HUE032401T2 - Dihydropyrazole GPR40 modulators - Google Patents
Dihydropyrazole GPR40 modulators Download PDFInfo
- Publication number
- HUE032401T2 HUE032401T2 HUE13811645A HUE13811645A HUE032401T2 HU E032401 T2 HUE032401 T2 HU E032401T2 HU E13811645 A HUE13811645 A HU E13811645A HU E13811645 A HUE13811645 A HU E13811645A HU E032401 T2 HUE032401 T2 HU E032401T2
- Authority
- HU
- Hungary
- Prior art keywords
- mmol
- methyl
- dihydro
- pyrazol
- trifluoromethyl
- Prior art date
Links
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims description 199
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 98
- 239000003795 chemical substances by application Substances 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 12
- 150000002632 lipids Chemical class 0.000 claims description 8
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 241000252254 Catostomidae Species 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 235000003325 Ilex Nutrition 0.000 claims 1
- 241000209035 Ilex Species 0.000 claims 1
- 241001346558 Pseudognaphalium sandwicensium Species 0.000 claims 1
- 206010061481 Renal injury Diseases 0.000 claims 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 230000007882 cirrhosis Effects 0.000 claims 1
- 235000019788 craving Nutrition 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 239000004009 herbicide Substances 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 206010022437 insomnia Diseases 0.000 claims 1
- 208000037806 kidney injury Diseases 0.000 claims 1
- 238000007443 liposuction Methods 0.000 claims 1
- 239000008267 milk Substances 0.000 claims 1
- 210000004080 milk Anatomy 0.000 claims 1
- 235000013336 milk Nutrition 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 230000001020 rhythmical effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 273
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 239
- 239000000203 mixture Substances 0.000 description 210
- 239000000243 solution Substances 0.000 description 180
- 238000000034 method Methods 0.000 description 173
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 169
- 239000011541 reaction mixture Substances 0.000 description 139
- 238000005160 1H NMR spectroscopy Methods 0.000 description 137
- 235000019439 ethyl acetate Nutrition 0.000 description 133
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 120
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 111
- 239000002904 solvent Substances 0.000 description 111
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 106
- 238000004128 high performance liquid chromatography Methods 0.000 description 102
- 239000007787 solid Substances 0.000 description 81
- 239000003921 oil Substances 0.000 description 66
- 239000012044 organic layer Substances 0.000 description 62
- 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 description 59
- -1 methoxy, ethoxy, propoxy Chemical group 0.000 description 59
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 57
- 239000012267 brine Substances 0.000 description 57
- 238000000746 purification Methods 0.000 description 57
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
- 102100026148 Free fatty acid receptor 1 Human genes 0.000 description 56
- 239000000284 extract Substances 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 238000010898 silica gel chromatography Methods 0.000 description 54
- 239000000047 product Substances 0.000 description 52
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 50
- 238000011282 treatment Methods 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 45
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 43
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 39
- 239000003814 drug Substances 0.000 description 38
- 239000010410 layer Substances 0.000 description 37
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 37
- 239000012453 solvate Substances 0.000 description 36
- 235000011054 acetic acid Nutrition 0.000 description 34
- 229960000583 acetic acid Drugs 0.000 description 34
- 239000006260 foam Substances 0.000 description 33
- 206010012601 diabetes mellitus Diseases 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
- 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 description 31
- 238000004587 chromatography analysis Methods 0.000 description 31
- 239000008103 glucose Substances 0.000 description 31
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 238000003756 stirring Methods 0.000 description 24
- 229940124597 therapeutic agent Drugs 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 239000003472 antidiabetic agent Substances 0.000 description 22
- 229910052786 argon Inorganic materials 0.000 description 22
- 239000008194 pharmaceutical composition Substances 0.000 description 22
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000012230 colorless oil Substances 0.000 description 20
- 238000011321 prophylaxis Methods 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- 208000035475 disorder Diseases 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 17
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 229940086542 triethylamine Drugs 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 125000003545 alkoxy group Chemical group 0.000 description 15
- 229940125708 antidiabetic agent Drugs 0.000 description 15
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- 125000004076 pyridyl group Chemical group 0.000 description 15
- 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 description 14
- 239000013078 crystal Substances 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- 208000011580 syndromic disease Diseases 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 239000003937 drug carrier Substances 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- LIIRHTYWPZEVRD-KWQFWETISA-N methyl 2-[(3s,4s)-2-(4-hydroxyphenyl)-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C1=CC=C(O)C=C1 LIIRHTYWPZEVRD-KWQFWETISA-N 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 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 description 12
- 230000003914 insulin secretion Effects 0.000 description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 12
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 11
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 11
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 11
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 11
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 11
- 238000000634 powder X-ray diffraction Methods 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 206010019280 Heart failures Diseases 0.000 description 10
- 230000001154 acute effect Effects 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 9
- 206010022489 Insulin Resistance Diseases 0.000 description 9
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 201000001119 neuropathy Diseases 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
- 208000008589 Obesity Diseases 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 208000017169 kidney disease Diseases 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 8
- 230000007823 neuropathy Effects 0.000 description 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 8
- 235000020824 obesity Nutrition 0.000 description 8
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 8
- 238000001144 powder X-ray diffraction data Methods 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 229940075993 receptor modulator Drugs 0.000 description 8
- 238000012552 review Methods 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- 125000001544 thienyl group Chemical group 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 229940088597 hormone Drugs 0.000 description 7
- 239000005556 hormone Substances 0.000 description 7
- 201000001421 hyperglycemia Diseases 0.000 description 7
- 125000002883 imidazolyl group Chemical group 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 7
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 7
- 125000003373 pyrazinyl group Chemical group 0.000 description 7
- 125000003226 pyrazolyl group Chemical group 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 7
- 238000012800 visualization Methods 0.000 description 7
- UHWFAUXEZWPVAY-KCJUWKMLSA-N (3r,4s)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-ol Chemical compound C1=NC(OC)=CC(N2C[C@@H](C)[C@@H](O)CC2)=C1Cl UHWFAUXEZWPVAY-KCJUWKMLSA-N 0.000 description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](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](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](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](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 6
- 208000028698 Cognitive impairment Diseases 0.000 description 6
- 206010012289 Dementia Diseases 0.000 description 6
- 208000032928 Dyslipidaemia Diseases 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 6
- 108090001061 Insulin Proteins 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 208000017170 Lipid metabolism disease Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 108010088847 Peptide YY Proteins 0.000 description 6
- 102100029909 Peptide YY Human genes 0.000 description 6
- 206010038923 Retinopathy Diseases 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000003524 antilipemic agent Substances 0.000 description 6
- 239000002830 appetite depressant Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- RKRKELORNFODMN-UHFFFAOYSA-N benzyl 3-fluoro-4-hydroxypiperidine-1-carboxylate Chemical compound C1C(F)C(O)CCN1C(=O)OCC1=CC=CC=C1 RKRKELORNFODMN-UHFFFAOYSA-N 0.000 description 6
- JECCYYOJLNSUHX-UHFFFAOYSA-N benzyl 3-fluoro-4-oxopiperidine-1-carboxylate Chemical compound C1CC(=O)C(F)CN1C(=O)OCC1=CC=CC=C1 JECCYYOJLNSUHX-UHFFFAOYSA-N 0.000 description 6
- SEQIAIADXKZAFN-UHFFFAOYSA-N benzyl 4-trimethylsilyloxy-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1CC(O[Si](C)(C)C)=CCN1C(=O)OCC1=CC=CC=C1 SEQIAIADXKZAFN-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 208000010877 cognitive disease Diseases 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 235000021588 free fatty acids Nutrition 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 201000008980 hyperinsulinism Diseases 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 125000001041 indolyl group Chemical group 0.000 description 6
- 229940125396 insulin Drugs 0.000 description 6
- 125000000842 isoxazolyl group Chemical group 0.000 description 6
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 6
- 208000031225 myocardial ischemia Diseases 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 125000002971 oxazolyl group Chemical group 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 125000003831 tetrazolyl group Chemical group 0.000 description 6
- 125000000335 thiazolyl group Chemical group 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 125000004306 triazinyl group Chemical group 0.000 description 6
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 5
- COTSUPLUZXZPNP-UHFFFAOYSA-N 1-(5-chloro-2-methoxypyridin-4-yl)-3-fluoropiperidin-4-ol Chemical compound C1=NC(OC)=CC(N2CC(F)C(O)CC2)=C1Cl COTSUPLUZXZPNP-UHFFFAOYSA-N 0.000 description 5
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 5
- RSSHUQXUQXYECT-UHFFFAOYSA-N 4-bromo-5-chloro-2-methoxypyridine Chemical compound COC1=CC(Br)=C(Cl)C=N1 RSSHUQXUQXYECT-UHFFFAOYSA-N 0.000 description 5
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 5
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 5
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 5
- 102000015779 HDL Lipoproteins Human genes 0.000 description 5
- 108010010234 HDL Lipoproteins Proteins 0.000 description 5
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 206010033645 Pancreatitis Diseases 0.000 description 5
- 108091006269 SLC5A2 Proteins 0.000 description 5
- 102000058081 Sodium-Glucose Transporter 2 Human genes 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 229960001667 alogliptin Drugs 0.000 description 5
- 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 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
- 229910052796 boron Inorganic materials 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 208000004104 gestational diabetes Diseases 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 125000002632 imidazolidinyl group Chemical group 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- UEOGUYLGLGKYBX-UHFFFAOYSA-N n'-(4-bromophenyl)-2,2,2-trifluoroacetohydrazide Chemical compound FC(F)(F)C(=O)NNC1=CC=C(Br)C=C1 UEOGUYLGLGKYBX-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 235000011056 potassium acetate Nutrition 0.000 description 5
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 5
- 125000000168 pyrrolyl group Chemical group 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 229960004937 saxagliptin Drugs 0.000 description 5
- 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 description 5
- 108010033693 saxagliptin Proteins 0.000 description 5
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 5
- 229910001958 silver carbonate Inorganic materials 0.000 description 5
- 229960004034 sitagliptin Drugs 0.000 description 5
- 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 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000002411 thermogravimetry Methods 0.000 description 5
- 238000000844 transformation Methods 0.000 description 5
- 125000001425 triazolyl group Chemical group 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 229960001254 vildagliptin Drugs 0.000 description 5
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 5
- UTHQSTVKYFRBRL-YGRLFVJLSA-N (3r,4s)-1-(5-ethoxy-2-fluorophenyl)-3-methylpiperidin-4-ol Chemical compound CCOC1=CC=C(F)C(N2C[C@@H](C)[C@@H](O)CC2)=C1 UTHQSTVKYFRBRL-YGRLFVJLSA-N 0.000 description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- ICWLZTJBOJJLRD-UHFFFAOYSA-N 1-(2-fluoro-5-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC=C(F)C(N2CCC(O)CC2)=C1 ICWLZTJBOJJLRD-UHFFFAOYSA-N 0.000 description 4
- PPVBEAMUJBJQGJ-UHFFFAOYSA-N 1-(5-ethoxy-2-fluorophenyl)piperidin-4-ol Chemical compound CCOC1=CC=C(F)C(N2CCC(O)CC2)=C1 PPVBEAMUJBJQGJ-UHFFFAOYSA-N 0.000 description 4
- FUAQRGIQWOTIER-JIQZGXBJSA-N 2-[(3s,4s)-2-[4-[(3r,4r)-1-(5-ethoxy-2-fluorophenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC=C(F)C(N2C[C@@H](C)[C@H](OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1 FUAQRGIQWOTIER-JIQZGXBJSA-N 0.000 description 4
- BWVDCOCOPJOZEH-UHFFFAOYSA-N 5-ethoxy-2-fluoroaniline Chemical compound CCOC1=CC=C(F)C(N)=C1 BWVDCOCOPJOZEH-UHFFFAOYSA-N 0.000 description 4
- 208000009304 Acute Kidney Injury Diseases 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 208000004990 Cardiorenal syndrome Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 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 description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 208000002705 Glucose Intolerance Diseases 0.000 description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 description 4
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- 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 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 4
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 4
- 208000033626 Renal failure acute Diseases 0.000 description 4
- 208000017442 Retinal disease Diseases 0.000 description 4
- 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 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 239000012346 acetyl chloride Substances 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 201000011040 acute kidney failure Diseases 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 239000000883 anti-obesity agent Substances 0.000 description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 4
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 4
- 229960001713 canagliflozin Drugs 0.000 description 4
- 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 description 4
- 230000019771 cognition Effects 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 229960003834 dapagliflozin Drugs 0.000 description 4
- 238000013480 data collection Methods 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- 208000033679 diabetic kidney disease Diseases 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 4
- 229960003345 empagliflozin Drugs 0.000 description 4
- 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 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 208000010706 fatty liver disease Diseases 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 125000004438 haloalkoxy group Chemical group 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 4
- 208000006575 hypertriglyceridemia Diseases 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(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](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)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=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 4
- 239000000859 incretin Substances 0.000 description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 229960002397 linagliptin Drugs 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 206010025482 malaise Diseases 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 4
- 239000006186 oral dosage form Substances 0.000 description 4
- 238000007410 oral glucose tolerance test Methods 0.000 description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 239000000123 paper Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 229960003611 pramlintide Drugs 0.000 description 4
- 108010029667 pramlintide Proteins 0.000 description 4
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 4
- 201000009104 prediabetes syndrome Diseases 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000012363 selectfluor Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000001757 thermogravimetry curve Methods 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
- GSIJWAWHEAADOE-NVNXTCNLSA-N (1z)-2,2,2-trifluoro-n-(4-methoxyphenyl)ethanehydrazonoyl chloride Chemical compound COC1=CC=C(N\N=C(/Cl)C(F)(F)F)C=C1 GSIJWAWHEAADOE-NVNXTCNLSA-N 0.000 description 3
- ZBSXDPMUKIODTI-CHHVJCJISA-N (1z)-n-(4-bromophenyl)-2,2,2-trifluoroethanehydrazonoyl chloride Chemical compound FC(F)(F)C(\Cl)=N\NC1=CC=C(Br)C=C1 ZBSXDPMUKIODTI-CHHVJCJISA-N 0.000 description 3
- DCVIMWRFFDRWJM-SZHMKSFOSA-N (4s)-3-[(e)-but-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)/C=C/C)[C@H]1C1=CC=CC=C1 DCVIMWRFFDRWJM-SZHMKSFOSA-N 0.000 description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 3
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 3
- HFFGMRSKOYNWJZ-UHFFFAOYSA-N 1-(2,3-difluoro-5-methoxyphenyl)-3-methylpiperidin-4-ol Chemical compound COC1=CC(F)=C(F)C(N2CC(C)C(O)CC2)=C1 HFFGMRSKOYNWJZ-UHFFFAOYSA-N 0.000 description 3
- GVUPQMIGZZDNKO-UHFFFAOYSA-N 1-(5-ethoxy-2-fluorophenyl)-3-ethylpiperidin-4-one Chemical compound CCOC1=CC=C(F)C(N2CC(CC)C(=O)CC2)=C1 GVUPQMIGZZDNKO-UHFFFAOYSA-N 0.000 description 3
- KTIVFHRVWNIZET-UHFFFAOYSA-N 1-(5-ethoxy-2-fluorophenyl)-3-methylpiperidin-4-one Chemical compound CCOC1=CC=C(F)C(N2CC(C)C(=O)CC2)=C1 KTIVFHRVWNIZET-UHFFFAOYSA-N 0.000 description 3
- IDIKDOJXPPQRDT-UHFFFAOYSA-N 1-(5-methoxy-2-methylphenyl)piperidin-4-ol Chemical compound COC1=CC=C(C)C(N2CCC(O)CC2)=C1 IDIKDOJXPPQRDT-UHFFFAOYSA-N 0.000 description 3
- PFXMXGJASCSPFP-UHFFFAOYSA-N 1-(5-methoxy-2-methylphenyl)piperidin-4-one Chemical compound COC1=CC=C(C)C(N2CCC(=O)CC2)=C1 PFXMXGJASCSPFP-UHFFFAOYSA-N 0.000 description 3
- NOJKOTKTVNLCCI-UHFFFAOYSA-N 1-benzyl-3-ethyl-1-methylpiperidin-1-ium-4-one Chemical compound C1CC(=O)C(CC)C[N+]1(C)CC1=CC=CC=C1 NOJKOTKTVNLCCI-UHFFFAOYSA-N 0.000 description 3
- ICYXRASQTVYPPQ-UHFFFAOYSA-N 2,2,2-trifluoro-n'-(4-methoxyphenyl)acetohydrazide Chemical compound COC1=CC=C(NNC(=O)C(F)(F)F)C=C1 ICYXRASQTVYPPQ-UHFFFAOYSA-N 0.000 description 3
- UBEJKUWOEALLJH-KWQFWETISA-N 2-[(3s,4s)-2-(4-bromophenyl)-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC#N)N1C1=CC=C(Br)C=C1 UBEJKUWOEALLJH-KWQFWETISA-N 0.000 description 3
- MPKZCMCABKRUDU-ZQCAWNDQSA-N 2-[(3s,4s)-2-[3-bromo-4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound C1=NC(OC)=CC(N2C[C@@H](C)[C@H](OC=3C(=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)Br)CC2)=C1Cl MPKZCMCABKRUDU-ZQCAWNDQSA-N 0.000 description 3
- LDSJDERGVBYYIP-OITFXXTJSA-N 2-[(3s,4s)-2-[3-bromo-4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound C1=NC(OC)=CC(N2C[C@@H](C)[C@H](OC=3C(=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC#N)Br)CC2)=C1Cl LDSJDERGVBYYIP-OITFXXTJSA-N 0.000 description 3
- KVAWEALSPOOAKM-LOLFCSDLSA-N 2-[(3s,4s)-2-[4-[1-(2,3-difluoro-5-methoxyphenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC(F)=C(F)C(N2CC(C)C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1 KVAWEALSPOOAKM-LOLFCSDLSA-N 0.000 description 3
- PJKKMAPKRNNJRU-XOBRGWDASA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-hydroxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(O)C=2)F)CC1 PJKKMAPKRNNJRU-XOBRGWDASA-N 0.000 description 3
- BDPNHWBEGPIVNU-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 BDPNHWBEGPIVNU-BTYIYWSLSA-N 0.000 description 3
- BFJHVWFZHAGHHO-GSVBMSIBSA-N 2-[(3s,4s)-2-[4-[1-(5-ethoxy-2,3-difluorophenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC(F)=C(F)C(N2CC(C)C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1 BFJHVWFZHAGHHO-GSVBMSIBSA-N 0.000 description 3
- DLBACUJDAKSTES-SBUREZEXSA-N 2-[(3s,4s)-2-[4-[1-(5-methoxy-2-methylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=C(C)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 DLBACUJDAKSTES-SBUREZEXSA-N 0.000 description 3
- ZVAIRDUEIIPREZ-UHFFFAOYSA-N 2-[4-ethyl-2-(4-hydroxyphenyl)-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)C(CC)C(CC#N)N1C1=CC=C(O)C=C1 ZVAIRDUEIIPREZ-UHFFFAOYSA-N 0.000 description 3
- QGNZBLWPGNSKII-UHFFFAOYSA-N 2-bromo-4-ethoxy-1-fluorobenzene Chemical compound CCOC1=CC=C(F)C(Br)=C1 QGNZBLWPGNSKII-UHFFFAOYSA-N 0.000 description 3
- ULIGTYXVGVMMAN-LIRRHRJNSA-N 4-[(3s,4s)-3-(cyanomethyl)-2-(4-methoxyphenyl)-4-methyl-3,4-dihydropyrazol-5-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1N1[C@@H](CC#N)[C@H](C)C(C=2C=CC(=CC=2)C#N)=N1 ULIGTYXVGVMMAN-LIRRHRJNSA-N 0.000 description 3
- VIZMARKIEQIMIG-UHFFFAOYSA-N 4-bromo-5-chloropyridin-2-amine Chemical compound NC1=CC(Br)=C(Cl)C=N1 VIZMARKIEQIMIG-UHFFFAOYSA-N 0.000 description 3
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 3
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 101100066621 Mus musculus Ffar1 gene Proteins 0.000 description 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
- DDYZLAFEDOMYQJ-UHFFFAOYSA-N [1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl] 4-methylbenzenesulfonate Chemical compound COC1=CC=C(F)C(N2CCC(CC2)OS(=O)(=O)C=2C=CC(C)=CC=2)=C1 DDYZLAFEDOMYQJ-UHFFFAOYSA-N 0.000 description 3
- RCIFYQBNZGUZTF-UHFFFAOYSA-N [3-fluoro-1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl] 4-methylbenzenesulfonate Chemical compound COC1=CC=C(F)C(N2CC(F)C(OS(=O)(=O)C=3C=CC(C)=CC=3)CC2)=C1 RCIFYQBNZGUZTF-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 229940125709 anorectic agent Drugs 0.000 description 3
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 3
- 230000001708 anti-dyslipidemic effect Effects 0.000 description 3
- 230000001346 anti-hypertriglyceridemic effect Effects 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 230000002253 anti-ischaemic effect Effects 0.000 description 3
- 230000003063 anti-neuropathic effect Effects 0.000 description 3
- 230000002946 anti-pancreatic effect Effects 0.000 description 3
- 230000002769 anti-restenotic effect Effects 0.000 description 3
- 239000003529 anticholesteremic agent Substances 0.000 description 3
- 229940125682 antidementia agent Drugs 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 229940030600 antihypertensive agent Drugs 0.000 description 3
- 229940125710 antiobesity agent Drugs 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 238000007876 drug discovery Methods 0.000 description 3
- HFZATOGOLXZCFF-UHFFFAOYSA-N ethyl 1-benzyl-3-ethyl-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)(CC)CN1CC1=CC=CC=C1 HFZATOGOLXZCFF-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 3
- 230000004217 heart function Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 210000004153 islets of langerhan Anatomy 0.000 description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- 125000001786 isothiazolyl group Chemical group 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000006883 memory enhancing effect Effects 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- XFVAWHUZQZSOLH-SVBQBFEESA-N methyl 2-[(3s,4s)-2-[2-bromo-4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C(=C1)Br)=CC=C1O[C@H]1[C@H](C)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 XFVAWHUZQZSOLH-SVBQBFEESA-N 0.000 description 3
- TUHGYOLOLFKFSS-OITFXXTJSA-N methyl 2-[(3s,4s)-2-[3-bromo-4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1Br)=CC=C1O[C@H]1[C@H](C)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 TUHGYOLOLFKFSS-OITFXXTJSA-N 0.000 description 3
- FKCFZPXVCBAQRX-UHFFFAOYSA-N methyl 4-ethyl-2-(4-methoxyphenyl)-5-(trifluoromethyl)-3,4-dihydropyrazole-3-carboxylate Chemical compound N1=C(C(F)(F)F)C(CC)C(C(=O)OC)N1C1=CC=C(OC)C=C1 FKCFZPXVCBAQRX-UHFFFAOYSA-N 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000002664 nootropic agent Substances 0.000 description 3
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- AAMSYYXUCUFULV-UHFFFAOYSA-N piperidin-1-ylmethanone Chemical compound O=[C]N1CCCCC1 AAMSYYXUCUFULV-UHFFFAOYSA-N 0.000 description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000009862 primary prevention Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 3
- 125000002098 pyridazinyl group Chemical group 0.000 description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000009863 secondary prevention Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 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 description 2
- PVRSIFAEUCUJPK-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine Chemical compound COC1=CC=C(NN)C=C1 PVRSIFAEUCUJPK-UHFFFAOYSA-N 0.000 description 2
- YBXSCDWZPXAJQR-JCURWCKSSA-N (4s)-3-[(3r,4s)-2-(4-bromophenyl)-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazole-3-carbonyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound N1([C@H]([C@@H](C(=N1)C(F)(F)F)C)C(=O)N1C(OC[C@@H]1C=1C=CC=CC=1)=O)C1=CC=C(Br)C=C1 YBXSCDWZPXAJQR-JCURWCKSSA-N 0.000 description 2
- IIIXNQYVSNHXHJ-AHAUYKDXSA-N (4s)-3-[(e)-pent-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)/C=C/CC)[C@H]1C1=CC=CC=C1 IIIXNQYVSNHXHJ-AHAUYKDXSA-N 0.000 description 2
- QDMNNMIOWVJVLY-MRVPVSSYSA-N (4s)-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1C1=CC=CC=C1 QDMNNMIOWVJVLY-MRVPVSSYSA-N 0.000 description 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 2
- WVGMXLCSROHOIY-UHFFFAOYSA-N 1,2,3-trifluoro-5-methoxybenzene Chemical compound COC1=CC(F)=C(F)C(F)=C1 WVGMXLCSROHOIY-UHFFFAOYSA-N 0.000 description 2
- MTDUJCDGQPJLKA-UHFFFAOYSA-N 1,2-difluoro-4-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=C(F)C(F)=C1 MTDUJCDGQPJLKA-UHFFFAOYSA-N 0.000 description 2
- VQMLJVBQIMTRGP-UHFFFAOYSA-N 1-(2,3-difluoro-5-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC(F)=C(F)C(N2CCC(O)CC2)=C1 VQMLJVBQIMTRGP-UHFFFAOYSA-N 0.000 description 2
- WQDYHLJSJROZGZ-UHFFFAOYSA-N 1-(2-fluoro-5-propan-2-yloxyphenyl)-3-methylpiperidin-4-ol Chemical compound CC(C)OC1=CC=C(F)C(N2CC(C)C(O)CC2)=C1 WQDYHLJSJROZGZ-UHFFFAOYSA-N 0.000 description 2
- NSJDQJPSBFQPSM-UHFFFAOYSA-N 1-(2-fluoro-5-propan-2-yloxyphenyl)piperidin-4-ol Chemical compound CC(C)OC1=CC=C(F)C(N2CCC(O)CC2)=C1 NSJDQJPSBFQPSM-UHFFFAOYSA-N 0.000 description 2
- OWQFJXUTZJGLGR-UHFFFAOYSA-N 1-benzyl-1,3-dimethylpiperidin-1-ium-4-one Chemical compound C1CC(=O)C(C)C[N+]1(C)CC1=CC=CC=C1 OWQFJXUTZJGLGR-UHFFFAOYSA-N 0.000 description 2
- JUSKDLRMHAPHCU-UHFFFAOYSA-N 1-benzyl-3-ethylpiperidin-4-one Chemical compound C1CC(=O)C(CC)CN1CC1=CC=CC=C1 JUSKDLRMHAPHCU-UHFFFAOYSA-N 0.000 description 2
- OVQAJYCAXPHYNV-UHFFFAOYSA-N 1-benzyl-3-methylpiperidin-4-one Chemical compound C1CC(=O)C(C)CN1CC1=CC=CC=C1 OVQAJYCAXPHYNV-UHFFFAOYSA-N 0.000 description 2
- 125000005955 1H-indazolyl group Chemical group 0.000 description 2
- VZVHBAYWDGQRNH-SJCJKPOMSA-N 2-[(3s,4s)-2-(4-bromophenyl)-5-(4-fluorophenyl)-4-methyl-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound C=1C=C(Br)C=CC=1N([C@@H](CC#N)[C@@H]1C)N=C1C1=CC=C(F)C=C1 VZVHBAYWDGQRNH-SJCJKPOMSA-N 0.000 description 2
- VRMSGGCQJJLWDM-SXGZUBKSSA-N 2-[(3s,4s)-2-[2-bromo-4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound C1=NC(OC)=CC(N2C[C@@H](C)[C@H](OC=3C=C(Br)C(N4[C@H]([C@H](C)C(=N4)C(F)(F)F)CC#N)=CC=3)CC2)=C1Cl VRMSGGCQJJLWDM-SXGZUBKSSA-N 0.000 description 2
- DXDAZXLANLVUME-XOBRGWDASA-N 2-[(3s,4s)-2-[4-[1-(2,3-difluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC(F)=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 DXDAZXLANLVUME-XOBRGWDASA-N 0.000 description 2
- OXMHBUYUBLHCHW-XOBRGWDASA-N 2-[(3s,4s)-2-[4-[1-(2,5-dichlorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(Cl)C=2)Cl)CC1 OXMHBUYUBLHCHW-XOBRGWDASA-N 0.000 description 2
- FAQMEFYIRZKBAG-XOBRGWDASA-N 2-[(3s,4s)-2-[4-[1-(2,5-difluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(F)C=2)F)CC1 FAQMEFYIRZKBAG-XOBRGWDASA-N 0.000 description 2
- JFJULKMBNGLSHZ-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(2-chlorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=CC=2)Cl)CC1 JFJULKMBNGLSHZ-BTYIYWSLSA-N 0.000 description 2
- HWFDEAZMSPPZTF-KKSFZXQISA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-methylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(C)C=2)F)CC1 HWFDEAZMSPPZTF-KKSFZXQISA-N 0.000 description 2
- DHFWTWNRGGDFLA-NXTUYVMSSA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-propan-2-yloxyphenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CC(C)OC1=CC=C(F)C(N2CC(C)C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1 DHFWTWNRGGDFLA-NXTUYVMSSA-N 0.000 description 2
- CBIPLAHSXILPHJ-YWZLYKJASA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-6-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=CC(F)=C1N1CCC(OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)CC1 CBIPLAHSXILPHJ-YWZLYKJASA-N 0.000 description 2
- HUQANINOPZFOMT-KKSFZXQISA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=CC=2C)F)CC1 HUQANINOPZFOMT-KKSFZXQISA-N 0.000 description 2
- RCJMDVZURPPRJD-KKSFZXQISA-N 2-[(3s,4s)-2-[4-[1-(2-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=CC=C1N1CCC(OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)CC1 RCJMDVZURPPRJD-KKSFZXQISA-N 0.000 description 2
- CKPIVZZALYEYSZ-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(3-fluoro-4-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound C1=C(F)C(OC)=CC=C1N1CCC(OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)CC1 CKPIVZZALYEYSZ-BTYIYWSLSA-N 0.000 description 2
- KIMOWMXFUAAVCZ-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(3-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C=C(F)C=CC=2)CC1 KIMOWMXFUAAVCZ-BTYIYWSLSA-N 0.000 description 2
- XRWKURCYXQDQTO-AOMKIAJQSA-N 2-[(3s,4s)-2-[4-[1-(3-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=CC(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 XRWKURCYXQDQTO-AOMKIAJQSA-N 0.000 description 2
- PTHAYZSMQXSBPR-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(4-chlorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C=CC(Cl)=CC=2)CC1 PTHAYZSMQXSBPR-BTYIYWSLSA-N 0.000 description 2
- PSDPPJUWKMGRJN-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(4-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C=CC(F)=CC=2)CC1 PSDPPJUWKMGRJN-BTYIYWSLSA-N 0.000 description 2
- XUPNWZPTVDHKKX-MBSDFSHPSA-N 2-[(3s,4s)-2-[4-[1-(4-methoxy-2,6-dimethylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CC1=CC(OC)=CC(C)=C1N1CCC(OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)CC1 XUPNWZPTVDHKKX-MBSDFSHPSA-N 0.000 description 2
- MCMOWZZALNRWOH-WFASDCNBSA-N 2-[(3s,4s)-4-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC#N)N1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1 MCMOWZZALNRWOH-WFASDCNBSA-N 0.000 description 2
- RRRXLETVDBFLOI-JTSKRJEESA-N 2-[(3s,4s)-4-methyl-2-[4-[1-(2-methylphenyl)piperidin-4-yl]oxyphenyl]-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=CC=2)C)CC1 RRRXLETVDBFLOI-JTSKRJEESA-N 0.000 description 2
- ZDEHFQYOZTXFQX-MVXLQIMRSA-N 2-[(3s,4s)-5-(4-cyanophenyl)-2-[4-[(3r,4r)-1-(5-ethoxy-2-fluorophenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-ethyl-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC=C(F)C(N2C[C@@H](C)[C@H](OC=3C=CC(=CC=3)N3[C@H]([C@H](CC)C(=N3)C=3C=CC(=CC=3)C#N)CC(O)=O)CC2)=C1 ZDEHFQYOZTXFQX-MVXLQIMRSA-N 0.000 description 2
- HPMIOSUHMIDHRQ-LGGPFLRQSA-N 2-[(3s,4s)-5-(4-cyanophenyl)-2-[4-[1-(5-ethoxy-2-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C=2C=CC(=CC=2)C#N)CC(O)=O)=C1 HPMIOSUHMIDHRQ-LGGPFLRQSA-N 0.000 description 2
- ZKFGTDVZUUMPNA-UHFFFAOYSA-N 2-[2-[4-[1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-ethyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)C(CC)C(CC#N)N1C(C=C1)=CC=C1OC1C(C)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 ZKFGTDVZUUMPNA-UHFFFAOYSA-N 0.000 description 2
- JAYJRUCDQMYLFV-UHFFFAOYSA-N 2-[4-ethyl-2-(4-methoxyphenyl)-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)C(CC)C(CC#N)N1C1=CC=C(OC)C=C1 JAYJRUCDQMYLFV-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- DPDLYHILBVSYEL-UHFFFAOYSA-N 4-[[(4-methoxyphenyl)hydrazinylidene]methyl]benzonitrile Chemical compound C1=CC(OC)=CC=C1NN=CC1=CC=C(C#N)C=C1 DPDLYHILBVSYEL-UHFFFAOYSA-N 0.000 description 2
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 2
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 2
- GDQCQXMYIKTEDN-UHFFFAOYSA-N 5-ethoxy-1,2,3-trifluorobenzene Chemical compound CCOC1=CC(F)=C(F)C(F)=C1 GDQCQXMYIKTEDN-UHFFFAOYSA-N 0.000 description 2
- CMFIWMWBTZQTQH-IDTAVKCVSA-N 9-[(2r,3r,4s,5s)-3,4-dihydroxy-5-(2-methylpropylsulfanylmethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CSCC(C)C)O[C@H]1N1C(NC=NC2=O)=C2N=C1 CMFIWMWBTZQTQH-IDTAVKCVSA-N 0.000 description 2
- 102100022622 Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Human genes 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 229910015845 BBr3 Inorganic materials 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910002483 Cu Ka Inorganic materials 0.000 description 2
- 229910016523 CuKa Inorganic materials 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010011459 Exenatide Proteins 0.000 description 2
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=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](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)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)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 2
- 102100040134 Free fatty acid receptor 4 Human genes 0.000 description 2
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 2
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 2
- 102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 description 2
- 102000030595 Glucokinase Human genes 0.000 description 2
- 108010021582 Glucokinase Proteins 0.000 description 2
- 102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 description 2
- 102000004366 Glucosidases Human genes 0.000 description 2
- 108010056771 Glucosidases Proteins 0.000 description 2
- 206010019708 Hepatic steatosis Diseases 0.000 description 2
- 101000972916 Homo sapiens Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Proteins 0.000 description 2
- 101000890672 Homo sapiens Free fatty acid receptor 4 Proteins 0.000 description 2
- 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 description 2
- 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000003071 IP-One HTRF Assay Methods 0.000 description 2
- 229940122199 Insulin secretagogue Drugs 0.000 description 2
- 229940122355 Insulin sensitizer Drugs 0.000 description 2
- 108010019598 Liraglutide Proteins 0.000 description 2
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)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](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)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=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 102100027375 Melanin-concentrating hormone receptor 1 Human genes 0.000 description 2
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 2
- IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 102100038991 Neuropeptide Y receptor type 2 Human genes 0.000 description 2
- 102100029549 Neuropeptide Y receptor type 5 Human genes 0.000 description 2
- 102000028435 Neuropeptide Y4 receptor Human genes 0.000 description 2
- 108010002245 Neuropeptide Y4 receptor Proteins 0.000 description 2
- 108010046593 Neuropeptide Y5 receptor Proteins 0.000 description 2
- 102400000319 Oxyntomodulin Human genes 0.000 description 2
- 101800001388 Oxyntomodulin Proteins 0.000 description 2
- MFOCDFTXLCYLKU-CMPLNLGQSA-N Phendimetrazine Chemical compound O1CCN(C)[C@@H](C)[C@@H]1C1=CC=CC=C1 MFOCDFTXLCYLKU-CMPLNLGQSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 101000930003 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- GHZXBFJJTBWYTH-KQQUZDAGSA-N [(E)-pent-2-enoyl] (E)-pent-2-enoate Chemical compound CC\C=C\C(=O)OC(=O)\C=C\CC GHZXBFJJTBWYTH-KQQUZDAGSA-N 0.000 description 2
- QCDMXIFQYROSFH-UHFFFAOYSA-N [1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl] methanesulfonate Chemical compound COC1=CC=C(F)C(N2CCC(CC2)OS(C)(=O)=O)=C1 QCDMXIFQYROSFH-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 229960002632 acarbose Drugs 0.000 description 2
- 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 description 2
- SAIXAWJRUGENIS-UHFFFAOYSA-N acetohydrazide Chemical compound CC(=O)NN.CC(=O)NN SAIXAWJRUGENIS-UHFFFAOYSA-N 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- DAYKLWSKQJBGCS-NRFANRHFSA-N aleglitazar Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-NRFANRHFSA-N 0.000 description 2
- 229950010157 aleglitazar Drugs 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229940127003 anti-diabetic drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000005512 benztetrazolyl group Chemical group 0.000 description 2
- KAIHBPOUDTWLKW-XBXARRHUSA-N benzyl (E)-4-cyclopropylbut-2-enoate Chemical compound C1CC1C/C=C/C(=O)OCC1=CC=CC=C1 KAIHBPOUDTWLKW-XBXARRHUSA-N 0.000 description 2
- VZOVOHRDLOYBJX-UHFFFAOYSA-N benzyl 4-oxopiperidine-1-carboxylate Chemical compound C1CC(=O)CCN1C(=O)OCC1=CC=CC=C1 VZOVOHRDLOYBJX-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 150000004283 biguanides Chemical class 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011111 cardboard Substances 0.000 description 2
- MVCQKIKWYUURMU-UHFFFAOYSA-N cetilistat Chemical compound C1=C(C)C=C2C(=O)OC(OCCCCCCCCCCCCCCCC)=NC2=C1 MVCQKIKWYUURMU-UHFFFAOYSA-N 0.000 description 2
- 229950002397 cetilistat Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 2
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 238000004807 desolvation Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 229960004890 diethylpropion Drugs 0.000 description 2
- XXEPPPIWZFICOJ-UHFFFAOYSA-N diethylpropion Chemical compound CCN(CC)C(C)C(=O)C1=CC=CC=C1 XXEPPPIWZFICOJ-UHFFFAOYSA-N 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- CFJPFWZYTWJGDH-AOMKIAJQSA-N ethyl 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-hydroxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound CCOC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(O)C=2)F)CC1 CFJPFWZYTWJGDH-AOMKIAJQSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229960001519 exenatide Drugs 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 2
- 229960004346 glimepiride Drugs 0.000 description 2
- 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 description 2
- 229960001381 glipizide Drugs 0.000 description 2
- 230000010030 glucose lowering effect Effects 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000008241 heterogeneous mixture Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000001639 hypophagic effect Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000004936 isatinoyl group Chemical group N1(C(=O)C(=O)C2=CC=CC=C12)C(=O)* 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- 229960002701 liraglutide Drugs 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 229960005060 lorcaserin Drugs 0.000 description 2
- XTTZERNUQAFMOF-QMMMGPOBSA-N lorcaserin Chemical compound C[C@H]1CNCCC2=CC=C(Cl)C=C12 XTTZERNUQAFMOF-QMMMGPOBSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- FKCFZPXVCBAQRX-NEPJUHHUSA-N methyl (3s,4r)-4-ethyl-2-(4-methoxyphenyl)-5-(trifluoromethyl)-3,4-dihydropyrazole-3-carboxylate Chemical compound N1=C(C(F)(F)F)[C@H](CC)[C@@H](C(=O)OC)N1C1=CC=C(OC)C=C1 FKCFZPXVCBAQRX-NEPJUHHUSA-N 0.000 description 2
- MBAHGFJTIVZLFB-SNAWJCMRSA-N methyl (e)-pent-2-enoate Chemical compound CC\C=C\C(=O)OC MBAHGFJTIVZLFB-SNAWJCMRSA-N 0.000 description 2
- OWBUHTGJBMIVJH-KWQFWETISA-N methyl 2-[(3s,4s)-2-(4-bromophenyl)-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C1=CC=C(Br)C=C1 OWBUHTGJBMIVJH-KWQFWETISA-N 0.000 description 2
- IYVVOPDPTDOJBE-GMMXXOHYSA-N methyl 2-[(3s,4s)-2-[4-[(3r,4r)-1-(5-ethoxy-2-fluorophenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound CCOC1=CC=C(F)C(N2C[C@@H](C)[C@H](OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(=O)OC)CC2)=C1 IYVVOPDPTDOJBE-GMMXXOHYSA-N 0.000 description 2
- KYRAFDVGHCVGIN-QUSPAXKCSA-N methyl 2-[(3s,4s)-2-[4-[1-(5-chloro-2-methoxypyridin-4-yl)-3-fluoropiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1C(F)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 KYRAFDVGHCVGIN-QUSPAXKCSA-N 0.000 description 2
- AFUBNLAUOCVQST-UUOWRZLLSA-N methyl 2-[(3s,4s)-2-[4-[1-(5-methoxy-2-methylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(OC)C=2)C)CC1 AFUBNLAUOCVQST-UUOWRZLLSA-N 0.000 description 2
- OYQQTNXTUZIZKY-LGGPFLRQSA-N methyl 4-[(3s,4s)-2-[4-[1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-3-(2-methoxy-2-oxoethyl)-4-methyl-3,4-dihydropyrazol-5-yl]benzoate Chemical compound C=1C=C(C(=O)OC)C=CC=1C([C@@H](C)[C@@H]1CC(=O)OC)=NN1C(C=C1)=CC=C1OC(CC1)CCN1C1=CC(OC)=CC=C1F OYQQTNXTUZIZKY-LGGPFLRQSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 229960001110 miglitol Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 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(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)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 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 description 2
- 229950001135 muraglitazar Drugs 0.000 description 2
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 2
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 2
- 229960003086 naltrexone Drugs 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 108010089579 neuropeptide Y2 receptor Proteins 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229960001243 orlistat Drugs 0.000 description 2
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 2
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229960000436 phendimetrazine Drugs 0.000 description 2
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 2
- 229960003243 phenformin Drugs 0.000 description 2
- 229960003562 phentermine Drugs 0.000 description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 2
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 2
- 238000012877 positron emission topography Methods 0.000 description 2
- 238000010149 post-hoc-test Methods 0.000 description 2
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 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(=O)NCC(O)=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 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- WPDCHTSXOPUOII-UHFFFAOYSA-N propan-2-yl 4-[5-methoxy-6-[(2-methyl-6-methylsulfonylpyridin-3-yl)amino]pyrimidin-4-yl]oxypiperidine-1-carboxylate Chemical compound N1=CN=C(OC2CCN(CC2)C(=O)OC(C)C)C(OC)=C1NC1=CC=C(S(C)(=O)=O)N=C1C WPDCHTSXOPUOII-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 108010002387 rat G-protein-coupled receptor 40 Proteins 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229960004586 rosiglitazone Drugs 0.000 description 2
- 230000036186 satiety Effects 0.000 description 2
- 235000019627 satiety Nutrition 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229960004425 sibutramine Drugs 0.000 description 2
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 150000003413 spiro compounds Chemical class 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 2
- 229950004704 tesaglitazar Drugs 0.000 description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 229960004394 topiramate Drugs 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- YKXCWZVUWWQSAV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O YKXCWZVUWWQSAV-BTVCFUMJSA-N 0.000 description 1
- NRESDXFFSNBDGP-UHFFFAOYSA-N (4-bromophenyl)hydrazine Chemical compound NNC1=CC=C(Br)C=C1 NRESDXFFSNBDGP-UHFFFAOYSA-N 0.000 description 1
- RGGOWBBBHWTTRE-UHFFFAOYSA-N (4-bromophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Br)C=C1 RGGOWBBBHWTTRE-UHFFFAOYSA-N 0.000 description 1
- FQHCPFMTXFJZJS-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.COC1=CC=C(NN)C=C1 FQHCPFMTXFJZJS-UHFFFAOYSA-N 0.000 description 1
- ISJGNUFTQTZLEZ-UHFFFAOYSA-N (5-ethoxy-2-fluorophenyl)boronic acid Chemical compound CCOC1=CC=C(F)C(B(O)O)=C1 ISJGNUFTQTZLEZ-UHFFFAOYSA-N 0.000 description 1
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- DTYGKGVYCRETGD-UHFFFAOYSA-N 1-(3-chloropyridin-2-yl)piperidin-4-ol Chemical compound C1CC(O)CCN1C1=NC=CC=C1Cl DTYGKGVYCRETGD-UHFFFAOYSA-N 0.000 description 1
- OXBUCKZAUJPPAG-UHFFFAOYSA-N 1-benzyl-1-methylpiperidin-1-ium-4-one Chemical compound C=1C=CC=CC=1C[N+]1(C)CCC(=O)CC1 OXBUCKZAUJPPAG-UHFFFAOYSA-N 0.000 description 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- GSIJWAWHEAADOE-UHFFFAOYSA-N 2,2,2-trifluoro-N-(4-methoxyphenyl)ethanehydrazonoyl chloride Chemical compound COC1=CC=C(NN=C(Cl)C(F)(F)F)C=C1 GSIJWAWHEAADOE-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- IIXKLOGFKNVIFZ-UHFFFAOYSA-N 2-(4-hydroxypiperidin-1-yl)-4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C(N2CCC(O)CC2)=C1 IIXKLOGFKNVIFZ-UHFFFAOYSA-N 0.000 description 1
- FOFXXEHXOCAJIW-GNAFDRTKSA-N 2-[(3s)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid;hydrate Chemical compound O.CC1=CC(OCCCS(C)(=O)=O)=CC(C)=C1C1=CC=CC(COC=2C=C3OC[C@@H](CC(O)=O)C3=CC=2)=C1 FOFXXEHXOCAJIW-GNAFDRTKSA-N 0.000 description 1
- NHRPLLYDAGPXEM-KWQFWETISA-N 2-[(3s,4s)-2-(4-hydroxyphenyl)-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC#N)N1C1=CC=C(O)C=C1 NHRPLLYDAGPXEM-KWQFWETISA-N 0.000 description 1
- ZHBGQAFMSVMGQK-PZXGUROGSA-N 2-[(3s,4s)-2-[2-bromo-4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound C1=NC(OC)=CC(N2C[C@@H](C)[C@H](OC=3C=C(Br)C(N4[C@H]([C@H](C)C(=N4)C(F)(F)F)CC(O)=O)=CC=3)CC2)=C1Cl ZHBGQAFMSVMGQK-PZXGUROGSA-N 0.000 description 1
- GKIUHMMLGAMMOO-OITFXXTJSA-N 2-[(3s,4s)-2-[4-[(3r,4r)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound C1=NC(OC)=CC(N2C[C@@H](C)[C@H](OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1Cl GKIUHMMLGAMMOO-OITFXXTJSA-N 0.000 description 1
- OXXWCNFGCMKWBQ-QKKBWIMNSA-N 2-[(3s,4s)-2-[4-[1-(2-chloro-4-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC(F)=CC=2)Cl)CC1 OXXWCNFGCMKWBQ-QKKBWIMNSA-N 0.000 description 1
- WFIAZYYRGHOSJV-XOBRGWDASA-N 2-[(3s,4s)-2-[4-[1-(2-chloro-5-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(F)C=2)Cl)CC1 WFIAZYYRGHOSJV-XOBRGWDASA-N 0.000 description 1
- LDEMUVRKIAJJIT-KKSFZXQISA-N 2-[(3s,4s)-2-[4-[1-(2-chloro-5-methylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(C)C=2)Cl)CC1 LDEMUVRKIAJJIT-KKSFZXQISA-N 0.000 description 1
- DQOFMAKUEQVNJT-SBUREZEXSA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-propan-2-yloxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CC(C)OC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 DQOFMAKUEQVNJT-SBUREZEXSA-N 0.000 description 1
- ONUDKIOYQKSUBP-SBUREZEXSA-N 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-propan-2-ylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CC(C)C1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 ONUDKIOYQKSUBP-SBUREZEXSA-N 0.000 description 1
- GGQJDBOKWQUBOZ-SBUREZEXSA-N 2-[(3s,4s)-2-[4-[1-(3-ethylphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCC1=CC=CC(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 GGQJDBOKWQUBOZ-SBUREZEXSA-N 0.000 description 1
- FDJSTRBHDCPCBS-YWZLYKJASA-N 2-[(3s,4s)-2-[4-[1-(3-fluoro-6-methylpyridin-2-yl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(C)N=2)F)CC1 FDJSTRBHDCPCBS-YWZLYKJASA-N 0.000 description 1
- XPADCVCRAXFACB-XOBRGWDASA-N 2-[(3s,4s)-2-[4-[1-(5-chloro-2-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(Cl)C=2)F)CC1 XPADCVCRAXFACB-XOBRGWDASA-N 0.000 description 1
- ZKFGTDVZUUMPNA-OXVDWMRYSA-N 2-[(3s,4s)-2-[4-[1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-ethyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound N1=C(C(F)(F)F)[C@@H](CC)[C@H](CC#N)N1C(C=C1)=CC=C1OC1C(C)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 ZKFGTDVZUUMPNA-OXVDWMRYSA-N 0.000 description 1
- GKIUHMMLGAMMOO-XUCZDEIVSA-N 2-[(3s,4s)-2-[4-[1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound C1=NC(OC)=CC(N2CC(C)C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1Cl GKIUHMMLGAMMOO-XUCZDEIVSA-N 0.000 description 1
- JMYJLQIGTXKKMX-BTYIYWSLSA-N 2-[(3s,4s)-2-[4-[1-(5-ethoxy-2,3-difluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC(F)=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 JMYJLQIGTXKKMX-BTYIYWSLSA-N 0.000 description 1
- DFZWAEBMOVDYJJ-CCBCBXNLSA-N 2-[(3s,4s)-2-[4-[1-(5-ethoxy-2-fluorophenyl)-3-(2-methylpropyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC=C(F)C(N2CC(CC(C)C)C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)=C1 DFZWAEBMOVDYJJ-CCBCBXNLSA-N 0.000 description 1
- PZGHKSONVASQOV-DBGXNLSQSA-N 2-[(3s,4s)-2-[4-[1-(5-ethoxy-2-fluorophenyl)-3-propan-2-ylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC=C(F)C(N2CC(C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(O)=O)CC2)C(C)C)=C1 PZGHKSONVASQOV-DBGXNLSQSA-N 0.000 description 1
- VUONWOPWXLYFSM-AOMKIAJQSA-N 2-[(3s,4s)-2-[4-[1-(5-ethoxy-2-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCOC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 VUONWOPWXLYFSM-AOMKIAJQSA-N 0.000 description 1
- WDNGSOMEBLSPOB-AOMKIAJQSA-N 2-[(3s,4s)-2-[4-[1-(5-ethyl-2-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound CCC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C(F)(F)F)CC(O)=O)=C1 WDNGSOMEBLSPOB-AOMKIAJQSA-N 0.000 description 1
- LQYLABAOJHAEJE-KXBFYZLASA-N 2-[(3s,4s)-4-methyl-2-[4-(1-pyridin-2-ylpiperidin-4-yl)oxyphenyl]-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2N=CC=CC=2)CC1 LQYLABAOJHAEJE-KXBFYZLASA-N 0.000 description 1
- AESDZOKSLPFBJN-YWZLYKJASA-N 2-[(3s,4s)-4-methyl-2-[4-(1-pyridin-3-ylpiperidin-4-yl)oxyphenyl]-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)[C@@H](C)[C@H](CC(O)=O)N1C(C=C1)=CC=C1OC1CCN(C=2C=NC=CC=2)CC1 AESDZOKSLPFBJN-YWZLYKJASA-N 0.000 description 1
- SVYHZELRVIHYPW-MMTVBGGISA-N 2-[(3s,4s)-5-(4-cyanophenyl)-2-[4-[1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C=2C=CC(=CC=2)C#N)CC(O)=O)=C1 SVYHZELRVIHYPW-MMTVBGGISA-N 0.000 description 1
- YVKYARITUXKCGJ-SJCJKPOMSA-N 2-[(3s,4s)-5-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-methyl-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound C=1C=C(O)C=CC=1N([C@@H](CC#N)[C@@H]1C)N=C1C1=CC=C(F)C=C1 YVKYARITUXKCGJ-SJCJKPOMSA-N 0.000 description 1
- WNUOPTPKKBBJGA-KKSFZXQISA-N 2-[(3s,4s)-5-(4-fluorophenyl)-4-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3,4-dihydropyrazol-3-yl]acetonitrile Chemical compound C=1C=C(B2OC(C)(C)C(C)(C)O2)C=CC=1N([C@@H](CC#N)[C@@H]1C)N=C1C1=CC=C(F)C=C1 WNUOPTPKKBBJGA-KKSFZXQISA-N 0.000 description 1
- HCEIREGNGXJBBH-UHFFFAOYSA-N 2-[1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl]-4-methylbenzenesulfonic acid Chemical compound COc1ccc(F)c(c1)N1CCC(CC1)c1cc(C)ccc1S(O)(=O)=O HCEIREGNGXJBBH-UHFFFAOYSA-N 0.000 description 1
- CUBLEMVUJFXFEK-UHFFFAOYSA-N 2-[2-[4-[1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-pyrimidin-2-yl-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound COC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2C(C(C)C(=N2)C=2N=CC=CN=2)CC(O)=O)=C1 CUBLEMVUJFXFEK-UHFFFAOYSA-N 0.000 description 1
- HQKYFCHKNWKZHJ-UHFFFAOYSA-N 2-[2-[4-[1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-ethyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetic acid Chemical compound N1=C(C(F)(F)F)C(CC)C(CC(O)=O)N1C(C=C1)=CC=C1OC1C(C)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 HQKYFCHKNWKZHJ-UHFFFAOYSA-N 0.000 description 1
- PTIFVLOBVCIMKL-UHFFFAOYSA-N 2-[3-[1-(4-chlorophenyl)cyclopropyl]-[1,2,4]triazolo[4,3-a]pyridin-8-yl]propan-2-ol Chemical compound N=1N=C2C(C(C)(O)C)=CC=CN2C=1C1(C=2C=CC(Cl)=CC=2)CC1 PTIFVLOBVCIMKL-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- LYIGJBQYDRJPIR-UHFFFAOYSA-N 2-bromo-1-fluoro-4-methoxybenzene Chemical compound COC1=CC=C(F)C(Br)=C1 LYIGJBQYDRJPIR-UHFFFAOYSA-N 0.000 description 1
- TUHIBIVYQLRGME-UHFFFAOYSA-N 2-cyclopropylacetaldehyde Chemical compound O=CCC1CC1 TUHIBIVYQLRGME-UHFFFAOYSA-N 0.000 description 1
- HWKUZTFIZATJPM-UHFFFAOYSA-N 2-fluoro-4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C(F)=C1 HWKUZTFIZATJPM-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- ZRTWIJKGTUGZJY-UHFFFAOYSA-N 3,4,5-trifluorophenol Chemical compound OC1=CC(F)=C(F)C(F)=C1 ZRTWIJKGTUGZJY-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- QWTULQLVGNZMLF-UHFFFAOYSA-N 3-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C(Br)=C1 QWTULQLVGNZMLF-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- GDPKNRYGURPYLM-UHFFFAOYSA-N 3-fluoro-1-(2-fluoro-5-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC=C(F)C(N2CC(F)C(O)CC2)=C1 GDPKNRYGURPYLM-UHFFFAOYSA-N 0.000 description 1
- QXHUSGWCFSXQMF-UHFFFAOYSA-N 3-fluoro-4-formylbenzonitrile Chemical compound FC1=CC(C#N)=CC=C1C=O QXHUSGWCFSXQMF-UHFFFAOYSA-N 0.000 description 1
- UNEODYCUKKLMFS-DETVKUJNSA-N 4-[(3r,4s)-2-(4-methoxyphenyl)-4-methyl-3-[(4s)-2-oxo-4-phenyl-1,3-oxazolidine-3-carbonyl]-3,4-dihydropyrazol-5-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1N1[C@@H](C(=O)N2C(OC[C@@H]2C=2C=CC=CC=2)=O)[C@H](C)C(C=2C=CC(=CC=2)C#N)=N1 UNEODYCUKKLMFS-DETVKUJNSA-N 0.000 description 1
- SIMVAULELCJICH-UGSOOPFHSA-N 4-[(3r,4s)-3-(hydroxymethyl)-2-(4-methoxyphenyl)-4-methyl-3,4-dihydropyrazol-5-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1N1[C@@H](CO)[C@H](C)C(C=2C=CC(=CC=2)C#N)=N1 SIMVAULELCJICH-UGSOOPFHSA-N 0.000 description 1
- UGHDJPAIZKGTAH-SGTLLEGYSA-N 4-[(3s,4s)-3-(cyanomethyl)-2-(4-hydroxyphenyl)-4-methyl-3,4-dihydropyrazol-5-yl]-3-fluorobenzonitrile Chemical compound C=1C=C(O)C=CC=1N([C@@H](CC#N)[C@@H]1C)N=C1C1=CC=C(C#N)C=C1F UGHDJPAIZKGTAH-SGTLLEGYSA-N 0.000 description 1
- HMSWZVDZLQOOOM-UGSOOPFHSA-N 4-[(3s,4s)-3-(cyanomethyl)-2-(4-hydroxyphenyl)-4-methyl-3,4-dihydropyrazol-5-yl]benzonitrile Chemical compound C=1C=C(O)C=CC=1N([C@@H](CC#N)[C@@H]1C)N=C1C1=CC=C(C#N)C=C1 HMSWZVDZLQOOOM-UGSOOPFHSA-N 0.000 description 1
- HTJZGZJTDAKICR-OALUTQOASA-N 4-[(3s,4s)-3-(cyanomethyl)-4-ethyl-2-(4-hydroxyphenyl)-3,4-dihydropyrazol-5-yl]benzonitrile Chemical compound C=1C=C(O)C=CC=1N([C@@H](CC#N)[C@@H]1CC)N=C1C1=CC=C(C#N)C=C1 HTJZGZJTDAKICR-OALUTQOASA-N 0.000 description 1
- BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 1
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
- DZIMITACCINBLU-UHFFFAOYSA-N 4-ethoxy-1,2-difluorobenzene Chemical compound CCOC1=CC=C(F)C(F)=C1 DZIMITACCINBLU-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- RPJXLEZOFUNGNZ-UHFFFAOYSA-N 5-methoxy-2-methylaniline Chemical compound COC1=CC=C(C)C(N)=C1 RPJXLEZOFUNGNZ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
- 208000011732 Abnormal glucose homeostasis Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 238000006218 Arndt-Eistert homologation reaction Methods 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 102100025892 Complement C1q tumor necrosis factor-related protein 1 Human genes 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 101000983970 Conus catus Alpha-conotoxin CIB Proteins 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- 229940125827 GPR40 agonist Drugs 0.000 description 1
- 101710196151 Gamma-glutamyl phosphate reductase 1 Proteins 0.000 description 1
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 1
- 241001295925 Gegenes Species 0.000 description 1
- 206010056740 Genital discharge Diseases 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000577121 Homo sapiens Monocarboxylate transporter 3 Proteins 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010049287 Lipodystrophy acquired Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 102100025275 Monocarboxylate transporter 3 Human genes 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- VJDDQSBNUHLBTD-GGWOSOGESA-N [(e)-but-2-enoyl] (e)-but-2-enoate Chemical compound C\C=C\C(=O)OC(=O)\C=C\C VJDDQSBNUHLBTD-GGWOSOGESA-N 0.000 description 1
- 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 1
- PLRRQJHCQDMKOU-UHFFFAOYSA-N [4-ethyl-2-(4-methoxyphenyl)-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]methyl methanesulfonate Chemical compound N1=C(C(F)(F)F)C(CC)C(COS(C)(=O)=O)N1C1=CC=C(OC)C=C1 PLRRQJHCQDMKOU-UHFFFAOYSA-N 0.000 description 1
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
- 201000010272 acanthosis nigricans Diseases 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- QYLGNJMIOVHLQQ-UHFFFAOYSA-N benzyl 2-dimethoxyphosphorylacetate Chemical compound COP(=O)(OC)CC(=O)OCC1=CC=CC=C1 QYLGNJMIOVHLQQ-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000005621 boronate group Chemical group 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 238000006795 borylation reaction Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000004452 carbocyclyl group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- AGCOMFFHXJMNLN-UHFFFAOYSA-N dichloromethane;dihydrochloride Chemical compound Cl.Cl.ClCCl AGCOMFFHXJMNLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 210000003158 enteroendocrine cell Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- ROSZJQBQGFBFSW-UHFFFAOYSA-N ethyl 1-benzyl-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC=CC=C1 ROSZJQBQGFBFSW-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003629 gastrointestinal hormone Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 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 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 125000004995 haloalkylthio group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
- 102000052080 human FFAR1 Human genes 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 150000004680 hydrogen peroxides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000004926 indolenyl group Chemical group 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000005438 isoindazolyl group Chemical group 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000006132 lipodystrophy Diseases 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229940057952 methanol Drugs 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- UPFKWTQHZNFBSJ-RUHLTRSKSA-N methyl 2-[(3s,4s)-2-[4-[(3r,4r)-1-(2,3-difluoro-5-methoxyphenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1O[C@H]1[C@H](C)CN(C=2C(=C(F)C=C(OC)C=2)F)CC1 UPFKWTQHZNFBSJ-RUHLTRSKSA-N 0.000 description 1
- JODZCDYQQXYRIJ-BTYIYWSLSA-N methyl 2-[(3s,4s)-2-[4-[1-(2,3-difluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1CCN(C=2C(=C(F)C=C(OC)C=2)F)CC1 JODZCDYQQXYRIJ-BTYIYWSLSA-N 0.000 description 1
- GSYWVMUQOWCVFI-AOMKIAJQSA-N methyl 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(OC)C=2)F)CC1 GSYWVMUQOWCVFI-AOMKIAJQSA-N 0.000 description 1
- PMZRXERLDNPDKB-DMXFUWGJSA-N methyl 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-propan-2-yloxyphenyl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1C(C)CN(C=2C(=CC=C(OC(C)C)C=2)F)CC1 PMZRXERLDNPDKB-DMXFUWGJSA-N 0.000 description 1
- TZYDKNDKEIVQKX-UUOWRZLLSA-N methyl 2-[(3s,4s)-2-[4-[1-(2-fluoro-5-propan-2-yloxyphenyl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=C(OC(C)C)C=2)F)CC1 TZYDKNDKEIVQKX-UUOWRZLLSA-N 0.000 description 1
- MMMCCFBIMFMDLS-YWZLYKJASA-N methyl 2-[(3s,4s)-2-[4-[1-(3-chloropyridin-2-yl)piperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1CCN(C=2C(=CC=CN=2)Cl)CC1 MMMCCFBIMFMDLS-YWZLYKJASA-N 0.000 description 1
- HINLLPFJTNQOIB-HQXCXSBDSA-N methyl 2-[(3s,4s)-2-[4-[1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C(C=C1)=CC=C1OC1C(C)CN(C=2C(=CN=C(OC)C=2)Cl)CC1 HINLLPFJTNQOIB-HQXCXSBDSA-N 0.000 description 1
- IRJZNNDXKGVBBH-HYIFPIRGSA-N methyl 2-[(3s,4s)-2-[4-[1-(5-ethoxy-2-fluorophenyl)-3-ethylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound CCOC1=CC=C(F)C(N2CC(CC)C(OC=3C=CC(=CC=3)N3[C@H]([C@H](C)C(=N3)C(F)(F)F)CC(=O)OC)CC2)=C1 IRJZNNDXKGVBBH-HYIFPIRGSA-N 0.000 description 1
- BGCYEHGRIQLVTN-WFASDCNBSA-N methyl 2-[(3s,4s)-4-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound COC(=O)C[C@H]1[C@H](C)C(C(F)(F)F)=NN1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1 BGCYEHGRIQLVTN-WFASDCNBSA-N 0.000 description 1
- UTSHMRAHRYYREY-CHJDUVSTSA-N methyl 2-[(3s,4s)-5-(4-cyanophenyl)-2-[4-[1-(5-ethoxy-2-fluorophenyl)piperidin-4-yl]oxyphenyl]-4-methyl-3,4-dihydropyrazol-3-yl]acetate Chemical compound CCOC1=CC=C(F)C(N2CCC(CC2)OC=2C=CC(=CC=2)N2[C@H]([C@H](C)C(=N2)C=2C=CC(=CC=2)C#N)CC(=O)OC)=C1 UTSHMRAHRYYREY-CHJDUVSTSA-N 0.000 description 1
- IRJZNNDXKGVBBH-UHFFFAOYSA-N methyl 2-[2-[4-[1-(5-ethoxy-2-fluorophenyl)-3-ethylpiperidin-4-yl]oxyphenyl]-4-methyl-5-(trifluoromethyl)-3,4-dihydropyrazol-3-yl]acetate Chemical compound CCOC1=CC=C(F)C(N2CC(CC)C(OC=3C=CC(=CC=3)N3C(C(C)C(=N3)C(F)(F)F)CC(=O)OC)CC2)=C1 IRJZNNDXKGVBBH-UHFFFAOYSA-N 0.000 description 1
- MCVVUJPXSBQTRZ-UHFFFAOYSA-N methyl but-2-enoate Chemical compound COC(=O)C=CC MCVVUJPXSBQTRZ-UHFFFAOYSA-N 0.000 description 1
- BRWZPVRDOUWXKE-UHFFFAOYSA-N methylsulfanylmethane;trifluoroborane Chemical compound CSC.FB(F)F BRWZPVRDOUWXKE-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- VDCLSGXZVUDARN-UHFFFAOYSA-N molecular bromine;pyridine;hydrobromide Chemical compound Br.BrBr.C1=CC=NC=C1 VDCLSGXZVUDARN-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006070 nanosuspension Substances 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 238000005016 nuclear Overhauser enhanced spectroscopy Methods 0.000 description 1
- 238000012587 nuclear overhauser effect experiment Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000029537 positive regulation of insulin secretion Effects 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000012041 precatalyst Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000033300 receptor internalization Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000003979 response to food Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010922 spray-dried dispersion Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000005403 thiohaloalkoxy group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VJDDQSBNUHLBTD-UHFFFAOYSA-N trans-crotonic acid-anhydride Natural products CC=CC(=O)OC(=O)C=CC VJDDQSBNUHLBTD-UHFFFAOYSA-N 0.000 description 1
- YIYBQIKDCADOSF-ONEGZZNKSA-N trans-pent-2-enoic acid Chemical compound CC\C=C\C(O)=O YIYBQIKDCADOSF-ONEGZZNKSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- 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
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Optical Integrated Circuits (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261727262P | 2012-11-16 | 2012-11-16 | |
| US201361777294P | 2013-03-12 | 2013-03-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE032401T2 true HUE032401T2 (en) | 2017-09-28 |
Family
ID=49876965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE13811645A HUE032401T2 (en) | 2012-11-16 | 2013-11-15 | Dihydropyrazole GPR40 modulators |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US9133163B2 (enExample) |
| EP (1) | EP2920165B1 (enExample) |
| JP (1) | JP6322203B2 (enExample) |
| KR (1) | KR102204804B1 (enExample) |
| CN (1) | CN104812748B (enExample) |
| AU (1) | AU2013344604B2 (enExample) |
| BR (1) | BR112015010779A2 (enExample) |
| CA (1) | CA2891574A1 (enExample) |
| CY (1) | CY1118365T1 (enExample) |
| DK (1) | DK2920165T3 (enExample) |
| EA (1) | EA026913B1 (enExample) |
| ES (1) | ES2606685T3 (enExample) |
| HR (1) | HRP20161631T1 (enExample) |
| HU (1) | HUE032401T2 (enExample) |
| IL (1) | IL238741A0 (enExample) |
| LT (1) | LT2920165T (enExample) |
| MX (1) | MX358499B (enExample) |
| PL (1) | PL2920165T3 (enExample) |
| PT (1) | PT2920165T (enExample) |
| RS (1) | RS55363B1 (enExample) |
| SG (1) | SG11201503558SA (enExample) |
| SI (1) | SI2920165T1 (enExample) |
| SM (1) | SMT201600410B (enExample) |
| TW (1) | TW201427971A (enExample) |
| UY (1) | UY35143A (enExample) |
| WO (1) | WO2014078610A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201503556PA (en) * | 2012-11-16 | 2015-06-29 | Bristol Myers Squibb Co | Dihydropyrazole gpr40 modulators |
| CA2928097A1 (en) | 2013-11-14 | 2015-07-02 | Cadila Healthcare Limited | Novel heterocyclic compounds |
| BR112016025188A2 (pt) * | 2014-05-07 | 2017-08-15 | Bristol Myers Squibb Co | moduladores de pirrolidina gpr40 para o tratamento de doenças tal como diabetes |
| BR112016024936A2 (pt) | 2014-05-07 | 2017-08-15 | Bristol Myers Squibb Co | moduladores de gpr40 à base de pirrolidina para tratamento de doenças como diabetes |
| WO2016019587A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | [7, 6]-fused bicyclic antidiabetic compounds |
| WO2016022448A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| WO2016022742A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| US10100042B2 (en) | 2014-08-08 | 2018-10-16 | Merck Sharp & Dohme Corp. | [5,6]—fused bicyclic antidiabetic compounds |
| CN110719903A (zh) | 2017-03-31 | 2020-01-21 | 武田药品工业株式会社 | 芳族环化合物 |
| SI3752501T1 (sl) | 2018-02-13 | 2023-08-31 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| CA3093130C (en) | 2018-04-19 | 2023-10-17 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| SI3820572T1 (sl) | 2018-07-13 | 2023-12-29 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ, インコーポレイテッド | Pd-1/pd-l1阻害剤 |
| CN115490638A (zh) * | 2022-09-22 | 2022-12-20 | 哈尔滨理工大学 | 5-官能团化吡唑啉及其制备方法 |
| CN115671105B (zh) * | 2022-11-22 | 2023-10-27 | 北京箭牧科技有限公司 | Ly2922470在制备预防或治疗肾脏疾病药物中的应用 |
| CN119431272B (zh) * | 2024-11-13 | 2025-07-25 | 北京斯利安药业有限公司 | (s)-3-甲基-(2-哌啶基苯基)-1-丁胺乙酰谷氨酸盐的制备方法 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5614492A (en) | 1986-05-05 | 1997-03-25 | The General Hospital Corporation | Insulinotropic hormone GLP-1 (7-36) and uses thereof |
| WO2003099793A1 (en) | 2002-05-24 | 2003-12-04 | Takeda Pharmaceutical Company Limited | 1,2-azole derivatives with hypoglycemic and hypolipidemic activity |
| WO2004004665A2 (en) | 2002-07-09 | 2004-01-15 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
| US7501440B2 (en) | 2003-03-07 | 2009-03-10 | Sanofi-Aventis Deutschland Gmbh | Substituted benzoylureidopyridylpiperidine-and-pyrrolidinecarboxylic acid derivatives, processes for preparing them and their use |
| US6995183B2 (en) | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
| KR20060135815A (ko) * | 2004-02-17 | 2006-12-29 | 라보라토리오스 델 드라. 에스테브.에스.에이. | 혈중 트리글리세리드를 감소시키기 위한 치환된 피라졸린화합물 |
| EP1637522A1 (en) * | 2004-09-16 | 2006-03-22 | Laboratorios Del Dr. Esteve, S.A. | Substituted pyrazoline compounds for reducing triglycerides in blood |
| US7816367B2 (en) | 2004-02-27 | 2010-10-19 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders |
| US7517910B2 (en) | 2004-03-30 | 2009-04-14 | Takeda Pharmaceutical Company Limited | Alkoxyphenylpropanoic acid derivatives |
| JP2007284350A (ja) | 2004-07-27 | 2007-11-01 | Takeda Chem Ind Ltd | 糖尿病治療剤 |
| US7465804B2 (en) | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
| EP1743894A1 (en) * | 2005-07-15 | 2007-01-17 | Laboratorios Del Dr. Esteve, S.A. | Heterocyclyl-substituted pyrazoline compounds, their preparation and use as medicaments |
| WO2007013689A1 (ja) | 2005-07-29 | 2007-02-01 | Takeda Pharmaceutical Company Limited | シクロプロパンカルボン酸化合物 |
| CA2621949A1 (en) | 2005-09-14 | 2007-03-22 | Amgen Inc. | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
| JP2009530281A (ja) | 2006-03-14 | 2009-08-27 | アムジエン・インコーポレーテツド | 代謝障害の治療に有用である二環式カルボン酸誘導体 |
| CL2007001873A1 (es) | 2006-06-27 | 2008-01-04 | Takeda Pharmaceutical | Acido((3s))-6-((¨2,6-dimetil-4-(3-(metilsulfonil)-propoxi)bifenil-3-il)metoxi-2,3-dihidro-1-benzofuran-3-il)acetico o una sal del mismo |
| EP2064193A1 (en) | 2006-09-07 | 2009-06-03 | Amgen, Inc | Heterocyclic gpr40 modulators |
| WO2008054675A2 (en) | 2006-10-31 | 2008-05-08 | Merck & Co., Inc. | Antidiabetic bicyclic compounds |
| ES2446419T3 (es) | 2007-04-16 | 2014-03-07 | Amgen, Inc | Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos |
| WO2009048527A1 (en) | 2007-10-10 | 2009-04-16 | Amgen Inc. | Substituted biphenyl gpr40 modulators |
| MX2010004435A (es) | 2007-10-26 | 2010-05-13 | Japan Tobacco Inc | Compuestos espiro y uso farmaceutico de los mismos. |
| AR070898A1 (es) * | 2008-03-18 | 2010-05-12 | Solvay Pharm Bv | Derivados de arilsulfonil pirazolin carboxamidina como antagonistas de 5-ht6 |
| US8236821B2 (en) * | 2008-05-19 | 2012-08-07 | Jenrin Discovery, Inc. | Substituted N-phenyl-5-phenyl-pyrazolin-3-yl amides as cannabinoid receptor antagonists/inverse agonists useful for treating obesity |
| EP2486005B1 (en) * | 2009-10-06 | 2014-06-18 | Bristol-Myers Squibb Company | Pyrrolidine gpr40 modulators |
| AR078522A1 (es) | 2009-10-15 | 2011-11-16 | Lilly Co Eli | Compuesto de espiropiperidina, composicion farmaceutica que lo comprende, su uso para preparar un medicamento util para tratar diabetes y compuesto intermediario para su sintesis |
| JP5946192B2 (ja) * | 2010-11-18 | 2016-07-05 | ジェンリン ディスカバリーJenrin Discovery | 肥満症及び糖尿病を含む代謝性疾患の処置に有用なカンナビノイド受容体拮抗薬/逆作動薬 |
| WO2012069917A1 (en) * | 2010-11-26 | 2012-05-31 | Lupin Limited | Bicyclic gpr119 modulators |
| US8791091B2 (en) | 2011-12-02 | 2014-07-29 | Bristol-Myers Squibb Company | Aryl dihydropyridinone and piperidinone MGAT2 inhibitors |
| US9326218B2 (en) * | 2012-11-02 | 2016-04-26 | Telefonaktiebolaget L M Ericsson (Publ) | Base-station-to-base-station gateway and related devices, methods, and systems |
| SG11201503556PA (en) * | 2012-11-16 | 2015-06-29 | Bristol Myers Squibb Co | Dihydropyrazole gpr40 modulators |
| US8962660B2 (en) * | 2013-03-14 | 2015-02-24 | Bristol-Myers Squibb Company | Oxabicyclo [2.2.2] acid GPR120 modulators |
-
2013
- 2013-11-15 EA EA201590954A patent/EA026913B1/ru not_active IP Right Cessation
- 2013-11-15 RS RS20161061A patent/RS55363B1/sr unknown
- 2013-11-15 CA CA2891574A patent/CA2891574A1/en not_active Abandoned
- 2013-11-15 SI SI201330340T patent/SI2920165T1/sl unknown
- 2013-11-15 LT LTEP13811645.4T patent/LT2920165T/lt unknown
- 2013-11-15 EP EP13811645.4A patent/EP2920165B1/en active Active
- 2013-11-15 KR KR1020157015541A patent/KR102204804B1/ko not_active Expired - Fee Related
- 2013-11-15 UY UY0001035143A patent/UY35143A/es not_active Application Discontinuation
- 2013-11-15 US US14/081,094 patent/US9133163B2/en active Active
- 2013-11-15 BR BR112015010779A patent/BR112015010779A2/pt not_active Application Discontinuation
- 2013-11-15 DK DK13811645.4T patent/DK2920165T3/en active
- 2013-11-15 ES ES13811645.4T patent/ES2606685T3/es active Active
- 2013-11-15 AU AU2013344604A patent/AU2013344604B2/en not_active Ceased
- 2013-11-15 PL PL13811645T patent/PL2920165T3/pl unknown
- 2013-11-15 WO PCT/US2013/070215 patent/WO2014078610A1/en not_active Ceased
- 2013-11-15 JP JP2015542798A patent/JP6322203B2/ja not_active Expired - Fee Related
- 2013-11-15 HR HRP20161631TT patent/HRP20161631T1/hr unknown
- 2013-11-15 HU HUE13811645A patent/HUE032401T2/en unknown
- 2013-11-15 PT PT138116454T patent/PT2920165T/pt unknown
- 2013-11-15 SG SG11201503558SA patent/SG11201503558SA/en unknown
- 2013-11-15 MX MX2015005735A patent/MX358499B/es active IP Right Grant
- 2013-11-15 CN CN201380059799.5A patent/CN104812748B/zh not_active Expired - Fee Related
- 2013-11-15 TW TW102141762A patent/TW201427971A/zh unknown
-
2015
- 2015-05-11 IL IL238741A patent/IL238741A0/en not_active IP Right Cessation
-
2016
- 2016-11-14 SM SM201600410T patent/SMT201600410B/it unknown
- 2016-12-16 CY CY20161101309T patent/CY1118365T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CY1118365T1 (el) | 2017-06-28 |
| BR112015010779A2 (pt) | 2017-07-11 |
| KR20150082616A (ko) | 2015-07-15 |
| EA026913B1 (ru) | 2017-05-31 |
| LT2920165T (lt) | 2016-12-12 |
| RS55363B1 (sr) | 2017-03-31 |
| SMT201600410B (it) | 2017-01-10 |
| EA201590954A1 (ru) | 2015-08-31 |
| AU2013344604B2 (en) | 2017-07-27 |
| US20140142139A1 (en) | 2014-05-22 |
| ES2606685T3 (es) | 2017-03-27 |
| US9133163B2 (en) | 2015-09-15 |
| KR102204804B1 (ko) | 2021-01-18 |
| CN104812748A (zh) | 2015-07-29 |
| AU2013344604A1 (en) | 2015-07-02 |
| UY35143A (es) | 2014-05-30 |
| CN104812748B (zh) | 2017-10-24 |
| PL2920165T3 (pl) | 2017-04-28 |
| MX2015005735A (es) | 2015-09-16 |
| DK2920165T3 (en) | 2017-01-16 |
| EP2920165A1 (en) | 2015-09-23 |
| CA2891574A1 (en) | 2014-05-22 |
| TW201427971A (zh) | 2014-07-16 |
| PT2920165T (pt) | 2016-12-20 |
| SG11201503558SA (en) | 2015-06-29 |
| HRP20161631T1 (hr) | 2017-01-13 |
| SI2920165T1 (sl) | 2017-02-28 |
| JP2016500063A (ja) | 2016-01-07 |
| IL238741A0 (en) | 2015-06-30 |
| JP6322203B2 (ja) | 2018-05-09 |
| EP2920165B1 (en) | 2016-09-28 |
| WO2014078610A1 (en) | 2014-05-22 |
| MX358499B (es) | 2018-08-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2920165T3 (en) | Dihydropyrazol-GPR40-MODULATORS | |
| EP2925749B1 (en) | Dihydropyrazole gpr40 modulators | |
| JP6322202B2 (ja) | ピロリジンgpr40修飾因子 | |
| EP2925726B1 (en) | Dihydropyrazole gpr40 modulators | |
| EP3140296A1 (en) | Pyrrolidine gpr40 modulators for the treatment of diseases such as diabetes |