AP824A - Lactam derivatives. - Google Patents

Info

Publication number

AP824A

AP824A APAP/P/1997/000955A AP9700955A AP824A AP 824 A AP824 A AP 824A AP 9700955 A AP9700955 A AP 9700955A AP 824 A AP824 A AP 824A

Authority

AP

ARIPO

Prior art keywords

disorder

methylpiperazin

benzylidene

disorders

treating

Prior art date

1996-03-29

Links

• Espacenet
• Global Dossier
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• 150000003951 lactams Chemical class 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 169
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 92
• 150000003839 salts Chemical class 0.000 claims abstract description 56
• -1 chloro, fluoro, bromo, iodo Chemical group 0.000 claims abstract description 45
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
• 239000001257 hydrogen Substances 0.000 claims abstract description 29
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
• 125000001424 substituent group Chemical group 0.000 claims abstract description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
• 125000003118 aryl group Chemical group 0.000 claims abstract description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
• 125000001624 naphthyl group Chemical group 0.000 claims abstract description 12
• 239000005557 antagonist Substances 0.000 claims abstract description 10
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
• 229910052760 oxygen Chemical group 0.000 claims abstract description 5
• 239000001301 oxygen Chemical group 0.000 claims abstract description 5
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
• 239000011593 sulfur Chemical group 0.000 claims abstract description 5
• 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 4
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 4
• 125000001425 triazolyl group Chemical group 0.000 claims abstract description 4
• AZFKQCNGMSSWDS-UHFFFAOYSA-N MCPA-thioethyl Chemical compound CCSC(=O)COC1=CC=C(Cl)C=C1C AZFKQCNGMSSWDS-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000002541 furyl group Chemical group 0.000 claims abstract description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims abstract description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 3
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 3
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract 2
• 125000004429 atom Chemical group 0.000 claims abstract 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 57
• 208000035475 disorder Diseases 0.000 claims description 57
• 238000000034 method Methods 0.000 claims description 54
• 241000124008 Mammalia Species 0.000 claims description 39
• 239000003112 inhibitor Substances 0.000 claims description 24
• 239000000126 substance Substances 0.000 claims description 22
• VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 claims description 21
• 208000018737 Parkinson disease Diseases 0.000 claims description 20
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• 208000019695 Migraine disease Diseases 0.000 claims description 16
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• 230000002265 prevention Effects 0.000 claims description 16
• 230000000862 serotonergic effect Effects 0.000 claims description 16
• 230000005062 synaptic transmission Effects 0.000 claims description 16
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 15
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• 230000002708 enhancing effect Effects 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
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• 235000014632 disordered eating Nutrition 0.000 claims description 12
• 231100000869 headache Toxicity 0.000 claims description 12
• 235000020824 obesity Nutrition 0.000 claims description 12
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims description 11
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• 206010009094 Chronic paroxysmal hemicrania Diseases 0.000 claims description 11
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• 208000019553 vascular disease Diseases 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 9
• 206010036596 premature ejaculation Diseases 0.000 claims description 9
• 229910052684 Cerium Inorganic materials 0.000 claims description 8
• 230000003042 antagnostic effect Effects 0.000 claims description 8
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 8
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 7
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
• 125000003386 piperidinyl group Chemical group 0.000 claims description 5
• 239000003727 serotonin 1A antagonist Substances 0.000 claims description 4
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• 150000003254 radicals Chemical class 0.000 claims description 3
• LNKUUOUGABSERJ-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-3-[[5-fluoro-2-(4-methylpiperazin-1-yl)phenyl]methyl]piperidin-2-one Chemical compound C1CN(C)CCN1C1=CC=C(F)C=C1CC1C(=O)N(C=2C=C(Cl)C(Cl)=CC=2)CCC1 LNKUUOUGABSERJ-UHFFFAOYSA-N 0.000 claims description 2
• OQYDLIREXXETDC-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-3-[[2-(4-methylpiperazin-1-yl)phenyl]methylidene]piperidin-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1C=C1C(=O)N(CC=2C=CC(Cl)=CC=2)CCC1 OQYDLIREXXETDC-UHFFFAOYSA-N 0.000 claims description 2
• TWFJKRVEOJPLHP-UHFFFAOYSA-N 3-[[2-(4-methylpiperazin-1-yl)phenyl]methyl]-1-phenylpyrrolidin-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1CC1C(=O)N(C=2C=CC=CC=2)CC1 TWFJKRVEOJPLHP-UHFFFAOYSA-N 0.000 claims description 2
• FJPZQQXEVVFGPJ-UHFFFAOYSA-N 3-[[2-(4-methylpiperazin-1-yl)phenyl]methylidene]-1-phenylindol-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1C=C1C2=CC=CC=C2N(C=2C=CC=CC=2)C1=O FJPZQQXEVVFGPJ-UHFFFAOYSA-N 0.000 claims description 2
• HXFUANDJXSGPMX-UHFFFAOYSA-N 3-[[2-(4-methylpiperazin-1-yl)phenyl]methylidene]piperidin-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1C=C1C(=O)NCCC1 HXFUANDJXSGPMX-UHFFFAOYSA-N 0.000 claims description 2
• QDUYHSWCSDUISH-UHFFFAOYSA-N 3-[[2-(4-methylpiperazin-1-yl)phenyl]methylidene]pyrrolidin-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1C=C1C(=O)NCC1 QDUYHSWCSDUISH-UHFFFAOYSA-N 0.000 claims description 2
• OPSDVIJHGJHJNS-UHFFFAOYSA-N 6-chloro-3-[[2-(4-methylpiperazin-1-yl)phenyl]methylidene]-1h-indol-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1C=C1C2=CC=C(Cl)C=C2NC1=O OPSDVIJHGJHJNS-UHFFFAOYSA-N 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 239000004001 serotonin 1D antagonist Substances 0.000 claims description 2
• 230000002792 vascular Effects 0.000 claims description 2
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims 2
• INABFYWUPQDDOX-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-3-[[2-fluoro-6-(4-methylpiperazin-1-yl)phenyl]methylidene]pyrrolidin-2-one Chemical compound C1CN(C)CCN1C1=CC=CC(F)=C1C=C1C(=O)N(C=2C=C(Cl)C(Cl)=CC=2)CC1 INABFYWUPQDDOX-UHFFFAOYSA-N 0.000 claims 1
• NBRKHSQLNPOVMR-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[[5-fluoro-2-(4-methylpiperazin-1-yl)phenyl]methylidene]piperidin-2-one Chemical compound C1CN(C)CCN1C1=CC=C(F)C=C1C=C1C(=O)N(C=2C=CC(Cl)=CC=2)CCC1 NBRKHSQLNPOVMR-UHFFFAOYSA-N 0.000 claims 1
• YMYPGNNKKHIXNU-UHFFFAOYSA-N 1-(4-methylphenyl)-3-[[2-(4-methylpiperazin-1-yl)phenyl]methylidene]pyrrolidin-2-one Chemical compound C1CN(C)CCN1C1=CC=CC=C1C=C1C(=O)N(C=2C=CC(C)=CC=2)CC1 YMYPGNNKKHIXNU-UHFFFAOYSA-N 0.000 claims 1
• SSORKNRKKWDREJ-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-3-[[5-fluoro-2-(4-methylpiperazin-1-yl)phenyl]methylidene]piperidin-2-one Chemical compound C1CN(C)CCN1C1=CC=C(F)C=C1C=C1C(=O)N(CCC=2C=CC(Cl)=CC=2)CCC1 SSORKNRKKWDREJ-UHFFFAOYSA-N 0.000 claims 1
• 230000001684 chronic effect Effects 0.000 claims 1
• QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims 1
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• 125000003226 pyrazolyl group Chemical group 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
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