JP2008546639A5 - - Google Patents
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- JP2008546639A5 JP2008546639A5 JP2008510301A JP2008510301A JP2008546639A5 JP 2008546639 A5 JP2008546639 A5 JP 2008546639A5 JP 2008510301 A JP2008510301 A JP 2008510301A JP 2008510301 A JP2008510301 A JP 2008510301A JP 2008546639 A5 JP2008546639 A5 JP 2008546639A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- aryl
- alkyl
- tetrahydro
- 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.)
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- 150000001875 compounds Chemical class 0.000 claims 32
- 125000003118 aryl group Chemical group 0.000 claims 26
- 125000001072 heteroaryl group Chemical group 0.000 claims 24
- 125000000217 alkyl group Chemical group 0.000 claims 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 18
- 125000004404 heteroalkyl group Chemical group 0.000 claims 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims 15
- 208000004296 neuralgia Diseases 0.000 claims 15
- 239000008194 pharmaceutical composition Substances 0.000 claims 15
- 229910052739 hydrogen Inorganic materials 0.000 claims 14
- 239000001257 hydrogen Substances 0.000 claims 14
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 14
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 12
- -1 cycloheteroalkyl Chemical group 0.000 claims 11
- 201000010099 disease Diseases 0.000 claims 11
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims 8
- 208000002193 Pain Diseases 0.000 claims 8
- 125000003545 alkoxy group Chemical group 0.000 claims 8
- 208000035475 disorder Diseases 0.000 claims 7
- 208000024891 symptom Diseases 0.000 claims 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 6
- 206010029240 Neuritis Diseases 0.000 claims 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 4
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims 4
- 125000004414 alkyl thio group Chemical group 0.000 claims 4
- 125000002947 alkylene group Chemical group 0.000 claims 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 4
- 150000001540 azides Chemical class 0.000 claims 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims 4
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 230000007794 irritation Effects 0.000 claims 4
- 230000000155 isotopic effect Effects 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 4
- 125000002837 carbocyclic group Chemical group 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 230000001404 mediated effect Effects 0.000 claims 3
- 208000021722 neuropathic pain Diseases 0.000 claims 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 206010019233 Headaches Diseases 0.000 claims 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- 206010061218 Inflammation Diseases 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 208000019695 Migraine disease Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 2
- 208000025966 Neurological disease Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 208000003251 Pruritus Diseases 0.000 claims 2
- 206010043269 Tension headache Diseases 0.000 claims 2
- 208000008548 Tension-Type Headache Diseases 0.000 claims 2
- 125000004104 aryloxy group Chemical group 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims 2
- 206010015037 epilepsy Diseases 0.000 claims 2
- 231100000869 headache Toxicity 0.000 claims 2
- 230000004054 inflammatory process Effects 0.000 claims 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 2
- 206010027599 migraine Diseases 0.000 claims 2
- 230000004770 neurodegeneration Effects 0.000 claims 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims 2
- 230000000926 neurological effect Effects 0.000 claims 2
- 201000008482 osteoarthritis Diseases 0.000 claims 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 230000001953 sensory effect Effects 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 208000004371 toothache Diseases 0.000 claims 2
- CJSLXKZWAVSNSS-UHFFFAOYSA-N 3-chloro-7-cyclohexyl-1-(cyclohexylamino)-6,8-dihydro-5h-2,7-naphthyridine-4-carbonitrile Chemical compound C=12CN(C3CCCCC3)CCC2=C(C#N)C(Cl)=NC=1NC1CCCCC1 CJSLXKZWAVSNSS-UHFFFAOYSA-N 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- CEKMYRMUKLEDAM-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-(2-phenylethyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C=CC=CC=3)N=CN=C2CC1 CEKMYRMUKLEDAM-UHFFFAOYSA-N 0.000 claims 1
- MCKATWNAHWWXNX-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-[2-[3-(trifluoromethyl)phenyl]ethyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C=C(C=CC=3)C(F)(F)F)N=CN=C2CC1 MCKATWNAHWWXNX-UHFFFAOYSA-N 0.000 claims 1
- QCPWBRUFKOYOBO-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-[[2-(trifluoromethoxy)phenyl]methyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical class N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)OC(F)(F)F)N=CN=C2CC1 QCPWBRUFKOYOBO-UHFFFAOYSA-N 0.000 claims 1
- FMCWYPCITGBOLX-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical class N1=CC(C)=CC=C1N1CC2=C(NCC=3C=CC(=CC=3)C(F)(F)F)N=CN=C2CC1 FMCWYPCITGBOLX-UHFFFAOYSA-N 0.000 claims 1
- ZZRLTCJZOJCIHC-UHFFFAOYSA-N 7-cyclohexyl-1-(cyclohexylamino)-3-morpholin-4-yl-6,8-dihydro-5h-2,7-naphthyridine-4-carbonitrile Chemical group N1=C(N2CCOCC2)C(C#N)=C2CCN(C3CCCCC3)CC2=C1NC1CCCCC1 ZZRLTCJZOJCIHC-UHFFFAOYSA-N 0.000 claims 1
- MBPDMPQGMKKBDF-UHFFFAOYSA-N 7-cyclohexyl-1-(cyclohexylamino)-3-piperidin-1-yl-6,8-dihydro-5h-2,7-naphthyridine-4-carbonitrile Chemical compound N1=C(N2CCCCC2)C(C#N)=C2CCN(C3CCCCC3)CC2=C1NC1CCCCC1 MBPDMPQGMKKBDF-UHFFFAOYSA-N 0.000 claims 1
- 235000003934 Abelmoschus esculentus Nutrition 0.000 claims 1
- 240000004507 Abelmoschus esculentus Species 0.000 claims 1
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 206010003399 Arthropod bite Diseases 0.000 claims 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 1
- 208000020925 Bipolar disease Diseases 0.000 claims 1
- 206010069632 Bladder dysfunction Diseases 0.000 claims 1
- 206010006482 Bronchospasm Diseases 0.000 claims 1
- 206010006784 Burning sensation Diseases 0.000 claims 1
- 208000001387 Causalgia Diseases 0.000 claims 1
- 206010008334 Cervicobrachial syndrome Diseases 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 208000006561 Cluster Headache Diseases 0.000 claims 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 208000030814 Eating disease Diseases 0.000 claims 1
- 206010015150 Erythema Diseases 0.000 claims 1
- 208000034347 Faecal incontinence Diseases 0.000 claims 1
- 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
- 208000001640 Fibromyalgia Diseases 0.000 claims 1
- 208000014540 Functional gastrointestinal disease Diseases 0.000 claims 1
- 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 claims 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 206010065390 Inflammatory pain Diseases 0.000 claims 1
- 208000006877 Insect Bites and Stings Diseases 0.000 claims 1
- 206010049949 Intercostal neuralgia Diseases 0.000 claims 1
- 206010026749 Mania Diseases 0.000 claims 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims 1
- 208000002472 Morton Neuroma Diseases 0.000 claims 1
- 208000020059 Morton neuralgia Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010068106 Occipital neuralgia Diseases 0.000 claims 1
- 208000004983 Phantom Limb Diseases 0.000 claims 1
- 206010056238 Phantom pain Diseases 0.000 claims 1
- 206010036105 Polyneuropathy Diseases 0.000 claims 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 206010039085 Rhinitis allergic Diseases 0.000 claims 1
- 208000008765 Sciatica Diseases 0.000 claims 1
- 208000004078 Snake Bites Diseases 0.000 claims 1
- 208000003589 Spider Bites Diseases 0.000 claims 1
- 206010046543 Urinary incontinence Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 201000010105 allergic rhinitis Diseases 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 1
- 230000036506 anxiety Effects 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 150000001602 bicycloalkyls Chemical group 0.000 claims 1
- 230000002146 bilateral effect Effects 0.000 claims 1
- 201000007637 bowel dysfunction Diseases 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 230000007885 bronchoconstriction Effects 0.000 claims 1
- 229960002504 capsaicin Drugs 0.000 claims 1
- 235000017663 capsaicin Nutrition 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 230000035606 childbirth Effects 0.000 claims 1
- 208000018912 cluster headache syndrome Diseases 0.000 claims 1
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 claims 1
- 235000014632 disordered eating Nutrition 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010014599 encephalitis Diseases 0.000 claims 1
- 231100000321 erythema Toxicity 0.000 claims 1
- 239000007789 gas Substances 0.000 claims 1
- 201000005442 glossopharyngeal neuralgia Diseases 0.000 claims 1
- 125000004474 heteroalkylene group Chemical group 0.000 claims 1
- 230000009610 hypersensitivity Effects 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 230000007803 itching Effects 0.000 claims 1
- 208000037805 labour Diseases 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 230000005906 menstruation Effects 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- OBPXACGGOMKVLV-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C4OCOC4=CC=3)N=CN=C2CC1 OBPXACGGOMKVLV-UHFFFAOYSA-N 0.000 claims 1
- DXGORADRDISYAD-UHFFFAOYSA-N n-(cyclohexylmethyl)-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC3CCCCC3)N=CN=C2CC1 DXGORADRDISYAD-UHFFFAOYSA-N 0.000 claims 1
- VOICQPYJFZIJSN-UHFFFAOYSA-N n-[(2,3-difluorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical class N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=C(F)C=CC=3)F)N=CN=C2CC1 VOICQPYJFZIJSN-UHFFFAOYSA-N 0.000 claims 1
- WFTRPAANKZLHNU-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)Cl)N=CN=C2CC1 WFTRPAANKZLHNU-UHFFFAOYSA-N 0.000 claims 1
- FIXOWTFOEIUTMF-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC=C1CNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 FIXOWTFOEIUTMF-UHFFFAOYSA-N 0.000 claims 1
- NPSGDTBYKGZOCT-UHFFFAOYSA-N n-[(2-methylphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)C)N=CN=C2CC1 NPSGDTBYKGZOCT-UHFFFAOYSA-N 0.000 claims 1
- ZFFRYTRFMCOESZ-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(Cl)C=CC=3)N=CN=C2CC1 ZFFRYTRFMCOESZ-UHFFFAOYSA-N 0.000 claims 1
- JOFHBLXBUDVYEL-UHFFFAOYSA-N n-[(3-fluorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(F)C=CC=3)N=CN=C2CC1 JOFHBLXBUDVYEL-UHFFFAOYSA-N 0.000 claims 1
- VRHHZTYCWGFIIU-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(CNC=2C=3CN(CCC=3N=CN=2)C=2N=CC(C)=CC=2)=C1 VRHHZTYCWGFIIU-UHFFFAOYSA-N 0.000 claims 1
- DLHPMQWXJJUYJE-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=CC(Cl)=CC=3)N=CN=C2CC1 DLHPMQWXJJUYJE-UHFFFAOYSA-N 0.000 claims 1
- NALREZXCDIQRQU-UHFFFAOYSA-N n-[(4-fluoro-3-methylphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(C)C(F)=CC=3)N=CN=C2CC1 NALREZXCDIQRQU-UHFFFAOYSA-N 0.000 claims 1
- CGMKVHOIAYZASS-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 CGMKVHOIAYZASS-UHFFFAOYSA-N 0.000 claims 1
- SSYSQHUWGQTOJV-UHFFFAOYSA-N n-[(4-methylphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1CNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 SSYSQHUWGQTOJV-UHFFFAOYSA-N 0.000 claims 1
- ORRVRGHOSLMGBL-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C(=CC=CC=3)Cl)N=CN=C2CC1 ORRVRGHOSLMGBL-UHFFFAOYSA-N 0.000 claims 1
- GBQJHHKPJDWIBU-UHFFFAOYSA-N n-[2-(4-chlorophenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C=CC(Cl)=CC=3)N=CN=C2CC1 GBQJHHKPJDWIBU-UHFFFAOYSA-N 0.000 claims 1
- SVERNLBOIJHNMU-UHFFFAOYSA-N n-[2-(4-methylphenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical class C1=CC(C)=CC=C1CCNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 SVERNLBOIJHNMU-UHFFFAOYSA-N 0.000 claims 1
- QGRXNGVPOGCLCO-UHFFFAOYSA-N n-[[2-(difluoromethoxy)phenyl]methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)OC(F)F)N=CN=C2CC1 QGRXNGVPOGCLCO-UHFFFAOYSA-N 0.000 claims 1
- 201000009985 neuronitis Diseases 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 210000003254 palate Anatomy 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 claims 1
- 208000019629 polyneuritis Diseases 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 208000036273 reactive airway disease Diseases 0.000 claims 1
- 230000011514 reflex Effects 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 201000009890 sinusitis Diseases 0.000 claims 1
- 208000019116 sleep disease Diseases 0.000 claims 1
- 239000003491 tear gas Substances 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
- 206010044652 trigeminal neuralgia Diseases 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67776005P | 2005-05-04 | 2005-05-04 | |
| US60/677,760 | 2005-05-04 | ||
| PCT/US2006/017614 WO2006119504A2 (en) | 2005-05-04 | 2006-05-04 | Fused heterocyclic compounds, and compositions and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012132675A Division JP5722280B2 (ja) | 2005-05-04 | 2012-06-12 | 縮合複素環式化合物、並びにそれらの組成物及び使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008546639A JP2008546639A (ja) | 2008-12-25 |
| JP2008546639A5 true JP2008546639A5 (https=) | 2009-06-25 |
| JP5198256B2 JP5198256B2 (ja) | 2013-05-15 |
Family
ID=37308747
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008510301A Expired - Lifetime JP5198256B2 (ja) | 2005-05-04 | 2006-05-04 | 縮合複素環式化合物、並びにそれらの組成物及び使用 |
| JP2012132675A Expired - Lifetime JP5722280B2 (ja) | 2005-05-04 | 2012-06-12 | 縮合複素環式化合物、並びにそれらの組成物及び使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012132675A Expired - Lifetime JP5722280B2 (ja) | 2005-05-04 | 2012-06-12 | 縮合複素環式化合物、並びにそれらの組成物及び使用 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7745451B2 (https=) |
| EP (1) | EP1885369B1 (https=) |
| JP (2) | JP5198256B2 (https=) |
| CA (1) | CA2606760C (https=) |
| ES (1) | ES2552804T3 (https=) |
| MX (1) | MX2007013595A (https=) |
| WO (1) | WO2006119504A2 (https=) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2007013595A (es) * | 2005-05-04 | 2008-01-24 | Renovis Inc | Compuestos heterociclicos fusionados y composiciones y usos de estos. |
| EP2136639B1 (en) * | 2007-04-02 | 2016-03-09 | Evotec AG | Pyrid-2-yl fused heterocyclic compounds, and compositions and uses thereof |
| PT2139334E (pt) * | 2007-04-17 | 2013-10-02 | Evotec Ag | Compostos heterocíclicos fusionados de 2-cianofenilo, e composições e utilizações dos mesmos |
| JP2011502148A (ja) | 2007-10-31 | 2011-01-20 | メルク・シャープ・エンド・ドーム・コーポレイション | 疼痛の治療用としてのｐ２ｘ３受容体アンタゴニスト |
| CA2703915C (en) | 2007-10-31 | 2015-02-24 | Merck Sharp & Dohme Corp. | P2x3 receptor antagonists for treatment of pain |
| SG187502A1 (en) | 2008-02-01 | 2013-02-28 | Takeda Pharmaceutical | Oxim derivatives as hsp90 inhibitors |
| CA2715835C (en) | 2008-02-29 | 2017-03-21 | Renovis, Inc. | Amide compounds, compositions and uses thereof |
| MX2011004570A (es) | 2008-10-31 | 2011-06-17 | Merck Sharp & Dohme | Antagonistas del receptor p2x3 para el tratamiento del dolor. |
| AU2012202178B2 (en) * | 2008-12-19 | 2012-11-01 | Amgen Inc. | Method for the preparation of 1-acetyl-6-amino-3, 3-dimethyl-2, 3 -dihydroindole |
| AU2009327349B2 (en) * | 2008-12-19 | 2012-03-15 | Amgen Inc. | Method for the preparation of 1-acetyl-6-amino-3, 3-dimethyl-2, 3 -dihydroindole |
| PL2399910T3 (pl) | 2009-02-13 | 2014-09-30 | Shionogi & Co | Pochodne triazyny jako antagoniści receptora p2x3 i/albo p2x2/3 i kompozycja farmaceutyczna zawierająca je |
| WO2010111059A1 (en) | 2009-03-23 | 2010-09-30 | Merck Sharp & Dohme Corp. | P2x3 receptor antagonists for treatment of pain |
| AU2010229142A1 (en) | 2009-03-23 | 2011-10-13 | Merck Sharp & Dohme Corp. | P2X3, receptor antagonists for treatment of pain |
| US8569512B2 (en) | 2009-03-23 | 2013-10-29 | Merck Sharp & Dohme Corp. | P2X3 receptor antagonists for treatment of pain |
| UA112517C2 (uk) * | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| JP6075621B2 (ja) * | 2010-08-10 | 2017-02-08 | 塩野義製薬株式会社 | 新規複素環誘導体およびそれらを含有する医薬組成物 |
| CN103153968B (zh) | 2010-08-10 | 2016-02-03 | 盐野义制药株式会社 | 三唑衍生物及含有其的具有镇痛作用的药物组合物 |
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| EP2790705B1 (en) | 2011-12-15 | 2017-12-06 | Novartis AG | Use of inhibitors of the activity or function of pi3k |
| FR2984323B1 (fr) * | 2011-12-16 | 2019-08-30 | L'oreal | Coupleur de structure 7 amino-1,2,3,4-tetrahydroquinoleines, composition tinctoriale en comprenant, procedes et utilisations |
| FR2984318B1 (fr) | 2011-12-16 | 2014-06-27 | Oreal | Coupleur de structure 7 amino-1,2,3,4-tetrahydroquinoleines cationiques, composition tinctoriale en comprenant, procedes et utilisations |
| WO2013118855A1 (ja) | 2012-02-09 | 2013-08-15 | 塩野義製薬株式会社 | 複素環および炭素環誘導体 |
| WO2013134518A1 (en) * | 2012-03-09 | 2013-09-12 | Amgen Inc. | Sulfamide sodium channel inhibitors |
| UA112897C2 (uk) | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань |
| RS58514B1 (sr) | 2012-06-13 | 2019-04-30 | Incyte Holdings Corp | Supstituisana triciklična jedinjenja kao inhibitori fgfr |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| TWI499591B (zh) * | 2013-01-11 | 2015-09-11 | Lilly Co Eli | 雙環嘧啶化合物 |
| PH12015502383B1 (en) | 2013-04-19 | 2023-02-03 | Incyte Holdings Corp | Bicyclic heterocycles as fgfr inhibitors |
| TWI637949B (zh) | 2013-06-14 | 2018-10-11 | 塩野義製藥股份有限公司 | 胺基三衍生物及含有其等之醫藥組合物 |
| PL3089971T3 (pl) | 2014-01-01 | 2021-01-25 | Medivation Technologies Llc | Związki i sposoby ich zastosowania |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| US10183937B2 (en) | 2014-12-09 | 2019-01-22 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides |
| EP3230281B1 (en) | 2014-12-09 | 2021-05-26 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| TWI712601B (zh) | 2015-02-20 | 2020-12-11 | 美商英塞特公司 | 作為fgfr抑制劑之雙環雜環 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| CN107597107A (zh) * | 2017-08-30 | 2018-01-19 | 重庆中邦科技有限公司 | 一种2,3‑二氯吡啶生产用催化剂及其制备方法 |
| HRP20241288T1 (hr) | 2018-05-04 | 2024-12-06 | Incyte Corporation | Čvrsti oblici fgfr inhibitora i postupci za njihovu proizvodnju |
| AU2019262579B2 (en) | 2018-05-04 | 2024-09-12 | Incyte Corporation | Salts of an FGFR inhibitor |
| IL282087B2 (en) * | 2018-10-10 | 2025-11-01 | Bellus Health Cough Inc | 4-(imidazo[1,2-a]pyridin-3-yl)-benzamide derivatives for treating pruritus |
| JP7578602B2 (ja) | 2019-02-25 | 2024-11-06 | グラクソスミスクライン、インテレクチュアル、プロパティー、（ナンバー３）、リミテッド | Ｐ２ｘ３修飾薬での治療 |
| MX2021010323A (es) * | 2019-03-01 | 2021-12-10 | Revolution Medicines Inc | Compuestos bicíclicos de heterociclilo y usos de este. |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| CN110256420B (zh) * | 2019-05-07 | 2020-04-28 | 江西中医药大学 | 四氢吡啶并嘧啶衍生物及其制备方法和用途 |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CA3157361A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CA3156359A1 (en) | 2019-11-08 | 2021-05-14 | Adrian Liam Gill | Bicyclic heteroaryl compounds and uses thereof |
| JP7832891B2 (ja) | 2019-12-04 | 2026-03-18 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤の誘導体 |
| CA3163875A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| CN116194446A (zh) * | 2020-08-06 | 2023-05-30 | 北京泰德制药股份有限公司 | Sos1抑制剂、包含其的药物组合物及其用途 |
| JP2023550830A (ja) * | 2020-11-27 | 2023-12-05 | キエシ・フアルマチエウテイチ・ソチエタ・ペル・アチオニ | Ｐ２ｘ３阻害剤としての（アザ）キノリン４－アミン誘導体 |
| WO2022221170A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
| CN115626922A (zh) * | 2021-04-29 | 2023-01-20 | 苏州恩华生物医药科技有限公司 | 5,6,7,8-四氢吡啶并[4,3-d]嘧啶-4-醇衍生物及其应用 |
| US11939331B2 (en) | 2021-06-09 | 2024-03-26 | Incyte Corporation | Tricyclic heterocycles as FGFR inhibitors |
| CA3220155A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1197466B (de) | 1962-03-22 | 1965-07-29 | Thomae Gmbh Dr K | Verfahren zur Herstellung von neuen 5, 6, 7, 8-Tetrahydropyrido-[4, 3-d]pyrimidinen |
| US3424760A (en) | 1966-03-07 | 1969-01-28 | Robins Co Inc A H | 3-ureidopyrrolidines |
| US3424761A (en) | 1966-03-07 | 1969-01-28 | Robins Co Inc A H | 3-ureidopyrrolidines |
| DE2502588A1 (de) | 1975-01-23 | 1976-07-29 | Troponwerke Dinklage & Co | Basisch substituierte derivate des 7-amino-2-chinolons, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| JPH04224580A (ja) | 1990-12-25 | 1992-08-13 | Nippon Soda Co Ltd | ピリミジン誘導体、その製造方法及び農園芸用殺菌剤 |
| AU778393B2 (en) | 1999-05-12 | 2004-12-02 | Ortho-Mcneil Pharmaceutical, Inc. | Pyrazole carboxamides useful for the treatment of obesity and other disorders |
| SV2002000205A (es) | 1999-11-01 | 2002-06-07 | Lilly Co Eli | Compuestos farmaceuticos ref. x-01095 |
| CN100335479C (zh) | 1999-12-17 | 2007-09-05 | 希龙公司 | 糖元合成酶激酶3的双环抑制剂 |
| US7087589B2 (en) * | 2000-01-14 | 2006-08-08 | The United States Of America As Represented By The Department Of Health And Human Services | Methanocarba cycloakyl nucleoside analogues |
| US6531478B2 (en) | 2000-02-24 | 2003-03-11 | Cheryl P. Kordik | Amino pyrazole derivatives useful for the treatment of obesity and other disorders |
| EP1301484A2 (en) | 2000-07-20 | 2003-04-16 | Neurogen Corporation | Capsaicin receptor ligands |
| WO2002022605A1 (en) | 2000-09-15 | 2002-03-21 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6989385B2 (en) | 2000-12-21 | 2006-01-24 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| WO2002053558A1 (en) * | 2001-01-02 | 2002-07-11 | F.Hoffman-La Roche Ag | Quinazolone derivatives as alpha 1a/b adrenergic receptor antagonists |
| DE60206363T2 (de) * | 2001-02-12 | 2006-07-06 | F. Hoffmann-La Roche Ag | 6-substituierte pyridopyrimidine |
| US7105667B2 (en) * | 2001-05-01 | 2006-09-12 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| PE20030008A1 (es) * | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| EP1470121B1 (en) | 2002-01-23 | 2012-07-11 | Bayer HealthCare LLC | Pyrimidine derivatives as rho-kinase inhibitors |
| GB0206033D0 (en) | 2002-03-14 | 2002-04-24 | Pfizer Ltd | Compounds useful in therapy |
| JPWO2003104230A1 (ja) * | 2002-06-07 | 2005-10-06 | 協和醗酵工業株式会社 | 二環性ピリミジン誘導体 |
| AU2003262230A1 (en) * | 2002-08-22 | 2004-03-11 | Kyowa Hakko Kogyo Co., Ltd. | Preventive and/or therapeutic drugs for itch |
| US20060239999A1 (en) * | 2002-08-22 | 2006-10-26 | Mayumi Saki | Preventive and/or therapeutic drugs for asthma |
| GB0225908D0 (en) | 2002-11-06 | 2002-12-11 | Pfizer Ltd | Treatment of female sexual dysfunction |
| WO2004056774A2 (en) | 2002-12-19 | 2004-07-08 | Neurogen Corporation | Substituted biphenyl-4-carboxylic acid arylamide analogues as capsaicin receptor modulators |
| US7223766B2 (en) | 2003-03-28 | 2007-05-29 | Scios, Inc. | Bi-cyclic pyrimidine inhibitors of TGFβ |
| US7232833B2 (en) * | 2003-03-28 | 2007-06-19 | Novexel | 4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them |
| WO2004093912A1 (ja) | 2003-04-23 | 2004-11-04 | Kyowa Hakko Kogyo Co. Ltd. | 好中球性炎症疾患の予防および／または治療剤 |
| CN1894222A (zh) * | 2003-08-05 | 2007-01-10 | 沃泰克斯药物股份有限公司 | 作为电压门控离子通道抑制剂的稠合嘧啶化合物 |
| US7390820B2 (en) | 2003-08-25 | 2008-06-24 | Amgen Inc. | Substituted quinolinone derivatives and methods of use |
| MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
| JP2005162673A (ja) | 2003-12-03 | 2005-06-23 | Kyowa Hakko Kogyo Co Ltd | 二環性ピリミジン誘導体 |
| KR20070058602A (ko) | 2004-09-30 | 2007-06-08 | 티보텍 파마슈티칼즈 리미티드 | Ｈｃｖ 저해 바이-사이클릭 피리미딘 |
| SE0403085D0 (sv) * | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Novel componds |
| MX2007013595A (es) * | 2005-05-04 | 2008-01-24 | Renovis Inc | Compuestos heterociclicos fusionados y composiciones y usos de estos. |
| WO2007070872A1 (en) | 2005-12-15 | 2007-06-21 | Rigel Pharmaceuticals, Inc. | Kinase inhibitors and their uses |
| WO2013033981A1 (zh) * | 2011-09-06 | 2013-03-14 | 江苏先声药物研究有限公司 | 一类2,7-萘啶衍生物及其制备方法和应用 |
-
2006
- 2006-05-04 MX MX2007013595A patent/MX2007013595A/es active IP Right Grant
- 2006-05-04 WO PCT/US2006/017614 patent/WO2006119504A2/en not_active Ceased
- 2006-05-04 US US11/429,026 patent/US7745451B2/en active Active
- 2006-05-04 EP EP06770066.6A patent/EP1885369B1/en not_active Expired - Lifetime
- 2006-05-04 CA CA2606760A patent/CA2606760C/en not_active Expired - Lifetime
- 2006-05-04 JP JP2008510301A patent/JP5198256B2/ja not_active Expired - Lifetime
- 2006-05-04 ES ES06770066.6T patent/ES2552804T3/es not_active Expired - Lifetime
-
2010
- 2010-03-01 US US12/660,588 patent/US8859545B2/en active Active
-
2012
- 2012-06-12 JP JP2012132675A patent/JP5722280B2/ja not_active Expired - Lifetime
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