NZ566914A - 2-amino-7, 8-dihydro-6H-pyrido[4,3-d] pyrimidin-5-ones - Google Patents

Info

Publication number

NZ566914A

NZ566914A NZ566914A NZ56691406A NZ566914A NZ 566914 A NZ566914 A NZ 566914A NZ 566914 A NZ566914 A NZ 566914A NZ 56691406 A NZ56691406 A NZ 56691406A NZ 566914 A NZ566914 A NZ 566914A

Authority

NZ

New Zealand

Prior art keywords

phenyl

methoxy

methyl

substituted

pyridin

Prior art date

2005-09-30

Links

• Espacenet
• Global Dossier
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• CZOQBGHFZWUWPV-UHFFFAOYSA-N 2-amino-7,8-dihydro-6h-pyrido[4,3-d]pyrimidin-5-one Chemical class O=C1NCCC2=NC(N)=NC=C21 CZOQBGHFZWUWPV-UHFFFAOYSA-N 0.000 title description 18
• -1 2-amino-7-[2-(pyridin-2-yl)-phenyl]-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compound Chemical class 0.000 claims abstract description 897
• 150000001875 compounds Chemical class 0.000 claims abstract description 216
• 150000003839 salts Chemical class 0.000 claims abstract description 91
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 55
• 238000000034 method Methods 0.000 claims abstract description 47
• 201000011510 cancer Diseases 0.000 claims abstract description 41
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims abstract description 17
• 239000002253 acid Substances 0.000 claims abstract description 17
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims abstract description 12
• 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims abstract description 11
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims abstract description 9
• 206010025323 Lymphomas Diseases 0.000 claims abstract description 9
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims abstract description 8
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims abstract description 8
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims abstract description 8
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 7
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 7
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims abstract description 7
• 208000032839 leukemia Diseases 0.000 claims abstract description 7
• 201000001441 melanoma Diseases 0.000 claims abstract description 7
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims abstract description 6
• 206010048832 Colon adenoma Diseases 0.000 claims abstract description 6
• 208000028018 Lymphocytic leukaemia Diseases 0.000 claims abstract description 6
• 208000034578 Multiple myelomas Diseases 0.000 claims abstract description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 claims abstract description 6
• 210000000621 bronchi Anatomy 0.000 claims abstract description 6
• 210000003228 intrahepatic bile duct Anatomy 0.000 claims abstract description 6
• 208000003747 lymphoid leukemia Diseases 0.000 claims abstract description 6
• 208000025113 myeloid leukemia Diseases 0.000 claims abstract description 6
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims abstract description 5
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 5
• 239000012458 free base Substances 0.000 claims abstract description 5
• 208000005017 glioblastoma Diseases 0.000 claims abstract description 5
• 206010009944 Colon cancer Diseases 0.000 claims abstract description 4
• 206010061968 Gastric neoplasm Diseases 0.000 claims abstract description 4
• 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 4
• 206010060862 Prostate cancer Diseases 0.000 claims abstract description 4
• 208000024313 Testicular Neoplasms Diseases 0.000 claims abstract description 4
• 208000024770 Thyroid neoplasm Diseases 0.000 claims abstract description 4
• 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 4
• 208000020816 lung neoplasm Diseases 0.000 claims abstract description 4
• 208000025189 neoplasm of testis Diseases 0.000 claims abstract description 4
• 201000003120 testicular cancer Diseases 0.000 claims abstract description 4
• 201000002510 thyroid cancer Diseases 0.000 claims abstract description 4
• 229910052705 radium Inorganic materials 0.000 claims abstract description 3
• 229910052701 rubidium Inorganic materials 0.000 claims abstract description 3
• 208000008839 Kidney Neoplasms Diseases 0.000 claims abstract 6
• 206010038389 Renal cancer Diseases 0.000 claims abstract 6
• 208000014829 head and neck neoplasm Diseases 0.000 claims abstract 6
• 201000010982 kidney cancer Diseases 0.000 claims abstract 6
• 208000003174 Brain Neoplasms Diseases 0.000 claims abstract 3
• 206010006417 Bronchial carcinoma Diseases 0.000 claims abstract 3
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims abstract 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims abstract 3
• 206010061336 Pelvic neoplasm Diseases 0.000 claims abstract 3
• 208000009565 Pharyngeal Neoplasms Diseases 0.000 claims abstract 3
• 208000015634 Rectal Neoplasms Diseases 0.000 claims abstract 3
• 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract 3
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims abstract 3
• 201000005200 bronchus cancer Diseases 0.000 claims abstract 3
• 201000010881 cervical cancer Diseases 0.000 claims abstract 3
• 201000004101 esophageal cancer Diseases 0.000 claims abstract 3
• 201000005619 esophageal carcinoma Diseases 0.000 claims abstract 3
• 206010017758 gastric cancer Diseases 0.000 claims abstract 3
• 201000005264 laryngeal carcinoma Diseases 0.000 claims abstract 3
• 206010023841 laryngeal neoplasm Diseases 0.000 claims abstract 3
• 201000004962 larynx cancer Diseases 0.000 claims abstract 3
• 201000007270 liver cancer Diseases 0.000 claims abstract 3
• 208000014018 liver neoplasm Diseases 0.000 claims abstract 3
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• 201000008006 pharynx cancer Diseases 0.000 claims abstract 3
• 201000002314 small intestine cancer Diseases 0.000 claims abstract 3
• 201000011549 stomach cancer Diseases 0.000 claims abstract 3
• 201000005112 urinary bladder cancer Diseases 0.000 claims abstract 3
• 125000000217 alkyl group Chemical group 0.000 claims description 116
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 99
• 229910052739 hydrogen Inorganic materials 0.000 claims description 94
• 239000001257 hydrogen Substances 0.000 claims description 93
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 93
• 125000003118 aryl group Chemical group 0.000 claims description 73
• 125000001072 heteroaryl group Chemical group 0.000 claims description 64
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 53
• 239000000203 mixture Substances 0.000 claims description 48
• 125000000623 heterocyclic group Chemical group 0.000 claims description 47
• 125000005843 halogen group Chemical group 0.000 claims description 44
• 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 42
• 101710113864 Heat shock protein 90 Proteins 0.000 claims description 41
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
• 125000003545 alkoxy group Chemical group 0.000 claims description 35
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 28
• 238000011282 treatment Methods 0.000 claims description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
• 125000004076 pyridyl group Chemical group 0.000 claims description 19
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 18
• 230000000694 effects Effects 0.000 claims description 18
• 125000000335 thiazolyl group Chemical group 0.000 claims description 18
• 239000003795 chemical substances by application Substances 0.000 claims description 17
• 125000001041 indolyl group Chemical group 0.000 claims description 17
• 125000001544 thienyl group Chemical group 0.000 claims description 17
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
• 125000003342 alkenyl group Chemical group 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
• 230000003612 virological effect Effects 0.000 claims description 12
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 11
• 125000002541 furyl group Chemical group 0.000 claims description 11
• 125000002971 oxazolyl group Chemical group 0.000 claims description 11
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 11
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 10
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 10
• 125000001425 triazolyl group Chemical group 0.000 claims description 10
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 9
• 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 9
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 9
• 125000002883 imidazolyl group Chemical group 0.000 claims description 9
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 9
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 9
• 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 8
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 8
• 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 8
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 8
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 8
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
• 150000001356 alkyl thiols Chemical class 0.000 claims description 8
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 8
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 8
• 125000003107 substituted aryl group Chemical group 0.000 claims description 8
• 150000003573 thiols Chemical class 0.000 claims description 8
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 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
• 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 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000000168 pyrrolyl group Chemical group 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 6
• 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 6
• 241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 6
• 108091000080 Phosphotransferase Proteins 0.000 claims description 6
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 102000020233 phosphotransferase Human genes 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
• 125000000882 C2-C6 alkenyl group Chemical group 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
• 229910052727 yttrium Inorganic materials 0.000 claims description 5
• 229960002411 imatinib Drugs 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• NIULRPKPBLEFJZ-SNVBAGLBSA-N (7r)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydro-6h-pyrido[4,3-d]pyrimidin-5-one Chemical compound C1([C@H]2CC=3N=C(N)N=C(C=3C(=O)N2)C)=CC=C(F)C=C1Br NIULRPKPBLEFJZ-SNVBAGLBSA-N 0.000 claims description 3
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
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• BMKDZUISNHGIBY-ZETCQYMHSA-N (+)-dexrazoxane Chemical compound C([C@H](C)N1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-ZETCQYMHSA-N 0.000 claims description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 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
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• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims 2
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims 1
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