ES2372332T3 - N-fenil-bipirrolidina carboxamidas sustituidas y su uso terapéutico. - Google Patents

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Publication number

ES2372332T3

ES2372332T3 ES08839959T ES08839959T ES2372332T3 ES 2372332 T3 ES2372332 T3 ES 2372332T3 ES 08839959 T ES08839959 T ES 08839959T ES 08839959 T ES08839959 T ES 08839959T ES 2372332 T3 ES2372332 T3 ES 2372332T3

Authority

ES

Spain

Prior art keywords

methyl

bipyrrolidinyl

phenyl

amide

carboxylic acid

Prior art date

2007-10-17

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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• 230000001225 therapeutic effect Effects 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 197
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
• 201000010099 disease Diseases 0.000 claims abstract description 24
• 238000002360 preparation method Methods 0.000 claims abstract description 18
• 238000011282 treatment Methods 0.000 claims abstract description 9
• -1 bicyclo [2,2,1] heptyl Chemical group 0.000 claims description 60
• 150000003839 salts Chemical class 0.000 claims description 41
• 239000002253 acid Substances 0.000 claims description 40
• 230000000694 effects Effects 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
• IJEUISLJVBUNRE-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C)=C1C(O)=O IJEUISLJVBUNRE-UHFFFAOYSA-N 0.000 claims description 8
• AVPKHOTUOHDTLW-UHFFFAOYSA-N oxane-4-carboxylic acid Chemical compound OC(=O)C1CCOCC1 AVPKHOTUOHDTLW-UHFFFAOYSA-N 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 7
• 208000024827 Alzheimer disease Diseases 0.000 claims description 6
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 6
• 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 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 208000019116 sleep disease Diseases 0.000 claims description 6
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• HXIYCKAAQPHZBM-UHFFFAOYSA-N 3-methyl-1,2-oxazole-5-carboxylic acid Chemical compound CC=1C=C(C(O)=O)ON=1 HXIYCKAAQPHZBM-UHFFFAOYSA-N 0.000 claims description 5
• WSMQKESQZFQMFW-UHFFFAOYSA-N 5-methyl-pyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1 WSMQKESQZFQMFW-UHFFFAOYSA-N 0.000 claims description 5
• 208000010877 cognitive disease Diseases 0.000 claims description 5
• 229940079593 drug Drugs 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
• IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 claims description 4
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• 206010041349 Somnolence Diseases 0.000 claims description 4
• JESWDXIHOJGWBP-UHFFFAOYSA-N bicyclo[2.2.1]heptane-3-carboxylic acid Chemical compound C1CC2C(C(=O)O)CC1C2 JESWDXIHOJGWBP-UHFFFAOYSA-N 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• DKVILNAQMBVZGF-UHFFFAOYSA-N 2-cyclopentyl-n-[2-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]acetamide Chemical compound CC1CCCN1C1CN(C=2C=C(C)C(NC(=O)CC3CCCC3)=CC=2)CC1 DKVILNAQMBVZGF-UHFFFAOYSA-N 0.000 claims description 3
• VLWVMXXYTWWGGK-UHFFFAOYSA-N 3,5-dimethyl-n-[3-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]-1,2-oxazole-4-carboxamide Chemical compound CC1CCCN1C1CN(C=2C(=CC(NC(=O)C3=C(ON=C3C)C)=CC=2)C)CC1 VLWVMXXYTWWGGK-UHFFFAOYSA-N 0.000 claims description 3
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 3
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• 201000003631 narcolepsy Diseases 0.000 claims description 3
• PCUQHNTZXLPGNX-JPCCIJSESA-N (1r,4s)-n-[2-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]bicyclo[2.2.1]heptane-3-carboxamide Chemical compound C1([C@@]2([H])CC[C@](C2)(C1)[H])C(=O)NC(C(=C1)C)=CC=C1N(C1)CCC1N1CCCC1C PCUQHNTZXLPGNX-JPCCIJSESA-N 0.000 claims description 2
• AEONKHQDKWWIPC-JPCCIJSESA-N (1r,4s)-n-[3-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]bicyclo[2.2.1]heptane-3-carboxamide Chemical compound C1([C@@]2([H])CC[C@](C2)(C1)[H])C(=O)NC(C=C1C)=CC=C1N(C1)CCC1N1CCCC1C AEONKHQDKWWIPC-JPCCIJSESA-N 0.000 claims description 2
• KWGIXLKUUUKGLB-RWMXSFHTSA-N (1r,4s)-n-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]bicyclo[2.2.1]heptane-3-carboxamide Chemical compound C1([C@@]2([H])CC[C@](C2)(C1)[H])C(=O)NC(C=C1)=CC=C1N(C1)CCC1N1CCCC1C KWGIXLKUUUKGLB-RWMXSFHTSA-N 0.000 claims description 2
• CJJRTJUBMZIMQU-UHFFFAOYSA-N 2,2,3,3-tetramethyl-n-[2-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]cyclopropane-1-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=C(C)C(NC(=O)C3C(C3(C)C)(C)C)=CC=2)CC1 CJJRTJUBMZIMQU-UHFFFAOYSA-N 0.000 claims description 2
• WXTBOKJYHOLEFC-UHFFFAOYSA-N 2,2,3,3-tetramethyl-n-[3-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]cyclopropane-1-carboxamide Chemical compound CC1CCCN1C1CN(C=2C(=CC(NC(=O)C3C(C3(C)C)(C)C)=CC=2)C)CC1 WXTBOKJYHOLEFC-UHFFFAOYSA-N 0.000 claims description 2
• ZETKRQDDYKMOPO-UHFFFAOYSA-N 2,2,3,3-tetramethyl-n-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]cyclopropane-1-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=CC(NC(=O)C3C(C3(C)C)(C)C)=CC=2)CC1 ZETKRQDDYKMOPO-UHFFFAOYSA-N 0.000 claims description 2
• DKVILNAQMBVZGF-RXVVDRJESA-N 2-cyclopentyl-n-[2-methyl-4-[(3s)-3-[(2s)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]phenyl]acetamide Chemical compound C[C@H]1CCCN1[C@@H]1CN(C=2C=C(C)C(NC(=O)CC3CCCC3)=CC=2)CC1 DKVILNAQMBVZGF-RXVVDRJESA-N 0.000 claims description 2
• YYOJXELLFPQIHG-UHFFFAOYSA-N 2-cyclopentyl-n-[3-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]acetamide Chemical compound CC1CCCN1C1CN(C=2C(=CC(NC(=O)CC3CCCC3)=CC=2)C)CC1 YYOJXELLFPQIHG-UHFFFAOYSA-N 0.000 claims description 2
• WRBZABSLXIGYJG-UHFFFAOYSA-N 2-cyclopentyl-n-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]acetamide Chemical compound CC1CCCN1C1CN(C=2C=CC(NC(=O)CC3CCCC3)=CC=2)CC1 WRBZABSLXIGYJG-UHFFFAOYSA-N 0.000 claims description 2
• SJCPAVQYCMSYEE-YJBOKZPZSA-N 2-methyl-n-[2-methyl-4-[(3s)-3-[(2s)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]phenyl]-1,3-oxazole-4-carboxamide Chemical compound C[C@H]1CCCN1[C@@H]1CN(C=2C=C(C)C(NC(=O)C=3N=C(C)OC=3)=CC=2)CC1 SJCPAVQYCMSYEE-YJBOKZPZSA-N 0.000 claims description 2
• CJUSJFAZUSWFLY-UHFFFAOYSA-N 3,5-dimethyl-n-[2-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]-1,2-oxazole-4-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=C(C)C(NC(=O)C3=C(ON=C3C)C)=CC=2)CC1 CJUSJFAZUSWFLY-UHFFFAOYSA-N 0.000 claims description 2
• QRBMQEJZPMHHQG-UHFFFAOYSA-N 3,5-dimethyl-n-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]-1,2-oxazole-4-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=CC(NC(=O)C3=C(ON=C3C)C)=CC=2)CC1 QRBMQEJZPMHHQG-UHFFFAOYSA-N 0.000 claims description 2
• MAVCXANXGDWPJD-UHFFFAOYSA-N 5-methyl-n-[2-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]-1h-pyrazole-3-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=C(C)C(NC(=O)C3=NNC(C)=C3)=CC=2)CC1 MAVCXANXGDWPJD-UHFFFAOYSA-N 0.000 claims description 2
• DJIDTTCTHGMHQF-UHFFFAOYSA-N 5-methyl-n-[3-methyl-4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]-1h-pyrazole-3-carboxamide Chemical compound CC1CCCN1C1CN(C=2C(=CC(NC(=O)C3=NNC(C)=C3)=CC=2)C)CC1 DJIDTTCTHGMHQF-UHFFFAOYSA-N 0.000 claims description 2
• KYEPLUXUECKUNH-UHFFFAOYSA-N 5-methyl-n-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]-2-(trifluoromethyl)phenyl]-1h-pyrazole-3-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=C(C(NC(=O)C3=NNC(C)=C3)=CC=2)C(F)(F)F)CC1 KYEPLUXUECKUNH-UHFFFAOYSA-N 0.000 claims description 2
• RCUFJSPQSAHGNP-UHFFFAOYSA-N 5-methyl-n-[4-[3-(2-methylpyrrolidin-1-yl)pyrrolidin-1-yl]phenyl]-1h-pyrazole-3-carboxamide Chemical compound CC1CCCN1C1CN(C=2C=CC(NC(=O)C3=NNC(C)=C3)=CC=2)CC1 RCUFJSPQSAHGNP-UHFFFAOYSA-N 0.000 claims description 2
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• WFSAHCWIQYOYHH-WMZOPIPTSA-N n-[2-methyl-4-[(3s)-3-[(2s)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]phenyl]furan-2-carboxamide Chemical compound C[C@H]1CCCN1[C@@H]1CN(C=2C=C(C)C(NC(=O)C=3OC=CC=3)=CC=2)CC1 WFSAHCWIQYOYHH-WMZOPIPTSA-N 0.000 claims description 2
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