SK62003A3 - A combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes - Google Patents

A combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes Download PDF

Info

Publication number: SK62003A3
Authority: SK; Slovakia
Prior art keywords: group; alkyl; aryl; hydrogen; alicyclic
Prior art date: 2000-07-06

Application number

SK6-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Poelje Paul D Van

Mark D Erion

Toshihiko Fujiwara

Original Assignee

Metabasis Therapeutics Inc

Sankyo Co

Priority date (The priority date 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 date listed.)

2000-07-06

Filing date

2001-07-05

Publication date

2003-09-11

2001-07-05 Application filed by Metabasis Therapeutics Inc, Sankyo Co filed Critical Metabasis Therapeutics Inc

2003-09-11 Publication of SK62003A3 publication Critical patent/SK62003A3/sk

Links

239000003112 inhibitor Substances 0.000 title claims abstract description 85
101710099475 3'-phosphoadenosine 5'-phosphate phosphatase Proteins 0.000 title claims abstract description 61
101710196411 Fructose-1,6-bisphosphatase Proteins 0.000 title claims abstract description 61
101710186733 Fructose-1,6-bisphosphatase, chloroplastic Proteins 0.000 title claims abstract description 61
101710109119 Fructose-1,6-bisphosphatase, cytosolic Proteins 0.000 title claims abstract description 61
101710198902 Fructose-1,6-bisphosphate aldolase/phosphatase Proteins 0.000 title claims abstract description 61
239000003472 antidiabetic agent Substances 0.000 title claims abstract description 46
229940125708 antidiabetic agent Drugs 0.000 title claims abstract description 45
206010012601 diabetes mellitus Diseases 0.000 title claims description 30
238000011282 treatment Methods 0.000 title claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 576
239000001257 hydrogen Substances 0.000 claims description 569
125000000217 alkyl group Chemical group 0.000 claims description 518
125000003118 aryl group Chemical group 0.000 claims description 492
125000004122 cyclic group Chemical group 0.000 claims description 264
125000003710 aryl alkyl group Chemical group 0.000 claims description 255
125000002723 alicyclic group Chemical group 0.000 claims description 253
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 241
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 225
125000001072 heteroaryl group Chemical group 0.000 claims description 171
125000004429 atom Chemical group 0.000 claims description 150
150000001875 compounds Chemical class 0.000 claims description 148
-1 substituted Chemical class 0.000 claims description 140
125000005842 heteroatom Chemical group 0.000 claims description 134
229910052736 halogen Inorganic materials 0.000 claims description 132
150000002367 halogens Chemical class 0.000 claims description 130
125000004093 cyano group Chemical group *C#N 0.000 claims description 102
125000003107 substituted aryl group Chemical group 0.000 claims description 91
229910052721 tungsten Inorganic materials 0.000 claims description 82
229910052717 sulfur Inorganic materials 0.000 claims description 78
229910052760 oxygen Inorganic materials 0.000 claims description 76
125000000304 alkynyl group Chemical group 0.000 claims description 72
239000000651 prodrug Substances 0.000 claims description 72
229940002612 prodrug Drugs 0.000 claims description 72
125000003342 alkenyl group Chemical group 0.000 claims description 70
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 66
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 62
PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 61
125000006165 cyclic alkyl group Chemical group 0.000 claims description 61
229910052799 carbon Inorganic materials 0.000 claims description 55
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
125000004432 carbon atom Chemical group C* 0.000 claims description 51
238000000034 method Methods 0.000 claims description 49
229910052698 phosphorus Inorganic materials 0.000 claims description 49
125000005843 halogen group Chemical group 0.000 claims description 47
150000003839 salts Chemical class 0.000 claims description 47
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 43
125000002947 alkylene group Chemical group 0.000 claims description 42
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 42
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 38
125000000623 heterocyclic group Chemical group 0.000 claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 31
239000011574 phosphorus Substances 0.000 claims description 31
125000001188 haloalkyl group Chemical group 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 29
229940122199 Insulin secretagogue Drugs 0.000 claims description 28
150000001721 carbon Chemical group 0.000 claims description 28
125000001543 furan-2,5-diyl group Chemical group O1C(=CC=C1*)* 0.000 claims description 28
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 28
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 26
102000004877 Insulin Human genes 0.000 claims description 26
108090001061 Insulin Proteins 0.000 claims description 26
229940100389 Sulfonylurea Drugs 0.000 claims description 26
239000008103 glucose Substances 0.000 claims description 26
229940125396 insulin Drugs 0.000 claims description 26
125000004423 acyloxy group Chemical group 0.000 claims description 24
239000003795 chemical substances by application Substances 0.000 claims description 24
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 24
101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
125000000753 cycloalkyl group Chemical group 0.000 claims description 21
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 21
239000000203 mixture Substances 0.000 claims description 21
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 20
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 19
125000004437 phosphorous atom Chemical group 0.000 claims description 19
125000006413 ring segment Chemical group 0.000 claims description 17
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 16
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
125000001424 substituent group Chemical group 0.000 claims description 16
150000003462 sulfoxides Chemical class 0.000 claims description 16
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 15
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 15
125000004414 alkyl thio group Chemical group 0.000 claims description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
125000005041 acyloxyalkyl group Chemical group 0.000 claims description 14
125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 14
150000002148 esters Chemical group 0.000 claims description 14
125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 13
229910052711 selenium Inorganic materials 0.000 claims description 13
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 12
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 12
125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 claims description 12
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
229940123208 Biguanide Drugs 0.000 claims description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
125000004103 aminoalkyl group Chemical group 0.000 claims description 11
230000002440 hepatic effect Effects 0.000 claims description 11
229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 10
FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 claims description 10
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 10
229960004580 glibenclamide Drugs 0.000 claims description 10
229960001381 glipizide Drugs 0.000 claims description 10
ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 claims description 10
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims description 10
125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 10
229960002354 repaglinide Drugs 0.000 claims description 10
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
238000001727 in vivo Methods 0.000 claims description 9
125000005647 linker group Chemical group 0.000 claims description 9
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 9
229960003105 metformin Drugs 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
102000051325 Glucagon Human genes 0.000 claims description 8
108060003199 Glucagon Proteins 0.000 claims description 8
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 8
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 8
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 8
229960004666 glucagon Drugs 0.000 claims description 8
ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 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
XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 7
125000003282 alkyl amino group Chemical group 0.000 claims description 7
150000001409 amidines Chemical class 0.000 claims description 7
239000005557 antagonist Substances 0.000 claims description 7
239000004202 carbamide Substances 0.000 claims description 7
230000009229 glucose formation Effects 0.000 claims description 7
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
238000000338 in vitro Methods 0.000 claims description 7
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
229960003243 phenformin Drugs 0.000 claims description 7
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical group O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 6
108010086800 Glucose-6-Phosphatase Proteins 0.000 claims description 6
102000003638 Glucose-6-Phosphatase Human genes 0.000 claims description 6
229960002632 acarbose Drugs 0.000 claims description 6
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
235000014113 dietary fatty acids Nutrition 0.000 claims description 6
239000000194 fatty acid Substances 0.000 claims description 6
229930195729 fatty acid Natural products 0.000 claims description 6
150000004665 fatty acids Chemical class 0.000 claims description 6
230000003647 oxidation Effects 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
102000007390 Glycogen Phosphorylase Human genes 0.000 claims description 5
108010046163 Glycogen Phosphorylase Proteins 0.000 claims description 5
108010041872 Islet Amyloid Polypeptide Proteins 0.000 claims description 5
102000036770 Islet Amyloid Polypeptide Human genes 0.000 claims description 5
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 5
201000001421 hyperglycemia Diseases 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 5
125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 4
229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 claims description 4
208000008589 Obesity Diseases 0.000 claims description 4
125000005275 alkylenearyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
125000000168 pyrrolyl group Chemical group 0.000 claims description 4
150000007970 thio esters Chemical group 0.000 claims description 4
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 3
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 3
125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 3
125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 3
125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000004475 heteroaralkyl group Chemical group 0.000 claims description 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
210000004185 liver Anatomy 0.000 claims description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
235000020824 obesity Nutrition 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000000335 thiazolyl group Chemical group 0.000 claims description 3
125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 2
208000003569 Central serous chorioretinopathy Diseases 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
150000001413 amino acids Chemical class 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 104
239000008194 pharmaceutical composition Substances 0.000 claims 69
AFOGBLYPWJJVAL-UHFFFAOYSA-N phenbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=CC=C1 AFOGBLYPWJJVAL-UHFFFAOYSA-N 0.000 claims 39
229950008557 phenbutamide Drugs 0.000 claims 39
102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims 19
241000124008 Mammalia Species 0.000 claims 16
FFEKJBVVAJTQST-WLHGVMLRSA-N (e)-but-2-enedioic acid;1,1-dimethyl-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound OC(=O)\C=C\C(O)=O.CN(C)C(N)=NC1=CC=CC=C1N1CCOCC1 FFEKJBVVAJTQST-WLHGVMLRSA-N 0.000 claims 9
BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 claims 9
LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 claims 9
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 claims 9
JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 claims 9
229960001466 acetohexamide Drugs 0.000 claims 9
VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 claims 9
229960001761 chlorpropamide Drugs 0.000 claims 9
229960001764 glibornuride Drugs 0.000 claims 9
RMTYNAPTNBJHQI-LLDVTBCESA-N glibornuride Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)N[C@H]1[C@H](C2(C)C)CC[C@@]2(C)[C@H]1O RMTYNAPTNBJHQI-LLDVTBCESA-N 0.000 claims 9
229960000346 gliclazide Drugs 0.000 claims 9
229960003468 gliquidone Drugs 0.000 claims 9
229960003236 glisoxepide Drugs 0.000 claims 9
ZKUDBRCEOBOWLF-UHFFFAOYSA-N glisoxepide Chemical compound O1C(C)=CC(C(=O)NCCC=2C=CC(=CC=2)S(=O)(=O)NC(=O)NN2CCCCCC2)=N1 ZKUDBRCEOBOWLF-UHFFFAOYSA-N 0.000 claims 9
NFRPNQDSKJJQGV-UHFFFAOYSA-N glyhexamide Chemical compound C=1C=C2CCCC2=CC=1S(=O)(=O)NC(=O)NC1CCCCC1 NFRPNQDSKJJQGV-UHFFFAOYSA-N 0.000 claims 9
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- A61P3/08—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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (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)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Epidemiology (AREA)
Obesity (AREA)
Hematology (AREA)
Child & Adolescent Psychology (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK6-2003A 2000-07-06 2001-07-05 A combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes SK62003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US21653100P	2000-07-06	2000-07-06
PCT/US2001/021557 WO2002003978A2 (fr)	2000-07-06	2001-07-05	Combinaison d'inhibiteurs de fbpase et d'agents antidiabetiques utile pour le traitement du diabete

Publications (1)

Publication Number	Publication Date
SK62003A3 true SK62003A3 (en)	2003-09-11

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SK6-2003A SK62003A3 (en)	2000-07-06	2001-07-05	A combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes

Country Status (18)

Country	Link
EP (1)	EP1372660A2 (fr)
JP (1)	JP2004508297A (fr)
KR (1)	KR100854851B1 (fr)
CN (2)	CN101301294A (fr)
AU (2)	AU7327101A (fr)
BR (1)	BR0112212A (fr)
CA (1)	CA2412142A1 (fr)
CZ (1)	CZ20035A3 (fr)
HU (1)	HUP0301830A3 (fr)
IL (2)	IL153513A0 (fr)
MX (1)	MXPA02012713A (fr)
NO (1)	NO20030034L (fr)
NZ (1)	NZ523227A (fr)
PL (1)	PL365779A1 (fr)
RU (1)	RU2328308C2 (fr)
SK (1)	SK62003A3 (fr)
WO (1)	WO2002003978A2 (fr)
ZA (1)	ZA200300044B (fr)

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US7048906B2 (en)	1995-05-17	2006-05-23	Cedars-Sinai Medical Center	Methods of diagnosing and treating small intestinal bacterial overgrowth (SIBO) and SIBO-related conditions
US6284748B1 (en)	1997-03-07	2001-09-04	Metabasis Therapeutics, Inc.	Purine inhibitors of fructose 1,6-bisphosphatase
EP1112275B9 (fr)	1998-09-09	2004-03-10	Metabasis Therapeutics, Inc.	Nouveaux inhibiteurs heteroaromatiques de fructose-1,6-biphosphatase
PL357251A1 (en)	2000-03-08	2004-07-26	Metabasis Therapeutics, Inc.	Novel aryl fructose-1,6-bisphosphatase inhibitors
US7563774B2 (en)	2000-06-29	2009-07-21	Metabasis Therapeutics, Inc.	Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
DE60230818D1 (de)	2001-09-24	2009-02-26	Imp Innovations Ltd	Pyy3-36 zur zur reduzierung oder vorbeugung von fettleibigkeit
EP1474163A2 (fr)	2002-01-10	2004-11-10	Imperial College Innovations Limited	Modification des habitudes alimentaires
GB0300571D0 (en)	2003-01-10	2003-02-12	Imp College Innovations Ltd	Modification of feeding behaviour
AU2004309279B2 (en)	2003-12-26	2010-07-15	Kyowa Kirin Co., Ltd.	Thiazole derivative
JP2008510018A (ja) *	2004-08-18	2008-04-03	メタバシス・セラピューティクス・インコーポレイテッド	フルクトース−１，６−ビスホスファターゼの新規チアゾール阻害物質
KR20070086007A (ko) *	2004-12-13	2007-08-27	다이이찌 산쿄 가부시키가이샤	당뇨병의 치료를 위한 의약 조성물
TW200738245A (en) *	2005-08-22	2007-10-16	Sankyo Co	Pharmaceutical composition containing FBPase inhibitor
WO2007129522A1 (fr) *	2006-04-10	2007-11-15	Daiichi Sankyo Company, Limited	Préparation obtenue par voie sèche
EP2089017A2 (fr)	2006-11-02	2009-08-19	Aestus Therapeutics, Inc.	Procédés de traitement de la douleur neuropathique par la modulation des voies de la glycogénolyse ou de la glycolyse
TWI428346B (zh)	2006-12-13	2014-03-01	Imp Innovations Ltd	新穎化合物及其等對進食行為影響
CN107312039B (zh)	2012-08-30	2019-06-25	江苏豪森药业集团有限公司	一种替诺福韦前药的制备方法
TWI606848B (zh) *	2012-10-08	2017-12-01	Ｌｇ生命科學股份有限公司	包含格米列汀與美氟明的組合藥物及其製備方法
CN104788350A (zh) *	2014-01-22	2015-07-22	天津大学	一种通过快速冷却结晶法获得甲糖宁药用优势晶型的方法
CN106831437B (zh) *	2016-02-03	2019-06-21	华中师范大学	含硝基乙烯基的酯类化合物及其制备方法和应用
CN114907285B (zh) *	2021-02-10	2023-09-22	华中师范大学	酰化糖精类化合物及其制备方法和应用、降血糖药物

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2001
- 2001-07-05 CZ CZ20035A patent/CZ20035A3/cs unknown
- 2001-07-05 CN CNA200810098112XA patent/CN101301294A/zh active Pending
- 2001-07-05 KR KR1020037000126A patent/KR100854851B1/ko not_active Expired - Fee Related
- 2001-07-05 AU AU7327101A patent/AU7327101A/xx active Pending
- 2001-07-05 BR BR0112212-6A patent/BR0112212A/pt not_active IP Right Cessation
- 2001-07-05 EP EP01952530A patent/EP1372660A2/fr not_active Withdrawn
- 2001-07-05 NZ NZ523227A patent/NZ523227A/en not_active IP Right Cessation
- 2001-07-05 IL IL15351301A patent/IL153513A0/xx unknown
- 2001-07-05 CN CNB018149243A patent/CN100396283C/zh not_active Expired - Fee Related
- 2001-07-05 RU RU2003103436/15A patent/RU2328308C2/ru not_active IP Right Cessation
- 2001-07-05 HU HU0301830A patent/HUP0301830A3/hu unknown
- 2001-07-05 MX MXPA02012713A patent/MXPA02012713A/es not_active Application Discontinuation
- 2001-07-05 SK SK6-2003A patent/SK62003A3/sk unknown
- 2001-07-05 JP JP2002508433A patent/JP2004508297A/ja active Pending
- 2001-07-05 CA CA002412142A patent/CA2412142A1/fr not_active Abandoned
- 2001-07-05 WO PCT/US2001/021557 patent/WO2002003978A2/fr not_active Ceased
- 2001-07-05 AU AU2001273271A patent/AU2001273271B2/en not_active Ceased
- 2001-07-05 PL PL01365779A patent/PL365779A1/xx unknown
2002
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2003
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Also Published As

Publication number	Publication date
WO2002003978A3 (fr)	2003-10-16
NO20030034D0 (no)	2003-01-03
HUP0301830A3 (en)	2007-10-29
CA2412142A1 (fr)	2002-01-17
IL153513A (en)	2014-07-31
WO2002003978A2 (fr)	2002-01-17
ZA200300044B (en)	2004-05-06
HUP0301830A2 (hu)	2003-11-28
KR20030031952A (ko)	2003-04-23
AU2001273271B2 (en)	2006-01-05
JP2004508297A (ja)	2004-03-18
IL153513A0 (en)	2003-07-06
NO20030034L (no)	2003-03-05
CN100396283C (zh)	2008-06-25
CZ20035A3 (cs)	2003-05-14
MXPA02012713A (es)	2004-09-10
CN101301294A (zh)	2008-11-12
AU7327101A (en)	2002-01-21
EP1372660A2 (fr)	2004-01-02
BR0112212A (pt)	2003-12-30
RU2328308C2 (ru)	2008-07-10
PL365779A1 (en)	2005-01-10
NZ523227A (en)	2005-04-29
CN1599612A (zh)	2005-03-23
KR100854851B1 (ko)	2008-08-27

Publication	Publication Date	Title
US20090197836A1 (en)	2009-08-06	Combination of FBPase Inhibitors and Antidiabetic Agents Useful for the Treatment of Diabetes
KR100854851B1 (ko)	2008-08-27	당뇨병 치료에 유용한 ＦＢＰａｓｅ 억제제와 항당뇨제의조합물
CN100352505C (zh)	2007-12-05	治疗糖尿病的fbp酶抑制剂与胰岛素致敏剂的组合
US20080004226A1 (en)	2008-01-03	Combination of FBPase Inhibitors and Insulin Sensitizers for the Treatment of Diabetes
AU2001273271A1 (en)	2002-04-18	A combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
SK8892002A3 (en)	2003-04-01	Novel bisamidate phosphonate prodrugs, process for their preparation and use thereof
NZ510209A (en)	2003-07-25	Method for treating diabetes, insulin resistance, hyperglycaemia, elevated fatty acids, or hypertriglyceridemia with an aP2 inhibitor in combination with another antidiabetic agent
EP2351567B1 (fr)	2017-11-22	Composition pharmaceutique et medicament pour la prevention et le traitement de diabetes ou de l'obesite comprenant comme principe actif, un compose qui inhibe l'activation de dipeptidyl peptidase-iv
AU2006201410A1 (en)	2006-04-27	A combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
US20100056460A1 (en)	2010-03-04	Combination of organic compounds
HK1075622A (en)	2005-12-23	A combination of fbpase inhibitors and insulin sensitizers for the treatment of diabetes
ERION	2012	QUN DANG*, PAUL D. VAN POELJE AND

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2010-11-08	FB9A	Suspension of patent application procedure