ZA200601175B - Cyclopropyl derivatives as NK3 receptor antagonists - Google Patents
Cyclopropyl derivatives as NK3 receptor antagonists Download PDFInfo
- Publication number
- ZA200601175B ZA200601175B ZA200601175A ZA200601175A ZA200601175B ZA 200601175 B ZA200601175 B ZA 200601175B ZA 200601175 A ZA200601175 A ZA 200601175A ZA 200601175 A ZA200601175 A ZA 200601175A ZA 200601175 B ZA200601175 B ZA 200601175B
- Authority
- ZA
- South Africa
- Prior art keywords
- methyl
- phenyl
- amide
- compound
- salt
- Prior art date
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- 102100029409 Neuromedin-K receptor Human genes 0.000 title description 31
- 101001125071 Homo sapiens Neuromedin-K receptor Proteins 0.000 title description 30
- 239000002464 receptor antagonist Substances 0.000 title description 11
- 229940044551 receptor antagonist Drugs 0.000 title description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 183
- 229910052739 hydrogen Inorganic materials 0.000 claims description 149
- 239000001257 hydrogen Substances 0.000 claims description 146
- 150000003839 salts Chemical class 0.000 claims description 144
- -1 perhydroazepinyl group Chemical group 0.000 claims description 104
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 99
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 125000003386 piperidinyl group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000004193 piperazinyl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000002757 morpholinyl group Chemical group 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 229910052799 carbon Inorganic materials 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
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 201000000980 schizophrenia Diseases 0.000 claims description 10
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 206010006482 Bronchospasm Diseases 0.000 claims description 6
- 206010011224 Cough Diseases 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
- 206010030113 Oedema Diseases 0.000 claims description 6
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 230000010085 airway hyperresponsiveness Effects 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 230000007885 bronchoconstriction Effects 0.000 claims description 6
- 230000009610 hypersensitivity Effects 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 230000019948 ion homeostasis Effects 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 230000007279 water homeostasis Effects 0.000 claims description 6
- 206010010904 Convulsion Diseases 0.000 claims description 5
- 206010015866 Extravasation Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 125000005251 aryl acyl group Chemical group 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 230000036461 convulsion Effects 0.000 claims description 5
- 230000036251 extravasation Effects 0.000 claims description 5
- 208000028867 ischemia Diseases 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
- 239000005977 Ethylene Substances 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000003441 thioacyl group Chemical group 0.000 claims description 3
- IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- SZJIQLSCDIEJFC-UHFFFAOYSA-N 1-(4-fluorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=C(F)C=C1 SZJIQLSCDIEJFC-UHFFFAOYSA-N 0.000 claims 21
- DIWGZVQKFSFNLH-UHFFFAOYSA-N 1-(2-chlorophenyl)-n-methylmethanamine Chemical compound CNCC1=CC=CC=C1Cl DIWGZVQKFSFNLH-UHFFFAOYSA-N 0.000 claims 13
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 claims 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 150000001408 amides Chemical class 0.000 claims 5
- RCSSHZGQHHEHPZ-QMMMGPOBSA-N (1s)-n-methyl-1-phenylethanamine Chemical compound CN[C@@H](C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-QMMMGPOBSA-N 0.000 claims 4
- RCSSHZGQHHEHPZ-MRVPVSSYSA-N (1r)-n-methyl-1-phenylethanamine Chemical compound CN[C@H](C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-MRVPVSSYSA-N 0.000 claims 3
- HRLBRKOUKOXSPJ-VCTRWQRLSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-(2-phenylpropan-2-yl)cyclopropane-1-carboxamide Chemical compound O=C([C@]1(C[C@H]1CN1CCC(CC1)(NC(=O)C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)NC(C)(C)C1=CC=CC=C1 HRLBRKOUKOXSPJ-VCTRWQRLSA-N 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 2
- MQRIUFVBEVFILS-UHFFFAOYSA-N n-methyl-1-naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CNC)=CC=CC2=C1 MQRIUFVBEVFILS-UHFFFAOYSA-N 0.000 claims 2
- RCSSHZGQHHEHPZ-UHFFFAOYSA-N n-methyl-1-phenylethanamine Chemical compound CNC(C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-UHFFFAOYSA-N 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- DGLDUQZIRFLLRH-UCGGBYDDSA-N (1r,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 DGLDUQZIRFLLRH-UCGGBYDDSA-N 0.000 claims 1
- DGLDUQZIRFLLRH-ZUKKLESISA-N (1r,2s)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@]1([C@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 DGLDUQZIRFLLRH-ZUKKLESISA-N 0.000 claims 1
- WDKKCWLRJSMLLL-RYWJPUDZSA-N (1s,2r)-1-(4-fluorophenyl)-n-[(4-fluorophenyl)methyl]-n-methyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(=O)N1CCCCC1)C=1C=CC=CC=1)C=1C=CC(F)=CC=1)N(C)CC1=CC=C(F)C=C1 WDKKCWLRJSMLLL-RYWJPUDZSA-N 0.000 claims 1
- MKSYTHNYVWQBHU-JEQDSNCJSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-[1-(4-methoxyphenyl)ethyl]-n-methylcyclopropane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1C(C)N(C)C(=O)[C@]1(C=2C=C(Cl)C(Cl)=CC=2)[C@H](CN2CCC(CC2)(NC(C)=O)C=2C=CC=CC=2)C1 MKSYTHNYVWQBHU-JEQDSNCJSA-N 0.000 claims 1
- PHOTVBNATRIMMP-WCFYSQIESA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-methyl-n-[(1r)-1-phenylethyl]cyclopropane-1-carboxamide Chemical compound C([C@@H]1C[C@@]1(C(=O)N(C)[C@H](C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(CC1)CCC1(NC(C)=O)C1=CC=CC=C1 PHOTVBNATRIMMP-WCFYSQIESA-N 0.000 claims 1
- DGWJZKUIZMZNGT-VVFBEHOQSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-methyl-n-phenylcyclopropane-1-carboxamide Chemical compound C([C@@H]1C[C@@]1(C(=O)N(C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(CC1)CCC1(NC(C)=O)C1=CC=CC=C1 DGWJZKUIZMZNGT-VVFBEHOQSA-N 0.000 claims 1
- JGYUUOSOFSYEAV-QABMSTFYSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-1-(3,4-dichlorophenyl)-n-phenylcyclopropane-1-carboxamide Chemical compound O=C([C@]1(C[C@H]1CN1CCC(CC1)(NC(=O)C)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)NC1=CC=CC=C1 JGYUUOSOFSYEAV-QABMSTFYSA-N 0.000 claims 1
- RHLMKFJIEFRHRH-XYFQYJLHSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-[(2-chlorophenyl)methyl]-1-(3,4-difluorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(F)C(F)=CC=1)N(C)CC1=CC=CC=C1Cl RHLMKFJIEFRHRH-XYFQYJLHSA-N 0.000 claims 1
- FQEMDHREFPEUDV-QPQHGXMVSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-[(4-fluorophenyl)methyl]-1-(3-methoxyphenyl)-n-methylcyclopropane-1-carboxamide Chemical compound COC1=CC=CC([C@]2([C@@H](C2)CN2CCC(CC2)(NC(C)=O)C=2C=CC=CC=2)C(=O)N(C)CC=2C=CC(F)=CC=2)=C1 FQEMDHREFPEUDV-QPQHGXMVSA-N 0.000 claims 1
- PYWFDBJXAYACSN-QPQHGXMVSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-[(4-fluorophenyl)methyl]-1-(4-methoxyphenyl)-n-methylcyclopropane-1-carboxamide Chemical compound C1=CC(OC)=CC=C1[C@@]1(C(=O)N(C)CC=2C=CC(F)=CC=2)[C@H](CN2CCC(CC2)(NC(C)=O)C=2C=CC=CC=2)C1 PYWFDBJXAYACSN-QPQHGXMVSA-N 0.000 claims 1
- QLRCKWYTUWTCTQ-RYCFQHDISA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-[(4-fluorophenyl)methyl]-n-methyl-1-(3-methylphenyl)cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(C)C=CC=1)N(C)CC1=CC=C(F)C=C1 QLRCKWYTUWTCTQ-RYCFQHDISA-N 0.000 claims 1
- MCBQGSWTDVDPQI-RYCFQHDISA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-[(4-fluorophenyl)methyl]-n-methyl-1-(4-methylphenyl)cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=CC(C)=CC=1)N(C)CC1=CC=C(F)C=C1 MCBQGSWTDVDPQI-RYCFQHDISA-N 0.000 claims 1
- QQKNISXNVVCXKA-GMCHKSTQSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-[(4-fluorophenyl)methyl]-n-methyl-1-phenylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=CC=CC=1)N(C)CC1=CC=C(F)C=C1 QQKNISXNVVCXKA-GMCHKSTQSA-N 0.000 claims 1
- QYPNIJMHKAKVCE-GMCHKSTQSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(4-chlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=CC=C1 QYPNIJMHKAKVCE-GMCHKSTQSA-N 0.000 claims 1
- UNIFQYCWCLZLKX-BZKUTMRRSA-N (1s,2r)-2-[(4-acetamido-4-phenylpiperidin-1-yl)methyl]-n-benzyl-n-methyl-1-(3-methylphenyl)cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(C)C=CC=1)N(C)CC1=CC=CC=C1 UNIFQYCWCLZLKX-BZKUTMRRSA-N 0.000 claims 1
- BUILODASCWNDIS-GMCHKSTQSA-N (1s,2r)-2-[(4-acetyl-4-phenylpiperidin-1-yl)methyl]-n-[(4-fluorophenyl)methyl]-n-methyl-1-phenylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(C)=O)C=1C=CC=CC=1)C=1C=CC=CC=1)N(C)CC1=CC=C(F)C=C1 BUILODASCWNDIS-GMCHKSTQSA-N 0.000 claims 1
- MZSWBCYZRMJXJL-QVWWMRLHSA-N (1s,2r)-2-[(4-acetyl-4-phenylpiperidin-1-yl)methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 MZSWBCYZRMJXJL-QVWWMRLHSA-N 0.000 claims 1
- JQFQYHQQXODQRT-FREGXXQWSA-N (1s,2r)-2-[(4-benzylpiperazin-1-yl)methyl]-1-(4-chlorophenyl)-n-[(4-fluorophenyl)methyl]-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCN(CC=2C=CC=CC=2)CC1)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=C(F)C=C1 JQFQYHQQXODQRT-FREGXXQWSA-N 0.000 claims 1
- CRTGAKMPIJDXLA-VCTRWQRLSA-N (1s,2r)-2-[2-(4-acetamido-4-phenylpiperidin-1-yl)ethyl]-1-(3,4-dichlorophenyl)-n-[(4-fluorophenyl)methyl]-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@H](C1)CCN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=C(F)C=C1 CRTGAKMPIJDXLA-VCTRWQRLSA-N 0.000 claims 1
- QIWOAVVQUIWADI-XQJOSWFISA-N (1s,2r)-2-[3-(4-acetamido-4-phenylpiperidin-1-yl)propyl]-1-(3,4-dichlorophenyl)-n-[(4-fluorophenyl)methyl]-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CCCN1CCC(CC1)(NC(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=C(F)C=C1 QIWOAVVQUIWADI-XQJOSWFISA-N 0.000 claims 1
- VGZDPDDYITWWGQ-NRUKRWIHSA-N (1s,2r)-2-[[4-(2-acetamido-5-fluorophenyl)piperidin-1-yl]methyl]-1-(3,4-dichlorophenyl)-n-[(4-fluorophenyl)methyl]-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)C=1C(=CC=C(F)C=1)NC(C)=O)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=C(F)C=C1 VGZDPDDYITWWGQ-NRUKRWIHSA-N 0.000 claims 1
- FVJHIGAOLKUWFD-SUYBVONHSA-N (1s,2r)-2-[[4-(carbamoylamino)-4-phenylpiperidin-1-yl]methyl]-n-[(4-fluorophenyl)methyl]-n-methyl-1-phenylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(NC(N)=O)C=1C=CC=CC=1)C=1C=CC=CC=1)N(C)CC1=CC=C(F)C=C1 FVJHIGAOLKUWFD-SUYBVONHSA-N 0.000 claims 1
- COSKLMGEBNJPON-BSGZQELJSA-N (1s,2r)-2-[[4-[acetyl(methyl)amino]-4-phenylpiperidin-1-yl]methyl]-1-(3,4-difluorophenyl)-n-methyl-n-[(1s)-1-phenylethyl]cyclopropane-1-carboxamide Chemical compound C([C@@H]1C[C@@]1(C(=O)N(C)[C@@H](C)C=1C=CC=CC=1)C=1C=C(F)C(F)=CC=1)N(CC1)CCC1(N(C)C(C)=O)C1=CC=CC=C1 COSKLMGEBNJPON-BSGZQELJSA-N 0.000 claims 1
- ILFDUQNEWNDDFJ-QPQHGXMVSA-N (1s,2r)-2-[[4-[acetyl(methyl)amino]-4-phenylpiperidin-1-yl]methyl]-n-[(2-chlorophenyl)methyl]-1-(4-fluorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(N(C)C(C)=O)C=1C=CC=CC=1)C=1C=CC(F)=CC=1)N(C)CC1=CC=CC=C1Cl ILFDUQNEWNDDFJ-QPQHGXMVSA-N 0.000 claims 1
- BAOSJUSHNIOEOW-QPQHGXMVSA-N (1s,2r)-2-[[4-[acetyl(methyl)amino]-4-phenylpiperidin-1-yl]methyl]-n-benzyl-1-(3,4-dichlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(N(C)C(C)=O)C=1C=CC=CC=1)C=1C=C(Cl)C(Cl)=CC=1)N(C)CC1=CC=CC=C1 BAOSJUSHNIOEOW-QPQHGXMVSA-N 0.000 claims 1
- PNZARYFMWGXKJU-RYCFQHDISA-N (1s,2r)-2-[[4-[acetyl(methyl)amino]-4-phenylpiperidin-1-yl]methyl]-n-benzyl-1-(4-chlorophenyl)-n-methylcyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(N(C)C(C)=O)C=1C=CC=CC=1)C=1C=CC(Cl)=CC=1)N(C)CC1=CC=CC=C1 PNZARYFMWGXKJU-RYCFQHDISA-N 0.000 claims 1
- TYPUSRBKPMTZKN-RHBXAEEVSA-N (1s,2r)-n-[(2-chlorophenyl)methyl]-1-(3,4-difluorophenyl)-n-methyl-2-[[4-phenyl-4-(piperidine-1-carbonyl)piperidin-1-yl]methyl]cyclopropane-1-carboxamide Chemical compound O=C([C@@]1([C@@H](C1)CN1CCC(CC1)(C(=O)N1CCCCC1)C=1C=CC=CC=1)C=1C=C(F)C(F)=CC=1)N(C)CC1=CC=CC=C1Cl TYPUSRBKPMTZKN-RHBXAEEVSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B55/00—Racemisation; Complete or partial inversion
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/64—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having an aryl radical as the second substituent in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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DKPA200301175 | 2003-08-15 |
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JP (1) | JP4713474B2 (es) |
KR (1) | KR20060066721A (es) |
CN (1) | CN1867549B (es) |
AR (1) | AR045368A1 (es) |
AT (1) | ATE528291T1 (es) |
EA (1) | EA009477B1 (es) |
IS (1) | IS8278A (es) |
ZA (1) | ZA200601175B (es) |
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GB0328908D0 (en) * | 2003-12-12 | 2004-01-14 | Syngenta Participations Ag | Chemical compounds |
PL2007756T3 (pl) * | 2006-04-07 | 2016-01-29 | Vertex Pharma | Modulatory transporterów posiadających kasetę wiążącą ATP |
WO2010086259A1 (en) * | 2009-01-30 | 2010-08-05 | F. Hoffmann-La Roche Ag | Piperidine derivatives as nk3 receptor antagonists |
US8324250B2 (en) * | 2009-03-19 | 2012-12-04 | Hoffmann-La Roche Inc. | Piperidine derivatives as NK3 receptor antagonists |
US20110144081A1 (en) * | 2009-12-15 | 2011-06-16 | Henner Knust | Pyrrolidine derivatives |
WO2014168262A1 (en) * | 2013-04-11 | 2014-10-16 | D.D.P. Corporation | Kinase inhibitors containing cyclopropane skeleton |
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FR2508035A1 (fr) * | 1981-06-23 | 1982-12-24 | Fabre Sa Pierre | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central |
FR2719311B1 (fr) * | 1994-03-18 | 1998-06-26 | Sanofi Sa | Composés antagonistes sélectifs du récepteur NK3 humain et leur utilisation comme médicaments et outils de diagnostic. |
US5434158A (en) * | 1994-04-26 | 1995-07-18 | Merck & Co., Inc. | Spiro-substituted azacycles as neurokinin-3 antagonists |
FR2738819B1 (fr) * | 1995-09-14 | 1997-12-05 | Sanofi Sa | Nouveaux composes antagonistes selectifs du recepteur nk3 humain, procede pour leur obtention et compositions pharmaceutiques les contenant |
US6713479B2 (en) * | 2001-03-02 | 2004-03-30 | Sepracor Inc. | Piperidine-piperazine ligands for neurotransmitter receptors |
EA006082B1 (ru) * | 2001-12-19 | 2005-08-25 | Х. Лундбекк А/С | Производные 3,4-дигидро-1h-изохинолин-2-ила |
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- 2004-08-13 AR ARP040102914A patent/AR045368A1/es not_active Application Discontinuation
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IS8278A (is) | 2006-01-31 |
KR20060066721A (ko) | 2006-06-16 |
EA009477B1 (ru) | 2008-02-28 |
JP2007502253A (ja) | 2007-02-08 |
ATE528291T1 (de) | 2011-10-15 |
EA200600416A1 (ru) | 2006-08-25 |
CN1867549A (zh) | 2006-11-22 |
CN1867549B (zh) | 2011-07-06 |
JP4713474B2 (ja) | 2011-06-29 |
AR045368A1 (es) | 2005-10-26 |
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