DE60311820T2 - Neue verwendung von pyrimidin- oder triazin-2-carbonsäurenitrilen zur behandlung von krankheiten, die mit cysteinproteaseaktivität assoziiert sind, und neue pyridimidin-2-carbonsäurenitrilderivate - Google Patents
Neue verwendung von pyrimidin- oder triazin-2-carbonsäurenitrilen zur behandlung von krankheiten, die mit cysteinproteaseaktivität assoziiert sind, und neue pyridimidin-2-carbonsäurenitrilderivate Download PDFInfo
- Publication number
- DE60311820T2 DE60311820T2 DE60311820T DE60311820T DE60311820T2 DE 60311820 T2 DE60311820 T2 DE 60311820T2 DE 60311820 T DE60311820 T DE 60311820T DE 60311820 T DE60311820 T DE 60311820T DE 60311820 T2 DE60311820 T2 DE 60311820T2
- Authority
- DE
- Germany
- Prior art keywords
- amino
- carbonitrile
- chlorophenyl
- alkyl
- morpholin
- 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 - Fee Related
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- 201000010099 disease Diseases 0.000 title abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 9
- 230000000694 effects Effects 0.000 title abstract description 5
- 239000004365 Protease Substances 0.000 title description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title description 2
- 239000002253 acid Substances 0.000 title 2
- 108091005804 Peptidases Proteins 0.000 title 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title 1
- 150000007513 acids Chemical class 0.000 title 1
- 239000010143 cystone Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 28
- -1 amino, hydroxy Chemical group 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 40
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- NMWMRLWGNJUBRC-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(dimethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N#CC1=NC(N(C)C)=NC(NC=2C=CC(Cl)=CC=2)=N1 NMWMRLWGNJUBRC-UHFFFAOYSA-N 0.000 claims description 4
- KHPHMGJSXDODOC-UHFFFAOYSA-N 4-morpholin-4-yl-6-(4-phenoxypiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(CC1)CCC1OC1=CC=CC=C1 KHPHMGJSXDODOC-UHFFFAOYSA-N 0.000 claims description 4
- GJHNZJNXSKYROP-UHFFFAOYSA-N 5-amino-4-(4-chloroanilino)-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCOCC2)C(N)=C1NC1=CC=C(Cl)C=C1 GJHNZJNXSKYROP-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- CMRHBNMOCLQRSF-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(NC=2C=C3OCCOC3=CC=2)=NC=1N1CCOCC1 CMRHBNMOCLQRSF-UHFFFAOYSA-N 0.000 claims description 3
- XWCQLQFUUUVLRU-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-6-(4-chloroanilino)-5-methoxypyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCC(N)CC2)C(OC)=C1NC1=CC=C(Cl)C=C1 XWCQLQFUUUVLRU-UHFFFAOYSA-N 0.000 claims description 3
- LNLMQGVSOHPCFR-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(3-pyrrolidin-1-ylpropylamino)pyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(NCCCN2CCCC2)=NC(C#N)=N1 LNLMQGVSOHPCFR-UHFFFAOYSA-N 0.000 claims description 3
- VCUKMSHUJDBTKR-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(dimethylamino)pyrimidine-2-carbonitrile Chemical compound N#CC1=NC(N(C)C)=CC(NC=2C=CC(Cl)=CC=2)=N1 VCUKMSHUJDBTKR-UHFFFAOYSA-N 0.000 claims description 3
- CFTYWZFVQURLDD-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(ethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N#CC1=NC(NCC)=NC(NC=2C=CC(Cl)=CC=2)=N1 CFTYWZFVQURLDD-UHFFFAOYSA-N 0.000 claims description 3
- GKWVLGLOAVNKNN-UHFFFAOYSA-N 4-(4-chloroanilino)-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCOCC2)=N1 GKWVLGLOAVNKNN-UHFFFAOYSA-N 0.000 claims description 3
- PHRFVDJKWANIIJ-UHFFFAOYSA-N 4-(4-chloroanilino)-6-piperazin-1-ylpyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(N2CCNCC2)=NC(C#N)=N1 PHRFVDJKWANIIJ-UHFFFAOYSA-N 0.000 claims description 3
- XUABEUVVOXVCEQ-UHFFFAOYSA-N 4-(4-chloroanilino)-6-piperidin-1-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCCCC2)=N1 XUABEUVVOXVCEQ-UHFFFAOYSA-N 0.000 claims description 3
- FNIDFZPHGCXTQD-UHFFFAOYSA-N 4-(4-chloroanilino)-6-pyrrolidin-1-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCCC2)=N1 FNIDFZPHGCXTQD-UHFFFAOYSA-N 0.000 claims description 3
- ICWNIFGBCIVBTL-UHFFFAOYSA-N 4-(4-imidazol-1-ylpiperidin-1-yl)-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(CC1)CCC1N1C=CN=C1 ICWNIFGBCIVBTL-UHFFFAOYSA-N 0.000 claims description 3
- NLPJWWPRAXCQIW-UHFFFAOYSA-N 4-(7-azabicyclo[2.2.1]heptan-7-yl)-6-(4-chloroanilino)-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2C3CCC2CC3)=N1 NLPJWWPRAXCQIW-UHFFFAOYSA-N 0.000 claims description 3
- NSXYUBSJTLTVOX-UHFFFAOYSA-N 4-[4-(5-chloropyridin-2-yl)piperazin-1-yl]-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N1=CC(Cl)=CC=C1N1CCN(C=2N=C(N=C(N=2)C#N)N2CCOCC2)CC1 NSXYUBSJTLTVOX-UHFFFAOYSA-N 0.000 claims description 3
- VVFZSWNCOHTYQS-UHFFFAOYSA-N 4-morpholin-4-yl-6-(2-pyridin-3-ylethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(N2CCOCC2)=NC(C#N)=NC=1NCCC1=CC=CN=C1 VVFZSWNCOHTYQS-UHFFFAOYSA-N 0.000 claims description 3
- ACPGGAROWYBYCA-UHFFFAOYSA-N 4-morpholin-4-yl-6-(3-phenylpiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(C1)CCCC1C1=CC=CC=C1 ACPGGAROWYBYCA-UHFFFAOYSA-N 0.000 claims description 3
- RSBVTQNOBXLYGL-UHFFFAOYSA-N 4-morpholin-4-yl-6-(4-morpholin-4-ylanilino)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(N2CCOCC2)=NC(C#N)=NC=1NC(C=C1)=CC=C1N1CCOCC1 RSBVTQNOBXLYGL-UHFFFAOYSA-N 0.000 claims description 3
- URMHHFDWPPZHIV-UHFFFAOYSA-N 4-morpholin-4-yl-6-(4-piperidin-1-ylpiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(CC1)CCC1N1CCCCC1 URMHHFDWPPZHIV-UHFFFAOYSA-N 0.000 claims description 3
- HLVUUIRENGTYML-UHFFFAOYSA-N 5-amino-4-(4-chloroanilino)-6-(ethylamino)pyrimidine-2-carbonitrile Chemical compound CCNC1=NC(C#N)=NC(NC=2C=CC(Cl)=CC=2)=C1N HLVUUIRENGTYML-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- FORGMRSGVSYZQR-UHFFFAOYSA-N 2-amino-4-methylpentanamide Chemical compound CC(C)CC(N)C(N)=O FORGMRSGVSYZQR-UHFFFAOYSA-N 0.000 claims description 2
- NMABGHZGYRXDKI-UHFFFAOYSA-N 4-(4-chloroanilino)-5-methoxy-6-(3-oxopiperazin-1-yl)pyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CC(=O)NCC2)C(OC)=C1NC1=CC=C(Cl)C=C1 NMABGHZGYRXDKI-UHFFFAOYSA-N 0.000 claims description 2
- XFOOFOWYROOZEA-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(4-methylpiperazin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound C1CN(C)CCN1C1=NC(NC=2C=CC(Cl)=CC=2)=NC(C#N)=N1 XFOOFOWYROOZEA-UHFFFAOYSA-N 0.000 claims description 2
- FKNPVHLJQRYZPP-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(dimethylamino)-5-methoxypyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N(C)C)C(OC)=C1NC1=CC=C(Cl)C=C1 FKNPVHLJQRYZPP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- HRXPLNARFGLXAV-UHFFFAOYSA-N 1-(4-cyano-6-morpholin-4-yl-1,3,5-triazin-2-yl)-n,n-diethylpiperidine-3-carboxamide Chemical compound C1C(C(=O)N(CC)CC)CCCN1C1=NC(C#N)=NC(N2CCOCC2)=N1 HRXPLNARFGLXAV-UHFFFAOYSA-N 0.000 claims 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- SUFCPBKDBKJNCC-UHFFFAOYSA-N 4-[6-(4-chlorophenoxy)pyrimidin-4-yl]morpholine Chemical compound C1=CC(Cl)=CC=C1OC1=CC(N2CCOCC2)=NC=N1 SUFCPBKDBKJNCC-UHFFFAOYSA-N 0.000 claims 1
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 150000002780 morpholines Chemical class 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 39
- 108090000613 Cathepsin S Proteins 0.000 abstract description 10
- 102100035654 Cathepsin S Human genes 0.000 abstract description 10
- 108010005843 Cysteine Proteases Proteins 0.000 abstract description 8
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- 238000000034 method Methods 0.000 abstract description 7
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 229910052700 potassium Inorganic materials 0.000 abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 230000002441 reversible effect Effects 0.000 abstract description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 114
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
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- 238000005481 NMR spectroscopy Methods 0.000 description 12
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- 238000004587 chromatography analysis Methods 0.000 description 9
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
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- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
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- 238000001990 intravenous administration Methods 0.000 description 3
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- 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
- C07D239/48—Two nitrogen atoms
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- 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
- C07D239/50—Three nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
- C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D487/08—Bridged systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
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- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201976A SE0201976D0 (sv) | 2002-06-24 | 2002-06-24 | Novel compounds |
| SE0201976 | 2002-06-24 | ||
| PCT/SE2003/001078 WO2004000819A1 (en) | 2002-06-24 | 2003-06-23 | New use of pyrimidine - or triazine- 2-carbonitiles for treating diseases associated with cysteine protease activity and novel pyrimidine-2-carbonitile derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60311820D1 DE60311820D1 (de) | 2007-03-29 |
| DE60311820T2 true DE60311820T2 (de) | 2007-11-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60311820T Expired - Fee Related DE60311820T2 (de) | 2002-06-24 | 2003-06-23 | Neue verwendung von pyrimidin- oder triazin-2-carbonsäurenitrilen zur behandlung von krankheiten, die mit cysteinproteaseaktivität assoziiert sind, und neue pyridimidin-2-carbonsäurenitrilderivate |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7125881B2 (enExample) |
| EP (1) | EP1532121B1 (enExample) |
| JP (1) | JP2005533803A (enExample) |
| AT (1) | ATE353880T1 (enExample) |
| AU (1) | AU2003243095A1 (enExample) |
| DE (1) | DE60311820T2 (enExample) |
| ES (1) | ES2280794T3 (enExample) |
| SE (1) | SE0201976D0 (enExample) |
| WO (1) | WO2004000819A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AR036375A1 (es) | 2001-08-30 | 2004-09-01 | Novartis Ag | Compuestos pirrolo [2,3-d] pirimidina -2- carbonitrilo, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de medicamentos |
| SE0201980D0 (sv) * | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| GB0220187D0 (en) * | 2002-08-30 | 2002-10-09 | Novartis Ag | Organic compounds |
| DE602004009295T2 (de) * | 2003-01-14 | 2008-07-03 | Arena Pharmaceuticals, Inc., San Diego | 1,2,3-trisubstituierte aryl- und heteroarylderivate als modulatoren des metabolismus zur vorbeugung und behandlung von metabolismus-bedingten krankheiten wie diabetes oder hyperglykämie |
| EP1927594A1 (en) | 2003-01-14 | 2008-06-04 | Arena Pharmaceuticals, Inc. | 1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| KR20050122220A (ko) | 2003-03-25 | 2005-12-28 | 다케다 샌디에고, 인코포레이티드 | 디펩티딜 펩티다제 억제제 |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| EP2292620A3 (en) | 2003-07-14 | 2011-06-22 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prohylaxis and treatment of disorders related thereto |
| KR20060041309A (ko) | 2003-08-13 | 2006-05-11 | 다케다 야쿠힌 고교 가부시키가이샤 | ４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도 |
| US7790734B2 (en) * | 2003-09-08 | 2010-09-07 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7534798B2 (en) | 2004-02-11 | 2009-05-19 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| EA013427B1 (ru) * | 2004-03-15 | 2010-04-30 | Такеда Фармасьютикал Компани Лимитед | Ингибиторы дипептидилпептидазы |
| TW200614993A (en) * | 2004-06-11 | 2006-05-16 | Akzo Nobel Nv | 4-phenyl-pyrimidine-2-carbonitrile derivatives |
| GB0418353D0 (en) * | 2004-08-17 | 2004-09-22 | Novartis Ag | Organic compounds |
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| WO2006040300A1 (en) * | 2004-10-12 | 2006-04-20 | N.V. Organon | 4-cycloalkyl-pyrimidine-2-carbonitrile derivatives |
| EP1828192B1 (en) | 2004-12-21 | 2014-12-03 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| GB0514684D0 (en) * | 2005-07-18 | 2005-08-24 | Novartis Ag | Organic compounds |
| PT1942898E (pt) | 2005-09-14 | 2011-12-20 | Takeda Pharmaceutical | Inibidores da dipeptidilpeptidase para o tratamento da diabetes |
| CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
| TW200745055A (en) * | 2005-09-23 | 2007-12-16 | Organon Nv | 4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives |
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| MA42807A (fr) | 2015-06-22 | 2018-07-25 | Arena Pharm Inc | Sel l-arginine cristallin d'acide (r)-2-(7-(4-cyclopentyl-3-(trifluorométhyl)benzyloxy)-1,2,3,4-tétrahydrocyclo-penta[b]indol-3-yl)acétique (composé 1) pour une utilisation dans des troubles associés au récepteur de s1p1 |
| WO2018151873A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| EP3801459B1 (en) | 2018-06-06 | 2024-08-07 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| WO2020201572A1 (en) | 2019-04-05 | 2020-10-08 | Université De Bretagne Occidentale | Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE870304C (de) * | 1951-05-08 | 1953-03-12 | Bayer Ag | Verfahren zur Herstellung von Azofarbstoffen |
| NL270922A (enExample) * | 1960-11-02 | |||
| DE1182667B (de) * | 1963-04-13 | 1964-12-03 | Degussa | Verfahren zur Herstellung von s-Triazinverbindungen |
| DE1172684B (de) * | 1962-09-15 | 1964-06-25 | Degussa | Verfahren zur Herstellung von substituierten 2, 4-Bis-alkylamino-1, 3, 5-triazinverbindungen |
| NL284584A (enExample) * | 1962-11-22 | |||
| US3553326A (en) * | 1968-04-17 | 1971-01-05 | Shell Oil Co | Use of 2-(cyanoalkyl)amino-4-amino-6-substituted-s-triazines for inducing depressant effects in animals |
| BR6915234D0 (pt) * | 1969-05-22 | 1973-06-07 | American Cyanamid Co | Novos derivados de melamina e processo para sua preparaca |
| CH627919A5 (de) * | 1977-04-14 | 1982-02-15 | Ciba Geigy Ag | Herbizide mittel. |
| ZA833328B (en) * | 1982-05-12 | 1984-12-24 | Du Pont | Herbicidal heterocyclic alkylaminocarbonylsulfonamides |
| HU212435B (en) * | 1990-06-07 | 1996-06-28 | Sandoz Ag | Herbicidal compositions containing substituted phthalides and heterocyclic phthalides as active ingredient and process for preparation of their active ingredients. |
| JP3213775B2 (ja) * | 1992-10-30 | 2001-10-02 | イハラケミカル工業株式会社 | ２−シアノ−４，６−ジメトキシピリミジンの製造方法 |
| AU695697B2 (en) * | 1993-05-27 | 1998-08-20 | Shell Internationale Research Maatschappij B.V. | Herbicidal compounds |
| JP3013752B2 (ja) * | 1995-05-16 | 2000-02-28 | 田辺製薬株式会社 | スルホンアミド誘導体 |
| WO1997009315A1 (en) * | 1995-09-01 | 1997-03-13 | Signal Pharmaceuticals, Inc. | Pyrimidine carboxamides and related compounds and methods for treating inflammatory conditions |
| JPH10226649A (ja) * | 1996-12-12 | 1998-08-25 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| HK1039108A1 (zh) | 1999-03-15 | 2002-04-12 | Axys Pharmaceuticals, Inc. | 以n-氰甲基酰胺作为蛋白酶抑制剂 |
| AU2001265871A1 (en) * | 2000-04-25 | 2001-11-07 | Actelion Pharmaceuticals Ltd | Substituted sulfonylaminopyrimidines |
| JP5230050B2 (ja) * | 2000-05-08 | 2013-07-10 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｈｉｖ複製阻害剤 |
| WO2002032879A1 (en) | 2000-10-19 | 2002-04-25 | Naeja Pharmaceutical Inc. | Dihydropyrimidine derivatives as cysteine protease inhibitors |
| DE10111649A1 (de) * | 2001-03-12 | 2002-09-19 | Bayer Ag | Substituierte Fluoralkoxyphenylsulfonylharnstoffe |
| AR036375A1 (es) * | 2001-08-30 | 2004-09-01 | Novartis Ag | Compuestos pirrolo [2,3-d] pirimidina -2- carbonitrilo, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de medicamentos |
-
2002
- 2002-06-24 SE SE0201976A patent/SE0201976D0/xx unknown
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- 2003-06-23 AU AU2003243095A patent/AU2003243095A1/en not_active Abandoned
- 2003-06-23 EP EP03761001A patent/EP1532121B1/en not_active Expired - Lifetime
- 2003-06-23 AT AT03761001T patent/ATE353880T1/de not_active IP Right Cessation
- 2003-06-23 US US10/518,817 patent/US7125881B2/en not_active Expired - Fee Related
- 2003-06-23 WO PCT/SE2003/001078 patent/WO2004000819A1/en not_active Ceased
- 2003-06-23 JP JP2004515328A patent/JP2005533803A/ja active Pending
- 2003-06-23 ES ES03761001T patent/ES2280794T3/es not_active Expired - Lifetime
- 2003-06-23 DE DE60311820T patent/DE60311820T2/de not_active Expired - Fee Related
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| AU2003243095A1 (en) | 2004-01-06 |
| ES2280794T3 (es) | 2007-09-16 |
| WO2004000819A1 (en) | 2003-12-31 |
| US7125881B2 (en) | 2006-10-24 |
| SE0201976D0 (sv) | 2002-06-24 |
| US20050222152A1 (en) | 2005-10-06 |
| EP1532121A1 (en) | 2005-05-25 |
| DE60311820D1 (de) | 2007-03-29 |
| JP2005533803A (ja) | 2005-11-10 |
| ATE353880T1 (de) | 2007-03-15 |
| EP1532121B1 (en) | 2007-02-14 |
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| 8381 | Inventor (new situation) |
Inventor name: BAILEY, ANDREW, LOUGHBOROUGH, LEICESTERSHIRE, GB Inventor name: PAIRAUDEAU, GARRY, LOUGHBOROUGH, LEICESTERSHIR, GB Inventor name: PATEL, ANIL, LOUGHBOROUGH, LEICESTERSHIRE, GB Inventor name: THOM, STEPHEN, LOUGHBOROUGH, LEICESTERSHIRE, GB |
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| 8339 | Ceased/non-payment of the annual fee |