FI113367B - Menetelmä terapeuttisesti käyttökelpoisten 3,4,5-substituoitujen bentsoyyliguanidiinien valmistamiseksi - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten 3,4,5-substituoitujen bentsoyyliguanidiinien valmistamiseksi Download PDFInfo
- Publication number
- FI113367B FI113367B FI932998A FI932998A FI113367B FI 113367 B FI113367 B FI 113367B FI 932998 A FI932998 A FI 932998A FI 932998 A FI932998 A FI 932998A FI 113367 B FI113367 B FI 113367B
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- substituted
- phenyl
- cycloalkyl
- hydrogen
- Prior art date
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- AJDQRQQNNLZLPM-UHFFFAOYSA-N n-(diaminomethylidene)benzamide Chemical class NC(N)=NC(=O)C1=CC=CC=C1 AJDQRQQNNLZLPM-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 11
- 230000008569 process Effects 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 43
- 239000001257 hydrogen Substances 0.000 claims abstract description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 25
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims abstract description 22
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims abstract description 11
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 31
- -1 C6H5- (C1-4) alkyl Chemical group 0.000 claims description 29
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
- 239000004305 biphenyl Substances 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 230000000269 nucleophilic effect Effects 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 230000004663 cell proliferation Effects 0.000 abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 208000028867 ischemia Diseases 0.000 abstract description 4
- 230000003389 potentiating effect Effects 0.000 abstract description 4
- 206010061216 Infarction Diseases 0.000 abstract description 3
- 239000003416 antiarrhythmic agent Substances 0.000 abstract description 3
- 230000007574 infarction Effects 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 2
- 230000003293 cardioprotective effect Effects 0.000 abstract description 2
- 230000001413 cellular effect Effects 0.000 abstract description 2
- 238000011161 development Methods 0.000 abstract description 2
- 208000035475 disorder Diseases 0.000 abstract description 2
- 201000002793 renal fibrosis Diseases 0.000 abstract description 2
- 206010019668 Hepatic fibrosis Diseases 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 102000052126 Sodium-Hydrogen Exchangers Human genes 0.000 abstract 1
- 108091006672 Sodium–hydrogen antiporter Proteins 0.000 abstract 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 230000003176 fibrotic effect Effects 0.000 abstract 1
- 230000002440 hepatic effect Effects 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 230000035778 pathophysiological process Effects 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 230000002685 pulmonary effect Effects 0.000 abstract 1
- 208000005069 pulmonary fibrosis Diseases 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000013078 crystal Substances 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 230000008018 melting Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 10
- QGAGCQPVCPGBJM-UHFFFAOYSA-N methyl 4-bromo-3-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C(S(C)(=O)=O)=C1 QGAGCQPVCPGBJM-UHFFFAOYSA-N 0.000 description 10
- 229960004198 guanidine Drugs 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
- 229960002576 amiloride Drugs 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000004132 cross linking Methods 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 235000010233 benzoic acid Nutrition 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- TVAWJXOBZYWQNX-UHFFFAOYSA-N n-(diaminomethylidene)benzamide;hydrochloride Chemical compound Cl.NC(=N)NC(=O)C1=CC=CC=C1 TVAWJXOBZYWQNX-UHFFFAOYSA-N 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010020880 Hypertrophy Diseases 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 206010003119 arrhythmia Diseases 0.000 description 3
- 150000001559 benzoic acids Chemical class 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- QDERNBXNXJCIQK-UHFFFAOYSA-N ethylisopropylamiloride Chemical compound CCN(C(C)C)C1=NC(N)=C(C(=O)N=C(N)N)N=C1Cl QDERNBXNXJCIQK-UHFFFAOYSA-N 0.000 description 3
- 230000004941 influx Effects 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
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- 230000035755 proliferation Effects 0.000 description 3
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- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- RWJAKMUWCQNRNP-UHFFFAOYSA-N 4-benzyl-n-(diaminomethylidene)-3-methylsulfonylbenzamide;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC(C(=O)NC(N)=N)=CC=C1CC1=CC=CC=C1 RWJAKMUWCQNRNP-UHFFFAOYSA-N 0.000 description 2
- WJIPYMULGUUBGX-UHFFFAOYSA-N 4-cyclohexyl-n-(diaminomethylidene)-3-methylsulfonylbenzamide;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC(C(=O)NC(N)=N)=CC=C1C1CCCCC1 WJIPYMULGUUBGX-UHFFFAOYSA-N 0.000 description 2
- BUWLZZLDJSRKMN-UHFFFAOYSA-N 4-cyclopentyl-n-(diaminomethylidene)-3-methylsulfonylbenzamide;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC(C(=O)NC(N)=N)=CC=C1C1CCCC1 BUWLZZLDJSRKMN-UHFFFAOYSA-N 0.000 description 2
- HSKPMVDLJHPEOK-UHFFFAOYSA-N 4-cyclopropyl-n-(diaminomethylidene)-3-methylsulfonylbenzamide;hydrochloride Chemical compound Cl.CS(=O)(=O)C1=CC(C(=O)NC(N)=N)=CC=C1C1CC1 HSKPMVDLJHPEOK-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- YPIAGTACDKOXKS-UHFFFAOYSA-M [Cl-].[Zn+]C1CCCC1 Chemical compound [Cl-].[Zn+]C1CCCC1 YPIAGTACDKOXKS-UHFFFAOYSA-M 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
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- 230000000144 pharmacologic effect Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- XPEIJWZLPWNNOK-UHFFFAOYSA-N (4-phenylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=CC=C1 XPEIJWZLPWNNOK-UHFFFAOYSA-N 0.000 description 1
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 1
- VXZBYIWNGKSFOJ-UHFFFAOYSA-N 2-[4-[5-(2,3-dihydro-1H-inden-2-ylamino)pyrazin-2-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC=1N=CC(=NC=1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 VXZBYIWNGKSFOJ-UHFFFAOYSA-N 0.000 description 1
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 1
- KBOBQLJBYKKAPN-UHFFFAOYSA-N 2-chloro-2-methylhexane Chemical compound CCCCC(C)(C)Cl KBOBQLJBYKKAPN-UHFFFAOYSA-N 0.000 description 1
- RXMUPNVSYKGKMY-UHFFFAOYSA-N 3-amino-6-chloro-n-(diaminomethylidene)-5-(dimethylamino)pyrazine-2-carboxamide Chemical compound CN(C)C1=NC(N)=C(C(=O)N=C(N)N)N=C1Cl RXMUPNVSYKGKMY-UHFFFAOYSA-N 0.000 description 1
- SGQDIUIVEWBSEB-UHFFFAOYSA-N 3-bromo-5-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC(Br)=CC(C(O)=O)=C1 SGQDIUIVEWBSEB-UHFFFAOYSA-N 0.000 description 1
- TYFNGDOECXNRBM-UHFFFAOYSA-N 3-chlorosulfonyl-4-cyclohexylbenzoic acid Chemical compound ClS(=O)(=O)C1=CC(C(=O)O)=CC=C1C1CCCCC1 TYFNGDOECXNRBM-UHFFFAOYSA-N 0.000 description 1
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- 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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Pregnancy & Childbirth (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4221594 | 1992-07-01 | ||
| DE4221594 | 1992-07-01 | ||
| DE4224107 | 1992-07-22 | ||
| DE4224107 | 1992-07-22 | ||
| DE4244319 | 1992-12-28 | ||
| DE4244319 | 1992-12-28 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI932998A0 FI932998A0 (fi) | 1993-06-29 |
| FI932998L FI932998L (fi) | 1994-01-02 |
| FI113367B true FI113367B (fi) | 2004-04-15 |
Family
ID=27203913
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI932998A FI113367B (fi) | 1992-07-01 | 1993-06-29 | Menetelmä terapeuttisesti käyttökelpoisten 3,4,5-substituoitujen bentsoyyliguanidiinien valmistamiseksi |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5693672A (cs) |
| EP (1) | EP0577024B1 (cs) |
| JP (1) | JP3490739B2 (cs) |
| AT (1) | ATE144248T1 (cs) |
| AU (1) | AU658309B2 (cs) |
| CA (1) | CA2099445A1 (cs) |
| DE (1) | DE59304166D1 (cs) |
| DK (1) | DK0577024T3 (cs) |
| ES (1) | ES2092729T3 (cs) |
| FI (1) | FI113367B (cs) |
| GR (1) | GR3021397T3 (cs) |
| IL (1) | IL106157A (cs) |
| NO (1) | NO179673C (cs) |
| NZ (1) | NZ248013A (cs) |
| TW (1) | TW328536B (cs) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL109570A0 (en) * | 1993-05-17 | 1994-08-26 | Fujisawa Pharmaceutical Co | Guanidine derivatives, pharmaceutical compositions containing the same and processes for the preparation thereof |
| DE4325822A1 (de) * | 1993-07-31 | 1995-02-02 | Hoechst Ag | Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE4412334A1 (de) * | 1994-04-11 | 1995-10-19 | Hoechst Ag | Substituierte N-Heteroaroylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE4417004A1 (de) * | 1994-05-13 | 1995-11-16 | Hoechst Ag | Perfluoralkyl-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| IL114670A0 (en) * | 1994-08-05 | 1995-11-27 | Fujisawa Pharmaceutical Co | Guanidine derivatives pharmaceutical compositions containing the same and processes for the preparation thereof |
| DE4430212A1 (de) * | 1994-08-28 | 1996-02-29 | Merck Patent Gmbh | Ortho-substituierte Benzoesäure-Derivate |
| DE4430213A1 (de) * | 1994-08-28 | 1996-02-29 | Merck Patent Gmbh | Arylbenzoylguanidine |
| DE4430916A1 (de) * | 1994-08-31 | 1996-03-07 | Merck Patent Gmbh | Alkyl-benzoylguanidin-Derivate |
| DE4432101A1 (de) * | 1994-09-09 | 1996-03-14 | Hoechst Ag | Aminosäure-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| AU670224B3 (en) * | 1994-09-28 | 1996-07-04 | Chain Reaction Sales Promotion Pty Ltd | Signage apparatus |
| TW372967B (en) * | 1994-12-27 | 1999-11-01 | Kanebo Ltd | 1,4 benzoxazine derivative, pharmaceutical composition containing the same and use thereof |
| DE19531138A1 (de) * | 1995-08-24 | 1997-02-27 | Merck Patent Gmbh | Alkenyl-benzoylguanidin-Derivate |
| DE19540995A1 (de) * | 1995-11-03 | 1997-05-07 | Hoechst Ag | Substituierte Sulfonimidamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE19542306A1 (de) * | 1995-11-14 | 1997-05-15 | Hoechst Ag | Sulfonylamino-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| PL316439A1 (en) * | 1995-11-20 | 1997-05-26 | Hoechst Ag | Novel substituted derivatives of benzoyloguanidine, method of obtaining them, their application in production of pharmaceutic and diagnostic agents and pharmaceutic agent as such |
| DE19546736A1 (de) * | 1995-12-14 | 1997-06-19 | Hoechst Ag | Substituierte Chromanylsulfonyl(thio)harnstoffe, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung pharmazeutischer Präparate |
| DE19622222A1 (de) * | 1996-06-03 | 1997-12-04 | Hoechst Ag | Verwendung von Inhibitoren des zellulären Na·+·/H·+·-Exchangers (NHE) zur Herstellung eines Medikament zur Normalisierung der Serumlipide |
| EP0972767A4 (en) | 1997-03-06 | 2000-05-24 | Toa Eiyo Ltd | CYCLOALKAN [b] PYRIDINE-3-CARBONYLGUANIDINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THEM |
| US6410563B1 (en) | 1999-12-22 | 2002-06-25 | Merck Frosst Canada & Co. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
| US6639077B2 (en) | 2000-03-23 | 2003-10-28 | Merck Frosst Canada & Co. | Tri-aryl-substituted-ethane PDE4 inhibitors |
| MY123585A (en) | 2000-03-23 | 2006-05-31 | Merck Canada Inc | Tri-aryl-substituted-ethane pde4 inhibitors. |
| JP2003534328A (ja) | 2000-05-25 | 2003-11-18 | メルク フロスト カナダ アンド カンパニー | フルオロアルコキシ置換ベンズアミドジクロロピリジニルｎ−オキシドｐｄｅ４阻害剤 |
| US6740666B2 (en) | 2000-12-20 | 2004-05-25 | Merck & Co., Inc. | Substituted 8-arylquinoline phosphodiesterase-4 inhibitors |
| ES2247325T3 (es) | 2001-05-24 | 2006-03-01 | MERCK FROSST CANADA & CO. | Inhibidores de 1-biaril-1,8-naftiridin-4-ona fosfodiesterasa-4. |
| JO2311B1 (en) | 2001-08-29 | 2005-09-12 | ميرك فروست كندا ليمتد | Alkyl inhibitors Ariel phosphodiesterase-4 |
| WO2003077918A1 (en) | 2002-03-12 | 2003-09-25 | Merck & Co., Inc. | Di-aryl substituted tetrazole modulators of metabotropic glutamate receptor-5 |
| US7365070B2 (en) * | 2002-12-04 | 2008-04-29 | Ore Pharmaceuticals Inc. | Modulators of melanocortin receptor |
| US7504401B2 (en) | 2003-08-29 | 2009-03-17 | Locus Pharmaceuticals, Inc. | Anti-cancer agents and uses thereof |
| AR046276A1 (es) | 2003-10-07 | 2005-11-30 | Renovis Inc | Derivados de amida como ligandos de canales ionicos y composiciones farmaceuticas y metodos que los utilizan. |
| KR20070119655A (ko) * | 2005-02-28 | 2007-12-20 | 레노비스, 인크. | 이온-채널 리간드로서의 아미드 유도체, 및 이를 사용한제약 조성물 및 방법 |
| US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| EA200701835A1 (ru) * | 2005-02-28 | 2008-02-28 | Реновис, Инк. | Амидные производные в качестве лигандов ионных каналов, их фармацевтические композиции и способы их применения |
| SMT202100683T1 (it) * | 2017-07-04 | 2022-01-10 | Sanofi Sa | Composti etinilici, loro preparazione e loro uso terapeutivo per il trattamento della malaria |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3420874A (en) * | 1962-09-28 | 1969-01-07 | Standard Oil Co | Amine addition salts of nitro-carboxyalkali metal phenolates |
| US3247035A (en) * | 1962-09-28 | 1966-04-19 | Standard Oil Co | Ammonium nitrate propellants containing a nitro-aminocarboxy-alkali metal phenolate combustion catalyst |
| US3780027A (en) * | 1970-04-29 | 1973-12-18 | Merck & Co Inc | Anthranilic acid derivatives |
| US3728332A (en) * | 1971-09-03 | 1973-04-17 | Nat Starch Chem Corp | Preparation of starch esters |
| US4178387A (en) * | 1976-03-30 | 1979-12-11 | William H. Rorer, Inc. | Method for the treatment of arrhythmia |
| US4251545A (en) * | 1979-09-19 | 1981-02-17 | Gaf Corporation | Fungicidal process using 1-(alkoxyaroyl)guanidines |
| DE3929582A1 (de) * | 1989-09-06 | 1991-03-07 | Hoechst Ag | Benzoylguanidine, verfahren zu ihrer herstellung, ihre verwendung als medikament sowie sie enthaltendes medikament |
| US5093194A (en) * | 1989-11-01 | 1992-03-03 | Mobil Oil Corporation | Oriented multilayer heat sealable packaging film |
| ATE139526T1 (de) * | 1992-02-15 | 1996-07-15 | Hoechst Ag | 3,5-substituierte benzoylguanidine, mit antiarrythmischer wirkung und inhibierender wirkung auf die proliferationen von zellen |
-
1993
- 1993-06-25 ES ES93110195T patent/ES2092729T3/es not_active Expired - Lifetime
- 1993-06-25 AT AT93110195T patent/ATE144248T1/de not_active IP Right Cessation
- 1993-06-25 DE DE59304166T patent/DE59304166D1/de not_active Expired - Lifetime
- 1993-06-25 EP EP93110195A patent/EP0577024B1/de not_active Expired - Lifetime
- 1993-06-25 DK DK93110195.0T patent/DK0577024T3/da active
- 1993-06-28 IL IL10615793A patent/IL106157A/en not_active IP Right Cessation
- 1993-06-29 FI FI932998A patent/FI113367B/fi not_active IP Right Cessation
- 1993-06-29 NZ NZ248013A patent/NZ248013A/en unknown
- 1993-06-30 AU AU41635/93A patent/AU658309B2/en not_active Ceased
- 1993-06-30 NO NO932392A patent/NO179673C/no unknown
- 1993-06-30 JP JP15988693A patent/JP3490739B2/ja not_active Expired - Fee Related
- 1993-06-30 CA CA002099445A patent/CA2099445A1/en not_active Abandoned
- 1993-08-23 TW TW082106777A patent/TW328536B/zh active
-
1995
- 1995-05-26 US US08/451,309 patent/US5693672A/en not_active Expired - Lifetime
-
1996
- 1996-10-17 GR GR960402615T patent/GR3021397T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0577024A1 (de) | 1994-01-05 |
| ES2092729T3 (es) | 1996-12-01 |
| JPH06116230A (ja) | 1994-04-26 |
| IL106157A (en) | 1999-11-30 |
| FI932998L (fi) | 1994-01-02 |
| CA2099445A1 (en) | 1994-01-02 |
| NO179673C (no) | 1996-11-27 |
| NZ248013A (en) | 1995-12-21 |
| TW328536B (en) | 1998-03-21 |
| AU658309B2 (en) | 1995-04-06 |
| AU4163593A (en) | 1994-01-06 |
| DK0577024T3 (cs) | 1997-02-24 |
| US5693672A (en) | 1997-12-02 |
| NO932392L (no) | 1994-01-03 |
| NO932392D0 (no) | 1993-06-30 |
| FI932998A0 (fi) | 1993-06-29 |
| JP3490739B2 (ja) | 2004-01-26 |
| IL106157A0 (en) | 1993-10-20 |
| GR3021397T3 (en) | 1997-01-31 |
| ATE144248T1 (de) | 1996-11-15 |
| EP0577024B1 (de) | 1996-10-16 |
| DE59304166D1 (de) | 1996-11-21 |
| NO179673B (no) | 1996-08-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |