996-12-27 AU AU12095/97A patent/AU722514B2/en not_active Ceased
- 1996-12-27 DK DK96943331T patent/DK0882718T3/da active
- 1996-12-27 DE DE69635135T patent/DE69635135T2/de not_active Expired - Lifetime
- 1996-12-27 EP EP96943331A patent/EP0882718B1/en not_active Expired - Lifetime
- 1996-12-27 CN CN96180137A patent/CN1211238A/zh active Pending
-
2000
- 2000-01-17 JP JP2000008395A patent/JP2000159749A/ja active Pending
- 2000-01-28 US US09/492,955 patent/US6352985B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0882718B1 (en) | 2005-08-31 |
| JP2000159749A (ja) | 2000-06-13 |
| EP0882718A1 (en) | 1998-12-09 |
| HUP9900625A3 (en) | 2003-04-28 |
| EA199800609A1 (ru) | 1999-02-25 |
| IL124969A0 (en) | 1999-01-26 |
| DE69635135D1 (en) | 2005-10-06 |
| TR199801249T2 (xx) | 1998-10-21 |
| BR9612434A (pt) | 1999-12-28 |
| ATE303365T1 (de) | 2005-09-15 |
| US6166219A (en) | 2000-12-26 |
| HUP9900625A2 (hu) | 1999-06-28 |
| DK0882718T3 (da) | 2005-12-12 |
| JP3063162B2 (ja) | 2000-07-12 |
| WO1997024334A1 (en) | 1997-07-10 |
| NZ324834A (en) | 2001-11-30 |
| EA002357B1 (ru) | 2002-04-25 |
| US6352985B1 (en) | 2002-03-05 |
| IL124969A (en) | 2002-09-12 |
| ES2244979T3 (es) | 2005-12-16 |
| EP0882718A4 (en) | 1999-08-04 |
| AU722514B2 (en) | 2000-08-03 |
| CN1211238A (zh) | 1999-03-17 |
| AU1209597A (en) | 1997-07-28 |
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| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: ASTELLAS PHARMA INC., TOKIO/TOKYO, JP |