CA2011143C - Derives amidiques de l'acide pyridine carboxylique et composes pharmaceutiques les contenant - Google Patents
Derives amidiques de l'acide pyridine carboxylique et composes pharmaceutiques les contenantInfo
- Publication number
- CA2011143C CA2011143C CA002011143A CA2011143A CA2011143C CA 2011143 C CA2011143 C CA 2011143C CA 002011143 A CA002011143 A CA 002011143A CA 2011143 A CA2011143 A CA 2011143A CA 2011143 C CA2011143 C CA 2011143C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- methyl
- piperazinyl
- nicotinamide
- formula
- 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.)
- Expired - Fee Related
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical class NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229910004679 ONO2 Inorganic materials 0.000 claims abstract description 9
- 239000008280 blood Substances 0.000 claims abstract description 8
- 210000004369 blood Anatomy 0.000 claims abstract description 8
- 230000001077 hypotensive effect Effects 0.000 claims abstract description 8
- 230000001965 increasing effect Effects 0.000 claims abstract description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 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 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- 210000000748 cardiovascular system Anatomy 0.000 abstract description 3
- 230000006806 disease prevention Effects 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 19
- 239000000243 solution Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical class NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
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- -1 Nitrate ester Chemical class 0.000 description 11
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- 238000000034 method Methods 0.000 description 8
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
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- 239000004480 active ingredient Substances 0.000 description 6
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 229960003966 nicotinamide Drugs 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- RCRGAUIECRGLAZ-UHFFFAOYSA-N 2-[[6-(4-methylpiperazin-1-yl)pyridine-3-carbonyl]amino]ethyl nitrate Chemical compound C1CN(C)CCN1C1=CC=C(C(=O)NCCO[N+]([O-])=O)C=N1 RCRGAUIECRGLAZ-UHFFFAOYSA-N 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- NCHQJWGRHFMSCO-UHFFFAOYSA-N n-(2-hydroxyethyl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(C(=O)NCCO)C=N1 NCHQJWGRHFMSCO-UHFFFAOYSA-N 0.000 description 4
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 4
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 4
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- 238000003756 stirring Methods 0.000 description 4
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- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- IPPHPXJQNAXASF-UHFFFAOYSA-N 2-[[2-(4-methylpiperazin-1-yl)pyridine-3-carbonyl]amino]ethyl nitrate Chemical compound C1CN(C)CCN1C1=NC=CC=C1C(=O)NCCO[N+]([O-])=O IPPHPXJQNAXASF-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- UQVXHYAVALLCBQ-UHFFFAOYSA-N methyl 6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1N1CCN(C)CC1 UQVXHYAVALLCBQ-UHFFFAOYSA-N 0.000 description 3
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- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000007942 layered tablet Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QKJSFFQUECXQEQ-UHFFFAOYSA-N methyl 2-(4-methylpiperazin-1-yl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1N1CCN(C)CC1 QKJSFFQUECXQEQ-UHFFFAOYSA-N 0.000 description 1
- JZGHZRINJSPUKC-UHFFFAOYSA-N methyl 6-(4-benzhydrylpiperazin-1-yl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 JZGHZRINJSPUKC-UHFFFAOYSA-N 0.000 description 1
- JJFCNJSZRMFZJU-UHFFFAOYSA-N methyl 6-(4-cyclopentylpiperazin-1-yl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1N1CCN(C2CCCC2)CC1 JJFCNJSZRMFZJU-UHFFFAOYSA-N 0.000 description 1
- PWLPXAALAIXFHZ-UHFFFAOYSA-N methyl 6-(4-ethylpiperazin-1-yl)pyridine-3-carboxylate Chemical compound C1CN(CC)CCN1C1=CC=C(C(=O)OC)C=N1 PWLPXAALAIXFHZ-UHFFFAOYSA-N 0.000 description 1
- VWDIABCCXMPPOG-UHFFFAOYSA-N methyl 6-[(4-benzhydrylpiperazin-1-yl)methyl]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1CN1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 VWDIABCCXMPPOG-UHFFFAOYSA-N 0.000 description 1
- HMFYTTJLIFNUCP-UHFFFAOYSA-N methyl 6-piperazin-1-ylpyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1N1CCNCC1 HMFYTTJLIFNUCP-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- DTNDJNLDFZPPCE-UHFFFAOYSA-N n-(2-hydroxyethyl)-6-piperazin-1-ylpyridine-3-carboxamide Chemical compound N1=CC(C(=O)NCCO)=CC=C1N1CCNCC1 DTNDJNLDFZPPCE-UHFFFAOYSA-N 0.000 description 1
- PITMPVAPPJLKJP-UHFFFAOYSA-N n-(8-hydroxyoctyl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(C(=O)NCCCCCCCCO)C=N1 PITMPVAPPJLKJP-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
-
- 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
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4664889 | 1989-03-01 | ||
| JP46648/1989 | 1989-03-01 | ||
| JP27202/1990 | 1990-02-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2011143A1 CA2011143A1 (fr) | 1990-09-01 |
| CA2011143C true CA2011143C (fr) | 1999-02-23 |
Family
ID=12753134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002011143A Expired - Fee Related CA2011143C (fr) | 1989-03-01 | 1990-02-28 | Derives amidiques de l'acide pyridine carboxylique et composes pharmaceutiques les contenant |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP2843632B2 (fr) |
| KR (1) | KR0130758B1 (fr) |
| CA (1) | CA2011143C (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3258674B2 (ja) * | 1996-11-19 | 2002-02-18 | 日清ファルマ株式会社 | ピリジンカルボキサミド誘導体 |
| EE04588B1 (et) * | 1997-10-27 | 2006-02-15 | Neurosearch A/S | Heteroarüüldiasatsükloalkaanid kui atsetüülkoliini nikotiinretseptorite kolinergilised ligandid, nende kasutamine ravimitena ning neid sisaldav farmatseutiline kompositsioon |
| JP5841529B2 (ja) * | 2010-05-27 | 2016-01-13 | あすか製薬株式会社 | 複素環化合物及びh1受容体拮抗剤 |
-
1990
- 1990-02-08 JP JP2027202A patent/JP2843632B2/ja not_active Expired - Fee Related
- 1990-02-28 KR KR1019900002605A patent/KR0130758B1/ko not_active Expired - Fee Related
- 1990-02-28 CA CA002011143A patent/CA2011143C/fr not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH037258A (ja) | 1991-01-14 |
| KR900014360A (ko) | 1990-10-23 |
| CA2011143A1 (fr) | 1990-09-01 |
| JP2843632B2 (ja) | 1999-01-06 |
| KR0130758B1 (ko) | 1998-04-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |