BG64356B1 - Производни на никотинамид - Google Patents
Производни на никотинамид Download PDFInfo
- Publication number
- BG64356B1 BG64356B1 BG103725A BG10372599A BG64356B1 BG 64356 B1 BG64356 B1 BG 64356B1 BG 103725 A BG103725 A BG 103725A BG 10372599 A BG10372599 A BG 10372599A BG 64356 B1 BG64356 B1 BG 64356B1
- Authority
- BG
- Bulgaria
- Prior art keywords
- nicotinamide
- methyl
- phenoxy
- ethyl
- hydroxy
- Prior art date
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- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical class NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 title claims description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 14
- 230000000172 allergic effect Effects 0.000 claims abstract description 10
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 10
- 230000000241 respiratory effect Effects 0.000 claims abstract description 10
- 230000033228 biological regulation Effects 0.000 claims abstract description 3
- -1 cyano, carboxy, amino Chemical group 0.000 claims description 248
- 238000002360 preparation method Methods 0.000 claims description 103
- 125000000217 alkyl group Chemical group 0.000 claims description 102
- 239000011570 nicotinamide Substances 0.000 claims description 61
- 229960003966 nicotinamide Drugs 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 56
- 125000003545 alkoxy group Chemical group 0.000 claims description 43
- 239000000460 chlorine Substances 0.000 claims description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 34
- 150000002367 halogens Chemical group 0.000 claims description 34
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 229920006395 saturated elastomer Polymers 0.000 claims description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 108010044467 Isoenzymes Proteins 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000004423 acyloxy group Chemical group 0.000 claims description 21
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 20
- 150000002431 hydrogen Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 19
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 19
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 18
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000004442 acylamino group Chemical group 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 239000011593 sulfur Substances 0.000 claims description 14
- 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 13
- 102100029170 cAMP-specific 3',5'-cyclic phosphodiesterase 4D Human genes 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 210000003979 eosinophil Anatomy 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 241000282412 Homo Species 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 235000005152 nicotinamide Nutrition 0.000 claims description 10
- 230000006583 body weight regulation Effects 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 239000011737 fluorine Chemical group 0.000 claims description 8
- 229910052731 fluorine Chemical group 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- STNXKQASTGTLKD-UHFFFAOYSA-N n-[[5-(1-hydroxyethyl)thiophen-2-yl]methyl]-2-pyridin-3-yloxypyridine-3-carboxamide Chemical compound S1C(C(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=CN=C1 STNXKQASTGTLKD-UHFFFAOYSA-N 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- NFIPEXBVZIKXDB-UHFFFAOYSA-N n-[1-(5-chlorothiophen-2-yl)ethyl]-2-(4-fluorophenoxy)pyridine-3-carboxamide Chemical compound C=1C=C(Cl)SC=1C(C)NC(=O)C1=CC=CN=C1OC1=CC=C(F)C=C1 NFIPEXBVZIKXDB-UHFFFAOYSA-N 0.000 claims description 5
- ODLJBQFKMHONDG-UHFFFAOYSA-N n-[1-(5-chlorothiophen-2-yl)ethyl]-2-pyridin-3-yloxypyridine-3-carboxamide Chemical compound C=1C=C(Cl)SC=1C(C)NC(=O)C1=CC=CN=C1OC1=CC=CN=C1 ODLJBQFKMHONDG-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- JHJWSJAXJVNGRT-UHFFFAOYSA-N 2-(3-aminophenoxy)-n-[(2-chlorophenyl)methyl]pyridine-3-carboxamide Chemical compound NC1=CC=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C(=CC=CC=2)Cl)=C1 JHJWSJAXJVNGRT-UHFFFAOYSA-N 0.000 claims description 4
- SWRWAZHNNGZBCY-UHFFFAOYSA-N 2-(4-fluorophenoxy)-n-[(2,4,6-trifluorophenyl)methyl]pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1OC1=NC=CC=C1C(=O)NCC1=C(F)C=C(F)C=C1F SWRWAZHNNGZBCY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 150000005480 nicotinamides Chemical class 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 3
- XYWZOKVLFFODAL-UHFFFAOYSA-N 2-(3-acetylphenoxy)-n-[[2-fluoro-4-(2-hydroxypropan-2-yl)phenyl]methyl]pyridine-3-carboxamide Chemical compound CC(=O)C1=CC=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C(=CC(=CC=2)C(C)(C)O)F)=C1 XYWZOKVLFFODAL-UHFFFAOYSA-N 0.000 claims description 3
- ZQRGBIKGKBYMMK-UHFFFAOYSA-N 2-(3-cyanophenoxy)-n-[(5-methylpyrazin-2-yl)methyl]pyridine-3-carboxamide Chemical compound C1=NC(C)=CN=C1CNC(=O)C1=CC=CN=C1OC1=CC=CC(C#N)=C1 ZQRGBIKGKBYMMK-UHFFFAOYSA-N 0.000 claims description 3
- UHBUSMAHWHZQKS-UHFFFAOYSA-N 2-(4-fluorophenoxy)-n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=C(F)C=C1 UHBUSMAHWHZQKS-UHFFFAOYSA-N 0.000 claims description 3
- AAERCXTYYBXPIQ-UHFFFAOYSA-N 2-(5-chloropyridin-3-yl)oxy-n-[(4-chlorothiophen-2-yl)methyl]pyridine-3-carboxamide Chemical compound ClC1=CSC(CNC(=O)C=2C(=NC=CC=2)OC=2C=C(Cl)C=NC=2)=C1 AAERCXTYYBXPIQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- QOEMLWABKFHXGK-UHFFFAOYSA-N n-(pyridin-4-ylmethyl)-2-pyridin-3-yloxypyridine-3-carboxamide Chemical compound C=1C=CN=C(OC=2C=NC=CC=2)C=1C(=O)NCC1=CC=NC=C1 QOEMLWABKFHXGK-UHFFFAOYSA-N 0.000 claims description 3
- DVRRRSRXSUVSIJ-UHFFFAOYSA-N n-[(2-chloro-6-fluorophenyl)methyl]-2-(4-fluorophenoxy)pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1OC1=NC=CC=C1C(=O)NCC1=C(F)C=CC=C1Cl DVRRRSRXSUVSIJ-UHFFFAOYSA-N 0.000 claims description 3
- XHZHDCRLOAYJGR-UHFFFAOYSA-N n-[(3,5-dichlorothiophen-2-yl)methyl]-2-(4-fluorophenoxy)pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1OC1=NC=CC=C1C(=O)NCC1=C(Cl)C=C(Cl)S1 XHZHDCRLOAYJGR-UHFFFAOYSA-N 0.000 claims description 3
- DPLXPUSNEXXAAY-UHFFFAOYSA-N n-[[3-chloro-5-(2-hydroxypropan-2-yl)thiophen-2-yl]methyl]-2-pyridin-3-yloxypyridine-3-carboxamide Chemical compound S1C(C(C)(O)C)=CC(Cl)=C1CNC(=O)C1=CC=CN=C1OC1=CC=CN=C1 DPLXPUSNEXXAAY-UHFFFAOYSA-N 0.000 claims description 3
- OVKMHYXBVKMBBB-UHFFFAOYSA-N n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-[3-(trifluoromethyl)phenoxy]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=CC(C(F)(F)F)=C1 OVKMHYXBVKMBBB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- MEWIXEPIWPRGDZ-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-6-yloxy)-n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=C(OCCO2)C2=C1 MEWIXEPIWPRGDZ-UHFFFAOYSA-N 0.000 claims description 2
- SKVJJLKKRKYFGR-UHFFFAOYSA-N 2-(3,5-difluorophenoxy)-n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC(F)=CC(F)=C1 SKVJJLKKRKYFGR-UHFFFAOYSA-N 0.000 claims description 2
- GAICFHSLEINDSL-UHFFFAOYSA-N 2-(3-acetyl-4-chlorophenoxy)-n-[[2-chloro-4-(2-hydroxypropan-2-yl)phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=C(Cl)C(C(=O)C)=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C(=CC(=CC=2)C(C)(C)O)Cl)=C1 GAICFHSLEINDSL-UHFFFAOYSA-N 0.000 claims description 2
- VYIVWEQCBFTBOI-UHFFFAOYSA-N 2-(3-acetyl-5-chlorophenoxy)-n-[[2-chloro-4-(2-hydroxypropan-2-yl)phenyl]methyl]pyridine-3-carboxamide Chemical compound CC(=O)C1=CC(Cl)=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C(=CC(=CC=2)C(C)(C)O)Cl)=C1 VYIVWEQCBFTBOI-UHFFFAOYSA-N 0.000 claims description 2
- CXRCFYZEDIJNOK-UHFFFAOYSA-N 2-(3-acetylphenoxy)-n-(pyridin-4-ylmethyl)pyridine-3-carboxamide Chemical compound CC(=O)C1=CC=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C=CN=CC=2)=C1 CXRCFYZEDIJNOK-UHFFFAOYSA-N 0.000 claims description 2
- XXKHIERGCLWKBC-OAHLLOKOSA-N 2-(3-acetylphenoxy)-n-[[4-[(1r)-1-hydroxyethyl]phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=CC([C@H](O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=CC(C(C)=O)=C1 XXKHIERGCLWKBC-OAHLLOKOSA-N 0.000 claims description 2
- XXKHIERGCLWKBC-HNNXBMFYSA-N 2-(3-acetylphenoxy)-n-[[4-[(1s)-1-hydroxyethyl]phenyl]methyl]pyridine-3-carboxamide Chemical compound C1=CC([C@@H](O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=CC(C(C)=O)=C1 XXKHIERGCLWKBC-HNNXBMFYSA-N 0.000 claims description 2
- XYSNLUIBBQSPTL-UHFFFAOYSA-N 2-(4-fluorophenoxy)-n-(1h-indol-5-ylmethyl)pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1OC1=NC=CC=C1C(=O)NCC1=CC=C(NC=C2)C2=C1 XYSNLUIBBQSPTL-UHFFFAOYSA-N 0.000 claims description 2
- RQACOXGAQDOEFC-UHFFFAOYSA-N 2-(4-fluorophenoxy)-n-[[4-(2-hydroxypropan-2-yl)cyclohexyl]methyl]pyridine-3-carboxamide Chemical compound C1CC(C(C)(O)C)CCC1CNC(=O)C1=CC=CN=C1OC1=CC=C(F)C=C1 RQACOXGAQDOEFC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- IGEBPPXGAJOLDQ-QAQDUYKDSA-N C1=C(Cl)C(C(=O)C)=CC(OC=2C(=CC=CN=2)C(=O)NC[C@@H]2CC[C@H](CC2)C(C)(C)O)=C1 Chemical compound C1=C(Cl)C(C(=O)C)=CC(OC=2C(=CC=CN=2)C(=O)NC[C@@H]2CC[C@H](CC2)C(C)(C)O)=C1 IGEBPPXGAJOLDQ-QAQDUYKDSA-N 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
- 206010056740 Genital discharge Diseases 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 125000001769 aryl amino group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical group COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims description 2
- IAEAJILBRLUUPM-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-2-(3-methoxyphenoxy)pyridine-3-carboxamide Chemical compound COC1=CC=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C(=CC=CC=2)Cl)=C1 IAEAJILBRLUUPM-UHFFFAOYSA-N 0.000 claims description 2
- AQIVOZRZMGARTM-UHFFFAOYSA-N n-[[2-chloro-4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-(3-cyano-4-fluorophenoxy)pyridine-3-carboxamide Chemical compound ClC1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=C(F)C(C#N)=C1 AQIVOZRZMGARTM-UHFFFAOYSA-N 0.000 claims description 2
- JXMMOCGPIQYYJV-UHFFFAOYSA-N n-[[2-fluoro-4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-(4-fluorophenoxy)pyridine-3-carboxamide Chemical compound FC1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=C(F)C=C1 JXMMOCGPIQYYJV-UHFFFAOYSA-N 0.000 claims description 2
- XIZBKNOADRPRPV-UHFFFAOYSA-N n-[[4-(2-hydroxypropan-2-yl)cyclohexyl]methyl]-2-(3-nitrophenoxy)pyridine-3-carboxamide Chemical compound C1CC(C(C)(O)C)CCC1CNC(=O)C1=CC=CN=C1OC1=CC=CC([N+]([O-])=O)=C1 XIZBKNOADRPRPV-UHFFFAOYSA-N 0.000 claims description 2
- KVCURDHMWWISMJ-UHFFFAOYSA-N n-[[4-(2-hydroxypropan-2-yl)cyclohexyl]methyl]-2-[(3-methyl-1,2-benzoxazol-5-yl)oxy]pyridine-3-carboxamide Chemical compound C1=C2C(C)=NOC2=CC=C1OC1=NC=CC=C1C(=O)NCC1CCC(C(C)(C)O)CC1 KVCURDHMWWISMJ-UHFFFAOYSA-N 0.000 claims description 2
- LBEFOOJGSWCEOX-UHFFFAOYSA-N n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-[(1-oxo-2,3-dihydroinden-4-yl)oxy]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=CC2=C1CCC2=O LBEFOOJGSWCEOX-UHFFFAOYSA-N 0.000 claims description 2
- JZDPNSTZBLNBFX-UHFFFAOYSA-N n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-[3-(trifluoromethoxy)phenoxy]pyridine-3-carboxamide Chemical compound C1=CC(C(C)(O)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=CC(OC(F)(F)F)=C1 JZDPNSTZBLNBFX-UHFFFAOYSA-N 0.000 claims description 2
- YHHNGYBEGHKTMG-UHFFFAOYSA-N n-[[4-(dimethylamino)phenyl]methyl]-2-(4-fluorophenoxy)pyridine-3-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1CNC(=O)C1=CC=CN=C1OC1=CC=C(F)C=C1 YHHNGYBEGHKTMG-UHFFFAOYSA-N 0.000 claims description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims 4
- USQXTVCIHJYYNN-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-6-yloxy)-n-[[4-(2-hydroxypropan-2-yl)cyclohexyl]methyl]pyridine-3-carboxamide Chemical compound C1CC(C(C)(O)C)CCC1CNC(=O)C1=CC=CN=C1OC1=CC=C(OCCO2)C2=C1 USQXTVCIHJYYNN-UHFFFAOYSA-N 0.000 claims 1
- NTBQLIRFKMOCOM-UHFFFAOYSA-N 2-(4-fluorophenoxy)-n-[[4-(2-hydroxypropan-2-yl)cyclohexen-1-yl]methyl]pyridine-3-carboxamide Chemical compound C1C(C(C)(O)C)CCC(CNC(=O)C=2C(=NC=CC=2)OC=2C=CC(F)=CC=2)=C1 NTBQLIRFKMOCOM-UHFFFAOYSA-N 0.000 claims 1
- BUDUHQWLNCFSKU-UHFFFAOYSA-N 2-[3-(2-hydroxypropan-2-yl)phenoxy]-n-(pyridin-4-ylmethyl)pyridine-3-carboxamide Chemical compound CC(C)(O)C1=CC=CC(OC=2C(=CC=CN=2)C(=O)NCC=2C=CN=CC=2)=C1 BUDUHQWLNCFSKU-UHFFFAOYSA-N 0.000 claims 1
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- BXSVEWPGZPEVOY-SAABIXHNSA-N CC(=O)C1=CC(Cl)=CC(OC=2C(=CC=CN=2)C(=O)NC[C@@H]2CC[C@H](CC2)C(C)(C)O)=C1 Chemical compound CC(=O)C1=CC(Cl)=CC(OC=2C(=CC=CN=2)C(=O)NC[C@@H]2CC[C@H](CC2)C(C)(C)O)=C1 BXSVEWPGZPEVOY-SAABIXHNSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- SOYHYBJHKONAAY-UHFFFAOYSA-N n-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-[(3-methyl-1,2-benzoxazol-5-yl)oxy]pyridine-3-carboxamide Chemical compound C1=C2C(C)=NOC2=CC=C1OC1=NC=CC=C1C(=O)NCC1=CC=C(C(C)(C)O)C=C1 SOYHYBJHKONAAY-UHFFFAOYSA-N 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
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- URCKEQOCXZBZHY-UHFFFAOYSA-N n-propan-2-yl-2-pyridin-3-yloxypyridine-3-carboxamide Chemical compound CC(C)NC(=O)C1=CC=CN=C1OC1=CC=CN=C1 URCKEQOCXZBZHY-UHFFFAOYSA-N 0.000 description 1
- QXNJJIBETSJEOA-UHFFFAOYSA-N n-propyl-2-pyridin-3-yloxypyridine-3-carboxamide Chemical compound CCCNC(=O)C1=CC=CN=C1OC1=CC=CN=C1 QXNJJIBETSJEOA-UHFFFAOYSA-N 0.000 description 1
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- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- SMPAPEKFGLKOIC-UHFFFAOYSA-N oxolane;hydrochloride Chemical compound Cl.C1CCOC1 SMPAPEKFGLKOIC-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
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- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
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- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
- CUYKNJBYIJFRCU-UHFFFAOYSA-N pyridine-3-amine Natural products NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- AFUTVGIDLNAANY-UHFFFAOYSA-N tert-butyl 2-[(3,5-difluorophenyl)methyl]-3-[2-(4-fluorophenoxy)pyridin-3-yl]-3-oxopropanoate Chemical compound C=1C=CN=C(OC=2C=CC(F)=CC=2)C=1C(=O)C(C(=O)OC(C)(C)C)CC1=CC(F)=CC(F)=C1 AFUTVGIDLNAANY-UHFFFAOYSA-N 0.000 description 1
- QFOKKBNNFHJFMI-UHFFFAOYSA-N tert-butyl 3-[2-(4-fluorophenoxy)pyridin-3-yl]-2-[(4-fluorophenyl)methyl]-3-oxopropanoate Chemical compound C=1C=CN=C(OC=2C=CC(F)=CC=2)C=1C(=O)C(C(=O)OC(C)(C)C)CC1=CC=C(F)C=C1 QFOKKBNNFHJFMI-UHFFFAOYSA-N 0.000 description 1
- XYUXBHLZHBEDAG-UHFFFAOYSA-N tert-butyl 3-[2-(4-fluorophenoxy)pyridin-3-yl]-3-oxo-2-[(2,4,6-trifluorophenyl)methyl]propanoate Chemical compound C=1C=CN=C(OC=2C=CC(F)=CC=2)C=1C(=O)C(C(=O)OC(C)(C)C)CC1=C(F)C=C(F)C=C1F XYUXBHLZHBEDAG-UHFFFAOYSA-N 0.000 description 1
- PUEUUPFADPPJIV-UHFFFAOYSA-N tert-butyl 3-[2-(4-fluorophenoxy)pyridin-3-yl]-3-oxo-2-[[4-(trifluoromethoxy)phenyl]methyl]propanoate Chemical compound C=1C=CN=C(OC=2C=CC(F)=CC=2)C=1C(=O)C(C(=O)OC(C)(C)C)CC1=CC=C(OC(F)(F)F)C=C1 PUEUUPFADPPJIV-UHFFFAOYSA-N 0.000 description 1
- ZHMALLVTEDIEBC-UHFFFAOYSA-N tert-butyl 3-[2-(4-fluorophenoxy)pyridin-3-yl]-3-oxo-2-[[4-(trifluoromethyl)phenyl]methyl]propanoate Chemical compound C=1C=CN=C(OC=2C=CC(F)=CC=2)C=1C(=O)C(C(=O)OC(C)(C)C)CC1=CC=C(C(F)(F)F)C=C1 ZHMALLVTEDIEBC-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- 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
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- 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
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- 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
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- 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
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- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US4340397P | 1997-04-04 | 1997-04-04 |
Publications (2)
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| BG103725A BG103725A (en) | 2000-07-31 |
| BG64356B1 true BG64356B1 (bg) | 2004-11-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| BG103725A BG64356B1 (bg) | 1997-04-04 | 1999-09-09 | Производни на никотинамид |
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| EP (1) | EP0971894A1 (id) |
| JP (2) | JP2000510481A (id) |
| KR (1) | KR20010005954A (id) |
| CN (1) | CN1254335A (id) |
| AP (1) | AP1388A (id) |
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| BG (1) | BG64356B1 (id) |
| BR (1) | BR9810733A (id) |
| CA (1) | CA2285548C (id) |
| CO (1) | CO4950625A1 (id) |
| DZ (1) | DZ2457A1 (id) |
| EA (1) | EA003528B1 (id) |
| GT (1) | GT199800058A (id) |
| HN (1) | HN1998000057A (id) |
| HR (1) | HRP980181B1 (id) |
| HU (1) | HUP0001243A3 (id) |
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- 1998-03-10 US US09/308,956 patent/US6380218B1/en not_active Expired - Fee Related
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- 1998-03-10 WO PCT/IB1998/000315 patent/WO1998045268A1/en not_active Ceased
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- 1998-03-10 AU AU62273/98A patent/AU738037B2/en not_active Ceased
- 1998-03-10 EA EA199900787A patent/EA003528B1/ru not_active IP Right Cessation
- 1998-03-10 KR KR1019997009031A patent/KR20010005954A/ko not_active Abandoned
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- 1998-03-31 PE PE1998000237A patent/PE73299A1/es not_active Application Discontinuation
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- 1998-04-01 MA MA25017A patent/MA26479A1/fr unknown
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