EA016152B1 - 2-АМИНО-7,8-ДИГИДРО-6Н-ПИРИДО[4,3-d]ПИРИМИДИН-5-ОНЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ, СПОСОБ ТЕРАПИИ С ИХ ПОМОЩЬЮ, КОМПОНЕНТ КОМПОЗИЦИИ, КОМПОЗИЦИЯ И ЛЕКАРСТВЕННОЕ СРЕДСТВО НА ИХ ОСНОВЕ, 2,4-ДИОКСОПИПЕРИДИНОВЫЕ СОЕДИНЕНИЯ ДЛЯ ИХ ПОЛУЧЕНИЯ - Google Patents

Info

Publication number

EA016152B1

EA016152B1 EA200800992A EA200800992A EA016152B1 EA 016152 B1 EA016152 B1 EA 016152B1 EA 200800992 A EA200800992 A EA 200800992A EA 200800992 A EA200800992 A EA 200800992A EA 016152 B1 EA016152 B1 EA 016152B1

Authority

EA

Eurasian Patent Office

Prior art keywords

substituted

fluoro

amino

unsubstituted

compounds

Prior art date

2005-09-30

Links

• Espacenet
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• 239000000203 mixture Substances 0.000 title claims abstract description 48
• 238000000034 method Methods 0.000 title claims abstract description 46
• 239000003814 drug Substances 0.000 title claims abstract description 19
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• 238000004519 manufacturing process Methods 0.000 title claims description 7
• 238000002560 therapeutic procedure Methods 0.000 title claims description 3
• 238000002360 preparation method Methods 0.000 title description 9
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 238000011282 treatment Methods 0.000 claims abstract description 22
• 239000003937 drug carrier Substances 0.000 claims abstract description 7
• -1 sulfonic Chemical group 0.000 claims description 912
• BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical class O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 claims description 214
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 159
• 229910052739 hydrogen Inorganic materials 0.000 claims description 90
• 239000001257 hydrogen Substances 0.000 claims description 76
• 125000003118 aryl group Chemical group 0.000 claims description 71
• 125000000217 alkyl group Chemical group 0.000 claims description 66
• 125000001072 heteroaryl group Chemical group 0.000 claims description 66
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
• 125000000623 heterocyclic group Chemical group 0.000 claims description 39
• 125000005843 halogen group Chemical group 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
• 206010028980 Neoplasm Diseases 0.000 claims description 34
• 201000011510 cancer Diseases 0.000 claims description 29
• 150000002431 hydrogen Chemical class 0.000 claims description 29
• 125000003545 alkoxy group Chemical group 0.000 claims description 27
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
• 125000000335 thiazolyl group Chemical group 0.000 claims description 22
• 230000000694 effects Effects 0.000 claims description 21
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 18
• 125000004076 pyridyl group Chemical group 0.000 claims description 18
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 16
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000001188 haloalkyl group Chemical group 0.000 claims description 16
• 125000001041 indolyl group Chemical group 0.000 claims description 16
• 239000003795 chemical substances by application Substances 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 15
• 125000001544 thienyl group Chemical group 0.000 claims description 15
• 241001465754 Metazoa Species 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 14
• 238000006243 chemical reaction Methods 0.000 claims description 14
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
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• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• 125000002541 furyl group Chemical group 0.000 claims description 11
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 11
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 9
• 125000002971 oxazolyl group Chemical group 0.000 claims description 9
• 229910052700 potassium Inorganic materials 0.000 claims description 9
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
• RRXSYZFVDIRTFB-UHFFFAOYSA-N C[CH]C1=CC=C(OC)C=C1 Chemical group C[CH]C1=CC=C(OC)C=C1 RRXSYZFVDIRTFB-UHFFFAOYSA-N 0.000 claims description 8
• 125000002883 imidazolyl group Chemical group 0.000 claims description 8
• 125000003107 substituted aryl group Chemical group 0.000 claims description 8
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 8
• 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 7
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 7
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 7
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 7
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 7
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 7
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 7
• 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 7
• 125000001769 aryl amino group Chemical group 0.000 claims description 7
• 125000004104 aryloxy group Chemical group 0.000 claims description 7
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 7
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 7
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 7
• 125000004043 oxo group Chemical group O=* 0.000 claims description 7
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 7
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 125000003368 amide group Chemical group 0.000 claims description 6
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
• 150000003973 alkyl amines Chemical class 0.000 claims description 5
• 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 5
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
• 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 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000004986 diarylamino group Chemical group 0.000 claims description 5
• 150000002081 enamines Chemical class 0.000 claims description 5
• 150000007857 hydrazones Chemical class 0.000 claims description 5
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 5
• 150000002825 nitriles Chemical class 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 150000002923 oximes Chemical class 0.000 claims description 5
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 5
• 125000003375 sulfoxide group Chemical group 0.000 claims description 5
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• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
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• 125000001425 triazolyl group Chemical group 0.000 claims description 4
• 229960004562 carboplatin Drugs 0.000 claims description 3
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• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
• 229960004641 rituximab Drugs 0.000 claims description 3
• VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 2
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
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• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
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• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 2
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