JP2017515797A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2017515797A5 JP2017515797A5 JP2016560726A JP2016560726A JP2017515797A5 JP 2017515797 A5 JP2017515797 A5 JP 2017515797A5 JP 2016560726 A JP2016560726 A JP 2016560726A JP 2016560726 A JP2016560726 A JP 2016560726A JP 2017515797 A5 JP2017515797 A5 JP 2017515797A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- oxo
- membered
- pyrrolidin
- cyclopropylmethoxy
- 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
- 150000001875 compounds Chemical class 0.000 claims 21
- 239000003112 inhibitor Substances 0.000 claims 20
- 229910052731 fluorine Inorganic materials 0.000 claims 17
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 13
- 229910052801 chlorine Inorganic materials 0.000 claims 13
- 229910052739 hydrogen Inorganic materials 0.000 claims 11
- 229910052794 bromium Inorganic materials 0.000 claims 10
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 125000000623 heterocyclic group Chemical group 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 8
- 239000000556 agonist Substances 0.000 claims 7
- -1 cyclopropylmethoxy Chemical group 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 6
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- 229910052760 oxygen Inorganic materials 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 229910052717 sulfur Inorganic materials 0.000 claims 6
- 230000009977 dual effect Effects 0.000 claims 5
- 125000005842 heteroatom Chemical group 0.000 claims 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 5
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims 4
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims 4
- 102100040918 Pro-glucagon Human genes 0.000 claims 4
- 239000005557 antagonist Substances 0.000 claims 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 3
- DGENZVKCTGIDRZ-UHFFFAOYSA-N 3-[4-[(3-phenoxyphenyl)methylamino]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1NCC1=CC=CC(OC=2C=CC=CC=2)=C1 DGENZVKCTGIDRZ-UHFFFAOYSA-N 0.000 claims 3
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 claims 3
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims 3
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 3
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 3
- 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 3
- 229940044601 receptor agonist Drugs 0.000 claims 3
- 239000000018 receptor agonist Substances 0.000 claims 3
- 229960005486 vaccine Drugs 0.000 claims 3
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 claims 2
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 claims 2
- 108010064733 Angiotensins Proteins 0.000 claims 2
- 102000015427 Angiotensins Human genes 0.000 claims 2
- AASMFGPLTAEVSZ-MZVUKIKXSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)O)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)O)=O)=O AASMFGPLTAEVSZ-MZVUKIKXSA-N 0.000 claims 2
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 2
- 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 claims 2
- 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 claims 2
- 229940125827 GPR40 agonist Drugs 0.000 claims 2
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 claims 2
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 claims 2
- 102000016267 Leptin Human genes 0.000 claims 2
- 108010092277 Leptin Proteins 0.000 claims 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 229940126033 PPAR agonist Drugs 0.000 claims 2
- 102000001253 Protein Kinase Human genes 0.000 claims 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 2
- 230000003276 anti-hypertensive effect Effects 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000002308 endothelin receptor antagonist Substances 0.000 claims 2
- 239000002792 enkephalinase inhibitor Substances 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 229940039781 leptin Drugs 0.000 claims 2
- 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 2
- 235000020824 obesity Nutrition 0.000 claims 2
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 claims 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 108060006633 protein kinase Proteins 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 claims 2
- 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 compound 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 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims 1
- 229940124681 11 beta HSD inhibitor Drugs 0.000 claims 1
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 claims 1
- FODHWOBAQBTTFS-UHFFFAOYSA-N 3-[4-[2-(2-methylphenyl)ethynyl]phenyl]propanoic acid Chemical compound CC1=CC=CC=C1C#CC1=CC=C(CCC(O)=O)C=C1 FODHWOBAQBTTFS-UHFFFAOYSA-N 0.000 claims 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims 1
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 claims 1
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 claims 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 claims 1
- USKXYXPBOMGLLD-BDPMCISCSA-N 5-[(3R)-3-[6-(cyclopropylmethoxy)pyridin-3-yl]oxy-2-oxopyrrolidin-1-yl]-7-fluoro-N,N-dimethyl-3-oxo-1,2-dihydroindene-1-carboxamide Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C1)F)C(=O)N(C)C)=O)=O USKXYXPBOMGLLD-BDPMCISCSA-N 0.000 claims 1
- MPLLLQUZNJSVTK-UHFFFAOYSA-N 5-[3-[4-[2-(4-fluorophenyl)ethoxy]phenyl]propyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1CCCC(C=C1)=CC=C1OCCC1=CC=C(F)C=C1 MPLLLQUZNJSVTK-UHFFFAOYSA-N 0.000 claims 1
- HFDKKNHCYWNNNQ-YOGANYHLSA-N 75976-10-2 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C1=CC=C(O)C=C1 HFDKKNHCYWNNNQ-YOGANYHLSA-N 0.000 claims 1
- 239000005541 ACE inhibitor Substances 0.000 claims 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 claims 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 claims 1
- 229940121969 Aminopeptidase A inhibitor Drugs 0.000 claims 1
- 102000008873 Angiotensin II receptor Human genes 0.000 claims 1
- 108050000824 Angiotensin II receptor Proteins 0.000 claims 1
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims 1
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims 1
- 101100460776 Arabidopsis thaliana NPY2 gene Proteins 0.000 claims 1
- 101100460782 Arabidopsis thaliana NPY4 gene Proteins 0.000 claims 1
- 101100460788 Arabidopsis thaliana NPY5 gene Proteins 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims 1
- 102100034159 Beta-3 adrenergic receptor Human genes 0.000 claims 1
- 229940123208 Biguanide Drugs 0.000 claims 1
- BAVBIEINCBQCIS-XJQHNOHDSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)(CC(=O)OC)CC(=O)O)F)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)(CC(=O)OC)CC(=O)O)F)=O BAVBIEINCBQCIS-XJQHNOHDSA-N 0.000 claims 1
- CVOBRTBACYTQDG-MZVUKIKXSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)NC)F)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)NC)F)=O CVOBRTBACYTQDG-MZVUKIKXSA-N 0.000 claims 1
- ZOMGPSDHJAEBMP-VXNXSFHZSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)NCCO)F)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)NCCO)F)=O ZOMGPSDHJAEBMP-VXNXSFHZSA-N 0.000 claims 1
- PTCLXIBMVGZCLW-YBMSBYLISA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)O)F)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)O)F)=O PTCLXIBMVGZCLW-YBMSBYLISA-N 0.000 claims 1
- HDMJFZVQKWIGHK-MZVUKIKXSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)OC)F)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC(=C2CC(C(C2=C1)=O)CC(=O)OC)F)=O HDMJFZVQKWIGHK-MZVUKIKXSA-N 0.000 claims 1
- VHKCUZZKFAOONF-GFOWMXPYSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC=C2CC(C(C2=C1)=O)C(=O)OC)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC=C2CC(C(C2=C1)=O)C(=O)OC)=O VHKCUZZKFAOONF-GFOWMXPYSA-N 0.000 claims 1
- XCPFCMJLLCURTH-FBLFFUNLSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC=C2CC(C(C2=C1)=O)CC(=O)OC)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C1=CC=C2CC(C(C2=C1)=O)CC(=O)OC)=O XCPFCMJLLCURTH-FBLFFUNLSA-N 0.000 claims 1
- KHMVPLWHVHKWBX-MZVUKIKXSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(C(CC2=C(C1)F)CCO)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(C(CC2=C(C1)F)CCO)=O)=O KHMVPLWHVHKWBX-MZVUKIKXSA-N 0.000 claims 1
- YFFNGNRATOREJB-VCUSLETLSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(C(CC2=C(C=1)F)CC(=O)N1CCOCC1)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(C(CC2=C(C=1)F)CC(=O)N1CCOCC1)=O)=O YFFNGNRATOREJB-VCUSLETLSA-N 0.000 claims 1
- VQQIQCMLBFIJBI-VXNXSFHZSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C1)F)CC(=O)N(C)C)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C1)F)CC(=O)N(C)C)=O)=O VQQIQCMLBFIJBI-VXNXSFHZSA-N 0.000 claims 1
- PPBVJDCNPZEOLC-YBMSBYLISA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C1)F)CC(=O)O)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C1)F)CC(=O)O)=O)=O PPBVJDCNPZEOLC-YBMSBYLISA-N 0.000 claims 1
- KNCCRZYEOLWZSA-YBMSBYLISA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C=1)F)CO)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=C(C=1)F)CO)=O)=O KNCCRZYEOLWZSA-YBMSBYLISA-N 0.000 claims 1
- HOBNXWPWQJXRMG-IRCUZVAFSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)N(C)C)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)N(C)C)=O)=O HOBNXWPWQJXRMG-IRCUZVAFSA-N 0.000 claims 1
- PPAPEDJRDXEEMY-VXNXSFHZSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)NC)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)NC)=O)=O PPAPEDJRDXEEMY-VXNXSFHZSA-N 0.000 claims 1
- JMNSEEZJYUMJBG-VXNXSFHZSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)OC)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CC(=O)OC)=O)=O JMNSEEZJYUMJBG-VXNXSFHZSA-N 0.000 claims 1
- XLZSUXDBSGHDKV-VXNXSFHZSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CCO)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC1)CCO)=O)=O XLZSUXDBSGHDKV-VXNXSFHZSA-N 0.000 claims 1
- SUVSQEXUGZOACJ-MZVUKIKXSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC=1)CO)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(CC(C2=CC=1)CO)=O)=O SUVSQEXUGZOACJ-MZVUKIKXSA-N 0.000 claims 1
- AASMFGPLTAEVSZ-YCRPNKLZSA-N C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(C[C@H](C2=CC1)CC(=O)O)=O)=O Chemical compound C1(CC1)COC1=CC=C(C=N1)O[C@H]1C(N(CC1)C=1C=C2C(C[C@H](C2=CC1)CC(=O)O)=O)=O AASMFGPLTAEVSZ-YCRPNKLZSA-N 0.000 claims 1
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 claims 1
- 229940123158 Cannabinoid CB1 receptor antagonist Drugs 0.000 claims 1
- 206010007558 Cardiac failure chronic Diseases 0.000 claims 1
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims 1
- 229940123239 Cholesterol synthesis inhibitor Drugs 0.000 claims 1
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 claims 1
- 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 claims 1
- 108050004099 Diacylglycerol O-acyltransferase 1 Proteins 0.000 claims 1
- 229940097420 Diuretic Drugs 0.000 claims 1
- DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 claims 1
- 208000032928 Dyslipidaemia Diseases 0.000 claims 1
- 102400000686 Endothelin-1 Human genes 0.000 claims 1
- 101800004490 Endothelin-1 Proteins 0.000 claims 1
- LCDDAGSJHKEABN-MLGOLLRUSA-N Evogliptin Chemical compound C1CNC(=O)[C@@H](COC(C)(C)C)N1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F LCDDAGSJHKEABN-MLGOLLRUSA-N 0.000 claims 1
- NNRMUDCEMYUOLQ-OODIQHKMSA-N FC1=CC=C(OC2=CC=C(C=N2)O[C@H]2C(N(CC2)C=2C=C3C(CC(C3=CC2)CCO)=O)=O)C=C1 Chemical compound FC1=CC=C(OC2=CC=C(C=N2)O[C@H]2C(N(CC2)C=2C=C3C(CC(C3=CC2)CCO)=O)=O)C=C1 NNRMUDCEMYUOLQ-OODIQHKMSA-N 0.000 claims 1
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 claims 1
- 101710182387 Fibroblast growth factor receptor 4 Proteins 0.000 claims 1
- 102100040134 Free fatty acid receptor 4 Human genes 0.000 claims 1
- 102000027487 Fructose-Bisphosphatase Human genes 0.000 claims 1
- 108010017464 Fructose-Bisphosphatase Proteins 0.000 claims 1
- 102100025353 G-protein coupled bile acid receptor 1 Human genes 0.000 claims 1
- 229940100607 GPR119 agonist Drugs 0.000 claims 1
- 229940123483 GPR142 agonist Drugs 0.000 claims 1
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 claims 1
- 102100039994 Gastric inhibitory polypeptide Human genes 0.000 claims 1
- ZWPRRQZNBDYKLH-VIFPVBQESA-N Gemigliptin Chemical compound C([C@@H](N)CC(=O)N1CC2=C(C(=NC(=N2)C(F)(F)F)C(F)(F)F)CC1)N1CC(F)(F)CCC1=O ZWPRRQZNBDYKLH-VIFPVBQESA-N 0.000 claims 1
- 206010071602 Genetic polymorphism Diseases 0.000 claims 1
- 101800001586 Ghrelin Proteins 0.000 claims 1
- 102400000442 Ghrelin-28 Human genes 0.000 claims 1
- 108010063919 Glucagon Receptors Proteins 0.000 claims 1
- 102100040890 Glucagon receptor Human genes 0.000 claims 1
- 229940123232 Glucagon receptor agonist Drugs 0.000 claims 1
- 229940122904 Glucagon receptor antagonist Drugs 0.000 claims 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims 1
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 claims 1
- 102000003638 Glucose-6-Phosphatase Human genes 0.000 claims 1
- 108010086800 Glucose-6-Phosphatase Proteins 0.000 claims 1
- 102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 claims 1
- 229920002527 Glycogen Polymers 0.000 claims 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 claims 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 claims 1
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 claims 1
- 101000890672 Homo sapiens Free fatty acid receptor 4 Proteins 0.000 claims 1
- 101000857733 Homo sapiens G-protein coupled bile acid receptor 1 Proteins 0.000 claims 1
- 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 claims 1
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims 1
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 claims 1
- 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 229940125922 IBAT inhibitor Drugs 0.000 claims 1
- 102000004877 Insulin Human genes 0.000 claims 1
- 108090001061 Insulin Proteins 0.000 claims 1
- 108010001831 LDL receptors Proteins 0.000 claims 1
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 claims 1
- 229940127470 Lipase Inhibitors Drugs 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 claims 1
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims 1
- 101150111774 NPY5R gene Proteins 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 102000018886 Pancreatic Polypeptide Human genes 0.000 claims 1
- 101710176384 Peptide 1 Proteins 0.000 claims 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims 1
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims 1
- GSINGUMRKGRYJP-VZWAGXQNSA-N Remogliflozin Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N(C(C)C)N=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 GSINGUMRKGRYJP-VZWAGXQNSA-N 0.000 claims 1
- 102000013272 Renalase Human genes 0.000 claims 1
- 108010090629 Renalase Proteins 0.000 claims 1
- 108090000783 Renin Proteins 0.000 claims 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims 1
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims 1
- 108091006300 SLC2A4 Proteins 0.000 claims 1
- 229940123451 Somatostatin receptor 3 agonist Drugs 0.000 claims 1
- 229940100389 Sulfonylurea Drugs 0.000 claims 1
- 101000983124 Sus scrofa Pancreatic prohormone precursor Proteins 0.000 claims 1
- 229940123464 Thiazolidinedione Drugs 0.000 claims 1
- 229940123876 Thyroid hormone receptor beta agonist Drugs 0.000 claims 1
- ZXOCGDDVNPDRIW-NHFZGCSJSA-N Tofogliflozin Chemical compound O.C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZXOCGDDVNPDRIW-NHFZGCSJSA-N 0.000 claims 1
- 102000008316 Type 4 Melanocortin Receptor Human genes 0.000 claims 1
- 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 claims 1
- 101710204865 Tyrosine-protein phosphatase 1 Proteins 0.000 claims 1
- 102400000752 Xenin Human genes 0.000 claims 1
- 229960002632 acarbose Drugs 0.000 claims 1
- 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 1
- 239000012190 activator Substances 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 239000000048 adrenergic agonist Substances 0.000 claims 1
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 claims 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims 1
- 229960002478 aldosterone Drugs 0.000 claims 1
- 239000002170 aldosterone antagonist Substances 0.000 claims 1
- 229940083712 aldosterone antagonist Drugs 0.000 claims 1
- 229960001667 alogliptin Drugs 0.000 claims 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 claims 1
- 239000002160 alpha blocker Substances 0.000 claims 1
- 108010028144 alpha-Glucosidases Proteins 0.000 claims 1
- 229950009977 anagliptin Drugs 0.000 claims 1
- LDXYBEHACFJIEL-HNNXBMFYSA-N anagliptin Chemical compound C=1N2N=C(C)C=C2N=CC=1C(=O)NCC(C)(C)NCC(=O)N1CCC[C@H]1C#N LDXYBEHACFJIEL-HNNXBMFYSA-N 0.000 claims 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims 1
- 239000004037 angiogenesis inhibitor Substances 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims 1
- 229940127218 antiplatelet drug Drugs 0.000 claims 1
- 239000000074 antisense oligonucleotide Substances 0.000 claims 1
- 238000012230 antisense oligonucleotides Methods 0.000 claims 1
- 229960005370 atorvastatin Drugs 0.000 claims 1
- 239000002876 beta blocker Substances 0.000 claims 1
- 229940097320 beta blocking agent Drugs 0.000 claims 1
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 claims 1
- 150000004283 biguanides Chemical class 0.000 claims 1
- 239000003613 bile acid Substances 0.000 claims 1
- 230000036772 blood pressure Effects 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 229960001713 canagliflozin Drugs 0.000 claims 1
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 claims 1
- 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 claims 1
- 229960005110 cerivastatin Drugs 0.000 claims 1
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000002604 chemokine receptor CCR2 antagonist Substances 0.000 claims 1
- 229960003834 dapagliflozin Drugs 0.000 claims 1
- 238000006356 dehydrogenation reaction Methods 0.000 claims 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000002934 diuretic Substances 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 claims 1
- 229940125542 dual agonist Drugs 0.000 claims 1
- 229940125436 dual inhibitor Drugs 0.000 claims 1
- 229950003693 dutogliptin Drugs 0.000 claims 1
- 229960003345 empagliflozin Drugs 0.000 claims 1
- OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 claims 1
- 239000003623 enhancer Substances 0.000 claims 1
- 229950011259 evogliptin Drugs 0.000 claims 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims 1
- 229960000815 ezetimibe Drugs 0.000 claims 1
- 229940125753 fibrate Drugs 0.000 claims 1
- 229960003765 fluvastatin Drugs 0.000 claims 1
- 108010036598 gastric inhibitory polypeptide receptor Proteins 0.000 claims 1
- 229960002458 gemigliptin Drugs 0.000 claims 1
- GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 0.000 claims 1
- 229940124828 glucokinase activator Drugs 0.000 claims 1
- 230000036252 glycation Effects 0.000 claims 1
- 229940096919 glycogen Drugs 0.000 claims 1
- 239000003395 histamine H3 receptor antagonist Substances 0.000 claims 1
- 229940125396 insulin Drugs 0.000 claims 1
- 229940125425 inverse agonist Drugs 0.000 claims 1
- 229950000991 ipragliflozin Drugs 0.000 claims 1
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 claims 1
- 229960002397 linagliptin Drugs 0.000 claims 1
- 230000037356 lipid metabolism Effects 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 229960004844 lovastatin Drugs 0.000 claims 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229950004994 meglitinide Drugs 0.000 claims 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 1
- 229960003105 metformin Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 229950009116 mevastatin Drugs 0.000 claims 1
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims 1
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims 1
- 239000002395 mineralocorticoid Substances 0.000 claims 1
- 229960003512 nicotinic acid Drugs 0.000 claims 1
- 235000001968 nicotinic acid Nutrition 0.000 claims 1
- 239000011664 nicotinic acid Substances 0.000 claims 1
- 229940012843 omega-3 fatty acid Drugs 0.000 claims 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims 1
- 239000004031 partial agonist Substances 0.000 claims 1
- 229930029653 phosphoenolpyruvate Natural products 0.000 claims 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 claims 1
- 239000003358 phospholipase A2 inhibitor Substances 0.000 claims 1
- 229960005095 pioglitazone Drugs 0.000 claims 1
- 229960002797 pitavastatin Drugs 0.000 claims 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 229960002965 pravastatin Drugs 0.000 claims 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims 1
- 102000016670 prohibitin Human genes 0.000 claims 1
- 108010028138 prohibitin Proteins 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 229940126844 remogliflozin Drugs 0.000 claims 1
- 229950011516 remogliflozin etabonate Drugs 0.000 claims 1
- UAOCLDQAQNNEAX-ABMICEGHSA-N remogliflozin etabonate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)OCC)O[C@H]1OC1=NN(C(C)C)C(C)=C1CC1=CC=C(OC(C)C)C=C1 UAOCLDQAQNNEAX-ABMICEGHSA-N 0.000 claims 1
- 239000002461 renin inhibitor Substances 0.000 claims 1
- 229940086526 renin-inhibitors Drugs 0.000 claims 1
- 229960004586 rosiglitazone Drugs 0.000 claims 1
- 229960000672 rosuvastatin Drugs 0.000 claims 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims 1
- 229960004937 saxagliptin Drugs 0.000 claims 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 claims 1
- 108010033693 saxagliptin Proteins 0.000 claims 1
- 229940126842 sergliflozin Drugs 0.000 claims 1
- HFLCZNNDZKKXCS-OUUBHVDSSA-N sergliflozin Chemical compound C1=CC(OC)=CC=C1CC1=CC=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HFLCZNNDZKKXCS-OUUBHVDSSA-N 0.000 claims 1
- 229960002855 simvastatin Drugs 0.000 claims 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims 1
- 229960004034 sitagliptin Drugs 0.000 claims 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000008685 targeting Effects 0.000 claims 1
- 229950000034 teneligliptin Drugs 0.000 claims 1
- WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 claims 1
- 150000001467 thiazolidinediones Chemical class 0.000 claims 1
- 229950006667 tofogliflozin Drugs 0.000 claims 1
- 239000003174 triple reuptake inhibitor Substances 0.000 claims 1
- 229960001254 vildagliptin Drugs 0.000 claims 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims 1
- IDHVLSACPFUBDY-QCDLPZBNSA-N xenin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CN=CN1 IDHVLSACPFUBDY-QCDLPZBNSA-N 0.000 claims 1
- 108010006643 xenin 25 Proteins 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14305491 | 2014-04-04 | ||
| EP14305491.4 | 2014-04-04 | ||
| PCT/EP2015/057413 WO2015150563A1 (en) | 2014-04-04 | 2015-04-02 | Substituted indanone compounds as gpr119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017515797A JP2017515797A (ja) | 2017-06-15 |
| JP2017515797A5 true JP2017515797A5 (enExample) | 2018-05-17 |
Family
ID=50513188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016560726A Abandoned JP2017515797A (ja) | 2014-04-04 | 2015-04-02 | 糖尿病、肥満、脂質異常症および関連障害の治療のためのｇｐｒ１１９モジュレーターとしての置換インダノン化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9896434B2 (enExample) |
| EP (1) | EP3126346B1 (enExample) |
| JP (1) | JP2017515797A (enExample) |
| KR (1) | KR20160132887A (enExample) |
| CN (1) | CN106132949A (enExample) |
| AU (1) | AU2015239020A1 (enExample) |
| CA (1) | CA2942121A1 (enExample) |
| IL (1) | IL248118A0 (enExample) |
| MX (1) | MX2016013029A (enExample) |
| RU (1) | RU2016143092A (enExample) |
| SG (1) | SG11201606619UA (enExample) |
| WO (1) | WO2015150563A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2016143092A (ru) | 2014-04-04 | 2018-05-08 | Санофи | Замещенные соединения инданона в качестве модуляторов gpr119 для лечения диабета, ожирения, дислипидемии и связанных с ними нарушений |
| AR110988A1 (es) | 2017-02-21 | 2019-05-22 | Sanofi Sa | Compuestos de azetidina como moduladores de gpr119 para el tratamiento de la diabetes, la obesidad, la dislipidemia y trastornos relacionados |
| KR101943382B1 (ko) | 2017-09-19 | 2019-01-29 | 오토텔릭바이오 주식회사 | Sglt-2 저해제 및 안지오텐신 수용체 차단제를 포함하는 의약 조성물 |
| LT3716979T (lt) * | 2017-11-30 | 2025-07-10 | Idorsia Pharmaceuticals Ltd | 4-pirimidinsulfamido darinio derinys su sglt-2 inhibitoriumi, skirtas su endotelinu susijusių ligų gydymui |
| KR102131359B1 (ko) * | 2018-09-07 | 2020-07-07 | 오토텔릭바이오 주식회사 | 안정성이 향상된 의약 조성물 |
| WO2020088961A1 (en) * | 2018-10-31 | 2020-05-07 | Basf Se | Process for producing hydroxymethyl-alcohols |
| WO2020150473A2 (en) | 2019-01-18 | 2020-07-23 | Dogma Therapeutics, Inc. | Pcsk9 inhibitors and methods of use thereof |
| BR112021013924A2 (pt) | 2019-01-18 | 2021-09-21 | Astrazeneca Ab | Inibidores de pcsk9 e métodos de uso do mesmo |
| US20220152164A1 (en) * | 2019-03-22 | 2022-05-19 | Kallyope, Inc. | Gpcr combination therapies |
| MX2021014410A (es) | 2019-05-31 | 2022-03-17 | Avolynt | Composiciones y métodos para tratar la enfermedad metabólica. |
| MX2022010548A (es) | 2020-02-28 | 2022-09-23 | Kallyope Inc | Agonistas de gpr40. |
| KR102289381B1 (ko) * | 2020-03-17 | 2021-08-17 | 주식회사 대웅테라퓨틱스 | 당뇨치료제 및 고지혈증 치료제를 포함하는 약학적 조성물 |
| MX2022014505A (es) | 2020-05-19 | 2022-12-13 | Kallyope Inc | Activadores de la ampk. |
| CA3183575A1 (en) | 2020-06-26 | 2021-12-30 | Iyassu Sebhat | Ampk activators |
| KR20250113341A (ko) * | 2024-01-18 | 2025-07-25 | 주식회사 티에치팜 | 나트륨 포도당 운반체-2 저해제 및 안지오텐신 ⅱ 수용체 차단제를 함유하는 비만 예방 또는 치료용 약학적 조성물 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002350366A1 (en) | 2001-12-31 | 2003-07-30 | Actelion Pharmaceuticals Ltd. | Pyrrolidone carboxamides |
| MXPA05013756A (es) * | 2003-06-18 | 2006-03-08 | Pfizer Prod Inc | Piperazinil-ariloxi y piperazinil-heteroariloxi-n-aril-lactamas novedosas. |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| AU2011256455A1 (en) * | 2010-05-17 | 2013-01-10 | Array Biopharma Inc. | Piperidinyl-substituted lactams as GPR119 modulators |
| AU2011202239C1 (en) | 2010-05-19 | 2017-03-16 | Sanofi | Long-acting formulations of insulins |
| CN103221046A (zh) | 2010-09-17 | 2013-07-24 | 阵列生物制药公司 | 作为gpr119调节剂的哌啶基取代的内酰胺 |
| CA2853784A1 (en) | 2011-11-11 | 2013-05-16 | Glaxosmithkline Llc | Treatment of blood lipid abnormalities and other conditions |
| AR092924A1 (es) * | 2012-10-09 | 2015-05-06 | Sanofi Sa | Derivados de pirrolidinona como moduladores de gpr119 para el tratamiento de diabetes, obesidad, dislipidemia y trastornos relacionados |
| RU2016143092A (ru) | 2014-04-04 | 2018-05-08 | Санофи | Замещенные соединения инданона в качестве модуляторов gpr119 для лечения диабета, ожирения, дислипидемии и связанных с ними нарушений |
-
2015
- 2015-04-02 RU RU2016143092A patent/RU2016143092A/ru not_active Application Discontinuation
- 2015-04-02 AU AU2015239020A patent/AU2015239020A1/en not_active Abandoned
- 2015-04-02 CA CA2942121A patent/CA2942121A1/en not_active Abandoned
- 2015-04-02 MX MX2016013029A patent/MX2016013029A/es unknown
- 2015-04-02 WO PCT/EP2015/057413 patent/WO2015150563A1/en not_active Ceased
- 2015-04-02 US US15/301,603 patent/US9896434B2/en not_active Expired - Fee Related
- 2015-04-02 SG SG11201606619UA patent/SG11201606619UA/en unknown
- 2015-04-02 JP JP2016560726A patent/JP2017515797A/ja not_active Abandoned
- 2015-04-02 CN CN201580017436.4A patent/CN106132949A/zh active Pending
- 2015-04-02 KR KR1020167027277A patent/KR20160132887A/ko not_active Withdrawn
- 2015-04-02 EP EP15713527.8A patent/EP3126346B1/en not_active Not-in-force
-
2016
- 2016-09-29 IL IL248118A patent/IL248118A0/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2017509678A5 (enExample) | ||
| JP2017509679A5 (enExample) | ||
| RU2016143092A (ru) | Замещенные соединения инданона в качестве модуляторов gpr119 для лечения диабета, ожирения, дислипидемии и связанных с ними нарушений | |
| US10428076B2 (en) | Soluble guanylate cyclase stimulators | |
| US12448384B2 (en) | Diacylglyceride O-acyltransferase 2 inhibitors | |
| IL197502A (en) | 2 - [6- (3-Amino piperidine-1-ram) -3-methyl-4,2-dioxo-4,3-dihydro-h2-pidicidin-1-alimethyl] -4-fluoro-benzonitrile for use as a suitable drug Weekly, mainly for the treatment of diabetes, cancer, autoimmune disorders and HIV | |
| KR20110067096A (ko) | 당뇨병 및 관련 상태를 치료하기 위한 병용 요법 | |
| EP3585775A1 (en) | Azetidine compounds as gpr119 modulators for the treatment of diabetes, obesity, dyslipidemia and related disorders | |
| JP2013523819A5 (enExample) | ||
| JP2017509678A (ja) | 糖尿病、肥満、脂質異常症および関連障害の治療のためのｇｐｒ１１９モジュレーターとしてのイソインドリノン化合物 | |
| KR20150038706A (ko) | 디펩티딜 펩티다아제 억제제의 주1회 투여 | |
| RU2009111378A (ru) | Терапевтические композиции, содержащие специфический антагонист рецептора эндотелина и ингибиторов pde5 | |
| AU2017360939A1 (en) | Indazole derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2 | |
| RS61874B1 (sr) | Derivati karboksamida | |
| WO2010107610A1 (en) | Method for treatment of diabetes and related conditions with combination therapy and compositions containing such compounds | |
| EP3541376A1 (en) | Indole derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2 | |
| JP2023541714A (ja) | 新規なジアシルグリセリドｏ－アシルトランスフェラーゼ２阻害剤としてのオキシインドール誘導体の製造 | |
| CN101822837A (zh) | 包含艾力沙坦酯盐的药物组合物 | |
| US11976061B2 (en) | Preparation of benzimidazolone derivatives as novel diacylglyceride O-acyltransferase 2 inhibitors | |
| CN101822836A (zh) | 包含艾力沙坦酯的药物组合物 | |
| CN101822667A (zh) | 包含咪唑-5-羧酸类衍生物的药物组合物 | |
| JP2025537517A (ja) | 新規ジアシルグリセリドｏ－アシルトランスフェラーゼ２阻害薬としてのピラゾロピリジン誘導体及びトリアゾロピリジン誘導体の調製 | |
| EP4267135A1 (en) | Preparation of tetrahydroindazole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors | |
| JP2010501499A (ja) | 線維症の処置 | |
| JP2017019724A (ja) | 置換ピリジン化合物および他の医薬の組み合わせ |