TW201406739A

TW201406739A - 新穎二氫茚基氧基二氫苯并呋喃乙酸

新穎二氫茚基氧基二氫苯并呋喃乙酸 Download PDF

Info

Publication number: TW201406739A
Authority: TW; Taiwan
Prior art keywords: group; alkyl; yloxy; indan; dihydro
Prior art date: 2012-04-30

Application number

TW102115310A

Other languages

English (en)

Chinese (zh)

Inventor

Frank Himmelsbach

Matthias Eckhardt

Elke Langkopf

Stefan Peters

Original Assignee

Boehringer Ingelheim Int

Priority date

2012-04-30

Filing date

2013-04-29

Publication date

2014-02-16

2013-04-29 Application filed by Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int

2014-02-16 Publication of TW201406739A publication Critical patent/TW201406739A/zh

Links

RSYYSLLENSVCGM-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-2-yl)-2-(2,3-dihydro-1h-inden-1-yloxy)acetic acid Chemical class C1C2=CC=CC=C2OC1C(C(=O)O)OC1C2=CC=CC=C2CC1 RSYYSLLENSVCGM-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 202
102100026148 Free fatty acid receptor 1 Human genes 0.000 claims abstract description 38
101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 claims abstract description 37
238000011282 treatment Methods 0.000 claims abstract description 35
208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 28
208000030159 metabolic disease Diseases 0.000 claims abstract description 15
239000000203 mixture Substances 0.000 claims description 102
150000003839 salts Chemical class 0.000 claims description 49
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
201000010099 disease Diseases 0.000 claims description 39
229910052731 fluorine Inorganic materials 0.000 claims description 31
239000003814 drug Substances 0.000 claims description 27
125000001072 heteroaryl group Chemical group 0.000 claims description 24
229940124597 therapeutic agent Drugs 0.000 claims description 24
229910052801 chlorine Inorganic materials 0.000 claims description 22
206010012601 diabetes mellitus Diseases 0.000 claims description 21
239000008194 pharmaceutical composition Substances 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
208000008589 Obesity Diseases 0.000 claims description 18
235000020824 obesity Nutrition 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 14
229910052740 iodine Inorganic materials 0.000 claims description 14
206010022489 Insulin Resistance Diseases 0.000 claims description 11
125000004429 atom Chemical group 0.000 claims description 9
229910052794 bromium Inorganic materials 0.000 claims description 9
208000032928 Dyslipidaemia Diseases 0.000 claims description 8
206010020772 Hypertension Diseases 0.000 claims description 8
208000017170 Lipid metabolism disease Diseases 0.000 claims description 8
239000000969 carrier Substances 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
239000003795 chemical substances by application Substances 0.000 claims description 7
208000024172 Cardiovascular disease Diseases 0.000 claims description 6
206010033307 Overweight Diseases 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
201000001320 Atherosclerosis Diseases 0.000 claims description 4
239000003472 antidiabetic agent Substances 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
230000002265 prevention Effects 0.000 claims description 4
229940125708 antidiabetic agent Drugs 0.000 claims description 3
206010019280 Heart failures Diseases 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
230000000694 effects Effects 0.000 abstract description 4
102000005962 receptors Human genes 0.000 abstract description 4
108020003175 receptors Proteins 0.000 abstract description 4
230000000144 pharmacologic effect Effects 0.000 abstract description 3
230000006806 disease prevention Effects 0.000 abstract 1
238000000034 method Methods 0.000 description 192
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 183
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 98
238000001819 mass spectrum Methods 0.000 description 86
235000019439 ethyl acetate Nutrition 0.000 description 82
239000000543 intermediate Substances 0.000 description 81
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
-1 benzyl ester Chemical class 0.000 description 50
239000000243 solution Substances 0.000 description 46
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
238000006243 chemical reaction Methods 0.000 description 36
239000011734 sodium Substances 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 26
239000003054 catalyst Substances 0.000 description 26
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000007864 aqueous solution Substances 0.000 description 21
150000002148 esters Chemical class 0.000 description 20
239000000460 chlorine Substances 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 18
238000002360 preparation method Methods 0.000 description 18
239000002253 acid Substances 0.000 description 17
125000004432 carbon atom Chemical group C* 0.000 description 17
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 17
239000002904 solvent Substances 0.000 description 17
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
239000012267 brine Substances 0.000 description 14
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 12
239000002244 precipitate Substances 0.000 description 12
125000001424 substituent group Chemical group 0.000 description 12
239000002585 base Substances 0.000 description 11
238000001816 cooling Methods 0.000 description 11
125000003963 dichloro group Chemical group Cl* 0.000 description 11
239000000284 extract Substances 0.000 description 11
QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 11
239000003112 inhibitor Substances 0.000 description 11
239000003960 organic solvent Substances 0.000 description 11
238000004458 analytical method Methods 0.000 description 10
125000003118 aryl group Chemical group 0.000 description 10
229910002091 carbon monoxide Inorganic materials 0.000 description 10
230000008569 process Effects 0.000 description 10
229910052723 transition metal Inorganic materials 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
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 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
239000000556 agonist Substances 0.000 description 9
239000008280 blood Substances 0.000 description 9
210000004369 blood Anatomy 0.000 description 9
239000008103 glucose Substances 0.000 description 9
238000004128 high performance liquid chromatography Methods 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
239000000126 substance Substances 0.000 description 9
150000003624 transition metals Chemical class 0.000 description 9
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 8
208000002249 Diabetes Complications Diseases 0.000 description 8
102000004877 Insulin Human genes 0.000 description 8
108090001061 Insulin Proteins 0.000 description 8
239000002841 Lewis acid Substances 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 8
150000001732 carboxylic acid derivatives Chemical group 0.000 description 8
210000004027 cell Anatomy 0.000 description 8
239000012043 crude product Substances 0.000 description 8
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 8
238000009472 formulation Methods 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
229940125396 insulin Drugs 0.000 description 8
230000003914 insulin secretion Effects 0.000 description 8
150000007517 lewis acids Chemical class 0.000 description 8
230000001404 mediated effect Effects 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
238000007127 saponification reaction Methods 0.000 description 8
239000012453 solvate Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000011701 zinc Substances 0.000 description 8
206010012655 Diabetic complications Diseases 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 7
230000006870 function Effects 0.000 description 7
125000005842 heteroatom Chemical group 0.000 description 7
239000000859 incretin Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 6
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
208000001145 Metabolic Syndrome Diseases 0.000 description 6
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 6
230000004913 activation Effects 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
150000004677 hydrates Chemical class 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
238000004007 reversed phase HPLC Methods 0.000 description 6
208000024891 symptom Diseases 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
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 6
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 5
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 5
210000002237 B-cell of pancreatic islet Anatomy 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
208000017442 Retinal disease Diseases 0.000 description 5
206010038923 Retinopathy Diseases 0.000 description 5
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 5
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
239000012298 atmosphere Substances 0.000 description 5
125000005604 azodicarboxylate group Chemical group 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
201000001421 hyperglycemia Diseases 0.000 description 5
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 5
208000017169 kidney disease Diseases 0.000 description 5
239000011777 magnesium Substances 0.000 description 5
229910052749 magnesium Inorganic materials 0.000 description 5
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 5
201000001119 neuropathy Diseases 0.000 description 5
230000007823 neuropathy Effects 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
208000033808 peripheral neuropathy Diseases 0.000 description 5
230000009467 reduction Effects 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
229910052725 zinc Inorganic materials 0.000 description 5
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
208000031226 Hyperlipidaemia Diseases 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
QXCYVRCWYBSSLJ-QLJPJBMISA-N OC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3c(F)ccc4Br)ccc12 Chemical compound OC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3c(F)ccc4Br)ccc12 QXCYVRCWYBSSLJ-QLJPJBMISA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
KHKWHTCWOCAWME-UHFFFAOYSA-N acetylene benzene Chemical compound C#C.C1=CC=CC=C1.C#C KHKWHTCWOCAWME-UHFFFAOYSA-N 0.000 description 4
239000000654 additive Substances 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
238000003556 assay Methods 0.000 description 4
230000009286 beneficial effect Effects 0.000 description 4
HJCMMOODWZOXML-UHFFFAOYSA-N bromo hypobromite Chemical compound BrOBr HJCMMOODWZOXML-UHFFFAOYSA-N 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
125000000623 heterocyclic group Chemical group 0.000 description 4
150000002430 hydrocarbons Chemical group 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
239000007937 lozenge Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000002243 precursor Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 3
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
DGENZVKCTGIDRZ-UHFFFAOYSA-N 3-[4-[(3-phenoxyphenyl)methylamino]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1NCC1=CC=CC(OC=2C=CC=CC=2)=C1 DGENZVKCTGIDRZ-UHFFFAOYSA-N 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
208000008960 Diabetic foot Diseases 0.000 description 3
206010056340 Diabetic ulcer Diseases 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
108070000009 Free fatty acid receptors Proteins 0.000 description 3
229940125827 GPR40 agonist Drugs 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
125000000304 alkynyl group Chemical group 0.000 description 3
125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 description 3
125000002619 bicyclic group Chemical group 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
125000004452 carbocyclyl group Chemical group 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
210000003890 endocrine cell Anatomy 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
229910052742 iron Inorganic materials 0.000 description 3
239000003446 ligand Substances 0.000 description 3
210000004185 liver Anatomy 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
229910000073 phosphorus hydride Inorganic materials 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
231100000397 ulcer Toxicity 0.000 description 3
JTUIVQVAMRVPQI-QMMMGPOBSA-N (1s)-4-bromo-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-ol Chemical compound C1=CC(C(F)(F)F)=C(Br)C2=C1[C@@H](O)CC2 JTUIVQVAMRVPQI-QMMMGPOBSA-N 0.000 description 2
NLVVNRITLSLCDP-QMMMGPOBSA-N (1s)-4-bromo-7-fluoro-2,3-dihydro-1h-inden-1-ol Chemical compound FC1=CC=C(Br)C2=C1[C@@H](O)CC2 NLVVNRITLSLCDP-QMMMGPOBSA-N 0.000 description 2
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical class [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 2
QSKMAUDTBDRMMH-UHFFFAOYSA-N 1,2,3,3a-tetrahydroinden-4-one Chemical compound O=C1C=CC=C2CCCC12 QSKMAUDTBDRMMH-UHFFFAOYSA-N 0.000 description 2
VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 2
RSBJMWJOKSSURV-UHFFFAOYSA-N 1-(2-bromoethyl)-2,4-difluorobenzene Chemical compound FC1=CC=C(CCBr)C(F)=C1 RSBJMWJOKSSURV-UHFFFAOYSA-N 0.000 description 2
YUGWUZOHOJMMHS-UHFFFAOYSA-N 1-(2-bromoethyl)-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(CCBr)C=C1 YUGWUZOHOJMMHS-UHFFFAOYSA-N 0.000 description 2
IPQIQERVBHGGCH-UHFFFAOYSA-N 1-(2-chloroethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CCCl IPQIQERVBHGGCH-UHFFFAOYSA-N 0.000 description 2
CTZNDDMTWBDMDR-UHFFFAOYSA-N 2-(2-bromoethyl)-1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1CCBr CTZNDDMTWBDMDR-UHFFFAOYSA-N 0.000 description 2
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
LPUXCSHVGJNEOT-WZONZLPQSA-N 2-[(3s)-6-[[(1r)-4-benzyl-7-fluoro-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)O)CC2=C1C(F)=CC=C2CC1=CC=CC=C1 LPUXCSHVGJNEOT-WZONZLPQSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
NANPAHUEDRWAJP-UHFFFAOYSA-N 2-bromo-1-iodo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(I)=C1Br NANPAHUEDRWAJP-UHFFFAOYSA-N 0.000 description 2
JFTLITRZMNKVBD-UHFFFAOYSA-N 3-(2-bromoethyl)benzonitrile Chemical compound BrCCC1=CC=CC(C#N)=C1 JFTLITRZMNKVBD-UHFFFAOYSA-N 0.000 description 2
FNQUZFUXAMUOPX-UHFFFAOYSA-N 3-[2-bromo-3-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC(C(F)(F)F)=C1Br FNQUZFUXAMUOPX-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
XLIDPIUKBDUFAG-UHFFFAOYSA-N 4-bromo-5-(trifluoromethyl)-2,3-dihydroinden-1-one Chemical compound FC(F)(F)C1=CC=C2C(=O)CCC2=C1Br XLIDPIUKBDUFAG-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010007558 Cardiac failure chronic Diseases 0.000 description 2
238000005750 Corey-Bakshi-Shibata reduction reaction Methods 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
108091006027 G proteins Proteins 0.000 description 2
102000030782 GTP binding Human genes 0.000 description 2
108091000058 GTP-Binding Proteins 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
206010060378 Hyperinsulinaemia Diseases 0.000 description 2
206010054805 Macroangiopathy Diseases 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
239000012190 activator Substances 0.000 description 2
125000002015 acyclic group Chemical group 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
230000008901 benefit Effects 0.000 description 2
125000005605 benzo group Chemical group 0.000 description 2
239000003613 bile acid Substances 0.000 description 2
238000004166 bioassay Methods 0.000 description 2
230000037396 body weight Effects 0.000 description 2
229910000085 borane Inorganic materials 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
DLIJPAHLBJIQHE-UHFFFAOYSA-N butylphosphane Chemical compound CCCCP DLIJPAHLBJIQHE-UHFFFAOYSA-N 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
150000001733 carboxylic acid esters Chemical class 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
238000006555 catalytic reaction Methods 0.000 description 2
230000003915 cell function Effects 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
239000000470 constituent Substances 0.000 description 2
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 2
230000006378 damage Effects 0.000 description 2
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
208000016097 disease of metabolism Diseases 0.000 description 2
239000002934 diuretic Substances 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
208000019622 heart disease Diseases 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
230000003451 hyperinsulinaemic effect Effects 0.000 description 2
201000008980 hyperinsulinism Diseases 0.000 description 2
125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000006698 induction Effects 0.000 description 2
210000002660 insulin-secreting cell Anatomy 0.000 description 2
210000004153 islets of langerhan Anatomy 0.000 description 2
125000000468 ketone group Chemical group 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
230000007774 longterm Effects 0.000 description 2
239000012139 lysis buffer Substances 0.000 description 2
IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
CJKCSAMGKFMACQ-UHFFFAOYSA-N methyl 3-[2-bromo-3-(trifluoromethyl)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(C(F)(F)F)=C1Br CJKCSAMGKFMACQ-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
229910052750 molybdenum Inorganic materials 0.000 description 2
239000011733 molybdenum Substances 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 2
229960000698 nateglinide Drugs 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
230000009257 reactivity Effects 0.000 description 2
229940044601 receptor agonist Drugs 0.000 description 2
239000000018 receptor agonist Substances 0.000 description 2
239000002464 receptor antagonist Substances 0.000 description 2
229940044551 receptor antagonist Drugs 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229940054269 sodium pyruvate Drugs 0.000 description 2
VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
230000000707 stereoselective effect Effects 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
230000002195 synergetic effect Effects 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
125000003396 thiol group Chemical group [H]S* 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
230000004580 weight loss Effects 0.000 description 2
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
ZTMNMYJKPHAESR-VIFPVBQESA-N (1s)-4-bromo-1-hydroxy-2,3-dihydro-1h-indene-5-carbonitrile Chemical compound C1=CC(C#N)=C(Br)C2=C1[C@@H](O)CC2 ZTMNMYJKPHAESR-VIFPVBQESA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 description 1
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 1
UAGWMIDWWYHFNL-UHFFFAOYSA-N 1,1'-biphenyl;dicyclohexylphosphane Chemical class C1=CC=CC=C1C1=CC=CC=C1.C1CCCCC1PC1CCCCC1 UAGWMIDWWYHFNL-UHFFFAOYSA-N 0.000 description 1
FSVXWHPAMOPZCT-UHFFFAOYSA-N 1,1'-biphenyl;ditert-butylphosphane Chemical class CC(C)(C)PC(C)(C)C.C1=CC=CC=C1C1=CC=CC=C1 FSVXWHPAMOPZCT-UHFFFAOYSA-N 0.000 description 1
BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
SSUJUUNLZQVZMO-UHFFFAOYSA-N 1,2,3,4,8,9,10,10a-octahydropyrimido[1,2-a]azepine Chemical compound C1CCC=CN2CCCNC21 SSUJUUNLZQVZMO-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
GNDFMCHYXPCYBW-UHFFFAOYSA-N 1-(2-bromoethyl)-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(CCBr)=C1 GNDFMCHYXPCYBW-UHFFFAOYSA-N 0.000 description 1
GLVSPVSJMYQIPJ-UHFFFAOYSA-N 1-(2-bromoethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CCBr)=C1 GLVSPVSJMYQIPJ-UHFFFAOYSA-N 0.000 description 1
LQDHVNHVHAYANB-UHFFFAOYSA-N 1-(2-bromoethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCBr)=C1 LQDHVNHVHAYANB-UHFFFAOYSA-N 0.000 description 1
FLRUNCJXOVYWDH-UHFFFAOYSA-N 1-(2-bromoethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCBr)C=C1 FLRUNCJXOVYWDH-UHFFFAOYSA-N 0.000 description 1
JVLRUIIRRJELIJ-UHFFFAOYSA-N 1-(2-chloroethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CCCl JVLRUIIRRJELIJ-UHFFFAOYSA-N 0.000 description 1
GYPFVSLTAQBJHV-UHFFFAOYSA-N 1-(2-chloroethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CCCl)=C1 GYPFVSLTAQBJHV-UHFFFAOYSA-N 0.000 description 1
YGYPCEPMUOKONV-UHFFFAOYSA-N 1-(2-chloroethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCCl)=C1 YGYPCEPMUOKONV-UHFFFAOYSA-N 0.000 description 1
LPUURRVXQCVXCX-UHFFFAOYSA-N 1-(2-chloroethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCCl)C=C1 LPUURRVXQCVXCX-UHFFFAOYSA-N 0.000 description 1
PMIAMRAWHYEPNH-UHFFFAOYSA-N 1-(2-chloroethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCCl)C=C1 PMIAMRAWHYEPNH-UHFFFAOYSA-N 0.000 description 1
FTBSGSZZESQDBM-UHFFFAOYSA-N 1-(bromomethyl)-2,3-difluorobenzene Chemical compound FC1=CC=CC(CBr)=C1F FTBSGSZZESQDBM-UHFFFAOYSA-N 0.000 description 1
FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 1
QAYLIWBLUTYRTC-UHFFFAOYSA-N 1-(bromomethyl)-4-ethoxybenzene Chemical compound CCOC1=CC=C(CBr)C=C1 QAYLIWBLUTYRTC-UHFFFAOYSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
KMXUKZCMNKLUTF-UHFFFAOYSA-N 1-chloro-4-(2-chloroethyl)benzene Chemical compound ClCCC1=CC=C(Cl)C=C1 KMXUKZCMNKLUTF-UHFFFAOYSA-N 0.000 description 1
XQQZRZQVBFHBHL-UHFFFAOYSA-N 12-crown-4 Chemical compound C1COCCOCCOCCO1 XQQZRZQVBFHBHL-UHFFFAOYSA-N 0.000 description 1
VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 1
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
NIRRKMHCNFJSIO-UHFFFAOYSA-N 1h-indole-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC=C2NC(C(=O)O)=CC2=C1 NIRRKMHCNFJSIO-UHFFFAOYSA-N 0.000 description 1
IYZRKPDDKSEWCW-UHFFFAOYSA-N 2-(2-bromoethyl)benzonitrile Chemical compound BrCCC1=CC=CC=C1C#N IYZRKPDDKSEWCW-UHFFFAOYSA-N 0.000 description 1
CQUYANXSZXKQAI-UHFFFAOYSA-N 2-(2-chloroethyl)-1,4-dimethoxybenzene Chemical compound COC1=CC=C(OC)C(CCCl)=C1 CQUYANXSZXKQAI-UHFFFAOYSA-N 0.000 description 1
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
PSRARXVEBZQEML-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dimethylbenzene Chemical compound CC1=CC=CC(C)=C1CBr PSRARXVEBZQEML-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
PKHCJOYBGYOBQJ-CRICUBBOSA-N 2-[(3s)-6-[[(1r)-1-[(6-chloropyridin-3-yl)methyl]-7-fluoro-2,3-dihydroinden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid Chemical compound C([C@@]1(OC=2C=C3OC[C@H](C3=CC=2)CC(=O)O)C2=C(F)C=CC=C2CC1)C1=CC=C(Cl)N=C1 PKHCJOYBGYOBQJ-CRICUBBOSA-N 0.000 description 1
MSHBNSXTPPDODY-GKRXRMOTSA-N 2-[(3s)-6-[[(1r)-5-cyano-4-[(4-methylsulfinylphenyl)methyl]-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid Chemical compound C1=CC(S(=O)C)=CC=C1CC1=C(CC[C@H]2OC=3C=C4OC[C@@H](CC(O)=O)C4=CC=3)C2=CC=C1C#N MSHBNSXTPPDODY-GKRXRMOTSA-N 0.000 description 1
XIUJCAJFRWDEKE-UHFFFAOYSA-N 2-bromo-3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1Br XIUJCAJFRWDEKE-UHFFFAOYSA-N 0.000 description 1
PQSXTBMHLNJQKD-UHFFFAOYSA-M 2-chloro-5-methanidylpyridine;chlorozinc(1+) Chemical compound [Zn+]Cl.[CH2-]C1=CC=C(Cl)N=C1 PQSXTBMHLNJQKD-UHFFFAOYSA-M 0.000 description 1
BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 1
VXIKDBJPBRMXBP-UHFFFAOYSA-N 3H-pyrrole Chemical compound C1C=CN=C1 VXIKDBJPBRMXBP-UHFFFAOYSA-N 0.000 description 1
NNNRGWOWXNCGCV-UHFFFAOYSA-N 4-(2-bromoethyl)benzonitrile Chemical compound BrCCC1=CC=C(C#N)C=C1 NNNRGWOWXNCGCV-UHFFFAOYSA-N 0.000 description 1
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 1
PTPAIKGALUBHCW-UHFFFAOYSA-N 4-bromo-5-hydroxy-2,3-dihydroinden-1-one Chemical compound OC1=CC=C2C(=O)CCC2=C1Br PTPAIKGALUBHCW-UHFFFAOYSA-N 0.000 description 1
ZVBMFHJZYVGNSX-UHFFFAOYSA-N 4-bromo-5-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2C(=O)CCC2=C1Br ZVBMFHJZYVGNSX-UHFFFAOYSA-N 0.000 description 1
HNXHWYGTXAJDEC-UHFFFAOYSA-N 4-bromo-7-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C(Br)C2=C1C(=O)CC2 HNXHWYGTXAJDEC-UHFFFAOYSA-N 0.000 description 1
125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000010444 Acidosis Diseases 0.000 description 1
101710134784 Agnoprotein Proteins 0.000 description 1
229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
101100460776 Arabidopsis thaliana NPY2 gene Proteins 0.000 description 1
101100460788 Arabidopsis thaliana NPY5 gene Proteins 0.000 description 1
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
229930188012 Bromoether Natural products 0.000 description 1
XESGYQQZWRXARZ-UHFFFAOYSA-L C(=O)(O)[Ru](Cl)Cl Chemical compound C(=O)(O)[Ru](Cl)Cl XESGYQQZWRXARZ-UHFFFAOYSA-L 0.000 description 1
WYQPTLZXXOIEMM-UHFFFAOYSA-N C(C)(=O)O.C1(CCC2=CC=CC=C12)OC1OC2=C(C1)C=CC=C2 Chemical compound C(C)(=O)O.C1(CCC2=CC=CC=C12)OC1OC2=C(C1)C=CC=C2 WYQPTLZXXOIEMM-UHFFFAOYSA-N 0.000 description 1
102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 1
KEQQEQKVLXYRQO-UHFFFAOYSA-N CCCCCCCCC(C)(C)C.Cl Chemical compound CCCCCCCCC(C)(C)C.Cl KEQQEQKVLXYRQO-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229940123158 Cannabinoid CB1 receptor antagonist Drugs 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
101150065749 Churc1 gene Proteins 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
229940126657 Compound 17 Drugs 0.000 description 1
208000027205 Congenital disease Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
101710088194 Dehydrogenase Proteins 0.000 description 1
101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
206010048554 Endothelial dysfunction Diseases 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
101150108864 Ffar1 gene Proteins 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
101710142060 Free fatty acid receptor 1 Proteins 0.000 description 1
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
241000237858 Gastropoda Species 0.000 description 1
108091006101 Gi proteins Proteins 0.000 description 1
102000034354 Gi proteins Human genes 0.000 description 1
FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
108010021582 Glucokinase Proteins 0.000 description 1
208000002705 Glucose Intolerance Diseases 0.000 description 1
102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
108091006065 Gs proteins Proteins 0.000 description 1
102100030488 HEAT repeat-containing protein 6 Human genes 0.000 description 1
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
102000001554 Hemoglobins Human genes 0.000 description 1
108010054147 Hemoglobins Proteins 0.000 description 1
101000990566 Homo sapiens HEAT repeat-containing protein 6 Proteins 0.000 description 1
101000801684 Homo sapiens Phospholipid-transporting ATPase ABCA1 Proteins 0.000 description 1
101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
208000035150 Hypercholesterolemia Diseases 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010010164 Hypertension complications Diseases 0.000 description 1
201000001431 Hyperuricemia Diseases 0.000 description 1
208000013016 Hypoglycemia Diseases 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
229910021617 Indium monochloride Inorganic materials 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
208000031773 Insulin resistance syndrome Diseases 0.000 description 1
208000007976 Ketosis Diseases 0.000 description 1
102000016267 Leptin Human genes 0.000 description 1
108010092277 Leptin Proteins 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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
206010027417 Metabolic acidosis Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
241000872931 Myoporum sandwicense Species 0.000 description 1
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
101150111774 NPY5R gene Proteins 0.000 description 1
KLPNXPQSHBDWGD-UHFFFAOYSA-N OC(C1=CC=CC2=C1CC1=CC=CC=C21)=O.F Chemical compound OC(C1=CC=CC2=C1CC1=CC=CC=C21)=O.F KLPNXPQSHBDWGD-UHFFFAOYSA-N 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
102000016978 Orphan receptors Human genes 0.000 description 1
108070000031 Orphan receptors Proteins 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
101710176384 Peptide 1 Proteins 0.000 description 1
208000018262 Peripheral vascular disease Diseases 0.000 description 1
102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 1
229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
102100038239 Protein Churchill Human genes 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
229910019023 PtO Inorganic materials 0.000 description 1
LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
239000012327 Ruthenium complex Substances 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
229940100389 Sulfonylurea Drugs 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
229940123464 Thiazolidinedione Drugs 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 1
108010021436 Type 4 Melanocortin Receptor Proteins 0.000 description 1
101710204865 Tyrosine-protein phosphatase 1 Proteins 0.000 description 1
101100264077 Xenopus laevis wrn gene Proteins 0.000 description 1
229910007926 ZrCl Inorganic materials 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
208000037919 acquired disease Diseases 0.000 description 1
HGINCPLSRVDWNT-UHFFFAOYSA-N acrylaldehyde Natural products C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
208000030961 allergic reaction Diseases 0.000 description 1
239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
229940127003 anti-diabetic drug Drugs 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000003524 antilipemic agent Substances 0.000 description 1
229940127218 antiplatelet drug Drugs 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
230000003143 atherosclerotic effect Effects 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
230000006470 autoimmune attack Effects 0.000 description 1
HKVFISRIUUGTIB-UHFFFAOYSA-O azanium;cerium;nitrate Chemical compound [NH4+].[Ce].[O-][N+]([O-])=O HKVFISRIUUGTIB-UHFFFAOYSA-O 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
229910052797 bismuth Inorganic materials 0.000 description 1
JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical group [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
NOJMTMIRQRDZMT-GSPXQYRGSA-N bromocriptine methanesulfonate Chemical compound CS(O)(=O)=O.C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 NOJMTMIRQRDZMT-GSPXQYRGSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000003555 cannabinoid 1 receptor antagonist Substances 0.000 description 1
CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical group C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 1
229960005286 carbaryl Drugs 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
230000001906 cholesterol absorption Effects 0.000 description 1
239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
150000001879 copper Chemical class 0.000 description 1
239000010949 copper Substances 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 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
150000003983 crown ethers Chemical class 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229940045803 cuprous chloride Drugs 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
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 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
125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229940015838 cycloset Drugs 0.000 description 1
230000002498 deadly effect Effects 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
230000001079 digestive effect Effects 0.000 description 1
125000005046 dihydronaphthyl group Chemical group 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
NCBFTYFOPLPRBX-UHFFFAOYSA-N dimethyl azodicarboxylate Substances COC(=O)N=NC(=O)OC NCBFTYFOPLPRBX-UHFFFAOYSA-N 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
230000008482 dysregulation Effects 0.000 description 1
239000012039 electrophile Substances 0.000 description 1
238000007350 electrophilic reaction Methods 0.000 description 1
ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
230000008694 endothelial dysfunction Effects 0.000 description 1
239000002792 enkephalinase inhibitor Substances 0.000 description 1
210000003158 enteroendocrine cell Anatomy 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
229940125532 enzyme inhibitor Drugs 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
238000007429 general method Methods 0.000 description 1
208000018914 glucose metabolism disease Diseases 0.000 description 1
230000002641 glycemic effect Effects 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
ATBKVKDEMSGMTQ-UHFFFAOYSA-N hydrazine triphenylphosphane Chemical compound NN.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 ATBKVKDEMSGMTQ-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
229960002003 hydrochlorothiazide Drugs 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
125000000879 imine group Chemical group 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
APHGZSBLRQFRCA-UHFFFAOYSA-M indium(1+);chloride Chemical compound [In]Cl APHGZSBLRQFRCA-UHFFFAOYSA-M 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
210000004347 intestinal mucosa Anatomy 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
230000004068 intracellular signaling Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
230000007794 irritation Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
230000004140 ketosis Effects 0.000 description 1
NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
229940039781 leptin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
238000012153 long-term therapy Methods 0.000 description 1
238000011866 long-term treatment Methods 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
230000006371 metabolic abnormality Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
229960003105 metformin Drugs 0.000 description 1
XHXXWWGGXFUMAJ-UHFFFAOYSA-N methanethiol;sodium Chemical compound [Na].SC XHXXWWGGXFUMAJ-UHFFFAOYSA-N 0.000 description 1
NCBFTYFOPLPRBX-AATRIKPKSA-N methyl (ne)-n-methoxycarbonyliminocarbamate Chemical compound COC(=O)\N=N\C(=O)OC NCBFTYFOPLPRBX-AATRIKPKSA-N 0.000 description 1
AWMMCJVXMIKIER-DNOBIOAJSA-N methyl 2-[(3s)-6-[[(1r)-4-[(2,5-dimethoxyphenyl)methyl]-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C(F)(F)F)=C2CC1=CC(OC)=CC=C1OC AWMMCJVXMIKIER-DNOBIOAJSA-N 0.000 description 1
XAGVLRNMLIRWHL-NIYFSFCBSA-N methyl 2-[(3s)-6-[[(1r)-4-[(2-cyanophenyl)methyl]-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C(F)(F)F)=C2CC1=CC=CC=C1C#N XAGVLRNMLIRWHL-NIYFSFCBSA-N 0.000 description 1
UBCAYEDWURNQRE-NIYFSFCBSA-N methyl 2-[(3s)-6-[[(1r)-4-[(2-methylphenyl)methyl]-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C(F)(F)F)=C2CC1=CC=CC=C1C UBCAYEDWURNQRE-NIYFSFCBSA-N 0.000 description 1
AZELDWLDFUHROH-NIYFSFCBSA-N methyl 2-[(3s)-6-[[(1r)-4-[(3-cyanophenyl)methyl]-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C(F)(F)F)=C2CC1=CC=CC(C#N)=C1 AZELDWLDFUHROH-NIYFSFCBSA-N 0.000 description 1
CQMXEQQHYLTPQB-WXTAPIANSA-N methyl 2-[(3s)-6-[[(1r)-4-[(3-methoxyphenyl)methyl]-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C(F)(F)F)=C2CC1=CC=CC(OC)=C1 CQMXEQQHYLTPQB-WXTAPIANSA-N 0.000 description 1
RKINFWXAPQOFRV-WXTAPIANSA-N methyl 2-[(3s)-6-[[(1r)-4-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C(F)(F)F)=C2CC1=CC=C(OC)C=C1 RKINFWXAPQOFRV-WXTAPIANSA-N 0.000 description 1
SLXYOECUDXUUAD-NTKDMRAZSA-N methyl 2-[(3s)-6-[[(1r)-4-benzyl-7-fluoro-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C(F)=CC=C2CC1=CC=CC=C1 SLXYOECUDXUUAD-NTKDMRAZSA-N 0.000 description 1
SDFKEUFOJKRSPS-IQGLISFBSA-N methyl 2-[(3s)-6-[[(1r)-5-cyano-4-[(2,3-difluorophenyl)methyl]-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C#N)=C2CC1=CC=CC(F)=C1F SDFKEUFOJKRSPS-IQGLISFBSA-N 0.000 description 1
QHXAXYOGUBSPBZ-WGDIFIGCSA-N methyl 2-[(3s)-6-[[(1r)-5-cyano-4-[(2,6-difluorophenyl)methyl]-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C#N)=C2CC1=C(F)C=CC=C1F QHXAXYOGUBSPBZ-WGDIFIGCSA-N 0.000 description 1
FHWXTHKFSQKJBL-LYZGTLIUSA-N methyl 2-[(3s)-6-[[(1r)-5-cyano-4-[(2,6-dimethylphenyl)methyl]-2,3-dihydro-1h-inden-1-yl]oxy]-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound C([C@H]1OC=2C=C3OC[C@H](C3=CC=2)CC(=O)OC)CC2=C1C=CC(C#N)=C2CC1=C(C)C=CC=C1C FHWXTHKFSQKJBL-LYZGTLIUSA-N 0.000 description 1
RHMDISFJOKCCAQ-SSDOTTSWSA-N methyl 2-[(3s)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate Chemical compound OC1=CC=C2[C@H](CC(=O)OC)COC2=C1 RHMDISFJOKCCAQ-SSDOTTSWSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
229910052901 montmorillonite Inorganic materials 0.000 description 1
VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
UOPFIWYXBIHPIP-SFTDATJTSA-N n-[(1s,2s)-2-amino-1,2-diphenylethyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 UOPFIWYXBIHPIP-SFTDATJTSA-N 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
238000007344 nucleophilic reaction Methods 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
238000005580 one pot reaction Methods 0.000 description 1
230000008816 organ damage Effects 0.000 description 1
230000004768 organ dysfunction Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000007170 pathology Effects 0.000 description 1
125000001151 peptidyl group Chemical group 0.000 description 1
108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
WDZOPGZTGVJDMZ-FOCLMDBBSA-N phenyl (ne)-n-phenoxycarbonyliminocarbamate Chemical compound C=1C=CC=CC=1OC(=O)/N=N/C(=O)OC1=CC=CC=C1 WDZOPGZTGVJDMZ-FOCLMDBBSA-N 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
150000003003 phosphines Chemical class 0.000 description 1
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
229930029653 phosphoenolpyruvate Natural products 0.000 description 1
DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
239000006187 pill Substances 0.000 description 1
IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
239000000106 platelet aggregation inhibitor Substances 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
230000000291 postprandial effect Effects 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride 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
201000009104 prediabetes syndrome Diseases 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
125000002577 pseudohalo group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
229940076788 pyruvate Drugs 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
229960002354 repaglinide Drugs 0.000 description 1
230000004044 response Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
229960004586 rosiglitazone Drugs 0.000 description 1
YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
208000037921 secondary disease Diseases 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
210000004989 spleen cell Anatomy 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000002636 symptomatic treatment Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000009466 transformation Effects 0.000 description 1
DNUYPCSVTPIXRE-UHFFFAOYSA-N tribromomethanesulfonic acid Chemical compound OS(=O)(=O)C(Br)(Br)Br DNUYPCSVTPIXRE-UHFFFAOYSA-N 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
230000009751 type B pancreatic cell apoptotic process Effects 0.000 description 1
238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
WRSWIWOVJBYZAW-UHFFFAOYSA-M zinc;methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=CC=C1 WRSWIWOVJBYZAW-UHFFFAOYSA-M 0.000 description 1