CA2436738A1 - Salts of pyrimidine derivatives for use against coronary heart disease and atherosclerose - Google Patents
Salts of pyrimidine derivatives for use against coronary heart disease and atherosclerose Download PDFInfo
- Publication number
- CA2436738A1 CA2436738A1 CA002436738A CA2436738A CA2436738A1 CA 2436738 A1 CA2436738 A1 CA 2436738A1 CA 002436738 A CA002436738 A CA 002436738A CA 2436738 A CA2436738 A CA 2436738A CA 2436738 A1 CA2436738 A1 CA 2436738A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- ethoxy
- oxo
- salt
- ethyl
- 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 45
- 208000029078 coronary artery disease Diseases 0.000 title claims description 26
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 239000012453 solvate Substances 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 166
- -1 azido, formyl Chemical group 0.000 claims description 165
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 156
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- 238000006243 chemical reaction Methods 0.000 claims description 60
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 60
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 54
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 54
- 206010022489 Insulin Resistance Diseases 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims description 31
- 208000008589 Obesity Diseases 0.000 claims description 29
- 235000020824 obesity Nutrition 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 29
- 206010020772 Hypertension Diseases 0.000 claims description 28
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 28
- 208000035475 disorder Diseases 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 27
- 235000012000 cholesterol Nutrition 0.000 claims description 26
- 208000017169 kidney disease Diseases 0.000 claims description 24
- XAWRDWCILPXSAR-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C(O)=O)C=C1 XAWRDWCILPXSAR-UHFFFAOYSA-N 0.000 claims description 23
- 206010036049 Polycystic ovaries Diseases 0.000 claims description 23
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 23
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 22
- UAPQKLTXQPVJGQ-UHFFFAOYSA-N 3-[4-[2-(1,5-dimethyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(C)N2CCOC1=CC=C(CC(OCC)C(O)=O)C=C1 UAPQKLTXQPVJGQ-UHFFFAOYSA-N 0.000 claims description 21
- 201000001320 Atherosclerosis Diseases 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- 208000001132 Osteoporosis Diseases 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
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- 102000016267 Leptin Human genes 0.000 claims description 18
- 108010092277 Leptin Proteins 0.000 claims description 18
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 claims description 18
- 229940039781 leptin Drugs 0.000 claims description 18
- 208000011580 syndromic disease Diseases 0.000 claims description 17
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 16
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- 239000008103 glucose Substances 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 14
- 229920001268 Cholestyramine Polymers 0.000 claims description 14
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 14
- 208000017442 Retinal disease Diseases 0.000 claims description 14
- 206010038923 Retinopathy Diseases 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 14
- 235000001968 nicotinic acid Nutrition 0.000 claims description 14
- 229960003512 nicotinic acid Drugs 0.000 claims description 14
- 239000011664 nicotinic acid Substances 0.000 claims description 14
- 229920002911 Colestipol Polymers 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 13
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 claims description 13
- 229960003912 probucol Drugs 0.000 claims description 13
- 150000003626 triacylglycerols Chemical class 0.000 claims description 13
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 12
- 206010012289 Dementia Diseases 0.000 claims description 12
- 208000002249 Diabetes Complications Diseases 0.000 claims description 12
- 206010012655 Diabetic complications Diseases 0.000 claims description 12
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 12
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 12
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 12
- 206010033645 Pancreatitis Diseases 0.000 claims description 12
- 201000004681 Psoriasis Diseases 0.000 claims description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 206010048214 Xanthoma Diseases 0.000 claims description 12
- 206010048215 Xanthomatosis Diseases 0.000 claims description 12
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 12
- 230000020411 cell activation Effects 0.000 claims description 12
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 claims description 12
- 229960002604 colestipol Drugs 0.000 claims description 12
- 210000002889 endothelial cell Anatomy 0.000 claims description 12
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 12
- 230000001631 hypertensive effect Effects 0.000 claims description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 201000009925 nephrosclerosis Diseases 0.000 claims description 12
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 12
- 208000030814 Eating disease Diseases 0.000 claims description 11
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 11
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 11
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 11
- 206010068871 Myotonic dystrophy Diseases 0.000 claims description 11
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 230000037396 body weight Effects 0.000 claims description 11
- 235000014632 disordered eating Nutrition 0.000 claims description 11
- 235000021588 free fatty acids Nutrition 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- MWGATWIBSKHFMR-UHFFFAOYSA-N 2-anilinoethanol Chemical compound OCCNC1=CC=CC=C1 MWGATWIBSKHFMR-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 10
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 10
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 10
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 230000001603 reducing effect Effects 0.000 claims description 10
- 239000003826 tablet Substances 0.000 claims description 10
- ZRRNJJURLBXWLL-REWJHTLYSA-N (2r,3r,4r,5s)-6-(octylamino)hexane-1,2,3,4,5-pentol Chemical compound CCCCCCCCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO ZRRNJJURLBXWLL-REWJHTLYSA-N 0.000 claims description 9
- OTXHZHQQWQTQMW-UHFFFAOYSA-N (diaminomethylideneamino)azanium;hydrogen carbonate Chemical compound OC([O-])=O.N[NH2+]C(N)=N OTXHZHQQWQTQMW-UHFFFAOYSA-N 0.000 claims description 9
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 9
- 108010069201 VLDL Cholesterol Proteins 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 201000001421 hyperglycemia Diseases 0.000 claims description 9
- 230000002757 inflammatory effect Effects 0.000 claims description 9
- 108010028554 LDL Cholesterol Proteins 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000556 agonist Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 8
- 239000000347 magnesium hydroxide Substances 0.000 claims description 8
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 8
- FWPKZPBXZJYCCE-UHFFFAOYSA-L CCOC(CC1=CC=C(C=C1)OCCN2C(=O)C3=CC=CC=C3N=C2N4CCOCC4)C(=O)[O-].CCOC(CC1=CC=C(C=C1)OCCN2C(=O)C3=CC=CC=C3N=C2N4CCOCC4)C(=O)[O-].[Mg+2] Chemical compound CCOC(CC1=CC=C(C=C1)OCCN2C(=O)C3=CC=CC=C3N=C2N4CCOCC4)C(=O)[O-].CCOC(CC1=CC=C(C=C1)OCCN2C(=O)C3=CC=CC=C3N=C2N4CCOCC4)C(=O)[O-].[Mg+2] FWPKZPBXZJYCCE-UHFFFAOYSA-L 0.000 claims description 7
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 7
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 7
- 229960003105 metformin Drugs 0.000 claims description 7
- RHLNBHVQUCRNKI-UHFFFAOYSA-M potassium;2-ethoxy-3-[4-[2-(2-ethyl-6-oxo-4-phenylpyrimidin-1-yl)ethoxy]phenyl]propanoate Chemical compound [K+].C1=CC(CC(OCC)C([O-])=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC RHLNBHVQUCRNKI-UHFFFAOYSA-M 0.000 claims description 7
- BHNOABDGWRVNFJ-ZSCHJXSPSA-N (2s)-2,6-diaminohexanoic acid;2-ethoxy-3-[4-[2-(2-ethyl-6-oxo-4-phenylpyrimidin-1-yl)ethoxy]phenyl]propanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.C1=CC(CC(OCC)C(O)=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC BHNOABDGWRVNFJ-ZSCHJXSPSA-N 0.000 claims description 6
- LTLZYEVVBNYXJJ-VWMHFEHESA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;2-ethoxy-3-[4-[2-(2-ethyl-6-oxo-4-phenylpyrimidin-1-yl)ethoxy]phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.C1=CC(CC(OCC)C(O)=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC LTLZYEVVBNYXJJ-VWMHFEHESA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 239000004475 Arginine Substances 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
- 235000009697 arginine Nutrition 0.000 claims description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 6
- VIHMMXMXJUBZLK-UHFFFAOYSA-L calcium;2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate Chemical compound [Ca+2].CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C([O-])=O)C=C1.CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C([O-])=O)C=C1 VIHMMXMXJUBZLK-UHFFFAOYSA-L 0.000 claims description 6
- YAJFHRPDYSJOTM-UHFFFAOYSA-M lithium;2-ethoxy-3-[4-[2-(2-ethyl-4-oxoquinazolin-3-yl)ethoxy]phenyl]propanoate Chemical compound [Li+].C1=CC(CC(OCC)C([O-])=O)=CC=C1OCCN1C(=O)C2=CC=CC=C2N=C1CC YAJFHRPDYSJOTM-UHFFFAOYSA-M 0.000 claims description 6
- JWXFVVCDYBJNIX-UHFFFAOYSA-M lithium;2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate Chemical compound [Li+].CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C([O-])=O)C=C1 JWXFVVCDYBJNIX-UHFFFAOYSA-M 0.000 claims description 6
- 235000018977 lysine Nutrition 0.000 claims description 6
- KGFHYUURPKAYFP-UHFFFAOYSA-L magnesium 3-[4-[2-(2-azido-4-oxoquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound [Mg++].CCOC(Cc1ccc(OCCn2c(N=[N+]=[N-])nc3ccccc3c2=O)cc1)C([O-])=O.CCOC(Cc1ccc(OCCn2c(N=[N+]=[N-])nc3ccccc3c2=O)cc1)C([O-])=O KGFHYUURPKAYFP-UHFFFAOYSA-L 0.000 claims description 6
- CWKXCPCLKVHOBR-UHFFFAOYSA-L magnesium;2-ethoxy-3-[4-[2-(2-ethyl-6-oxo-4-phenylpyrimidin-1-yl)ethoxy]phenyl]propanoate Chemical compound [Mg+2].C1=CC(CC(OCC)C([O-])=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC.C1=CC(CC(OCC)C([O-])=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC CWKXCPCLKVHOBR-UHFFFAOYSA-L 0.000 claims description 6
- PLIAHAHOOGEATK-UHFFFAOYSA-L magnesium;2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate Chemical compound [Mg+2].CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C([O-])=O)C=C1.CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C([O-])=O)C=C1 PLIAHAHOOGEATK-UHFFFAOYSA-L 0.000 claims description 6
- OVXHMIWSVYZPEY-UHFFFAOYSA-N n-cyclohexylcyclohexanamine;2-ethoxy-3-[4-[2-(2-ethyl-6-oxo-4-phenylpyrimidin-1-yl)ethoxy]phenyl]propanoic acid Chemical compound C1CCCCC1NC1CCCCC1.C1=CC(CC(OCC)C(O)=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC OVXHMIWSVYZPEY-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- KYFZPRNJKCLFBX-UHFFFAOYSA-M sodium;2-ethoxy-3-[4-[2-(2-ethyl-6-oxo-4-phenylpyrimidin-1-yl)ethoxy]phenyl]propanoate Chemical compound [Na+].C1=CC(CC(OCC)C([O-])=O)=CC=C1OCCN1C(=O)C=C(C=2C=CC=CC=2)N=C1CC KYFZPRNJKCLFBX-UHFFFAOYSA-M 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
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- JRZWZCNPHDSCRM-ZSCHJXSPSA-N (2s)-2,6-diaminohexanoic acid;2-ethoxy-3-[4-[2-(2-ethyl-4-oxoquinazolin-3-yl)ethoxy]phenyl]propanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.C1=CC(CC(OCC)C(O)=O)=CC=C1OCCN1C(=O)C2=CC=CC=C2N=C1CC JRZWZCNPHDSCRM-ZSCHJXSPSA-N 0.000 claims description 5
- LSTOEDCJTSIOHJ-ZSCHJXSPSA-N (2s)-2,6-diaminohexanoic acid;3-[4-[2-(1,5-dimethyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.CCCC1=NN(C)C(C2=O)=C1N=C(C)N2CCOC1=CC=C(CC(OCC)C(O)=O)C=C1 LSTOEDCJTSIOHJ-ZSCHJXSPSA-N 0.000 claims description 5
- UJSDOSZEZGTXNE-UHFFFAOYSA-N 2-aminoguanidine;3-[4-[2-(1,5-dimethyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound NN=C(N)N.CCCC1=NN(C)C(C2=O)=C1N=C(C)N2CCOC1=CC=C(CC(OCC)C(O)=O)C=C1 UJSDOSZEZGTXNE-UHFFFAOYSA-N 0.000 claims description 5
- WRUKUEDMHMSEJH-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-(2-ethyl-4-oxoquinazolin-3-yl)ethoxy]phenyl]propanoic acid;n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1.C1=CC(CC(OCC)C(O)=O)=CC=C1OCCN1C(=O)C2=CC=CC=C2N=C1CC WRUKUEDMHMSEJH-UHFFFAOYSA-N 0.000 claims description 5
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- 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
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Reproductive Health (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26659501P | 2001-02-05 | 2001-02-05 | |
| US60/266,595 | 2001-02-05 | ||
| IN813CH2001 | 2001-10-04 | ||
| IN813/MAS/2001 | 2001-10-04 | ||
| PCT/IB2002/000312 WO2002062798A2 (en) | 2001-02-05 | 2002-02-05 | Salts of pyrimidine derivatives for use against coronary heart disease and atherosclerose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2436738A1 true CA2436738A1 (en) | 2002-08-15 |
Family
ID=26324876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002436738A Abandoned CA2436738A1 (en) | 2001-02-05 | 2002-02-05 | Salts of pyrimidine derivatives for use against coronary heart disease and atherosclerose |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1363913A2 (enExample) |
| JP (1) | JP2004520393A (enExample) |
| CA (1) | CA2436738A1 (enExample) |
| WO (1) | WO2002062798A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| WO2001082916A2 (en) | 2000-05-03 | 2001-11-08 | Tularik Inc. | Combination therapeutic compositions and methods of use |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| EP1398032A1 (en) * | 2002-09-10 | 2004-03-17 | PheneX Pharmaceuticals AG | 4-Oxo-quinazolines as LXR nuclear receptor binding compounds |
| EP1407774A1 (en) * | 2002-09-10 | 2004-04-14 | LION Bioscience AG | 2-Amino-4-quinazolinones as LXR nuclear receptor binding compounds |
| US7820682B2 (en) | 2002-10-03 | 2010-10-26 | Ono Pharmaceutical Co., Ltd. | LPA receptor antagonist |
| US7550590B2 (en) * | 2003-03-25 | 2009-06-23 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| CN104202977A (zh) * | 2012-03-22 | 2014-12-10 | 转化技术制药有限责任公司 | 小分子glp1r激动剂的三(羟甲基)氨基甲烷盐及其药物组合物和用途 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE246190T1 (de) * | 1996-12-31 | 2003-08-15 | Reddys Lab Ltd Dr | Heterozyklische verbindungen, verfahren zu ihrer herstellung, pharmazeutische zusammensetzungen die diese enthalten und ihre anwendung in der behandlung von diabetis und verwandten krankheiten |
| DE69828445D1 (de) * | 1998-04-23 | 2005-02-03 | Reddys Lab Ltd Dr | Heterozyklische verbindungen,und deren verwendung in arzneimittel,verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammenstellungen |
-
2002
- 2002-02-05 CA CA002436738A patent/CA2436738A1/en not_active Abandoned
- 2002-02-05 WO PCT/IB2002/000312 patent/WO2002062798A2/en not_active Ceased
- 2002-02-05 EP EP02711124A patent/EP1363913A2/en not_active Withdrawn
- 2002-02-05 JP JP2002563151A patent/JP2004520393A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002062798A2 (en) | 2002-08-15 |
| WO2002062798A3 (en) | 2002-12-05 |
| EP1363913A2 (en) | 2003-11-26 |
| JP2004520393A (ja) | 2004-07-08 |
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| Date | Code | Title | Description |
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