CA2459527A1 - Aryl substituted pyridinecarboxamides and their use as sodium channel blockers - Google Patents
Aryl substituted pyridinecarboxamides and their use as sodium channel blockers Download PDFInfo
- Publication number
- CA2459527A1 CA2459527A1 CA002459527A CA2459527A CA2459527A1 CA 2459527 A1 CA2459527 A1 CA 2459527A1 CA 002459527 A CA002459527 A CA 002459527A CA 2459527 A CA2459527 A CA 2459527A CA 2459527 A1 CA2459527 A1 CA 2459527A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- hydrogen
- compound
- optionally substituted
- amino
- 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.)
- Abandoned
Links
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 31
- 239000003195 sodium channel blocking agent Substances 0.000 title description 3
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical class NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 180
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 229940002612 prodrug Drugs 0.000 claims abstract description 30
- 239000000651 prodrug Substances 0.000 claims abstract description 30
- 239000012453 solvate Substances 0.000 claims abstract description 27
- 208000002193 Pain Diseases 0.000 claims abstract description 24
- 208000000094 Chronic Pain Diseases 0.000 claims abstract description 10
- 208000028867 ischemia Diseases 0.000 claims abstract description 10
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 4
- -1 2-imidazolinyl Chemical group 0.000 claims description 128
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 239000001257 hydrogen Substances 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 68
- 150000002431 hydrogen Chemical class 0.000 claims description 52
- 125000003342 alkenyl group Chemical group 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 40
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 21
- 125000003282 alkyl amino group Chemical group 0.000 claims description 20
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 102000018674 Sodium Channels Human genes 0.000 claims description 16
- 108010052164 Sodium Channels Proteins 0.000 claims description 16
- 150000001356 alkyl thiols Chemical class 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000001188 haloalkyl group Chemical group 0.000 claims description 16
- 241001465754 Metazoa Species 0.000 claims description 15
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 13
- 125000004423 acyloxy group Chemical group 0.000 claims description 12
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 12
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 12
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 12
- 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 claims description 12
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 12
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 12
- 235000005152 nicotinamide Nutrition 0.000 claims description 12
- 239000011570 nicotinamide Substances 0.000 claims description 12
- 125000004442 acylamino group Chemical group 0.000 claims description 11
- 125000006323 alkenyl amino group Chemical group 0.000 claims description 11
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 11
- 150000003573 thiols Chemical class 0.000 claims description 11
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 230000036407 pain Effects 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 150000001340 alkali metals Chemical class 0.000 claims description 9
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 9
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 9
- MKRVOXRLAFVYCF-UHFFFAOYSA-N C(#N)NN([N+](=O)[O-])O Chemical compound C(#N)NN([N+](=O)[O-])O MKRVOXRLAFVYCF-UHFFFAOYSA-N 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- AZRJZSBTABPTDT-UHFFFAOYSA-N 6-naphthalen-2-ylpyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1C1=CC=C(C=CC=C2)C2=C1 AZRJZSBTABPTDT-UHFFFAOYSA-N 0.000 claims description 7
- 206010010904 Convulsion Diseases 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- VNPFVKSKEFHPRR-UHFFFAOYSA-N 2-(4-phenylphenyl)pyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 VNPFVKSKEFHPRR-UHFFFAOYSA-N 0.000 claims description 6
- XZZYNUNFRCYDOM-UHFFFAOYSA-N 5-[4-(trifluoromethoxy)phenyl]pyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(C=2C=CC(OC(F)(F)F)=CC=2)=C1 XZZYNUNFRCYDOM-UHFFFAOYSA-N 0.000 claims description 6
- HEVKBJMYPITUHR-UHFFFAOYSA-N 6-(4-phenylphenyl)pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 HEVKBJMYPITUHR-UHFFFAOYSA-N 0.000 claims description 6
- YDKVYRUABBVXMG-UHFFFAOYSA-N 6-[4-(trifluoromethoxy)phenyl]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1C1=CC=C(OC(F)(F)F)C=C1 YDKVYRUABBVXMG-UHFFFAOYSA-N 0.000 claims description 6
- ABJKZJZQWXRYSF-UHFFFAOYSA-N 6-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1C1=CC=C(C(F)(F)F)C=C1 ABJKZJZQWXRYSF-UHFFFAOYSA-N 0.000 claims description 6
- 208000009205 Tinnitus Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 231100000886 tinnitus Toxicity 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- WLRQGJFLMSNZAK-UHFFFAOYSA-N 2-(4-phenoxyphenyl)pyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1 WLRQGJFLMSNZAK-UHFFFAOYSA-N 0.000 claims description 5
- BJDVPFFVBMRFFL-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]pyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(C=2C=CC(OC(F)(F)F)=CC=2)=C1 BJDVPFFVBMRFFL-UHFFFAOYSA-N 0.000 claims description 5
- NDMXIRHNMLYEII-UHFFFAOYSA-N 5-[4-(4-fluorophenoxy)phenyl]-n-(2-piperidin-1-ylethyl)pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1OC1=CC=C(C=2C=C(C=NC=2)C(=O)NCCN2CCCCC2)C=C1 NDMXIRHNMLYEII-UHFFFAOYSA-N 0.000 claims description 5
- LUFWKGBIGOZMLC-UHFFFAOYSA-N 6-(4-phenoxyphenyl)pyridine-3-carboxamide Chemical compound N1=CC(C(=O)N)=CC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 LUFWKGBIGOZMLC-UHFFFAOYSA-N 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- XAFONVMAPPEAIT-UHFFFAOYSA-N 2-[4-(4-fluorophenoxy)phenyl]pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1C(C=C1)=CC=C1OC1=CC=C(F)C=C1 XAFONVMAPPEAIT-UHFFFAOYSA-N 0.000 claims description 4
- QBDHMBXQBPQDEA-UHFFFAOYSA-N 5-naphthalen-2-ylpyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(C=2C=C3C=CC=CC3=CC=2)=C1 QBDHMBXQBPQDEA-UHFFFAOYSA-N 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 208000028683 bipolar I disease Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 239000002287 radioligand Substances 0.000 claims description 4
- FHYAIJCEEYITHI-UHFFFAOYSA-N 2-[4-(4-fluorophenoxy)phenyl]pyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(C=2C=CC(OC=3C=CC(F)=CC=3)=CC=2)=C1 FHYAIJCEEYITHI-UHFFFAOYSA-N 0.000 claims description 3
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical group NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 claims description 3
- XVISMMCVDVDVIN-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(C=2C=CC(=CC=2)C(F)(F)F)=C1 XVISMMCVDVDVIN-UHFFFAOYSA-N 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 230000036461 convulsion Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- LYARUKOWFXTMRY-UHFFFAOYSA-N 6-[4-(4-fluorophenoxy)phenyl]-n-(2-piperidin-1-ylethyl)pyridine-3-carboxamide;5-(4-phenoxyphenyl)pyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=C1.C1=CC(F)=CC=C1OC1=CC=C(C=2N=CC(=CC=2)C(=O)NCCN2CCCCC2)C=C1 LYARUKOWFXTMRY-UHFFFAOYSA-N 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 7
- UTHASJFQCPZOKF-UHFFFAOYSA-N 2-(4-tert-butylphenyl)pyridine-4-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC(C(N)=O)=CC=N1 UTHASJFQCPZOKF-UHFFFAOYSA-N 0.000 claims 1
- GRKCWUVREMQJCO-UHFFFAOYSA-N 5-(4-tert-butylphenyl)pyridine-3-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CN=CC(C(N)=O)=C1 GRKCWUVREMQJCO-UHFFFAOYSA-N 0.000 claims 1
- ILEDWCRVDBEZBH-UHFFFAOYSA-N 6-(4-tert-butylphenyl)pyridine-3-carboxamide 2-(4-propylphenyl)pyridine-4-carboxamide Chemical compound C(CC)C1=CC=C(C=C1)C1=NC=CC(=C1)C(=O)N.C(C)(C)(C)C1=CC=C(C=C1)C1=NC=C(C=C1)C(=O)N ILEDWCRVDBEZBH-UHFFFAOYSA-N 0.000 claims 1
- 238000002690 local anesthesia Methods 0.000 claims 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims 1
- 150000003222 pyridines Chemical class 0.000 abstract description 14
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 abstract description 8
- 239000001961 anticonvulsive agent Substances 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 6
- 230000001154 acute effect Effects 0.000 abstract description 5
- 230000003288 anthiarrhythmic effect Effects 0.000 abstract description 5
- 239000003416 antiarrhythmic agent Substances 0.000 abstract description 5
- 239000003589 local anesthetic agent Substances 0.000 abstract description 5
- 229960005015 local anesthetics Drugs 0.000 abstract description 5
- 208000005298 acute pain Diseases 0.000 abstract description 4
- 230000003561 anti-manic effect Effects 0.000 abstract description 4
- 229940125681 anticonvulsant agent Drugs 0.000 abstract description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 abstract description 3
- 230000003961 neuronal insult Effects 0.000 abstract description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- 108091006146 Channels Proteins 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- 229910001415 sodium ion Inorganic materials 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 15
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 210000000287 oocyte Anatomy 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 11
- STWNGMSGPBZFMX-UHFFFAOYSA-N pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1.NC(=O)C1=CC=CN=C1 STWNGMSGPBZFMX-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 9
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- FMPUEKVQOVFQCT-UHFFFAOYSA-N 2-(4-ethoxyphenyl)pyridine-4-carboxamide Chemical compound C1=CC(OCC)=CC=C1C1=CC(C(N)=O)=CC=N1 FMPUEKVQOVFQCT-UHFFFAOYSA-N 0.000 description 6
- OAOYLRNVFXVARA-UHFFFAOYSA-N 2-(4-propylphenyl)pyridine-4-carboxamide Chemical compound C1=CC(CCC)=CC=C1C1=CC(C(N)=O)=CC=N1 OAOYLRNVFXVARA-UHFFFAOYSA-N 0.000 description 6
- OFYGSCMHWJTHQF-UHFFFAOYSA-N 5-(4-methoxyphenyl)pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=CN=CC(C(N)=O)=C1 OFYGSCMHWJTHQF-UHFFFAOYSA-N 0.000 description 6
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- 229920002472 Starch Polymers 0.000 description 6
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- 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
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31752601P | 2001-09-07 | 2001-09-07 | |
| US60/317,526 | 2001-09-07 | ||
| PCT/US2002/028298 WO2003022276A1 (en) | 2001-09-07 | 2002-09-06 | Aryl substituted pyridinecarboxamides and their use as sodium channel blockers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2459527A1 true CA2459527A1 (en) | 2003-03-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002459527A Abandoned CA2459527A1 (en) | 2001-09-07 | 2002-09-06 | Aryl substituted pyridinecarboxamides and their use as sodium channel blockers |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US7105549B2 (enExample) |
| EP (1) | EP1432419A1 (enExample) |
| JP (1) | JP2005506981A (enExample) |
| KR (1) | KR20040031053A (enExample) |
| AR (1) | AR037233A1 (enExample) |
| BR (1) | BR0212338A (enExample) |
| CA (1) | CA2459527A1 (enExample) |
| HU (1) | HUP0500131A3 (enExample) |
| IL (1) | IL160716A0 (enExample) |
| MX (1) | MXPA04002171A (enExample) |
| RU (1) | RU2004110721A (enExample) |
| WO (1) | WO2003022276A1 (enExample) |
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| JP2004538285A (ja) * | 2001-07-16 | 2004-12-24 | ユーロ−セルティック エス． ア． | アリール置換チアゾリジノンおよびその使用 |
| AR037233A1 (es) * | 2001-09-07 | 2004-11-03 | Euro Celtique Sa | Piridinas aril sustituidas, composiciones farmaceuticas y el uso de dichos compuestos para la elaboracion de un medicamento |
| GB0124938D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
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| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| WO2003068747A1 (en) | 2002-02-12 | 2003-08-21 | Smithkline Beecham Corporation | Nicotinamide derivates useful as p38 inhibitors |
| EP1483247B1 (en) * | 2002-03-13 | 2009-06-24 | Euro-Celtique S.A. | Aryl substituted pyrimidines and the use thereof |
| EP1532119A2 (en) * | 2002-07-31 | 2005-05-25 | Euro-Celtique S.A. | Aryl substituted benzimidazoles and their use as sodium channel blockers |
| GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
| US20050227974A9 (en) * | 2002-08-01 | 2005-10-13 | Euro-Celtique S.A. | Aminoalkyl-substituted aryl compounds and their use as sodium channel blockers |
| US20040152696A1 (en) * | 2002-08-01 | 2004-08-05 | Euro-Celtique S.A. | 2-substituted bicyclic benzoheterocyclic compounds and their use as sodium channel blockers |
| AU2004224392A1 (en) * | 2003-03-24 | 2004-10-07 | Merck & Co., Inc. | Biaryl substituted 6-membered heterocyles as sodium channel blockers |
| GB0308185D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| CN1922156A (zh) * | 2003-11-10 | 2007-02-28 | 默克公司 | 作为钠通道阻断剂的取代的三唑 |
| GB0402143D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| WO2006011050A2 (en) | 2004-07-23 | 2006-02-02 | Pfizer Limited | Pyridine derivatives |
| US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
| GB0512429D0 (en) * | 2005-06-17 | 2005-07-27 | Smithkline Beecham Corp | Novel compound |
| WO2007011760A2 (en) * | 2005-07-15 | 2007-01-25 | Kalypsys, Inc. | Inhibitors of mitotic kinesin |
| TW200728258A (en) * | 2005-10-10 | 2007-08-01 | Glaxo Group Ltd | Novel compounds |
| JP4159586B2 (ja) * | 2006-08-03 | 2008-10-01 | エヌイーシーコンピュータテクノ株式会社 | 情報処理装置および情報処理の高速化方法 |
| JP4657384B2 (ja) | 2007-05-03 | 2011-03-23 | ファイザー・リミテッド | ナトリウムチャンネルモジュレーターとしての２−ピリジンカルボキサミド誘導体 |
| KR200451955Y1 (ko) * | 2008-05-09 | 2011-01-25 | 박영주 | 차량진입 방지대 |
| NZ601483A (en) | 2008-08-04 | 2013-10-25 | Chdi Foundation Inc | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| JP2013518046A (ja) | 2010-01-25 | 2013-05-20 | シーエイチディーアイ ファウンデーション，インコーポレーテッド | 特定のキヌレニン−３−モノオキシゲナーゼインヒビターおよびその医薬組成物ならびにこれらの使用方法 |
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| AR083023A1 (es) | 2010-09-17 | 2013-01-23 | Purdue Pharma Lp | Compuestos de piridina y una composicion farmaceutica que los comprende |
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-
2002
- 2002-08-27 AR ARP020103213A patent/AR037233A1/es unknown
- 2002-09-06 RU RU2004110721/04A patent/RU2004110721A/ru not_active Application Discontinuation
- 2002-09-06 WO PCT/US2002/028298 patent/WO2003022276A1/en not_active Ceased
- 2002-09-06 IL IL16071602A patent/IL160716A0/xx unknown
- 2002-09-06 HU HU0500131A patent/HUP0500131A3/hu unknown
- 2002-09-06 JP JP2003526405A patent/JP2005506981A/ja not_active Withdrawn
- 2002-09-06 MX MXPA04002171A patent/MXPA04002171A/es unknown
- 2002-09-06 US US10/235,673 patent/US7105549B2/en not_active Expired - Lifetime
- 2002-09-06 CA CA002459527A patent/CA2459527A1/en not_active Abandoned
- 2002-09-06 KR KR10-2004-7003314A patent/KR20040031053A/ko not_active Withdrawn
- 2002-09-06 EP EP02773292A patent/EP1432419A1/en not_active Withdrawn
- 2002-09-06 BR BR0212338-0A patent/BR0212338A/pt not_active Application Discontinuation
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2006
- 2006-09-11 US US11/518,448 patent/US7579367B2/en not_active Expired - Fee Related
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2009
- 2009-08-24 US US12/546,572 patent/US7943643B2/en not_active Expired - Fee Related
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| US20030055088A1 (en) | 2003-03-20 |
| EP1432419A1 (en) | 2004-06-30 |
| US20080194627A9 (en) | 2008-08-14 |
| WO2003022276A1 (en) | 2003-03-20 |
| US7105549B2 (en) | 2006-09-12 |
| AR037233A1 (es) | 2004-11-03 |
| KR20040031053A (ko) | 2004-04-09 |
| MXPA04002171A (es) | 2004-07-23 |
| US7579367B2 (en) | 2009-08-25 |
| IL160716A0 (en) | 2004-08-31 |
| JP2005506981A (ja) | 2005-03-10 |
| US20100048626A1 (en) | 2010-02-25 |
| US20070010554A1 (en) | 2007-01-11 |
| BR0212338A (pt) | 2004-09-21 |
| RU2004110721A (ru) | 2005-10-10 |
| HUP0500131A3 (en) | 2005-07-28 |
| US7943643B2 (en) | 2011-05-17 |
| HUP0500131A2 (hu) | 2005-05-30 |
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