ES2222389T3 - Derivados de 6-fenilpirrolopirimidindiona. - Google Patents
Derivados de 6-fenilpirrolopirimidindiona.Info
- Publication number
- ES2222389T3 ES2222389T3 ES01960264T ES01960264T ES2222389T3 ES 2222389 T3 ES2222389 T3 ES 2222389T3 ES 01960264 T ES01960264 T ES 01960264T ES 01960264 T ES01960264 T ES 01960264T ES 2222389 T3 ES2222389 T3 ES 2222389T3
- Authority
- ES
- Spain
- Prior art keywords
- group
- substituted
- groups
- methyl
- unsubstituted
- 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
- -1 hydroxy, phenyl Chemical group 0.000 claims abstract description 159
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 36
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 35
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 20
- 125000005843 halogen group Chemical group 0.000 claims abstract description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 15
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 239000001301 oxygen Substances 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 239000011593 sulfur Substances 0.000 claims abstract description 11
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 8
- 125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- BPZYTYKVRIOQSN-UHFFFAOYSA-N 6-phenylpyrrolo[3,2-d]pyrimidine-2,4-dione Chemical class C=1C2=NC(=O)NC(=O)C2=NC=1C1=CC=CC=C1 BPZYTYKVRIOQSN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 126
- 238000002360 preparation method Methods 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 45
- 125000004429 atom Chemical group 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000004193 piperazinyl group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000002757 morpholinyl group Chemical group 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000005936 piperidyl group Chemical group 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 8
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000005188 oxoalkyl group Chemical group 0.000 claims description 7
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 claims description 6
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 6
- 150000001204 N-oxides Chemical class 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 6
- CPYWUBNSLNEDFN-UHFFFAOYSA-N 3-methyl-6-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C=2NC=3C(=O)N(C)C(=O)N(CCC)C=3C=2)C(OCCC)=CC=C1S(=O)(=O)N1CCN(C)CC1 CPYWUBNSLNEDFN-UHFFFAOYSA-N 0.000 claims description 5
- GBLNSFUQJHRVKQ-UHFFFAOYSA-N 6-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-3-methyl-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C=2NC=3C(=O)N(C)C(=O)N(CCC)C=3C=2)C(OCCC)=CC=C1S(=O)(=O)N1CCN(CC)CC1 GBLNSFUQJHRVKQ-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 206010057671 Female sexual dysfunction Diseases 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- PFLYTCRYCSXVFR-UHFFFAOYSA-N 7-bromo-6-[2-ethoxy-5-[4-(3-hydroxypropyl)piperazin-1-yl]sulfonylphenyl]-3-methyl-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound N1C=2C(=O)N(C)C(=O)N(CCC)C=2C(Br)=C1C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CCCO)CC1 PFLYTCRYCSXVFR-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 208000007718 Stable Angina Diseases 0.000 claims description 3
- 201000009961 allergic asthma Diseases 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- 230000008991 intestinal motility Effects 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
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 208000015891 sexual disease Diseases 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 208000019553 vascular disease Diseases 0.000 claims description 3
- LNDZXOWGUAIUBG-UHFFFAOYSA-N 6-aminouracil Chemical compound NC1=CC(=O)NC(=O)N1 LNDZXOWGUAIUBG-UHFFFAOYSA-N 0.000 claims description 2
- QJHZALCNLOJLPG-UHFFFAOYSA-N 7-bromo-6-[5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl-2-propoxyphenyl]-3-methyl-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C2=C(C3=C(C(N(C)C(=O)N3CCC)=O)N2)Br)C(OCCC)=CC=C1S(=O)(=O)N1CCN(CCO)CC1 QJHZALCNLOJLPG-UHFFFAOYSA-N 0.000 claims description 2
- PUULIDJFGBYZPM-UHFFFAOYSA-N 7-bromo-6-[5-[4-(3-hydroxypropyl)piperazin-1-yl]sulfonyl-2-propoxyphenyl]-3-methyl-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C2=C(C3=C(C(N(C)C(=O)N3CCC)=O)N2)Br)C(OCCC)=CC=C1S(=O)(=O)N1CCN(CCCO)CC1 PUULIDJFGBYZPM-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 206010002388 Angina unstable Diseases 0.000 claims 2
- 201000001068 Prinzmetal angina Diseases 0.000 claims 2
- 208000007814 Unstable Angina Diseases 0.000 claims 2
- 210000004204 blood vessel Anatomy 0.000 claims 2
- 208000023819 chronic asthma Diseases 0.000 claims 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 2
- QTQGWONXBULRFZ-UHFFFAOYSA-N 7-bromo-3-methyl-6-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C2=C(C3=C(C(N(C)C(=O)N3CCC)=O)N2)Br)C(OCCC)=CC=C1S(=O)(=O)N1CCN(C)CC1 QTQGWONXBULRFZ-UHFFFAOYSA-N 0.000 claims 1
- DDWRYJJJTASJDZ-UHFFFAOYSA-N 7-chloro-3-methyl-6-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-1-propyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C2=C(C3=C(C(N(C)C(=O)N3CCC)=O)N2)Cl)C(OCCC)=CC=C1S(=O)(=O)N1CCN(C)CC1 DDWRYJJJTASJDZ-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 239000007787 solid Substances 0.000 description 41
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 13
- 230000014759 maintenance of location Effects 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- SHQYZHCVGVXICO-UHFFFAOYSA-N 6-phenyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione Chemical class N1C=2C(=O)NC(=O)NC=2C=C1C1=CC=CC=C1 SHQYZHCVGVXICO-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- AVLYZVIFLPENOU-UHFFFAOYSA-N 6-phenyl-1,7-dihydropyrrolo[2,3-d]pyrimidine-2,4-dione Chemical class C=1C=2C(=O)NC(=O)NC=2NC=1C1=CC=CC=C1 AVLYZVIFLPENOU-UHFFFAOYSA-N 0.000 description 8
- 101100296726 Caenorhabditis elegans pde-5 gene Proteins 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 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 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 6
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 5
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 4
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
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- 239000011780 sodium chloride Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- GTILCVOGKHZRBS-UHFFFAOYSA-N dichloromethane;ethanol;hydrate Chemical compound O.CCO.ClCCl GTILCVOGKHZRBS-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
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- SZCRKKLYFJHWES-UHFFFAOYSA-N 7-chloro-6-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-3-methyl-1-(2-methylpropyl)-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound C1=C(C2=C(C3=C(C(N(C)C(=O)N3CC(C)C)=O)N2)Cl)C(OCC)=CC=C1S(=O)(=O)N1CCN(CCO)CC1 SZCRKKLYFJHWES-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- STFSJTPVIIDAQX-LTRPLHCISA-M sodium;(e)-4-octadecoxy-4-oxobut-2-enoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O STFSJTPVIIDAQX-LTRPLHCISA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- 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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (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)
- Public Health (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Reproductive Health (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Hospice & Palliative Care (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200001436 | 2000-06-07 | ||
| ES200001436 | 2000-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2222389T3 true ES2222389T3 (es) | 2005-02-01 |
Family
ID=8493813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01960264T Expired - Lifetime ES2222389T3 (es) | 2000-06-07 | 2001-06-01 | Derivados de 6-fenilpirrolopirimidindiona. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6943253B2 (enExample) |
| EP (1) | EP1286997B1 (enExample) |
| JP (1) | JP2003535864A (enExample) |
| AR (1) | AR030424A1 (enExample) |
| AT (1) | ATE273980T1 (enExample) |
| AU (1) | AU2001281802A1 (enExample) |
| CA (1) | CA2411013A1 (enExample) |
| DE (1) | DE60105020T2 (enExample) |
| ES (1) | ES2222389T3 (enExample) |
| MY (1) | MY133995A (enExample) |
| PE (1) | PE20020219A1 (enExample) |
| WO (1) | WO2001094350A1 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2193839B1 (es) * | 2001-06-22 | 2005-02-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de 6-fenildihidropirrolpirimidindiona. |
| ES2208063B1 (es) | 2002-04-01 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de la 4-(pirrolopirimidin-6-il)bencenosulfonamida. |
| DE10229778A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Neue Verwendung von Imidazotriazinonen |
| PL1644021T3 (pl) * | 2003-06-13 | 2013-01-31 | Ironwood Pharmaceuticals Inc | Sposoby i kompozycje do leczenia zaburzeń żołądkowo-jelitowych |
| US7449473B2 (en) | 2003-10-31 | 2008-11-11 | Cv Therapeutics, Inc. | Substituted pyrrolo[3,2-d]pyrimidin-2,4-diones as A2b adenosine receptor antagonists |
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| AT512084A1 (de) * | 2011-10-20 | 2013-05-15 | Univ Wien Tech | Diazabicyclo- und diazaspiro-alkanderivate als phosphodiesterase-5 inhibitoren |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5260322A (en) | 1990-10-08 | 1993-11-09 | Merck & Co., Inc. | Angiotension II antagonists in the treatment of hyperuricemia |
| FR2737494B1 (fr) * | 1995-08-04 | 1997-08-29 | Synthelabo | Derives de benzenesulfonamide, leur preparation et leur application en therapeutique |
| WO1999062905A1 (en) * | 1998-06-03 | 1999-12-09 | Almirall Prodesfarma, S.A. | 8-phenylxanthine derivatives and their use as phosphodiesterase inhibitors |
-
2001
- 2001-06-01 CA CA002411013A patent/CA2411013A1/en not_active Abandoned
- 2001-06-01 WO PCT/EP2001/006306 patent/WO2001094350A1/en not_active Ceased
- 2001-06-01 EP EP01960264A patent/EP1286997B1/en not_active Expired - Lifetime
- 2001-06-01 AT AT01960264T patent/ATE273980T1/de not_active IP Right Cessation
- 2001-06-01 AU AU2001281802A patent/AU2001281802A1/en not_active Abandoned
- 2001-06-01 DE DE60105020T patent/DE60105020T2/de not_active Expired - Lifetime
- 2001-06-01 JP JP2002501899A patent/JP2003535864A/ja not_active Withdrawn
- 2001-06-01 ES ES01960264T patent/ES2222389T3/es not_active Expired - Lifetime
- 2001-06-06 PE PE2001000521A patent/PE20020219A1/es not_active Application Discontinuation
- 2001-06-06 AR ARP010102696A patent/AR030424A1/es unknown
- 2001-06-06 MY MYPI20012656 patent/MY133995A/en unknown
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2002
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|---|---|
| PE20020219A1 (es) | 2002-04-17 |
| CA2411013A1 (en) | 2001-12-13 |
| MY133995A (en) | 2007-11-30 |
| ATE273980T1 (de) | 2004-09-15 |
| US6943253B2 (en) | 2005-09-13 |
| DE60105020D1 (de) | 2004-09-23 |
| AR030424A1 (es) | 2003-08-20 |
| AU2001281802A1 (en) | 2001-12-17 |
| EP1286997A1 (en) | 2003-03-05 |
| WO2001094350A1 (en) | 2001-12-13 |
| US20030232838A1 (en) | 2003-12-18 |
| EP1286997B1 (en) | 2004-08-18 |
| JP2003535864A (ja) | 2003-12-02 |
| DE60105020T2 (de) | 2005-08-18 |
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