CA2870886A1 - Novel beta-alanine derivative, pharmaceutically acceptable salts thereof, and pharmaceutical composition comprising same as active ingredient - Google Patents
Novel beta-alanine derivative, pharmaceutically acceptable salts thereof, and pharmaceutical composition comprising same as active ingredient Download PDFInfo
- Publication number
- CA2870886A1 CA2870886A1 CA2870886A CA2870886A CA2870886A1 CA 2870886 A1 CA2870886 A1 CA 2870886A1 CA 2870886 A CA2870886 A CA 2870886A CA 2870886 A CA2870886 A CA 2870886A CA 2870886 A1 CA2870886 A1 CA 2870886A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- trans
- cyclohexyl
- acetic acid
- propionylamino
- 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
- 150000003839 salts Chemical class 0.000 title claims abstract description 44
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 27
- 239000004480 active ingredient Substances 0.000 title claims abstract description 8
- 230000000694 effects Effects 0.000 claims abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 12
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 11
- 208000004930 Fatty Liver Diseases 0.000 claims abstract description 11
- 206010019708 Hepatic steatosis Diseases 0.000 claims abstract description 11
- 208000010706 fatty liver disease Diseases 0.000 claims abstract description 11
- 208000006454 hepatitis Diseases 0.000 claims abstract description 11
- 231100000283 hepatitis Toxicity 0.000 claims abstract description 11
- 231100000240 steatosis hepatitis Toxicity 0.000 claims abstract description 11
- 208000031773 Insulin resistance syndrome Diseases 0.000 claims abstract description 10
- 208000008589 Obesity Diseases 0.000 claims abstract description 10
- 235000020824 obesity Nutrition 0.000 claims abstract description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 190
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 114
- 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 79
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 76
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 45
- -1 4-methyl-2-phenylthiazole-5-carbonyl Chemical group 0.000 claims description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 239000000126 substance Substances 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 206010012601 diabetes mellitus Diseases 0.000 claims description 21
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 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 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000011734 sodium Substances 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 206010022489 Insulin Resistance Diseases 0.000 claims description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 7
- 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 claims description 7
- 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 claims description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 7
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 239000000883 anti-obesity agent Substances 0.000 claims description 6
- 229940125710 antiobesity agent Drugs 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- HYZYGCHBDSQESV-AFARHQOCSA-N OC(=O)C[C@H]1CC[C@@H](CC1)c1ccc(NC(=O)CCNC(=O)c2ccc(cc2)-c2ccccc2)cc1 Chemical compound OC(=O)C[C@H]1CC[C@@H](CC1)c1ccc(NC(=O)CCNC(=O)c2ccc(cc2)-c2ccccc2)cc1 HYZYGCHBDSQESV-AFARHQOCSA-N 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 208000035180 MODY Diseases 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 201000006950 maturity-onset diabetes of the young Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- RIXALDPMZWLDCB-MXVIHJGJSA-N C(C)OC=1C=C(C(=O)NCCC(=O)NC2=CC=C(C=C2)[C@@H]2CC[C@H](CC2)CC(=O)O)C=CC1OCC Chemical compound C(C)OC=1C=C(C(=O)NCCC(=O)NC2=CC=C(C=C2)[C@@H]2CC[C@H](CC2)CC(=O)O)C=CC1OCC RIXALDPMZWLDCB-MXVIHJGJSA-N 0.000 claims description 3
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 3
- 229940125708 antidiabetic agent Drugs 0.000 claims description 3
- 239000003472 antidiabetic agent Substances 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 3
- 201000008980 hyperinsulinism Diseases 0.000 claims description 3
- 208000002720 Malnutrition Diseases 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 208000004104 gestational diabetes Diseases 0.000 claims description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 230000001071 malnutrition Effects 0.000 claims description 2
- 235000000824 malnutrition Nutrition 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 2
- 208000015380 nutritional deficiency disease Diseases 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008177 pharmaceutical agent Substances 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- JAWKFUAPEMFQPR-UHFFFAOYSA-N C1=C(C(=CC=C1)C1=NC(=C(O1)C(F)(F)F)C(=O)NCCC(=O)NC1=CC=C(C2CCC(CC(=O)O)CC2)C=C1)Cl Chemical compound C1=C(C(=CC=C1)C1=NC(=C(O1)C(F)(F)F)C(=O)NCCC(=O)NC1=CC=C(C2CCC(CC(=O)O)CC2)C=C1)Cl JAWKFUAPEMFQPR-UHFFFAOYSA-N 0.000 claims 2
- LAUJJMJFRJSSRD-WGSAOQKQSA-N CCOc1ccc(cc1)C(=O)NCCC(=O)Nc1ccc(cc1)[C@H]1CC[C@H](CC(O)=O)CC1 Chemical compound CCOc1ccc(cc1)C(=O)NCCC(=O)Nc1ccc(cc1)[C@H]1CC[C@H](CC(O)=O)CC1 LAUJJMJFRJSSRD-WGSAOQKQSA-N 0.000 claims 2
- KUQNBMSJMDAQOM-ALOJWSFFSA-N CCc1ccc(cc1)-c1ccc(cc1)C(=O)NCCC(=O)Nc1ccc(cc1)[C@H]1CC[C@H](CC(O)=O)CC1 Chemical compound CCc1ccc(cc1)-c1ccc(cc1)C(=O)NCCC(=O)Nc1ccc(cc1)[C@H]1CC[C@H](CC(O)=O)CC1 KUQNBMSJMDAQOM-ALOJWSFFSA-N 0.000 claims 2
- QYUKMLKGZCNFIY-UHFFFAOYSA-N N=1C(=C(OC=1C1=C(C=C(Cl)C=C1)Cl)C(F)(F)F)C(=O)NCCC(=O)NC1=CC=C(C2CCC(CC2)CC(=O)O)C=C1 Chemical compound N=1C(=C(OC=1C1=C(C=C(Cl)C=C1)Cl)C(F)(F)F)C(=O)NCCC(=O)NC1=CC=C(C2CCC(CC2)CC(=O)O)C=C1 QYUKMLKGZCNFIY-UHFFFAOYSA-N 0.000 claims 2
- FYVLBWXBLBMYHH-UHFFFAOYSA-N NC(=O)CC1CCC(CC1)C1=CC=C(NC(=O)CCNC(=O)C2=C(OC(=N2)C2=CC=CC=C2)C(F)(F)F)C=C1 Chemical compound NC(=O)CC1CCC(CC1)C1=CC=C(NC(=O)CCNC(=O)C2=C(OC(=N2)C2=CC=CC=C2)C(F)(F)F)C=C1 FYVLBWXBLBMYHH-UHFFFAOYSA-N 0.000 claims 2
- VRSRWKTUHXYBEX-UHFFFAOYSA-N O=C(C=1N=C(OC=1C(F)(F)F)C1=C(C=CC=C1)C(F)(F)F)NCCC(=O)NC1=CC=C(C2CCC(CC2)CC(=O)O)C=C1 Chemical compound O=C(C=1N=C(OC=1C(F)(F)F)C1=C(C=CC=C1)C(F)(F)F)NCCC(=O)NC1=CC=C(C2CCC(CC2)CC(=O)O)C=C1 VRSRWKTUHXYBEX-UHFFFAOYSA-N 0.000 claims 2
- ABYRSZHHAIRFCR-UHFFFAOYSA-N O=C(C=1N=C(OC=1C(F)(F)F)C1=C(C=CC=C1)F)NCCC(=O)NC1=CC=C(C2CCC(CC(=O)O)CC2)C=C1 Chemical compound O=C(C=1N=C(OC=1C(F)(F)F)C1=C(C=CC=C1)F)NCCC(=O)NC1=CC=C(C2CCC(CC(=O)O)CC2)C=C1 ABYRSZHHAIRFCR-UHFFFAOYSA-N 0.000 claims 2
- LGVGYQGUEJOUPF-UHFFFAOYSA-N OC(=O)CC1CCC(C2=CC=C(NC(=O)CCNC(=O)C3=C(OC(=N3)C3=CC=CC=C3)C(F)(F)F)C=C2)CC1 Chemical compound OC(=O)CC1CCC(C2=CC=C(NC(=O)CCNC(=O)C3=C(OC(=N3)C3=CC=CC=C3)C(F)(F)F)C=C2)CC1 LGVGYQGUEJOUPF-UHFFFAOYSA-N 0.000 claims 2
- SRUSIWMXURTYKN-MEMLXQNLSA-N OC(=O)C[C@H]1CC[C@@H](CC1)c1ccc(NC(=O)CCNC(=O)c2ccc(c(Cl)c2)-c2ccccc2)cc1 Chemical compound OC(=O)C[C@H]1CC[C@@H](CC1)c1ccc(NC(=O)CCNC(=O)c2ccc(c(Cl)c2)-c2ccccc2)cc1 SRUSIWMXURTYKN-MEMLXQNLSA-N 0.000 claims 2
- IHYWGBVXKKBDKC-SHTZXODSSA-N OC(=O)C[C@H]1CC[C@@H](CC1)c1ccc(NC(=O)CCNC(=O)c2nc(oc2C(F)(F)F)-c2c(Cl)cc(F)cc2Cl)cc1 Chemical compound OC(=O)C[C@H]1CC[C@@H](CC1)c1ccc(NC(=O)CCNC(=O)c2nc(oc2C(F)(F)F)-c2c(Cl)cc(F)cc2Cl)cc1 IHYWGBVXKKBDKC-SHTZXODSSA-N 0.000 claims 2
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- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
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- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2012-0043189 | 2012-04-25 | ||
| KR20120043189 | 2012-04-25 | ||
| KR10-2013-0045811 | 2013-04-25 | ||
| KR1020130045811A KR101472279B1 (ko) | 2012-04-25 | 2013-04-25 | 신규한 베타 알라닌 유도체, 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 약제학적 조성물 |
| PCT/KR2013/003557 WO2013162298A1 (ko) | 2012-04-25 | 2013-04-25 | 신규한 베타 알라닌 유도체, 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 약제학적 조성물 |
Publications (1)
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| CA2870886A1 true CA2870886A1 (en) | 2013-10-31 |
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| CA2870886A Abandoned CA2870886A1 (en) | 2012-04-25 | 2013-04-25 | Novel beta-alanine derivative, pharmaceutically acceptable salts thereof, and pharmaceutical composition comprising same as active ingredient |
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| EP (1) | EP2842938A4 (https=) |
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| RU (1) | RU2014147220A (https=) |
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| US10882841B2 (en) | 2016-03-01 | 2021-01-05 | University Of Maryland, Baltimore | Wnt signaling pathway inhibitors for treatments of disease |
| CN115246774A (zh) * | 2021-04-27 | 2022-10-28 | 南昌弘益科技有限公司 | 一类新型双羰基类阿魏酸衍生物 |
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| AU751950B2 (en) * | 1997-11-24 | 2002-09-05 | Merck & Co., Inc. | Substituted beta-alanine derivatives as cell adhesion inhibitors |
| JP4261639B2 (ja) * | 1998-08-05 | 2009-04-30 | 日本曹達株式会社 | フェニルイミダゾール系抗高脂血症薬 |
| JP2003128639A (ja) * | 2001-10-25 | 2003-05-08 | Sankyo Co Ltd | ベンツアミド誘導体 |
| AU2003241833A1 (en) * | 2002-05-28 | 2003-12-12 | Ono Pharmaceutical Co., Ltd. | Beta-ALANINE DERIVATIVE AND USE THEREOF |
| WO2008099221A1 (en) * | 2007-02-15 | 2008-08-21 | Prosidion Limited | Amide and urea derivatives for the treatment of metabolic diseases |
| US20090036425A1 (en) | 2007-08-02 | 2009-02-05 | Pfizer Inc | Substituted bicyclolactam compounds |
| EP2423182A4 (en) * | 2009-04-21 | 2012-11-07 | Astellas Pharma Inc | DIACYLETHYLENEDIAMINE COMPOUND |
| NZ602125A (en) * | 2010-03-30 | 2014-01-31 | Novartis Ag | Uses of dgat1 inhibitors |
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- 2013-04-25 CA CA2870886A patent/CA2870886A1/en not_active Abandoned
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Also Published As
| Publication number | Publication date |
|---|---|
| CN104254519A (zh) | 2014-12-31 |
| JP2015520136A (ja) | 2015-07-16 |
| KR101472279B1 (ko) | 2014-12-16 |
| BR112014026910A2 (pt) | 2017-06-27 |
| US9321728B2 (en) | 2016-04-26 |
| CN104254519B (zh) | 2016-04-20 |
| MX2014012937A (es) | 2015-05-11 |
| RU2014147220A (ru) | 2016-06-10 |
| WO2013162298A8 (ko) | 2013-12-27 |
| IN2014MN02135A (https=) | 2015-09-04 |
| EP2842938A4 (en) | 2015-12-23 |
| US20150329504A1 (en) | 2015-11-19 |
| WO2013162298A1 (ko) | 2013-10-31 |
| EP2842938A1 (en) | 2015-03-04 |
| BR112014026910A8 (pt) | 2018-01-09 |
| KR20130120414A (ko) | 2013-11-04 |
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