AU2013278873B2 - 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives - Google Patents
1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives Download PDFInfo
- Publication number
- AU2013278873B2 AU2013278873B2 AU2013278873A AU2013278873A AU2013278873B2 AU 2013278873 B2 AU2013278873 B2 AU 2013278873B2 AU 2013278873 A AU2013278873 A AU 2013278873A AU 2013278873 A AU2013278873 A AU 2013278873A AU 2013278873 B2 AU2013278873 B2 AU 2013278873B2
- Authority
- AU
- Australia
- Prior art keywords
- phenyl
- ylmethyl
- benzyl
- piperidine
- carboxylic acid
- 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.)
- Ceased
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- -1 1,2,3,4-tetrahydronaphthalenyl Chemical group 0.000 claims description 305
- 150000001875 compounds Chemical class 0.000 claims description 229
- 125000000217 alkyl group Chemical group 0.000 claims description 175
- 125000001424 substituent group Chemical group 0.000 claims description 78
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 77
- 125000003545 alkoxy group Chemical group 0.000 claims description 70
- 239000002253 acid Substances 0.000 claims description 65
- 229910052736 halogen Inorganic materials 0.000 claims description 64
- 150000002367 halogens Chemical class 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 63
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 59
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 206010028980 Neoplasm Diseases 0.000 claims description 42
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 40
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 40
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 29
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 claims description 28
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 26
- 150000002431 hydrogen Chemical group 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 24
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 24
- 201000011510 cancer Diseases 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 239000011737 fluorine Substances 0.000 claims description 23
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 22
- OKBHXGBLXDNJJD-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(C(F)(F)F)=N1 OKBHXGBLXDNJJD-UHFFFAOYSA-N 0.000 claims description 21
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 20
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 239000001301 oxygen Substances 0.000 claims description 19
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 19
- NFFASAJHNHQAMQ-UHFFFAOYSA-N 1-[(3-aminophenyl)methyl]-n-cyclohexylpiperidine-4-carboxamide Chemical compound NC1=CC=CC(CN2CCC(CC2)C(=O)NC2CCCCC2)=C1 NFFASAJHNHQAMQ-UHFFFAOYSA-N 0.000 claims description 18
- ZLJHBKDDUOKRQH-UHFFFAOYSA-N 1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)C=2C=CC(Cl)=CC=2)=C1 ZLJHBKDDUOKRQH-UHFFFAOYSA-N 0.000 claims description 18
- 125000005549 heteroarylene group Chemical group 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
- 208000023275 Autoimmune disease Diseases 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 239000011570 nicotinamide Substances 0.000 claims description 13
- 229960003966 nicotinamide Drugs 0.000 claims description 13
- 125000004193 piperazinyl group Chemical group 0.000 claims description 13
- 102000005962 receptors Human genes 0.000 claims description 13
- 108020003175 receptors Proteins 0.000 claims description 13
- 150000001204 N-oxides Chemical class 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000003725 azepanyl group Chemical group 0.000 claims description 11
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 11
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 10
- FUYHFQRMFJNQNY-UHFFFAOYSA-N 1-[(3-aminophenyl)methyl]-n-tert-butylpiperidine-4-carboxamide Chemical compound C1CC(C(=O)NC(C)(C)C)CCN1CC1=CC=CC(N)=C1 FUYHFQRMFJNQNY-UHFFFAOYSA-N 0.000 claims description 10
- 206010016654 Fibrosis Diseases 0.000 claims description 9
- 206010052779 Transplant rejections Diseases 0.000 claims description 9
- 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 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 230000004761 fibrosis Effects 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 125000002837 carbocyclic group Chemical group 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 230000037361 pathway Effects 0.000 claims description 8
- NIOPLTJRTDQUMS-UHFFFAOYSA-N 1-[(3-aminophenyl)methyl]-N-(2-methylbutan-2-yl)piperidine-4-carboxamide Chemical compound CC(CC)(C)NC(=O)C1CCN(CC1)CC1=CC(=CC=C1)N NIOPLTJRTDQUMS-UHFFFAOYSA-N 0.000 claims description 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- SMEXURCBVPOHAM-UHFFFAOYSA-N 1-[[3-[(4-fluorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)C=2C=CC(F)=CC=2)=C1 SMEXURCBVPOHAM-UHFFFAOYSA-N 0.000 claims description 6
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000004044 response Effects 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 5
- AZIWYCVYBYMBJL-UHFFFAOYSA-N 1-[1-(3-benzamidophenyl)ethyl]-N-[(4-fluorophenyl)methyl]piperidine-4-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=CC=CC=2)=CC=1C(C)N(CC1)CCC1C(=O)NCC1=CC=C(F)C=C1 AZIWYCVYBYMBJL-UHFFFAOYSA-N 0.000 claims description 4
- KSPOBZHOVRJBHT-UHFFFAOYSA-N N-[3-[1-[4-(pyrrolidine-1-carbonyl)piperidin-1-yl]ethyl]phenyl]benzamide Chemical compound C=1C=CC(NC(=O)C=2C=CC=CC=2)=CC=1C(C)N(CC1)CCC1C(=O)N1CCCC1 KSPOBZHOVRJBHT-UHFFFAOYSA-N 0.000 claims description 4
- QTVBVEWPHVTULP-ICSRJNTNSA-N N-[3-[[(2S,4S)-4-(cyclohexylcarbamoyl)-2-methylpiperidin-1-yl]methyl]phenyl]-6-(trifluoromethyl)pyridine-2-carboxamide Chemical compound C[C@H]1C[C@H](CCN1Cc1cccc(NC(=O)c2cccc(n2)C(F)(F)F)c1)C(=O)NC1CCCCC1 QTVBVEWPHVTULP-ICSRJNTNSA-N 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 4
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 4
- KRDAZCQNLFQBKF-UHFFFAOYSA-N 1-[(3-aminophenyl)methyl]-N-cyclopentylpiperidine-4-carboxamide Chemical compound NC1=CC=CC(CN2CCC(CC2)C(=O)NC2CCCC2)=C1 KRDAZCQNLFQBKF-UHFFFAOYSA-N 0.000 claims description 3
- VAZTUKKRUFELFU-UHFFFAOYSA-N 1-[(5-amino-2-chlorophenyl)methyl]-N-cyclopentylpiperidine-4-carboxamide Chemical compound NC1=CC=C(Cl)C(CN2CCC(CC2)C(=O)NC2CCCC2)=C1 VAZTUKKRUFELFU-UHFFFAOYSA-N 0.000 claims description 3
- REWCOXFGNNRNJM-UHFFFAOYSA-N 2-methyl-propan-1,1-diyl Chemical group [CH2]C([CH2+])=[CH-] REWCOXFGNNRNJM-UHFFFAOYSA-N 0.000 claims description 3
- NJHGVAYLDHROPT-UHFFFAOYSA-N 5-(trifluoromethyl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C=N1 NJHGVAYLDHROPT-UHFFFAOYSA-N 0.000 claims description 3
- WDJARUKOMOGTHA-UHFFFAOYSA-N 5-aminopyridine-2-carboxylic acid Chemical compound NC1=CC=C(C(O)=O)N=C1 WDJARUKOMOGTHA-UHFFFAOYSA-N 0.000 claims description 3
- JTKFIIQGMVKDNZ-UHFFFAOYSA-N 5-fluoropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(F)C=N1 JTKFIIQGMVKDNZ-UHFFFAOYSA-N 0.000 claims description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
- 239000005977 Ethylene Substances 0.000 claims description 3
- QTVBVEWPHVTULP-UYAOXDASSA-N N-[3-[[(2R,4R)-4-(cyclohexylcarbamoyl)-2-methylpiperidin-1-yl]methyl]phenyl]-6-(trifluoromethyl)pyridine-2-carboxamide Chemical compound C[C@@H]1C[C@@H](CCN1Cc1cccc(NC(=O)c2cccc(n2)C(F)(F)F)c1)C(=O)NC1CCCCC1 QTVBVEWPHVTULP-UYAOXDASSA-N 0.000 claims description 3
- WFHKDNAGIUCHRL-UHFFFAOYSA-N N-[6-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]pyrimidin-4-yl]-6-(trifluoromethyl)pyridine-2-carboxamide Chemical compound C1CC(C(=O)NC(C)(C)C)CCN1CC1=CC(NC(=O)C=2N=C(C=CC=2)C(F)(F)F)=NC=N1 WFHKDNAGIUCHRL-UHFFFAOYSA-N 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- PAURUYBABKHNHH-UHFFFAOYSA-N n-[3-[[4-(cyclohexylcarbamoyl)-4-fluoropiperidin-1-yl]methyl]phenyl]-5-methylpyridine-3-carboxamide Chemical compound CC1=CN=CC(C(=O)NC=2C=C(CN3CCC(F)(CC3)C(=O)NC3CCCCC3)C=CC=2)=C1 PAURUYBABKHNHH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 3
- OJHZCZLLUBZANO-UHFFFAOYSA-N 1-[(3-amino-4-ethylphenyl)methyl]-N-tert-butylpiperidine-4-carboxamide Chemical compound CCc1ccc(CN2CCC(CC2)C(=O)NC(C)(C)C)cc1N OJHZCZLLUBZANO-UHFFFAOYSA-N 0.000 claims description 2
- HIFRNNPTJMGJRD-UHFFFAOYSA-N 1-[(3-benzamidophenyl)methyl]-n-cyclohexylpiperidine-4-carboxamide Chemical compound C1CN(CC=2C=C(NC(=O)C=3C=CC=CC=3)C=CC=2)CCC1C(=O)NC1CCCCC1 HIFRNNPTJMGJRD-UHFFFAOYSA-N 0.000 claims description 2
- ZRYOJLQMTNIZQV-UHFFFAOYSA-N 1-[(5-amino-2-ethylphenyl)methyl]-N-tert-butylpiperidine-4-carboxamide Chemical compound CCc1ccc(N)cc1CN1CCC(CC1)C(=O)NC(C)(C)C ZRYOJLQMTNIZQV-UHFFFAOYSA-N 0.000 claims description 2
- JSKNQKMZHOBIND-UHFFFAOYSA-N 1-[(5-amino-2-methylphenyl)methyl]-n-tert-butylpiperidine-4-carboxamide Chemical compound CC1=CC=C(N)C=C1CN1CCC(C(=O)NC(C)(C)C)CC1 JSKNQKMZHOBIND-UHFFFAOYSA-N 0.000 claims description 2
- KEWMZDGJLUQISJ-UHFFFAOYSA-N 1-[(5-benzamido-2-chlorophenyl)methyl]-n-cyclopentylpiperidine-4-carboxamide Chemical compound C1=C(CN2CCC(CC2)C(=O)NC2CCCC2)C(Cl)=CC=C1NC(=O)C1=CC=CC=C1 KEWMZDGJLUQISJ-UHFFFAOYSA-N 0.000 claims description 2
- QEYZPKVWXJWSNK-UHFFFAOYSA-N 1-[[2-chloro-5-[(4-fluorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound ClC1=C(CN2CCC(CC2)C(=O)O)C=C(C=C1)NC(C1=CC=C(C=C1)F)=O QEYZPKVWXJWSNK-UHFFFAOYSA-N 0.000 claims description 2
- MKLSOJYDZOGGNC-UHFFFAOYSA-N 1-[[3-(1H-pyrrole-2-carbonylamino)phenyl]methyl]piperidine-4-carboxylic acid Chemical compound N1C(=CC=C1)C(=O)NC=1C=C(CN2CCC(CC2)C(=O)O)C=CC1 MKLSOJYDZOGGNC-UHFFFAOYSA-N 0.000 claims description 2
- GXECLSDPSBJDHO-UHFFFAOYSA-N 1-[[3-(3,3-dimethylbutanoylamino)phenyl]methyl]piperidine-4-carboxylic acid Chemical compound CC(CC(=O)NC=1C=C(CN2CCC(CC2)C(=O)O)C=CC1)(C)C GXECLSDPSBJDHO-UHFFFAOYSA-N 0.000 claims description 2
- MXYGHWXYFPGCGQ-UHFFFAOYSA-N 1-[[3-(thiophene-2-carbonylamino)phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)C=2SC=CC=2)=C1 MXYGHWXYFPGCGQ-UHFFFAOYSA-N 0.000 claims description 2
- FPJOCUZGVJGOHS-UHFFFAOYSA-N 1-[[3-[(2-chlorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)C=2C(=CC=CC=2)Cl)=C1 FPJOCUZGVJGOHS-UHFFFAOYSA-N 0.000 claims description 2
- FYEFKGFWPHKCTA-UHFFFAOYSA-N 1-[[3-[(2-fluorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)C=2C(=CC=CC=2)F)=C1 FYEFKGFWPHKCTA-UHFFFAOYSA-N 0.000 claims description 2
- JAJKOZLXESOUQF-UHFFFAOYSA-N 1-[[3-[(2-phenylacetyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)CC=2C=CC=CC=2)=C1 JAJKOZLXESOUQF-UHFFFAOYSA-N 0.000 claims description 2
- BDKGKWWSEOSCJX-UHFFFAOYSA-N 1-[[3-[(3-chlorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=CC(NC(=O)C=2C=C(Cl)C=CC=2)=C1 BDKGKWWSEOSCJX-UHFFFAOYSA-N 0.000 claims description 2
- ZAGPTLSBGGNZJU-UHFFFAOYSA-N 1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)piperidine-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NC1=CC=CC(CN2CCC(CC2)C(=O)NC2C3=CC=CC=C3CCC2)=C1 ZAGPTLSBGGNZJU-UHFFFAOYSA-N 0.000 claims description 2
- AKXDBIHZEOMCMQ-UHFFFAOYSA-N 1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N-[(2-chlorophenyl)methyl]piperidine-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NC1=CC=CC(CN2CCC(CC2)C(=O)NCC=2C(=CC=CC=2)Cl)=C1 AKXDBIHZEOMCMQ-UHFFFAOYSA-N 0.000 claims description 2
- LYLKMNXLWGWXCK-UHFFFAOYSA-N 1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N-[(2-methoxyphenyl)methyl]piperidine-4-carboxamide Chemical compound COC1=CC=CC=C1CNC(=O)C1CCN(CC=2C=C(NC(=O)C=3C=CC(Cl)=CC=3)C=CC=2)CC1 LYLKMNXLWGWXCK-UHFFFAOYSA-N 0.000 claims description 2
- ZHUMBVIWUSFPAQ-UHFFFAOYSA-N 1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-n-(2,2,2-trifluoroethyl)piperidine-4-carboxamide Chemical compound C1CC(C(=O)NCC(F)(F)F)CCN1CC1=CC=CC(NC(=O)C=2C=CC(Cl)=CC=2)=C1 ZHUMBVIWUSFPAQ-UHFFFAOYSA-N 0.000 claims description 2
- GKCFGLBUEJGUOQ-UHFFFAOYSA-N 1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-n-propan-2-ylpiperidine-4-carboxamide Chemical compound C1CC(C(=O)NC(C)C)CCN1CC1=CC=CC(NC(=O)C=2C=CC(Cl)=CC=2)=C1 GKCFGLBUEJGUOQ-UHFFFAOYSA-N 0.000 claims description 2
- XFRBPLHZOIAUGT-UHFFFAOYSA-N 1-[[3-[(5-chlorothiophene-2-carbonyl)amino]phenyl]methyl]-n-cyclohexylpiperidine-4-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC1=CC=CC(CN2CCC(CC2)C(=O)NC2CCCCC2)=C1 XFRBPLHZOIAUGT-UHFFFAOYSA-N 0.000 claims description 2
- UFIYRLCEYHWOND-RZTXVSJASA-N 1-[[3-[[(1S,2R,4R)-bicyclo[2.2.1]heptane-2-carbonyl]amino]phenyl]methyl]-N-cyclohexylpiperidine-4-carboxamide Chemical compound O=C([C@H]1[C@@]2([H])CC[C@](C2)(C1)[H])NC(C=1)=CC=CC=1CN(CC1)CCC1C(=O)NC1CCCCC1 UFIYRLCEYHWOND-RZTXVSJASA-N 0.000 claims description 2
- MZCNOTIDWAXVDJ-UHFFFAOYSA-N 1-[[3-[[(E)-but-2-enoyl]amino]phenyl]methyl]-N-tert-butylpiperidine-4-carboxamide Chemical compound C(C)(C)(C)NC(=O)C1CCN(CC1)CC1=CC(=CC=C1)NC(C=CC)=O MZCNOTIDWAXVDJ-UHFFFAOYSA-N 0.000 claims description 2
- ASSGWVBTWBZKGL-UHFFFAOYSA-N 1-[[3-[[2-(2-chlorophenyl)acetyl]amino]phenyl]methyl]-N-cyclohexylpiperidine-4-carboxamide Chemical compound ClC1=CC=CC=C1CC(=O)NC1=CC=CC(CN2CCC(CC2)C(=O)NC2CCCCC2)=C1 ASSGWVBTWBZKGL-UHFFFAOYSA-N 0.000 claims description 2
- LANYNRULEGIZIV-UHFFFAOYSA-N 2,6-dichloro-N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-fluoropyridine-3-carboxamide Chemical compound N1=C(Cl)C(F)=CC(C(=O)NC=2C=C(CN3CCC(CC3)C(=O)NC3CCCCC3)C=CC=2)=C1Cl LANYNRULEGIZIV-UHFFFAOYSA-N 0.000 claims description 2
- FCKIWUZNKVHGKF-UHFFFAOYSA-N 2-chloro-N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]-6-methoxypyridine-4-carboxamide Chemical compound ClC1=NC(OC)=CC(C(=O)NC=2C=C(CN3CCC(CC3)C(=O)NC3CCCCC3)C=CC=2)=C1 FCKIWUZNKVHGKF-UHFFFAOYSA-N 0.000 claims description 2
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 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
- C07D211/36—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
- C07D211/66—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 a hetero atom as the second substituent in position 4
-
- 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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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A—HUMAN NECESSITIES
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- A—HUMAN NECESSITIES
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D471/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12173227.5 | 2012-06-22 | ||
| EP12173227 | 2012-06-22 | ||
| PCT/IB2013/055095 WO2013190508A2 (en) | 2012-06-22 | 2013-06-21 | 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives |
Publications (2)
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| AU2013278873A1 AU2013278873A1 (en) | 2015-02-12 |
| AU2013278873B2 true AU2013278873B2 (en) | 2017-09-28 |
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| AR091516A1 (es) | 2012-06-22 | 2015-02-11 | Actelion Pharmaceuticals Ltd | Derivados de 1-[m-carboxamido(hetero)aril-metil]-heterociclil-carboxamida |
| LT3004082T (lt) * | 2013-05-30 | 2017-10-25 | Idorsia Pharmaceuticals Ltd | Cxcr7 receptoriaus moduliatoriai |
| UA118034C2 (uk) * | 2013-11-14 | 2018-11-12 | Елі Ліллі Енд Компані | Заміщений піперидилетилпіримідин як інгібітор грелін-o-ацилтрансферази |
| WO2016087370A1 (en) | 2014-12-01 | 2016-06-09 | Actelion Pharmaceuticals Ltd | Cxcr7 receptor modulators |
| SI3798217T1 (sl) * | 2016-07-28 | 2023-05-31 | Idorsia Pharmaceuticals Ltd | Piperidinski modulatorji cxcr7 receptorja |
| US11091466B2 (en) | 2017-03-17 | 2021-08-17 | Cardio Therapeutics Pty Ltd | Heterocyclic inhibitors of PCSK9 |
| BR112020015024A2 (pt) | 2018-01-26 | 2021-01-19 | Idorsia Pharmaceuticals Ltd | Forma cristalina, composição farmacêutica, uso de uma forma cristalina, e, método de profilaxia ou tratamento de câncer, distúrbios autoimunes, doenças inflamatórias, rejeição a transplante ou fibrose |
| RU2677268C9 (ru) * | 2018-06-15 | 2019-07-23 | Общество с ограниченной ответственностью "Научно-исследовательский институт ХимРар", (ООО "НИИ ХимРар") | Частичный агонист допаминовых D2/D3 рецепторов - метиламид 4-{ 2-[4-(2,3-дихлорфенил)-пиперазин-1-ил]-этил} -пиперидин-1-карбоновой кислоты, способы его получения (варианты) и применения |
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| WO2008045564A2 (en) * | 2006-10-12 | 2008-04-17 | Epix Delaware, Inc. | Carboxamide compounds and their use as antagonists of the chemokine ccr2 receptor |
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|---|---|---|---|---|
| CA1233818A (en) | 1981-03-09 | 1988-03-08 | David J. Gilman | Guanidine derivatives as histamine h-2 receptor antagonists |
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- 2013-06-19 AR ARP130102184 patent/AR091516A1/es unknown
- 2013-06-21 US US13/923,981 patent/US20130345199A1/en not_active Abandoned
- 2013-06-21 BR BR112014031755A patent/BR112014031755A8/pt not_active Application Discontinuation
- 2013-06-21 CA CA2875389A patent/CA2875389C/en active Active
- 2013-06-21 EP EP13759008.9A patent/EP2864315B1/en active Active
- 2013-06-21 AU AU2013278873A patent/AU2013278873B2/en not_active Ceased
- 2013-06-21 WO PCT/IB2013/055095 patent/WO2013190508A2/en not_active Ceased
- 2013-06-21 US US14/410,426 patent/US9428456B2/en not_active Expired - Fee Related
- 2013-06-21 RU RU2015101751A patent/RU2644761C2/ru not_active IP Right Cessation
- 2013-06-21 JP JP2015517912A patent/JP6182602B2/ja not_active Expired - Fee Related
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- 2013-06-21 MX MX2014015691A patent/MX364610B/es active IP Right Grant
- 2013-06-21 ES ES13759008T patent/ES2768399T3/es active Active
- 2013-06-21 TW TW102122237A patent/TWI623522B/zh not_active IP Right Cessation
- 2013-06-21 KR KR1020157001830A patent/KR102101047B1/ko not_active Expired - Fee Related
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| WO2008045564A2 (en) * | 2006-10-12 | 2008-04-17 | Epix Delaware, Inc. | Carboxamide compounds and their use as antagonists of the chemokine ccr2 receptor |
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| CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER 1279884-55-7 * |
| CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER 1279926-53-2 * |
| CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER 1287852-41-8 * |
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|---|---|
| AU2013278873A1 (en) | 2015-02-12 |
| US20150336893A1 (en) | 2015-11-26 |
| BR112014031755A2 (pt) | 2017-06-27 |
| KR20150023956A (ko) | 2015-03-05 |
| US9428456B2 (en) | 2016-08-30 |
| TW201402546A (zh) | 2014-01-16 |
| JP6182602B2 (ja) | 2017-08-16 |
| CA2875389A1 (en) | 2013-12-27 |
| KR102101047B1 (ko) | 2020-04-16 |
| WO2013190508A2 (en) | 2013-12-27 |
| WO2013190508A3 (en) | 2014-03-13 |
| JP2015520224A (ja) | 2015-07-16 |
| MX364610B (es) | 2019-05-02 |
| RU2015101751A (ru) | 2016-08-10 |
| MX2014015691A (es) | 2015-08-05 |
| CN104395302A (zh) | 2015-03-04 |
| BR112014031755A8 (pt) | 2017-12-26 |
| TWI623522B (zh) | 2018-05-11 |
| CA2875389C (en) | 2020-09-15 |
| ES2768399T3 (es) | 2020-06-22 |
| EP2864315A2 (en) | 2015-04-29 |
| RU2644761C2 (ru) | 2018-02-14 |
| EP2864315B1 (en) | 2019-11-27 |
| US20130345199A1 (en) | 2013-12-26 |
| AR091516A1 (es) | 2015-02-11 |
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