JPH0789958A - ４−アミノピリミジン誘導体、その製造方法およびそれを含有する医薬品 - Google Patents
４−アミノピリミジン誘導体、その製造方法およびそれを含有する医薬品Info
- Publication number
- JPH0789958A JPH0789958A JP6222654A JP22265494A JPH0789958A JP H0789958 A JPH0789958 A JP H0789958A JP 6222654 A JP6222654 A JP 6222654A JP 22265494 A JP22265494 A JP 22265494A JP H0789958 A JPH0789958 A JP H0789958A
- Authority
- JP
- Japan
- Prior art keywords
- group
- imidazolyl
- compound according
- thienyl
- methylaminopyrimidine
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 112
- -1 amine compound Chemical class 0.000 claims abstract description 34
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 16
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 14
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 10
- 150000005007 4-aminopyrimidines Chemical class 0.000 claims abstract description 6
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 6
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 4
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 4
- 125000005529 alkyleneoxy group Chemical group 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 13
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- BHLSDEMYHGXDEB-UHFFFAOYSA-N n-benzyl-2-imidazol-1-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC(N=1)=CC=NC=1N1C=CN=C1 BHLSDEMYHGXDEB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- ZXTKRBHQYKODTC-UHFFFAOYSA-N 2-imidazol-1-yl-n-methyl-6-naphthalen-1-yl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C3=CC=CC=C3C=CC=2)=C1C1=CC=CS1 ZXTKRBHQYKODTC-UHFFFAOYSA-N 0.000 claims description 2
- KDVGNFQFXLZNRD-UHFFFAOYSA-N N-benzyl-2,5-di(imidazol-1-yl)-6-methylpyrimidin-4-amine Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)NCC1=CC=CC=C1)N1C=NC=C1)C KDVGNFQFXLZNRD-UHFFFAOYSA-N 0.000 claims description 2
- NREXKPJLVSIFCZ-UHFFFAOYSA-N N1(C=NC=C1)C1=NC(=C(C(=N1)CCOC)C1=CC(=CC=C1)OC)NC Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)CCOC)C1=CC(=CC=C1)OC)NC NREXKPJLVSIFCZ-UHFFFAOYSA-N 0.000 claims description 2
- PYMJPDXIMXUVLS-UHFFFAOYSA-N N1(C=NC=C1)C1=NC(=C(C(=N1)CCOC)C1=CC=C(C=C1)OC)NC Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)CCOC)C1=CC=C(C=C1)OC)NC PYMJPDXIMXUVLS-UHFFFAOYSA-N 0.000 claims description 2
- UOQFJYNFKDAPRW-UHFFFAOYSA-N N1(C=NC=C1)C1=NC(=C(C(=N1)CCOCCO)C1=CC(=CC=C1)OC)CN Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)CCOCCO)C1=CC(=CC=C1)OC)CN UOQFJYNFKDAPRW-UHFFFAOYSA-N 0.000 claims description 2
- UJURKDORYHEVNZ-UHFFFAOYSA-N N1(C=NC=C1)C1=NC(=C(C(=N1)CCOCCO)C1=CC=C(C=C1)OC)NC Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)CCOCCO)C1=CC=C(C=C1)OC)NC UJURKDORYHEVNZ-UHFFFAOYSA-N 0.000 claims description 2
- XCVWIZAKZPQBSH-UHFFFAOYSA-N N1(C=NC=C1)C1=NC(=C(C(=N1)NCC1=CC=CC=C1)C1=CC=C(C=C1)OC)C Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)NCC1=CC=CC=C1)C1=CC=C(C=C1)OC)C XCVWIZAKZPQBSH-UHFFFAOYSA-N 0.000 claims description 2
- QQVVZSWZMVHIBX-UHFFFAOYSA-N N1(C=NC=C1)C1=NC=C(C(=N1)CCOC)N Chemical compound N1(C=NC=C1)C1=NC=C(C(=N1)CCOC)N QQVVZSWZMVHIBX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([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
- 125000005843 halogen group Chemical group 0.000 claims description 2
- DEXBJDYTILITIS-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5,6-dimethylpyrimidin-4-amine Chemical compound CC=1C(C)=NC(N2C=NC=C2)=NC=1NCC1=CC=CC=C1 DEXBJDYTILITIS-UHFFFAOYSA-N 0.000 claims description 2
- ZOQGANUYHAUGMO-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-methylpyrimidin-4-amine Chemical compound CC1=CN=C(N2C=NC=C2)N=C1NCC1=CC=CC=C1 ZOQGANUYHAUGMO-UHFFFAOYSA-N 0.000 claims description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 2
- 239000003768 thromboxane synthase inhibitor Substances 0.000 claims description 2
- BQNXHDSGGRTFNX-UHFFFAOYSA-N n-methylpyrimidin-2-amine Chemical compound CNC1=NC=CC=N1 BQNXHDSGGRTFNX-UHFFFAOYSA-N 0.000 claims 6
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- RFMKUWJJIQLQOB-UHFFFAOYSA-N 2-(benzimidazol-1-yl)-6-(1,3-benzodioxol-5-yl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound CNC1=NC(N2C3=CC=CC=C3N=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CS1 RFMKUWJJIQLQOB-UHFFFAOYSA-N 0.000 claims 1
- KIENUZLCJVIMNJ-UHFFFAOYSA-N 2-[2-(6-amino-2-imidazol-1-yl-5-thiophen-2-ylpyrimidin-4-yl)ethoxy]ethanol Chemical compound NC1=NC(N2C=NC=C2)=NC(CCOCCO)=C1C1=CC=CS1 KIENUZLCJVIMNJ-UHFFFAOYSA-N 0.000 claims 1
- GNZWOKRRXWMIDK-UHFFFAOYSA-N 2-imidazol-1-yl-6-(3-methoxyphenyl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=CC(OC)=C1 GNZWOKRRXWMIDK-UHFFFAOYSA-N 0.000 claims 1
- ZJSAXCMSIZBQLN-UHFFFAOYSA-N 2-imidazol-1-yl-6-(4-imidazol-1-ylphenyl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C(C=C1)=CC=C1N1C=CN=C1 ZJSAXCMSIZBQLN-UHFFFAOYSA-N 0.000 claims 1
- OHUYWGMVSLMENX-UHFFFAOYSA-N 2-imidazol-1-yl-6-(4-methoxyphenyl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=C(OC)C=C1 OHUYWGMVSLMENX-UHFFFAOYSA-N 0.000 claims 1
- LPKBWLXQDDORSB-UHFFFAOYSA-N 2-imidazol-1-yl-n-methyl-5,6-dithiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=CS1 LPKBWLXQDDORSB-UHFFFAOYSA-N 0.000 claims 1
- WCGINXSHHXTUOI-UHFFFAOYSA-N 2-imidazol-1-yl-n-methyl-6-pyridin-3-yl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=CN=C1 WCGINXSHHXTUOI-UHFFFAOYSA-N 0.000 claims 1
- QLFGUSQOQSNXIL-UHFFFAOYSA-N 2-imidazol-1-yl-n-phenylmethoxy-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CONC1=NC(N2C=NC=C2)=NC=C1C1=CC=CS1 QLFGUSQOQSNXIL-UHFFFAOYSA-N 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- UCZQXJKDCHCTAI-UHFFFAOYSA-N 4h-1,3-dioxine Chemical compound C1OCC=CO1 UCZQXJKDCHCTAI-UHFFFAOYSA-N 0.000 claims 1
- ZAQXWRSCILOFCP-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-imidazol-1-yl-n-methyl-5-naphthalen-2-ylpyrimidin-4-amine Chemical compound N=1C(C=2C=C3OCOC3=CC=2)=C(C=2C=C3C=CC=CC3=CC=2)C(NC)=NC=1N1C=CN=C1 ZAQXWRSCILOFCP-UHFFFAOYSA-N 0.000 claims 1
- MPMFYXIJPYJMTO-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-5-(4-chlorophenyl)-2-imidazol-1-yl-n-methylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=C(Cl)C=C1 MPMFYXIJPYJMTO-UHFFFAOYSA-N 0.000 claims 1
- WPIASDUYUDJBEI-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-5-(furan-3-yl)-2-imidazol-1-yl-n-methylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C=1C=COC=1 WPIASDUYUDJBEI-UHFFFAOYSA-N 0.000 claims 1
- FTNOSRSQAXGUTI-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-n-methyl-2-(2-pyridin-3-ylethenyl)-5-thiophen-2-ylpyrimidin-4-amine Chemical compound N=1C(C=2C=C3OCOC3=CC=2)=C(C=2SC=CC=2)C(NC)=NC=1C=CC1=CC=CN=C1 FTNOSRSQAXGUTI-UHFFFAOYSA-N 0.000 claims 1
- KXCYFCXHGDMIGV-UHFFFAOYSA-N 6-(3-chlorophenyl)-2-imidazol-1-yl-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=CC(Cl)=C1 KXCYFCXHGDMIGV-UHFFFAOYSA-N 0.000 claims 1
- FOSQODJYRAMXHJ-UHFFFAOYSA-N 6-(4-chlorophenyl)-2-imidazol-1-yl-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=C(Cl)C=C1 FOSQODJYRAMXHJ-UHFFFAOYSA-N 0.000 claims 1
- DWTLTDDXIGGKJD-UHFFFAOYSA-N 6-(furan-2-yl)-2-imidazol-1-yl-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=CO1 DWTLTDDXIGGKJD-UHFFFAOYSA-N 0.000 claims 1
- XUVQJSVONJKPQP-UHFFFAOYSA-N ethyl 4-[2-imidazol-1-yl-6-(methylamino)-5-thiophen-2-ylpyrimidin-4-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=NC(N2C=NC=C2)=NC(NC)=C1C1=CC=CS1 XUVQJSVONJKPQP-UHFFFAOYSA-N 0.000 claims 1
- 150000004712 monophosphates Chemical class 0.000 claims 1
- VZEJCDIVUXCCAS-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-(1,3-thiazol-2-yl)pyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC1=NC(N2C=NC=C2)=NC=C1C1=NC=CS1 VZEJCDIVUXCCAS-UHFFFAOYSA-N 0.000 claims 1
- UZUAFAASMLJDJH-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-(phenoxymethyl)pyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC1=NC(N2C=NC=C2)=NC=C1COC1=CC=CC=C1 UZUAFAASMLJDJH-UHFFFAOYSA-N 0.000 claims 1
- AVCXSNRZOPWGDP-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-pyridin-3-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC1=NC(N2C=NC=C2)=NC=C1C1=CC=CN=C1 AVCXSNRZOPWGDP-UHFFFAOYSA-N 0.000 claims 1
- JHQRICWXVQWKPS-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC1=NC(N2C=NC=C2)=NC=C1C1=CC=CS1 JHQRICWXVQWKPS-UHFFFAOYSA-N 0.000 claims 1
- IWTFKBMRGPGAFO-UHFFFAOYSA-N n-benzyl-5-(1-chloroethenyl)-2-imidazol-1-ylpyrimidin-4-amine Chemical compound ClC(=C)C1=CN=C(N2C=NC=C2)N=C1NCC1=CC=CC=C1 IWTFKBMRGPGAFO-UHFFFAOYSA-N 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 20
- 125000005842 heteroatom Chemical group 0.000 abstract description 7
- 206010061218 Inflammation Diseases 0.000 abstract description 3
- 230000004054 inflammatory process Effects 0.000 abstract description 3
- 125000005702 oxyalkylene group Chemical group 0.000 abstract description 3
- 150000003230 pyrimidines Chemical class 0.000 abstract description 3
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 2
- 208000019622 heart disease Diseases 0.000 abstract 1
- 239000000126 substance Substances 0.000 description 72
- 229910052739 hydrogen Inorganic materials 0.000 description 33
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000000203 mixture Substances 0.000 description 23
- 239000001257 hydrogen Substances 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 12
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 125000001246 bromo group Chemical group Br* 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 206010002383 Angina Pectoris Diseases 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 206010019280 Heart failures Diseases 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 5
- 239000003701 inert diluent Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 125000002971 oxazolyl group Chemical group 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 125000001425 triazolyl group Chemical group 0.000 description 5
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
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- SHZKQBHERIJWAO-AATRIKPKSA-N ozagrel Chemical compound C1=CC(/C=C/C(=O)O)=CC=C1CN1C=NC=C1 SHZKQBHERIJWAO-AATRIKPKSA-N 0.000 description 1
- 229950003837 ozagrel Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- SGUKUZOVHSFKPH-YNNPMVKQSA-N prostaglandin G2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](OO)CCCCC)[C@H]2C\C=C/CCCC(O)=O SGUKUZOVHSFKPH-YNNPMVKQSA-N 0.000 description 1
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- ZAPOSLLMEZKFQS-NBYYMMLRSA-M sodium;(e)-2-methyl-3-[4-(pyridin-3-ylmethyl)phenyl]prop-2-enoate Chemical compound [Na+].C1=CC(\C=C(/C)C([O-])=O)=CC=C1CC1=CC=CN=C1 ZAPOSLLMEZKFQS-NBYYMMLRSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000000225 synapse Anatomy 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
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- REZGGXNDEMKIQB-UHFFFAOYSA-N zaprinast Chemical compound CCCOC1=CC=CC=C1C1=NC(=O)C2=NNNC2=N1 REZGGXNDEMKIQB-UHFFFAOYSA-N 0.000 description 1
- 229950005371 zaprinast Drugs 0.000 description 1
Classifications
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- 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
- C07D231/12—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11190693A | 1993-08-26 | 1993-08-26 | |
| US08/111,906 | 1993-08-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0789958A true JPH0789958A (ja) | 1995-04-04 |
Family
ID=22341063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6222654A Pending JPH0789958A (ja) | 1993-08-26 | 1994-08-24 | ４−アミノピリミジン誘導体、その製造方法およびそれを含有する医薬品 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5525604A (OSRAM) |
| EP (1) | EP0640599B1 (OSRAM) |
| JP (1) | JPH0789958A (OSRAM) |
| KR (1) | KR100204433B1 (OSRAM) |
| CN (1) | CN1109055A (OSRAM) |
| AT (1) | ATE163647T1 (OSRAM) |
| CA (1) | CA2130878C (OSRAM) |
| DE (1) | DE69408750T2 (OSRAM) |
| DK (1) | DK0640599T3 (OSRAM) |
| ES (1) | ES2114662T3 (OSRAM) |
| TW (1) | TW273548B (OSRAM) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006123639A1 (ja) * | 2005-05-18 | 2006-11-23 | Asahi Kasei Pharma Corporation | ピリミジン誘導体 |
| JP2012501961A (ja) * | 2008-09-04 | 2012-01-26 | 田辺三菱製薬株式会社 | 三置換ピリミジン化合物及びそのｐｄｅ１０阻害薬としての使用 |
| JP2014520767A (ja) * | 2011-07-07 | 2014-08-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | がんの処置のための置換されたアザ複素環 |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| EP1005343A1 (en) * | 1996-03-08 | 2000-06-07 | Smithkline Beecham Corporation | Use of csaid?tm compounds as inhibitors of angiogenesis |
| DE19644228A1 (de) * | 1996-10-24 | 1998-04-30 | Merck Patent Gmbh | Thienopyrimidine |
| KR100239800B1 (ko) * | 1996-11-28 | 2000-03-02 | 손경식 | 4,5-디아미노 피리미딘 유도체 및 이의 제조방법 |
| US6432947B1 (en) | 1997-02-19 | 2002-08-13 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| NZ337861A (en) * | 1997-02-19 | 2001-02-23 | Berlex Lab | N-heterocyclic derivatives for treating multiple sclerosis, HIV dementia, Parkinson's disease, meningitis, atherosclerosis, cancer, inflammatory skin diseases |
| IN188411B (OSRAM) | 1997-03-27 | 2002-09-21 | Yuhan Corp | |
| US6440965B1 (en) * | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
| NZ506417A (en) | 1998-02-17 | 2003-05-30 | Tularik Inc | Anti-viral pyrimidine derivatives |
| DE19819023A1 (de) * | 1998-04-29 | 1999-11-04 | Merck Patent Gmbh | Thienopyrimidine |
| KR100272471B1 (ko) | 1998-11-17 | 2000-11-15 | 김선진 | 신규의 피리미딘 유도체 및 그의 제조방법 |
| WO2000043385A1 (fr) * | 1999-01-25 | 2000-07-27 | Zenyaku Kogyo Kabushiki Kaisha | Composes heterocycliques et agents antitumoraux les comprenant en tant que principe actif |
| US6583148B1 (en) | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
| KR100546992B1 (ko) * | 1999-04-09 | 2006-02-01 | 씨제이 주식회사 | 4,5-다이아미노 피리미딘 유도체 및 이의 제조방법 |
| US7037916B2 (en) | 1999-07-15 | 2006-05-02 | Pharmacopeia Drug Discovery, Inc. | Pyrimidine derivatives as IL-8 receptor antagonists |
| MY123528A (en) * | 1999-09-16 | 2006-05-31 | Mitsubihsi Tanabe Pharma Corp | Aromatic nitrogen-containing 6-membered cyclic compounds. |
| EP1223170B1 (en) * | 1999-10-12 | 2005-12-28 | Takeda Pharmaceutical Company Limited | Pyrimidine-5-carboxamide compounds, process for producing the same and use thereof |
| CA2395418A1 (en) * | 1999-12-24 | 2001-07-05 | Bayer Aktiengesellschaft | Isoxazolo pyrimidinones and the use thereof |
| US6943161B2 (en) * | 1999-12-28 | 2005-09-13 | Pharmacopela Drug Discovery, Inc. | Pyrimidine and triazine kinase inhibitors |
| US6410726B1 (en) | 2000-01-12 | 2002-06-25 | Tularik Inc. | Arylsulfonic acid salts of pyrimidine-based antiviral |
| US6525051B2 (en) | 2000-03-27 | 2003-02-25 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| ES2346513T3 (es) | 2000-07-24 | 2010-10-18 | Krenitsky Pharmaceuticals, Inc. | 5-alquinil pirimidinas sustituidas que tienen actividad neurotrofica. |
| IT1318674B1 (it) * | 2000-08-08 | 2003-08-27 | Nicox Sa | Faramaci per l'incontinenza. |
| US6716851B2 (en) | 2000-12-12 | 2004-04-06 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof |
| EP1351691A4 (en) * | 2000-12-12 | 2005-06-22 | Cytovia Inc | SUBSTITUTED 2-ARYL-4-ARYLAMINOPYRIMIDINES AND ANALOGUES AS ACTIVATORS OF CASPASES AND APOPTOSIS INDUCERS, AND USE THEREOF |
| US20040127502A1 (en) | 2001-01-31 | 2004-07-01 | Synaptic Pharmaceutical Corporation | Use of GAL3 antagonist for treatment of depression |
| US7081470B2 (en) | 2001-01-31 | 2006-07-25 | H. Lundbeck A/S | Use of GALR3 receptor antagonists for the treatment of depression and/or anxiety and compounds useful in such methods |
| EP1364950A4 (en) * | 2001-02-26 | 2005-03-09 | Tanabe Seiyaku Co | Pyridopyrimidine and naphthyridine derivatives |
| DK1389617T3 (da) | 2001-04-27 | 2007-05-07 | Zenyaku Kogyo Kk | Heterocyclisk forbindelse og antitumormiddel indeholdende denne som den aktive bestanddel |
| US6982259B2 (en) | 2002-04-30 | 2006-01-03 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| AU2003246587A1 (en) | 2002-07-02 | 2004-01-23 | F. Hoffmann-La Roche Ag | 2, 5-substituted pyrimidine derivatives as ccr-3 receptor antagonists ix |
| WO2005110416A2 (en) * | 2004-05-08 | 2005-11-24 | Neurogen Corporation | 4,5-disubstituted-2-aryl pyrimidines |
| BRPI0517737A (pt) | 2004-11-17 | 2008-10-21 | Miikana Therapeutics Inc | inibidores de quinase |
| PT1864665E (pt) | 2005-03-11 | 2012-06-27 | Zenyaku Kogyo Kk | Agente imunossupressor compreendendo um composto heterocíclico como ingrediente activo |
| US20060293343A1 (en) * | 2005-05-18 | 2006-12-28 | Asahi Kasei Pharma Corporation | Pyrimidine derivatives |
| ES2535854T3 (es) * | 2005-09-30 | 2015-05-18 | Miikana Therapeutics, Inc. | Compuestos de pirazol sustituidos |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| EP2166849A4 (en) * | 2007-06-11 | 2010-09-15 | Miikana Therapeutics Inc | SUBSTITUTED PYRAZOL COMPOUNDS |
| US20110124649A1 (en) * | 2007-11-09 | 2011-05-26 | The Johns Hopkins University | Inhibitors of human methionine aminopeptidase 1 and methods of treating disorders |
| CN103002738A (zh) | 2010-05-21 | 2013-03-27 | 英特利凯恩有限责任公司 | 用于激酶调节的化学化合物、组合物和方法 |
| AR091790A1 (es) | 2011-08-29 | 2015-03-04 | Infinity Pharmaceuticals Inc | Derivados de isoquinolin-1-ona y sus usos |
| US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| WO2015089218A1 (en) * | 2013-12-10 | 2015-06-18 | David Wustrow | Monocyclic pyrimidine/pyridine compounds as inhibitors of p97 complex |
| SI3089971T1 (sl) | 2014-01-01 | 2020-11-30 | Medivation Technologies Llc | Spojine in postopki za uporabo |
| US9828363B2 (en) | 2014-01-20 | 2017-11-28 | Cleave Biosciences, Inc. | Fused pyrimidines as inhibitors of P97 complex |
| CN105294661B (zh) * | 2015-07-27 | 2017-10-24 | 西南大学 | 5‑氟尿嘧啶苯并咪唑类化合物及其制备方法和应用 |
| GB201705263D0 (en) * | 2017-03-31 | 2017-05-17 | Probiodrug Ag | Novel inhibitors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3992320A (en) * | 1974-08-24 | 1976-11-16 | Basf Aktiengesellschaft | Manufacture of a modified titanium component for catalysts of the Ziegler-Natta type |
| US4018770A (en) * | 1975-03-03 | 1977-04-19 | Sterling Drug Inc. | N-(2-(pyridinyl)-4-pyrimidinyl)-aminomethylenemalonates and analogs |
| US4032523A (en) * | 1975-03-03 | 1977-06-28 | Sterling Drug Inc. | 4-amino (or halo or hydroxy or hydrazino)-2-(pyridinyl)pyrimidines |
| US3992380A (en) * | 1975-03-03 | 1976-11-16 | Sterling Drug Inc. | 5,8-Dihydro-5-oxo-2-(4-or 3-pyridinyl)pyrido[2,3-d]pyrimidine-6-carboxylic acids and esters |
| DE3922735A1 (de) * | 1989-07-11 | 1991-01-24 | Hoechst Ag | Aminopyrimidin-derivate, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide |
| JP2789134B2 (ja) * | 1992-09-28 | 1998-08-20 | ファイザー・インク． | 糖尿病の合併症を制御する置換ピリミジン類 |
| US5318975A (en) * | 1993-02-16 | 1994-06-07 | Berlex Laboratories, Inc. | 5-pyrimdineamine derivatives |
-
1994
- 1994-08-12 DK DK94305973T patent/DK0640599T3/da active
- 1994-08-12 DE DE69408750T patent/DE69408750T2/de not_active Expired - Fee Related
- 1994-08-12 AT AT94305973T patent/ATE163647T1/de not_active IP Right Cessation
- 1994-08-12 EP EP94305973A patent/EP0640599B1/en not_active Expired - Lifetime
- 1994-08-12 ES ES94305973T patent/ES2114662T3/es not_active Expired - Lifetime
- 1994-08-24 US US08/295,377 patent/US5525604A/en not_active Expired - Fee Related
- 1994-08-24 JP JP6222654A patent/JPH0789958A/ja active Pending
- 1994-08-25 CN CN94109363A patent/CN1109055A/zh active Pending
- 1994-08-25 KR KR1019940021017A patent/KR100204433B1/ko not_active Expired - Fee Related
- 1994-08-25 CA CA002130878A patent/CA2130878C/en not_active Expired - Fee Related
- 1994-08-29 TW TW083107897A patent/TW273548B/zh active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006123639A1 (ja) * | 2005-05-18 | 2006-11-23 | Asahi Kasei Pharma Corporation | ピリミジン誘導体 |
| JP2012501961A (ja) * | 2008-09-04 | 2012-01-26 | 田辺三菱製薬株式会社 | 三置換ピリミジン化合物及びそのｐｄｅ１０阻害薬としての使用 |
| JP2014520767A (ja) * | 2011-07-07 | 2014-08-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | がんの処置のための置換されたアザ複素環 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR950005825A (ko) | 1995-03-20 |
| DE69408750D1 (de) | 1998-04-09 |
| CA2130878A1 (en) | 1995-02-27 |
| EP0640599A1 (en) | 1995-03-01 |
| CA2130878C (en) | 1999-03-23 |
| KR100204433B1 (ko) | 1999-06-15 |
| CN1109055A (zh) | 1995-09-27 |
| ATE163647T1 (de) | 1998-03-15 |
| DK0640599T3 (da) | 1998-09-28 |
| US5525604A (en) | 1996-06-11 |
| DE69408750T2 (de) | 1998-07-23 |
| ES2114662T3 (es) | 1998-06-01 |
| TW273548B (OSRAM) | 1996-04-01 |
| EP0640599B1 (en) | 1998-03-04 |
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