KR20140057652A - Hdl-콜레스테롤 상승제로서의 3-피리딘 카복실산 하이드라자이드 - Google Patents
Hdl-콜레스테롤 상승제로서의 3-피리딘 카복실산 하이드라자이드 Download PDFInfo
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- KR20140057652A KR20140057652A KR1020147008882A KR20147008882A KR20140057652A KR 20140057652 A KR20140057652 A KR 20140057652A KR 1020147008882 A KR1020147008882 A KR 1020147008882A KR 20147008882 A KR20147008882 A KR 20147008882A KR 20140057652 A KR20140057652 A KR 20140057652A
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- Prior art keywords
- alkyl
- phenyl
- halogen
- methyl
- ethoxy
- 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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- 108010023302 HDL Cholesterol Proteins 0.000 title claims abstract description 32
- KFUSANSHCADHNJ-UHFFFAOYSA-N pyridine-3-carbohydrazide Chemical class NNC(=O)C1=CC=CN=C1 KFUSANSHCADHNJ-UHFFFAOYSA-N 0.000 title claims description 6
- 239000004131 EU approved raising agent Substances 0.000 title 1
- 235000010855 food raising agent Nutrition 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 259
- 238000000034 method Methods 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 238000011282 treatment Methods 0.000 claims abstract description 33
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 18
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 17
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 238000011321 prophylaxis Methods 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 230000003028 elevating effect Effects 0.000 claims abstract description 4
- -1 -C 1 -7-alkyl Chemical group 0.000 claims description 122
- 229910052736 halogen Inorganic materials 0.000 claims description 91
- 150000002367 halogens Chemical class 0.000 claims description 90
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000011570 nicotinamide Substances 0.000 claims description 31
- 229960003966 nicotinamide Drugs 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 239000011664 nicotinic acid Substances 0.000 claims description 23
- 229960003512 nicotinic acid Drugs 0.000 claims description 23
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 20
- 230000008878 coupling Effects 0.000 claims description 19
- 238000010168 coupling process Methods 0.000 claims description 19
- 238000005859 coupling reaction Methods 0.000 claims description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 17
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
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- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 11
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- 235000020824 obesity Nutrition 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- YXMIQJXMAJAQFD-UHFFFAOYSA-N 5-cyclopropyl-6-(cyclopropylmethoxy)-n'-(4-fluorophenyl)-n'-methylpyridine-3-carbohydrazide Chemical compound C=1C=C(F)C=CC=1N(C)NC(=O)C(C=C1C2CC2)=CN=C1OCC1CC1 YXMIQJXMAJAQFD-UHFFFAOYSA-N 0.000 claims description 10
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- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 10
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 208000031225 myocardial ischemia Diseases 0.000 claims description 9
- 206010021024 Hypolipidaemia Diseases 0.000 claims description 8
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 208000026621 hypolipoproteinemia Diseases 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- CUQZGBSEDZOUEI-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclobutyloxy-n-(4-hydroxypiperidin-1-yl)pyridine-3-carboxamide Chemical compound C1CC(O)CCN1NC(=O)C(C=C1C=2C=CC(Cl)=CC=2)=CN=C1OC1CCC1 CUQZGBSEDZOUEI-UHFFFAOYSA-N 0.000 claims description 6
- BLXKBXAIPYKIMF-UHFFFAOYSA-N 5-cyclohexyl-n-(4-hydroxypiperidin-1-yl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound C1CC(O)CCN1NC(=O)C1=CN=C(OCC(F)(F)F)C(C2CCCCC2)=C1 BLXKBXAIPYKIMF-UHFFFAOYSA-N 0.000 claims description 6
- LPRUZRPAFIALRF-UHFFFAOYSA-N 6-cyclobutyloxy-5-(furan-2-yl)pyridine-3-carboxylic acid Chemical compound C=1C=COC=1C1=CC(C(=O)O)=CN=C1OC1CCC1 LPRUZRPAFIALRF-UHFFFAOYSA-N 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 6
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- 230000002641 glycemic effect Effects 0.000 claims description 6
- 208000028867 ischemia Diseases 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- UKSJFPJNCLXWSY-UHFFFAOYSA-N 5-cyclopropyl-n'-(4-fluorophenyl)-n'-methyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound C=1C=C(F)C=CC=1N(C)NC(=O)C(C=1)=CN=C(OCC(F)(F)F)C=1C1CC1 UKSJFPJNCLXWSY-UHFFFAOYSA-N 0.000 claims description 5
- 206010002383 Angina Pectoris Diseases 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
- ONEZQSDDZYQSQQ-UHFFFAOYSA-N 5-(3-fluorophenyl)-n'-methyl-n'-phenyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound C=1C=CC=CC=1N(C)NC(=O)C(C=1)=CN=C(OCC(F)(F)F)C=1C1=CC=CC(F)=C1 ONEZQSDDZYQSQQ-UHFFFAOYSA-N 0.000 claims description 4
- MFIYRECNFTZQJQ-UHFFFAOYSA-N 5-(4-chloro-3-fluorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound NNC(=O)C1=CN=C(OCC(F)(F)F)C(C=2C=C(F)C(Cl)=CC=2)=C1 MFIYRECNFTZQJQ-UHFFFAOYSA-N 0.000 claims description 4
- RKVTXARFCMZBNX-UHFFFAOYSA-N 5-(4-chlorophenyl)-n'-methyl-n'-phenyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound C=1C=CC=CC=1N(C)NC(=O)C(C=1)=CN=C(OCC(F)(F)F)C=1C1=CC=C(Cl)C=C1 RKVTXARFCMZBNX-UHFFFAOYSA-N 0.000 claims description 4
- RQHVKGJMPBAXHH-UHFFFAOYSA-N 5-(4-cyanophenyl)-n-(4-hydroxypiperidin-1-yl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound C1CC(O)CCN1NC(=O)C1=CN=C(OCC(F)(F)F)C(C=2C=CC(=CC=2)C#N)=C1 RQHVKGJMPBAXHH-UHFFFAOYSA-N 0.000 claims description 4
- VUWPBFVPAGTLTH-UHFFFAOYSA-N 5-cyclopentyl-n'-methyl-n'-phenyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound C=1C=CC=CC=1N(C)NC(=O)C(C=1)=CN=C(OCC(F)(F)F)C=1C1CCCC1 VUWPBFVPAGTLTH-UHFFFAOYSA-N 0.000 claims description 4
- UWSOZBSWZBRYOH-UHFFFAOYSA-N 5-cyclopentyl-n-morpholin-4-yl-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound FC(F)(F)COC1=NC=C(C(=O)NN2CCOCC2)C=C1C1CCCC1 UWSOZBSWZBRYOH-UHFFFAOYSA-N 0.000 claims description 4
- YABHUHBMGUTQCM-UHFFFAOYSA-N 5-cyclopropyl-n'-(pyridin-4-ylmethyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound FC(F)(F)COC1=NC=C(C(=O)NNCC=2C=CN=CC=2)C=C1C1CC1 YABHUHBMGUTQCM-UHFFFAOYSA-N 0.000 claims description 4
- PSSRMWWAGFEYGQ-ZDUSSCGKSA-N 5-cyclopropyl-n-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound COC[C@@H]1CCCN1NC(=O)C1=CN=C(OCC(F)(F)F)C(C2CC2)=C1 PSSRMWWAGFEYGQ-ZDUSSCGKSA-N 0.000 claims description 4
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- 125000006413 ring segment Chemical group 0.000 claims description 4
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 3
- ZQSLHUCGSTXSGC-UHFFFAOYSA-N 5-(4-chlorophenyl)-n-morpholin-4-yl-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound FC(F)(F)COC1=NC=C(C(=O)NN2CCOCC2)C=C1C1=CC=C(Cl)C=C1 ZQSLHUCGSTXSGC-UHFFFAOYSA-N 0.000 claims description 3
- ZALMXDAKFFZMCI-INIZCTEOSA-N 5-cyclohexyl-n-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound COC[C@@H]1CCCN1NC(=O)C1=CN=C(OCC(F)(F)F)C(C2CCCCC2)=C1 ZALMXDAKFFZMCI-INIZCTEOSA-N 0.000 claims description 3
- DDOOXPDNFMCJNZ-UHFFFAOYSA-N 5-cyclohexyl-n-morpholin-4-yl-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound FC(F)(F)COC1=NC=C(C(=O)NN2CCOCC2)C=C1C1CCCCC1 DDOOXPDNFMCJNZ-UHFFFAOYSA-N 0.000 claims description 3
- UVYIWCZDIVRFQF-UHFFFAOYSA-N 5-cyclopentyl-n-(2-oxopyrrolidin-1-yl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide Chemical compound FC(F)(F)COC1=NC=C(C(=O)NN2C(CCC2)=O)C=C1C1CCCC1 UVYIWCZDIVRFQF-UHFFFAOYSA-N 0.000 claims description 3
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- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
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- WBPULFKJXCKTKX-UHFFFAOYSA-N n'-methyl-5-(oxan-4-yl)-n'-phenyl-6-(2,2,2-trifluoroethoxy)pyridine-3-carbohydrazide Chemical compound C=1C=CC=CC=1N(C)NC(=O)C(C=1)=CN=C(OCC(F)(F)F)C=1C1CCOCC1 WBPULFKJXCKTKX-UHFFFAOYSA-N 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
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- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
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- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 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
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- FNNIAKKPBXJGNJ-UHFFFAOYSA-N pyrazolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCN1 FNNIAKKPBXJGNJ-UHFFFAOYSA-N 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
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- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DDOKGZLQKHJNOU-UHFFFAOYSA-N tert-butyl 2-[5-(4-chlorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carbonyl]pyrazolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCN1C(=O)C1=CN=C(OCC(F)(F)F)C(C=2C=CC(Cl)=CC=2)=C1 DDOKGZLQKHJNOU-UHFFFAOYSA-N 0.000 description 1
- NHGBXSBAIAMLEX-UHFFFAOYSA-N tert-butyl 4-[[5-(4-chlorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carbonyl]amino]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1NC(=O)C1=CN=C(OCC(F)(F)F)C(C=2C=CC(Cl)=CC=2)=C1 NHGBXSBAIAMLEX-UHFFFAOYSA-N 0.000 description 1
- PADGJNOHLWFTLG-UHFFFAOYSA-N tert-butyl n-(4-methyl-3-oxopiperazin-1-yl)carbamate Chemical compound CN1CCN(NC(=O)OC(C)(C)C)CC1=O PADGJNOHLWFTLG-UHFFFAOYSA-N 0.000 description 1
- HBGFARJLOOVHPQ-UHFFFAOYSA-N tert-butyl n-[4-[2-[tert-butyl(dimethyl)silyl]oxyethyl]piperidin-1-yl]carbamate Chemical compound CC(C)(C)OC(=O)NN1CCC(CCO[Si](C)(C)C(C)(C)C)CC1 HBGFARJLOOVHPQ-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- IAFSUZIBZMPMPK-UHFFFAOYSA-N thiomorpholin-4-amine Chemical compound NN1CCSCC1 IAFSUZIBZMPMPK-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent 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
- C07D213/86—Hydrazides; Thio or imino analogues thereof
- C07D213/87—Hydrazides; Thio or imino analogues thereof in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D401/02—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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
- 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
- C07D413/14—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
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11180929 | 2011-09-12 | ||
| EP11180929.9 | 2011-09-12 | ||
| PCT/EP2012/067469 WO2013037703A1 (en) | 2011-09-12 | 2012-09-07 | 3 -pyridine carboxylic acid hydrazides as hdl-cholesterol raising agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20140057652A true KR20140057652A (ko) | 2014-05-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020147008882A Ceased KR20140057652A (ko) | 2011-09-12 | 2012-09-07 | Hdl-콜레스테롤 상승제로서의 3-피리딘 카복실산 하이드라자이드 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8648099B2 (enExample) |
| EP (1) | EP2755953A1 (enExample) |
| JP (1) | JP5815874B2 (enExample) |
| KR (1) | KR20140057652A (enExample) |
| CN (1) | CN103781765A (enExample) |
| BR (1) | BR112014005634A2 (enExample) |
| CA (1) | CA2844865A1 (enExample) |
| MX (1) | MX2014001860A (enExample) |
| RU (1) | RU2014111321A (enExample) |
| WO (1) | WO2013037703A1 (enExample) |
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| KR20210038884A (ko) * | 2018-07-26 | 2021-04-08 | 에프. 호프만-라 로슈 아게 | 신장 장애 치료에 사용하기 위한 화합물 |
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| CN104725353A (zh) * | 2015-03-12 | 2015-06-24 | 佛山市赛维斯医药科技有限公司 | 一类含烟酸酰胺和哌啶结构ptp1b抑制剂及其用途 |
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| JP2005531520A (ja) * | 2002-03-28 | 2005-10-20 | メルク エンド カムパニー インコーポレーテッド | 置換2,3−ジフェニルピリジン類 |
| KR100970050B1 (ko) * | 2005-04-06 | 2010-07-16 | 에프. 호프만-라 로슈 아게 | Cb1 역 작용제로서 피리딘-3-카복사마이드 유도체 |
| WO2007011760A2 (en) * | 2005-07-15 | 2007-01-25 | Kalypsys, Inc. | Inhibitors of mitotic kinesin |
| US7629346B2 (en) * | 2006-06-19 | 2009-12-08 | Hoffmann-La Roche Inc. | Pyrazinecarboxamide derivatives as CB1 antagonists |
| JP2010505789A (ja) * | 2006-10-04 | 2010-02-25 | エフ.ホフマン−ラ ロシュ アーゲー | Hdl−コレステロール上昇剤としての3−ピリジンカルボキサミド及び2−ピラジンカルボキサミド誘導体 |
| TW200940537A (en) * | 2008-02-26 | 2009-10-01 | Astrazeneca Ab | Heterocyclic urea derivatives and methods of use thereof |
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2012
- 2012-09-07 RU RU2014111321/04A patent/RU2014111321A/ru not_active Application Discontinuation
- 2012-09-07 MX MX2014001860A patent/MX2014001860A/es unknown
- 2012-09-07 BR BR112014005634A patent/BR112014005634A2/pt not_active IP Right Cessation
- 2012-09-07 WO PCT/EP2012/067469 patent/WO2013037703A1/en not_active Ceased
- 2012-09-07 KR KR1020147008882A patent/KR20140057652A/ko not_active Ceased
- 2012-09-07 JP JP2014530158A patent/JP5815874B2/ja not_active Expired - Fee Related
- 2012-09-07 CN CN201280044104.1A patent/CN103781765A/zh active Pending
- 2012-09-07 EP EP12754017.7A patent/EP2755953A1/en not_active Withdrawn
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- 2012-09-11 US US13/609,429 patent/US8648099B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210038884A (ko) * | 2018-07-26 | 2021-04-08 | 에프. 호프만-라 로슈 아게 | 신장 장애 치료에 사용하기 위한 화합물 |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2014111321A (ru) | 2015-10-20 |
| US20130065876A1 (en) | 2013-03-14 |
| EP2755953A1 (en) | 2014-07-23 |
| US8648099B2 (en) | 2014-02-11 |
| MX2014001860A (es) | 2014-05-30 |
| JP5815874B2 (ja) | 2015-11-17 |
| JP2014527073A (ja) | 2014-10-09 |
| BR112014005634A2 (pt) | 2017-03-28 |
| CA2844865A1 (en) | 2013-03-21 |
| WO2013037703A1 (en) | 2013-03-21 |
| CN103781765A (zh) | 2014-05-07 |
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