JP2009536651A - 置換されたアザスピロ誘導体 - Google Patents
置換されたアザスピロ誘導体 Download PDFInfo
- Publication number
- JP2009536651A JP2009536651A JP2009509820A JP2009509820A JP2009536651A JP 2009536651 A JP2009536651 A JP 2009536651A JP 2009509820 A JP2009509820 A JP 2009509820A JP 2009509820 A JP2009509820 A JP 2009509820A JP 2009536651 A JP2009536651 A JP 2009536651A
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- JP
- Japan
- Prior art keywords
- cyclobutyl
- diazaspiro
- undecane
- undes
- alkyl
- 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.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 267
- 102000004384 Histamine H3 receptors Human genes 0.000 claims abstract description 162
- 108090000981 Histamine H3 receptors Proteins 0.000 claims abstract description 162
- 238000000034 method Methods 0.000 claims abstract description 101
- 230000027455 binding Effects 0.000 claims abstract description 46
- 230000000694 effects Effects 0.000 claims abstract description 38
- 102000005962 receptors Human genes 0.000 claims abstract description 25
- 108020003175 receptors Proteins 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 129
- -1 amino, cyano, hydroxy, aminocarbonyl Chemical group 0.000 claims description 117
- 239000000203 mixture Substances 0.000 claims description 107
- 125000001424 substituent group Chemical group 0.000 claims description 82
- 150000003839 salts Chemical class 0.000 claims description 79
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 74
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 55
- 229910052736 halogen Inorganic materials 0.000 claims description 53
- 150000002367 halogens Chemical class 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
- 238000003556 assay Methods 0.000 claims description 50
- 239000000243 solution Substances 0.000 claims description 45
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 39
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 39
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 31
- 125000004043 oxo group Chemical group O=* 0.000 claims description 31
- 206010016256 fatigue Diseases 0.000 claims description 30
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 25
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 25
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 20
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 20
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 20
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 18
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
- 150000005215 alkyl ethers Chemical class 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 208000010877 cognitive disease Diseases 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 16
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 16
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 208000018737 Parkinson disease Diseases 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 12
- 208000028698 Cognitive impairment Diseases 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 208000019695 Migraine disease Diseases 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 10
- 208000002173 dizziness Diseases 0.000 claims description 10
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 10
- 206010027599 migraine Diseases 0.000 claims description 10
- 201000000980 schizophrenia Diseases 0.000 claims description 10
- ZKSUKUDYXFGCAE-UHFFFAOYSA-N 3-(6-chloropyridazin-3-yl)-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound N1=NC(Cl)=CC=C1N1CCC2(CCN(CC2)C2CCC2)CC1 ZKSUKUDYXFGCAE-UHFFFAOYSA-N 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 208000030814 Eating disease Diseases 0.000 claims description 9
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 9
- 201000010105 allergic rhinitis Diseases 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 235000014632 disordered eating Nutrition 0.000 claims description 9
- 206010015037 epilepsy Diseases 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 201000003152 motion sickness Diseases 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
- 201000003631 narcolepsy Diseases 0.000 claims description 8
- 208000019116 sleep disease Diseases 0.000 claims description 8
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 claims description 8
- 206010041349 Somnolence Diseases 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims description 5
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 5
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 5
- 206010027175 memory impairment Diseases 0.000 claims description 5
- 201000002859 sleep apnea Diseases 0.000 claims description 5
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- MHCJEILYZBIMOR-UHFFFAOYSA-N 2-(5-bromopyridin-2-yl)-8-cyclobutyl-2,8-diazaspiro[4.5]decane Chemical compound N1=CC(Br)=CC=C1N1CC2(CCN(CC2)C2CCC2)CC1 MHCJEILYZBIMOR-UHFFFAOYSA-N 0.000 claims description 4
- CFJLCRXTEBBGGQ-UHFFFAOYSA-N 2-cyclobutyl-8-[4-(1-methylpyrazol-4-yl)phenyl]-2,8-diazaspiro[4.5]decane Chemical compound C1=NN(C)C=C1C1=CC=C(N2CCC3(CN(CC3)C3CCC3)CC2)C=C1 CFJLCRXTEBBGGQ-UHFFFAOYSA-N 0.000 claims description 4
- IBEYJYAEHDQICE-UHFFFAOYSA-N 8-cyclobutyl-2-[4-(1-methylpyrazol-4-yl)phenyl]-2,8-diazaspiro[4.5]decane Chemical compound C1=NN(C)C=C1C1=CC=C(N2CC3(CC2)CCN(CC3)C2CCC2)C=C1 IBEYJYAEHDQICE-UHFFFAOYSA-N 0.000 claims description 4
- 208000026139 Memory disease Diseases 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000003395 histamine H3 receptor antagonist Substances 0.000 claims description 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
- XNLFCCRBRSIOCO-UHFFFAOYSA-N 8-(5-bromopyridin-2-yl)-2-cyclobutyl-2,8-diazaspiro[4.5]decane Chemical compound N1=CC(Br)=CC=C1N1CCC2(CN(CC2)C2CCC2)CC1 XNLFCCRBRSIOCO-UHFFFAOYSA-N 0.000 claims description 3
- TUJCQMZABNGISZ-UHFFFAOYSA-N 9-cyclobutyl-3-(4-imidazo[1,2-a]pyrimidin-6-ylphenyl)-3,9-diazaspiro[5.5]undecane Chemical compound C1CCC1N1CCC2(CCN(CC2)C=2C=CC(=CC=2)C2=CN3C=CN=C3N=C2)CC1 TUJCQMZABNGISZ-UHFFFAOYSA-N 0.000 claims description 3
- MHANAHOIGTXVMJ-UHFFFAOYSA-N 9-cyclobutyl-3-(6-methoxypyridazin-3-yl)-3,9-diazaspiro[5.5]undecane Chemical compound N1=NC(OC)=CC=C1N1CCC2(CCN(CC2)C2CCC2)CC1 MHANAHOIGTXVMJ-UHFFFAOYSA-N 0.000 claims description 3
- KZKKGCYHAYKDPE-UHFFFAOYSA-N 9-cyclobutyl-3-[4-[(2-methylpyrrolidin-1-yl)methyl]phenyl]-3,9-diazaspiro[5.5]undecane Chemical compound CC1CCCN1CC1=CC=C(N2CCC3(CCN(CC3)C3CCC3)CC2)C=C1 KZKKGCYHAYKDPE-UHFFFAOYSA-N 0.000 claims description 3
- ALFJRBRBERGVEQ-UHFFFAOYSA-N 9-cyclobutyl-3-[5-[(2-methylpyrrolidin-1-yl)methyl]pyridin-2-yl]-3,9-diazaspiro[5.5]undecane Chemical compound CC1CCCN1CC1=CC=C(N2CCC3(CCN(CC3)C3CCC3)CC2)N=C1 ALFJRBRBERGVEQ-UHFFFAOYSA-N 0.000 claims description 3
- DPCCTMBQJHVKSV-UHFFFAOYSA-N 9-cyclobutyl-3-pyrazin-2-yl-3,9-diazaspiro[5.5]undecane Chemical compound C1CCC1N1CCC2(CCN(CC2)C=2N=CC=NC=2)CC1 DPCCTMBQJHVKSV-UHFFFAOYSA-N 0.000 claims description 3
- MDACIZIWKVTGSZ-UHFFFAOYSA-N [6-(9-cyclobutyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-3-yl]-(2-methylpyrrolidin-1-yl)methanone Chemical compound CC1CCCN1C(=O)C1=CC=C(N2CCC3(CCN(CC3)C3CCC3)CC2)N=C1 MDACIZIWKVTGSZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- STRNGIPUCOZAMG-UHFFFAOYSA-N 9-cyclobutyl-3-(1-methylbenzimidazol-5-yl)-3,9-diazaspiro[5.5]undecane Chemical compound C=1C=C2N(C)C=NC2=CC=1N(CC1)CCC1(CC1)CCN1C1CCC1 STRNGIPUCOZAMG-UHFFFAOYSA-N 0.000 claims description 2
- TVFSRWDEHXIQDN-UHFFFAOYSA-N 9-cyclobutyl-3-(5-pyridin-3-ylpyrazin-2-yl)-3,9-diazaspiro[5.5]undecane Chemical compound C1CCC1N1CCC2(CCN(CC2)C=2N=CC(=NC=2)C=2C=NC=CC=2)CC1 TVFSRWDEHXIQDN-UHFFFAOYSA-N 0.000 claims description 2
- SBHKIBKMVMOSFU-UHFFFAOYSA-N 9-cyclobutyl-3-(6-methylsulfonylpyridazin-3-yl)-3,9-diazaspiro[5.5]undecane Chemical compound N1=NC(S(=O)(=O)C)=CC=C1N1CCC2(CCN(CC2)C2CCC2)CC1 SBHKIBKMVMOSFU-UHFFFAOYSA-N 0.000 claims description 2
- GWGINUBOZNKZLP-UHFFFAOYSA-N 9-cyclobutyl-3-(6-pyrimidin-5-ylpyridazin-3-yl)-3,9-diazaspiro[5.5]undecane Chemical compound C1CCC1N1CCC2(CCN(CC2)C=2N=NC(=CC=2)C=2C=NC=NC=2)CC1 GWGINUBOZNKZLP-UHFFFAOYSA-N 0.000 claims description 2
- FGJWDESWBTUSKB-UHFFFAOYSA-N 9-cyclobutyl-3-[6-(4-methylsulfonylphenyl)pyridazin-3-yl]-3,9-diazaspiro[5.5]undecane Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC=C(N2CCC3(CCN(CC3)C3CCC3)CC2)N=N1 FGJWDESWBTUSKB-UHFFFAOYSA-N 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 9
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 8
- 125000001589 carboacyl group Chemical group 0.000 claims 4
- 235000005152 nicotinamide Nutrition 0.000 claims 4
- 239000011570 nicotinamide Substances 0.000 claims 4
- 229960003966 nicotinamide Drugs 0.000 claims 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 3
- 208000020685 sleep-wake disease Diseases 0.000 claims 3
- QEXPZZLZBPAMMK-UHFFFAOYSA-N 9-cyclobutyl-3-[4-(piperidin-1-ylmethyl)phenyl]-3,9-diazaspiro[5.5]undecane Chemical compound C=1C=C(N2CCC3(CCN(CC3)C3CCC3)CC2)C=CC=1CN1CCCCC1 QEXPZZLZBPAMMK-UHFFFAOYSA-N 0.000 claims 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims 2
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims 2
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 2
- DLMJEFNQSGXWFE-UHFFFAOYSA-N (9-cyclobutyl-3,9-diazaspiro[5.5]undecan-3-yl)-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)N(CC1)CCC1(CC1)CCN1C1CCC1 DLMJEFNQSGXWFE-UHFFFAOYSA-N 0.000 claims 1
- BYEXLPMZDSDQOZ-UHFFFAOYSA-N 1-[4-[6-(9-cyclobutyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridin-3-yl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C1=CC=C(N2CCC3(CCN(CC3)C3CCC3)CC2)N=C1 BYEXLPMZDSDQOZ-UHFFFAOYSA-N 0.000 claims 1
- ZSASNKWSKWZNRE-UHFFFAOYSA-N 2-(6-chloropyridazin-3-yl)-8-cyclobutyl-2,8-diazaspiro[4.5]decane Chemical compound N1=NC(Cl)=CC=C1N1CC2(CCN(CC2)C2CCC2)CC1 ZSASNKWSKWZNRE-UHFFFAOYSA-N 0.000 claims 1
- MBXRGGFPRCGEEN-UHFFFAOYSA-N 2-[6-(9-cyclobutyl-3,9-diazaspiro[5.5]undecan-3-yl)pyridazin-3-yl]-1,3-thiazole Chemical compound C1CCC1N1CCC2(CCN(CC2)C=2N=NC(=CC=2)C=2SC=CN=2)CC1 MBXRGGFPRCGEEN-UHFFFAOYSA-N 0.000 claims 1
- HPJJWQFTTPCSMT-UHFFFAOYSA-N 2-cyclobutyl-8-(4-pyridin-3-ylphenyl)-2,8-diazaspiro[4.5]decane Chemical compound C1CCC1N1CC2(CCN(CC2)C=2C=CC(=CC=2)C=2C=NC=CC=2)CC1 HPJJWQFTTPCSMT-UHFFFAOYSA-N 0.000 claims 1
- CWXYUJNGEZVIRO-UHFFFAOYSA-N 2-cyclobutyl-8-(6-pyridin-4-ylpyridazin-3-yl)-2,8-diazaspiro[4.5]decane Chemical compound C1CCC1N1CC2(CCN(CC2)C=2N=NC(=CC=2)C=2C=CN=CC=2)CC1 CWXYUJNGEZVIRO-UHFFFAOYSA-N 0.000 claims 1
- MJJYENJYHFWQEO-UHFFFAOYSA-N 2-cyclobutyl-8-[6-(6-methoxypyridin-3-yl)pyridazin-3-yl]-2,8-diazaspiro[4.5]decane Chemical compound C1=NC(OC)=CC=C1C1=CC=C(N2CCC3(CN(CC3)C3CCC3)CC2)N=N1 MJJYENJYHFWQEO-UHFFFAOYSA-N 0.000 claims 1
- ZKPNSBJNPXNSDD-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[4-(9-cyclobutyl-3,9-diazaspiro[5.5]undecan-3-yl)phenyl]methanone Chemical compound C1CCC2CCCCC2N1C(=O)C(C=C1)=CC=C1N(CC1)CCC1(CC1)CCN1C1CCC1 ZKPNSBJNPXNSDD-UHFFFAOYSA-N 0.000 claims 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- MCIHESAUOBHVKE-UHFFFAOYSA-N 3-(3-bromophenyl)-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound BrC1=CC=CC(N2CCC3(CCN(CC3)C3CCC3)CC2)=C1 MCIHESAUOBHVKE-UHFFFAOYSA-N 0.000 claims 1
- SWMWOVXBSUABRR-UHFFFAOYSA-N 3-[4-(3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-ylmethyl)phenyl]-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound C1CCC2CCCCC2N1CC(C=C1)=CC=C1N(CC1)CCC1(CC1)CCN1C1CCC1 SWMWOVXBSUABRR-UHFFFAOYSA-N 0.000 claims 1
- VDCDQBIYJKKNJC-UHFFFAOYSA-N 3-[4-(azepan-1-ylmethyl)phenyl]-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound C=1C=C(N2CCC3(CCN(CC3)C3CCC3)CC2)C=CC=1CN1CCCCCC1 VDCDQBIYJKKNJC-UHFFFAOYSA-N 0.000 claims 1
- HWGDYGVGHVFVCD-CLJLJLNGSA-N 3-[4-[[(4ar,8as)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]methyl]phenyl]-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound C([C@H]1CCCC[C@@H]1CC1)N1CC(C=C1)=CC=C1N(CC1)CCC1(CC1)CCN1C1CCC1 HWGDYGVGHVFVCD-CLJLJLNGSA-N 0.000 claims 1
- HWGDYGVGHVFVCD-IZZNHLLZSA-N 3-[4-[[(4as,8as)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]methyl]phenyl]-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound C([C@H]1CCCC[C@H]1CC1)N1CC(C=C1)=CC=C1N(CC1)CCC1(CC1)CCN1C1CCC1 HWGDYGVGHVFVCD-IZZNHLLZSA-N 0.000 claims 1
- CUOLVYBQCKSCDI-UHFFFAOYSA-N 3-[5-(4-benzylpiperazin-1-yl)pyridin-2-yl]-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound C=1C=CC=CC=1CN(CC1)CCN1C(C=N1)=CC=C1N(CC1)CCC1(CC1)CCN1C1CCC1 CUOLVYBQCKSCDI-UHFFFAOYSA-N 0.000 claims 1
- ABKBGKLIWLSTGT-UHFFFAOYSA-N 3-[6-(1,3-benzodioxol-5-yl)pyridazin-3-yl]-9-cyclobutyl-3,9-diazaspiro[5.5]undecane Chemical compound C1CCC1N1CCC2(CCN(CC2)C=2N=NC(=CC=2)C=2C=C3OCOC3=CC=2)CC1 ABKBGKLIWLSTGT-UHFFFAOYSA-N 0.000 claims 1
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- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- XXPJRAVPVRZQPZ-UHFFFAOYSA-N tert-butyl 8-benzyl-2,8-diazaspiro[4.5]decane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC21CCN(CC=1C=CC=CC=1)CC2 XXPJRAVPVRZQPZ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
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- 125000004306 triazinyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 229960003223 tripelennamine Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000003211 trypan blue cell staining Methods 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- 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
- C07D401/12—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
Landscapes
- Health & Medical Sciences (AREA)
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- Immunology (AREA)
- Child & Adolescent Psychology (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74668006P | 2006-05-08 | 2006-05-08 | |
| US11/745,448 US20080247964A1 (en) | 2006-05-08 | 2007-05-07 | Substituted azaspiro derivatives |
| PCT/US2007/011135 WO2007133561A2 (en) | 2006-05-08 | 2007-05-08 | Substituted azaspiro derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009536651A true JP2009536651A (ja) | 2009-10-15 |
| JP2009536651A5 JP2009536651A5 (https=) | 2010-07-01 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009509820A Withdrawn JP2009536651A (ja) | 2006-05-08 | 2007-05-08 | 置換されたアザスピロ誘導体 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20080247964A1 (https=) |
| EP (1) | EP2021004A4 (https=) |
| JP (1) | JP2009536651A (https=) |
| KR (1) | KR20090015956A (https=) |
| AU (1) | AU2007249925A1 (https=) |
| CA (1) | CA2651654A1 (https=) |
| IL (1) | IL195132A0 (https=) |
| WO (1) | WO2007133561A2 (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015524842A (ja) * | 2012-08-13 | 2015-08-27 | ノバルティス アーゲー | １，４−二置換ピリダジン類似体およびｓｍｎ欠損に関連する状態を処置するための方法 |
| JP2017507986A (ja) * | 2014-03-17 | 2017-03-23 | リマインド エヌヴイＲｅｍｙｎｄ Ｎｖ | ２，７−ジアザスピロ［３．５］ノナン化合物 |
| JP2019059783A (ja) * | 2013-07-31 | 2019-04-18 | ノバルティス アーゲー | １，４−二置換ピリダジン誘導体およびｓｍｎ欠損に関連する状態を処置するためのその使用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| AR074467A1 (es) | 2008-12-05 | 2011-01-19 | Sanofi Aventis | Tetrahidropiran espiro pirrolidinonas y piperidinonas sustituidas, composiciones farmaceuticas que las contienen y uso de las mismas en el tratamiento y/o prevencion de enfermedades del snc ,tales como alzheimer y parkinson, entre otras. |
| AR074466A1 (es) | 2008-12-05 | 2011-01-19 | Sanofi Aventis | Piperidina espiro pirrolidinona y piperidinona sustituidas y su uso terapeutico en enfermedades mediadas por la modulacion de los receptores h3. |
| TW201206898A (en) * | 2010-05-11 | 2012-02-16 | Sanofi Aventis | Substituted N-phenyl spirolactam bipyrrolidines, preparation and therapeutic use thereof |
| EP2569297A1 (en) | 2010-05-11 | 2013-03-20 | Sanofi | Substituted n-heterocycloalkyl bipyrrolidinylphenyl amide derivatives, preparation and therapeutic use thereof |
| TW201206889A (en) | 2010-05-11 | 2012-02-16 | Sanofi Aventis | Substituted N-alkyl and N-acyl tetrahydro-isoquinoline derivatives, preparation and therapeutic use thereof |
| WO2011143162A1 (en) | 2010-05-11 | 2011-11-17 | Sanofi | Substituted n-heteroaryl bipyrrolidine carboxamides, preparation and therapeutic use thereof |
| AR083718A1 (es) | 2010-05-11 | 2013-03-20 | Sanofi Aventis | Fenil cicloalquil pirrolidina (piperidina) espirolactamas y amidas sustituidas, preparacion y uso terapeutico de las mismas |
| JP5833105B2 (ja) | 2010-05-11 | 2015-12-16 | サノフイ | 置換ｎ−ヘテロアリールスピロラクタムビピロリジン類、その製造及び治療的使用 |
| WO2011143155A1 (en) | 2010-05-11 | 2011-11-17 | Sanofi | Substituted n-heteroaryl tetrahydro-isoquinoline derivatives, preparation and therapeutic use thereof |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| JP6215315B2 (ja) * | 2012-06-12 | 2017-10-18 | アッヴィ・インコーポレイテッド | ピリジノンおよびピリダジノン誘導体 |
| US9096528B2 (en) | 2012-07-04 | 2015-08-04 | Agro-Kanesho Co., Ltd. | 2-aminonicotinic acid ester derivative and bactericide containing same as active ingredient |
| CN103288845B (zh) * | 2013-05-24 | 2015-05-20 | 武汉工程大学 | 螺环化合物2,4,8,10-四羰基-3,9-二氧杂螺环[5,5]十一烷及其合成方法 |
| DK3212637T3 (da) | 2014-10-31 | 2021-07-12 | Indivior Uk Ltd | Dopamin-d3-receptorantagonistforbindelser |
| WO2016100940A1 (en) | 2014-12-19 | 2016-06-23 | The Broad Institute, Inc. | Dopamine d2 receptor ligands |
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| EP3053577A1 (en) * | 2015-02-09 | 2016-08-10 | F. Hoffmann-La Roche AG | Compounds for the treatment of cancer |
| EP3256126B1 (en) * | 2015-02-09 | 2024-03-27 | F. Hoffmann-La Roche AG | Compounds for the treatment of cancer |
| EA201800367A1 (ru) * | 2015-12-10 | 2019-02-28 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы лечения болезни хантингтона |
| WO2018068296A1 (en) * | 2016-10-14 | 2018-04-19 | Merck Sharp & Dohme Corp. | PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE |
| EP3634953B1 (en) | 2017-06-05 | 2024-01-03 | PTC Therapeutics, Inc. | Compounds for treating huntington's disease |
| MX2019015580A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| CN111182898B (zh) | 2017-06-28 | 2024-04-16 | Ptc医疗公司 | 用于治疗亨廷顿氏病的方法 |
| EA202092001A1 (ru) | 2018-03-27 | 2021-01-29 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения болезни гентингтона |
| HRP20240935T1 (hr) | 2018-06-27 | 2024-11-22 | Ptc Therapeutics, Inc. | Heterociklični i heteroaril spojevi za liječenje huntingtonove bolesti |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| EP3814360B8 (en) | 2018-06-27 | 2024-11-06 | PTC Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| KR20210102887A (ko) * | 2018-11-14 | 2021-08-20 | 알타반트 사이언시스 게엠베하 | 말초 세로토닌과 관련된 질병 또는 장애를 치료하기 위한 트립토판 하이드록실라제 1 (tph1)의 결정질 스피로사이클릭 화합물 억제제 |
| CN109485648A (zh) * | 2018-12-17 | 2019-03-19 | 无锡合全药业有限公司 | 叔丁基-1-甲基-5-氧亚基三氮杂螺[5.5]十一烷-8-甲酸基酯的制备方法 |
| JP7649257B2 (ja) | 2019-05-13 | 2025-03-19 | ピーティーシー セラピューティクス， インコーポレイテッド | ハンチントン病を処置するための化合物 |
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| JPWO2005047286A1 (ja) * | 2003-11-13 | 2007-05-31 | 小野薬品工業株式会社 | スピロ複素環化合物 |
| AU2005277410B2 (en) * | 2004-08-20 | 2010-06-24 | Targacept, Inc. | The use of N-aryl diazaspiracyclic compounds in the treatment of addiction |
| WO2006040329A1 (en) * | 2004-10-12 | 2006-04-20 | Novo Nordisk A/S | 1 ibeta- hydroxysteroid dehydrogenase type 1 active spiro compounds |
| EP1917264B1 (en) * | 2005-06-28 | 2010-11-17 | NeuroSearch A/S | Novel 3,9-diaza-spiro[5.5]undecane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| AR057579A1 (es) * | 2005-11-23 | 2007-12-05 | Merck & Co Inc | Compuestos espirociclicos como inhibidores de histona de acetilasa (hdac) |
-
2007
- 2007-05-07 US US11/745,448 patent/US20080247964A1/en not_active Abandoned
- 2007-05-08 JP JP2009509820A patent/JP2009536651A/ja not_active Withdrawn
- 2007-05-08 AU AU2007249925A patent/AU2007249925A1/en not_active Abandoned
- 2007-05-08 EP EP07756232A patent/EP2021004A4/en not_active Withdrawn
- 2007-05-08 KR KR1020087029820A patent/KR20090015956A/ko not_active Withdrawn
- 2007-05-08 CA CA002651654A patent/CA2651654A1/en not_active Abandoned
- 2007-05-08 WO PCT/US2007/011135 patent/WO2007133561A2/en not_active Ceased
-
2008
- 2008-11-05 IL IL195132A patent/IL195132A0/en unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015524842A (ja) * | 2012-08-13 | 2015-08-27 | ノバルティス アーゲー | １，４−二置換ピリダジン類似体およびｓｍｎ欠損に関連する状態を処置するための方法 |
| JP2019059783A (ja) * | 2013-07-31 | 2019-04-18 | ノバルティス アーゲー | １，４−二置換ピリダジン誘導体およびｓｍｎ欠損に関連する状態を処置するためのその使用 |
| JP2017507986A (ja) * | 2014-03-17 | 2017-03-23 | リマインド エヌヴイＲｅｍｙｎｄ Ｎｖ | ２，７−ジアザスピロ［３．５］ノナン化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20080247964A1 (en) | 2008-10-09 |
| IL195132A0 (en) | 2009-09-22 |
| AU2007249925A1 (en) | 2007-11-22 |
| KR20090015956A (ko) | 2009-02-12 |
| EP2021004A2 (en) | 2009-02-11 |
| WO2007133561A3 (en) | 2008-10-02 |
| WO2007133561A2 (en) | 2007-11-22 |
| EP2021004A4 (en) | 2011-06-22 |
| CA2651654A1 (en) | 2007-11-22 |
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