CA2436741A1 - Aryl substituted alkylcarboxylic acids as hypocholesterolemic agents - Google Patents
Aryl substituted alkylcarboxylic acids as hypocholesterolemic agents Download PDFInfo
- Publication number
- CA2436741A1 CA2436741A1 CA002436741A CA2436741A CA2436741A1 CA 2436741 A1 CA2436741 A1 CA 2436741A1 CA 002436741 A CA002436741 A CA 002436741A CA 2436741 A CA2436741 A CA 2436741A CA 2436741 A1 CA2436741 A1 CA 2436741A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- compound
- ethoxy
- formula
- aralkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000003118 aryl group Chemical group 0.000 title claims description 134
- 239000002253 acid Substances 0.000 title abstract description 38
- 150000007513 acids Chemical class 0.000 title abstract description 12
- 239000003529 anticholesteremic agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 275
- 150000003839 salts Chemical class 0.000 claims abstract description 89
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 239000012453 solvate Substances 0.000 claims abstract description 30
- -1 aralkanoyl Chemical group 0.000 claims description 365
- 125000000217 alkyl group Chemical group 0.000 claims description 146
- 239000001257 hydrogen Substances 0.000 claims description 146
- 229910052739 hydrogen Inorganic materials 0.000 claims description 146
- 125000000623 heterocyclic group Chemical group 0.000 claims description 125
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 121
- 125000001072 heteroaryl group Chemical group 0.000 claims description 109
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 94
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 92
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 90
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
- 125000003545 alkoxy group Chemical group 0.000 claims description 88
- 229910052736 halogen Inorganic materials 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 73
- 150000002367 halogens Chemical group 0.000 claims description 72
- 125000004104 aryloxy group Chemical group 0.000 claims description 71
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 70
- 125000001769 aryl amino group Chemical group 0.000 claims description 66
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 66
- 125000001589 carboacyl group Chemical group 0.000 claims description 61
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 60
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 60
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 53
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 52
- 125000003435 aroyl group Chemical group 0.000 claims description 51
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 50
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
- 238000002360 preparation method Methods 0.000 claims description 48
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 46
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 45
- 125000004414 alkyl thio group Chemical group 0.000 claims description 43
- 125000004001 thioalkyl group Chemical group 0.000 claims description 43
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 41
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 41
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 40
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- 229910052760 oxygen Inorganic materials 0.000 claims description 38
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 37
- 125000004423 acyloxy group Chemical group 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 35
- 206010022489 Insulin Resistance Diseases 0.000 claims description 31
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 30
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 30
- 229910052708 sodium Inorganic materials 0.000 claims description 28
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 27
- 208000008589 Obesity Diseases 0.000 claims description 26
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 26
- 235000020824 obesity Nutrition 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 239000004475 Arginine Substances 0.000 claims description 25
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 25
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 25
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 25
- 239000004472 Lysine Substances 0.000 claims description 25
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 25
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 25
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 25
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 25
- 229910052749 magnesium Inorganic materials 0.000 claims description 25
- 229910052700 potassium Inorganic materials 0.000 claims description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 24
- 206010020772 Hypertension Diseases 0.000 claims description 24
- 125000004442 acylamino group Chemical group 0.000 claims description 24
- 229910052791 calcium Inorganic materials 0.000 claims description 24
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 24
- 229960001231 choline Drugs 0.000 claims description 24
- 229910052744 lithium Inorganic materials 0.000 claims description 24
- 239000011777 magnesium Substances 0.000 claims description 24
- 150000003863 ammonium salts Chemical class 0.000 claims description 23
- 239000011575 calcium Substances 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 208000029078 coronary artery disease Diseases 0.000 claims description 22
- 125000004122 cyclic group Chemical group 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 229920001268 Cholestyramine Polymers 0.000 claims description 20
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 20
- 235000001968 nicotinic acid Nutrition 0.000 claims description 20
- 229960003512 nicotinic acid Drugs 0.000 claims description 20
- 239000011664 nicotinic acid Substances 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- 229920002911 Colestipol Polymers 0.000 claims description 19
- 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 19
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 19
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 claims description 19
- 229960002604 colestipol Drugs 0.000 claims description 19
- 239000008103 glucose Substances 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 19
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 19
- 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 19
- 229960003912 probucol Drugs 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 229940125753 fibrate Drugs 0.000 claims description 18
- 208000017169 kidney disease Diseases 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- 201000001320 Atherosclerosis Diseases 0.000 claims description 17
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 17
- 208000001132 Osteoporosis Diseases 0.000 claims description 16
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 16
- 208000011580 syndromic disease Diseases 0.000 claims description 16
- 150000003626 triacylglycerols Chemical class 0.000 claims description 16
- 102000016267 Leptin Human genes 0.000 claims description 15
- 108010092277 Leptin Proteins 0.000 claims description 15
- 206010036049 Polycystic ovaries Diseases 0.000 claims description 15
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 15
- 229910052786 argon Inorganic materials 0.000 claims description 15
- 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 15
- 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 15
- 229940039781 leptin Drugs 0.000 claims description 15
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 15
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 15
- 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 14
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 13
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 13
- 108010069201 VLDL Cholesterol Proteins 0.000 claims description 13
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 235000021588 free fatty acids Nutrition 0.000 claims description 13
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 12
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 12
- 108010028554 LDL Cholesterol Proteins 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 10
- 208000002249 Diabetes Complications Diseases 0.000 claims description 10
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 239000000556 agonist Substances 0.000 claims description 10
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 238000011321 prophylaxis Methods 0.000 claims description 10
- RUFUUNYWEHLOBL-UHFFFAOYSA-N 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound CCCC1=NN(C)C(C(N2CCOC=3C=CC(CC(OCC)C(O)=O)=CC=3)=O)=C1N=C2CC1=CC=CC=C1 RUFUUNYWEHLOBL-UHFFFAOYSA-N 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 206010012289 Dementia Diseases 0.000 claims description 9
- 206010012655 Diabetic complications Diseases 0.000 claims description 9
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 9
- 206010033645 Pancreatitis Diseases 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 9
- 208000017442 Retinal disease Diseases 0.000 claims description 9
- 206010038923 Retinopathy Diseases 0.000 claims description 9
- 206010048214 Xanthoma Diseases 0.000 claims description 9
- 206010048215 Xanthomatosis Diseases 0.000 claims description 9
- 230000020411 cell activation Effects 0.000 claims description 9
- 238000007796 conventional method Methods 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 210000002889 endothelial cell Anatomy 0.000 claims description 9
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 9
- 201000001421 hyperglycemia Diseases 0.000 claims description 9
- 230000001631 hypertensive effect Effects 0.000 claims description 9
- 201000009925 nephrosclerosis Diseases 0.000 claims description 9
- 235000019260 propionic acid Nutrition 0.000 claims description 9
- 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 8
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 206010068871 Myotonic dystrophy Diseases 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 230000008289 pathophysiological mechanism Effects 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- MEXINNDTWUQJLN-UHFFFAOYSA-N 3-[4-[2-(1,5-dimethyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(C)N2CCOC(C=C1)=CC=C1CC(C(O)=O)OC1=CC=CC=C1 MEXINNDTWUQJLN-UHFFFAOYSA-N 0.000 claims description 7
- DRPVKFGJSHSDFA-UHFFFAOYSA-N 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC(C=C1)=CC=C1CC(C(O)=O)OC1=CC=CC=C1 DRPVKFGJSHSDFA-UHFFFAOYSA-N 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 230000003301 hydrolyzing effect Effects 0.000 claims description 7
- 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 6
- IXVLDWMUCMXRBE-UHFFFAOYSA-N 3-[4-[2-(1-methyl-7-oxo-3,5-dipropylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(CCC)N2CCOC(C=C1)=CC=C1CC(C(O)=O)OC1=CC=CC=C1 IXVLDWMUCMXRBE-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 6
- UZPMGYAFUIMKJY-UHFFFAOYSA-N ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound CCCC1=NN(C)C(C(N2CCOC=3C=CC(CC(OCC)C(=O)OCC)=CC=3)=O)=C1N=C2CC1=CC=CC=C1 UZPMGYAFUIMKJY-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 239000003288 aldose reductase inhibitor Substances 0.000 claims description 5
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 230000003920 cognitive function Effects 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- WFVCDQKXRSVQLS-UHFFFAOYSA-N ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oxo-3,5-dipropylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(CCC)N2CCOC1=CC=C(CC(OCC)C(=O)OCC)C=C1 WFVCDQKXRSVQLS-UHFFFAOYSA-N 0.000 claims description 5
- NGMTUSGXHQCOBY-UHFFFAOYSA-N ethyl 2-ethoxy-3-[4-[2-[1-methyl-7-oxo-3-propyl-5-(trifluoromethyl)pyrazolo[4,3-d]pyrimidin-6-yl]ethoxy]phenyl]propanoate Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(C(F)(F)F)N2CCOC1=CC=C(CC(OCC)C(=O)OCC)C=C1 NGMTUSGXHQCOBY-UHFFFAOYSA-N 0.000 claims description 5
- ALSHATAKPJWDIL-UHFFFAOYSA-N ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(C)N2CCOC(C=C1)=CC=C1CC(C(=O)OCC)OC1=CC=CC=C1 ALSHATAKPJWDIL-UHFFFAOYSA-N 0.000 claims description 5
- JBTCMKNCZRWNIH-UHFFFAOYSA-N ethyl 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC(C=C1)=CC=C1CC(C(=O)OCC)OC1=CC=CC=C1 JBTCMKNCZRWNIH-UHFFFAOYSA-N 0.000 claims description 5
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 5
- 239000006188 syrup Substances 0.000 claims description 5
- 235000020357 syrup Nutrition 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- SZIHXQXQPZLKOK-UHFFFAOYSA-N ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(CC)N2CCOC1=CC=C(CC(OCC)C(=O)OCC)C=C1 SZIHXQXQPZLKOK-UHFFFAOYSA-N 0.000 claims description 4
- RUKRXLNEIPWUSK-UHFFFAOYSA-N ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound CCCC1=NN(C)C(C2=O)=C1N=C(C)N2CCOC1=CC=C(CC(OCC)C(=O)OCC)C=C1 RUKRXLNEIPWUSK-UHFFFAOYSA-N 0.000 claims description 4
- VUDNLHWOTCGUON-UHFFFAOYSA-N ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propylpyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate Chemical compound CCCC1=NN(C)C(C(N2CCOC=3C=CC(CC(OC=4C=CC=CC=4)C(=O)OCC)=CC=3)=O)=C1N=C2CC1=CC=CC=C1 VUDNLHWOTCGUON-UHFFFAOYSA-N 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 125000004957 naphthylene group Chemical group 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 2
- 150000008064 anhydrides Chemical group 0.000 claims description 2
- 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 52
- 159000000013 aluminium salts Chemical class 0.000 claims 23
- 206010018364 Glomerulonephritis Diseases 0.000 claims 7
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Classifications
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- 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
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- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
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- Biomedical Technology (AREA)
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- Urology & Nephrology (AREA)
- Dermatology (AREA)
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- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (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 | ||
| IN569CH2001 | 2001-07-10 | ||
| IN569/MAS/2001 | 2001-07-10 | ||
| PCT/IB2002/000342 WO2002062799A1 (en) | 2001-02-05 | 2002-02-05 | Aryl substituted alkylcarboxylic acids as hypocholesterolemic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2436741A1 true CA2436741A1 (en) | 2002-08-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002436741A Abandoned CA2436741A1 (en) | 2001-02-05 | 2002-02-05 | Aryl substituted alkylcarboxylic acids as hypocholesterolemic agents |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1363914A1 (enExample) |
| JP (1) | JP2004534733A (enExample) |
| CA (1) | CA2436741A1 (enExample) |
| WO (1) | WO2002062799A1 (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| HN2002000317A (es) * | 2001-11-02 | 2003-05-21 | Pfizer | Inhibidores de pde9 para tratamiento de trastornos cardiovasculares |
| US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| EP2305352A1 (en) | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | 5-alpha-reductase inhibitors for use in the treatment of men with metabolic and anthropometric disorders |
| EP1793828A4 (en) * | 2004-09-06 | 2009-09-02 | Reddys Lab Ltd Dr | FIBRATE CONNECTION WITH PRAR AGONIST ACTIVITY |
| US7674822B2 (en) | 2004-11-24 | 2010-03-09 | Wyeth | PTP1b inhibitors |
| DK2170930T3 (da) | 2007-06-04 | 2012-11-05 | Synergy Pharmaceuticals Inc | Agonister af guanylatcyclase, anvendelige til behandlingen af gastrointestinale sygdomme, inflammation, cancer og andre sygdomme |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2328910B1 (en) | 2008-06-04 | 2014-08-06 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| ES2624828T3 (es) | 2008-07-16 | 2017-07-17 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros |
| US8410284B2 (en) | 2008-10-22 | 2013-04-02 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| EP2362731B1 (en) | 2008-10-31 | 2016-04-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| JP2013520502A (ja) | 2010-02-25 | 2013-06-06 | メルク・シャープ・エンド・ドーム・コーポレイション | 有用な抗糖尿病薬である新規な環状ベンズイミダゾール誘導体 |
| US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| SG192941A1 (en) | 2011-02-25 | 2013-09-30 | Merck Sharp & Dohme | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| WO2013082106A1 (en) | 2011-12-02 | 2013-06-06 | The General Hospital Corporation | Differentiation into brown adipocytes |
| WO2014022528A1 (en) | 2012-08-02 | 2014-02-06 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| JP2016516004A (ja) | 2013-02-22 | 2016-06-02 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | 抗糖尿病二環式化合物 |
| EP2970119B1 (en) | 2013-03-14 | 2021-11-03 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| CA2905438A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| JP6606491B2 (ja) | 2013-06-05 | 2019-11-13 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼｃの超高純度アゴニスト、その作成および使用方法 |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2018106518A1 (en) | 2016-12-06 | 2018-06-14 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| WO2018118670A1 (en) | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0903343B1 (en) * | 1997-09-19 | 2003-05-28 | SSP Co., Ltd. | Alpha-Substituted phenylpropionic acid derivative and medicine containing the same |
| WO1999008501A2 (en) * | 1998-04-23 | 1999-02-25 | Dr. Reddy's Research Foundation | New heterocyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
-
2002
- 2002-02-05 JP JP2002563152A patent/JP2004534733A/ja active Pending
- 2002-02-05 EP EP02711126A patent/EP1363914A1/en not_active Withdrawn
- 2002-02-05 CA CA002436741A patent/CA2436741A1/en not_active Abandoned
- 2002-02-05 WO PCT/IB2002/000342 patent/WO2002062799A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004534733A (ja) | 2004-11-18 |
| WO2002062799A1 (en) | 2002-08-15 |
| EP1363914A1 (en) | 2003-11-26 |
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