NO311516B1 - Derivater av substituerte 4-hydroksy-fenylalkanosyrer med agonistisk aktivitet for PPAR-gamma, farmasöytiske preparaterinneholdende dem, anvendelse av dem og fremgangsmåte forfremstilling av dem - Google Patents
Derivater av substituerte 4-hydroksy-fenylalkanosyrer med agonistisk aktivitet for PPAR-gamma, farmasöytiske preparaterinneholdende dem, anvendelse av dem og fremgangsmåte forfremstilling av dem Download PDFInfo
- Publication number
- NO311516B1 NO311516B1 NO19983940A NO983940A NO311516B1 NO 311516 B1 NO311516 B1 NO 311516B1 NO 19983940 A NO19983940 A NO 19983940A NO 983940 A NO983940 A NO 983940A NO 311516 B1 NO311516 B1 NO 311516B1
- Authority
- NO
- Norway
- Prior art keywords
- mmol
- phenyl
- alkyl
- methyl
- etoac
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 27
- 239000002253 acid Substances 0.000 title claims description 21
- 108010016731 PPAR gamma Proteins 0.000 title claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 3
- 102000000536 PPAR gamma Human genes 0.000 title claims 2
- 150000007513 acids Chemical class 0.000 title description 2
- 230000001270 agonistic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 380
- 238000000034 method Methods 0.000 claims description 208
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 105
- 239000011541 reaction mixture Substances 0.000 claims description 75
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 74
- 238000006243 chemical reaction Methods 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 34
- -1 C1-4-alkoxycarbonyl Chemical group 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 239000005711 Benzoic acid Substances 0.000 claims description 9
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 238000006356 dehydrogenation reaction Methods 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 229910052717 sulfur Chemical group 0.000 claims description 5
- 238000006751 Mitsunobu reaction Methods 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 230000027455 binding Effects 0.000 claims description 4
- 238000009739 binding Methods 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 150000003852 triazoles Chemical class 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 206010022489 Insulin Resistance Diseases 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 201000001421 hyperglycemia Diseases 0.000 claims description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 2
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 208000032841 Bulimia Diseases 0.000 claims 1
- 101100377255 Caenorhabditis elegans zer-1 gene Proteins 0.000 claims 1
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 567
- 239000000543 intermediate Substances 0.000 description 551
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 463
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 372
- 235000019439 ethyl acetate Nutrition 0.000 description 282
- 239000000243 solution Substances 0.000 description 260
- 238000001819 mass spectrum Methods 0.000 description 241
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 178
- 238000000746 purification Methods 0.000 description 172
- 239000003480 eluent Substances 0.000 description 157
- 238000000132 electrospray ionisation Methods 0.000 description 156
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 146
- 239000000741 silica gel Substances 0.000 description 132
- 229910002027 silica gel Inorganic materials 0.000 description 132
- 238000003818 flash chromatography Methods 0.000 description 120
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 112
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 105
- 229910001868 water Inorganic materials 0.000 description 104
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 103
- 239000007787 solid Substances 0.000 description 92
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- 239000002904 solvent Substances 0.000 description 73
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 70
- 239000000203 mixture Substances 0.000 description 64
- 239000000460 chlorine Substances 0.000 description 59
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 59
- 238000010898 silica gel chromatography Methods 0.000 description 59
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 58
- 239000003921 oil Substances 0.000 description 58
- 235000019198 oils Nutrition 0.000 description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
- 238000004809 thin layer chromatography Methods 0.000 description 47
- 239000012074 organic phase Substances 0.000 description 43
- 238000001704 evaporation Methods 0.000 description 42
- 230000008020 evaporation Effects 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
- 238000004007 reversed phase HPLC Methods 0.000 description 37
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
- 238000003756 stirring Methods 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000000872 buffer Substances 0.000 description 30
- 229960004756 ethanol Drugs 0.000 description 30
- 238000001665 trituration Methods 0.000 description 30
- 239000000463 material Substances 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 26
- 239000000725 suspension Substances 0.000 description 25
- 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 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 238000004128 high performance liquid chromatography Methods 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 239000010410 layer Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- 239000011734 sodium Substances 0.000 description 17
- 229960000583 acetic acid Drugs 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- 238000007792 addition Methods 0.000 description 15
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 15
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 15
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 15
- 238000010992 reflux Methods 0.000 description 14
- 239000002002 slurry Substances 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 102000012132 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 11
- 238000010265 fast atom bombardment Methods 0.000 description 11
- HCBQTGAZENNMLM-UHFFFAOYSA-N methyl 4-bromo-3-oxopentanoate Chemical compound COC(=O)CC(=O)C(C)Br HCBQTGAZENNMLM-UHFFFAOYSA-N 0.000 description 11
- 150000004702 methyl esters Chemical class 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 229940123464 Thiazolidinedione Drugs 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000008186 active pharmaceutical agent Substances 0.000 description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 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 8
- 239000013067 intermediate product Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 150000001467 thiazolidinediones Chemical class 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 229910004373 HOAc Inorganic materials 0.000 description 7
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical class [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 7
- 238000002390 rotary evaporation Methods 0.000 description 7
- BBVQDWDBTWSGHQ-UHFFFAOYSA-N 2-chloro-1,3-benzoxazole Chemical compound C1=CC=C2OC(Cl)=NC2=C1 BBVQDWDBTWSGHQ-UHFFFAOYSA-N 0.000 description 6
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 5
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 5
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- VUPQHSHTKBZVML-UHFFFAOYSA-J rhodium(3+);tetraacetate Chemical compound [Rh+3].[Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O VUPQHSHTKBZVML-UHFFFAOYSA-J 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- YTVQIZRDLKWECQ-UHFFFAOYSA-N 2-benzoylcyclohexan-1-one Chemical compound C=1C=CC=CC=1C(=O)C1CCCCC1=O YTVQIZRDLKWECQ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 206010022998 Irritability Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000003472 antidiabetic agent Substances 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
- MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 3
- VXIMIQNIBMDZCM-UHFFFAOYSA-N (2-aminothiophen-3-yl)-phenylmethanone Chemical compound S1C=CC(C(=O)C=2C=CC=CC=2)=C1N VXIMIQNIBMDZCM-UHFFFAOYSA-N 0.000 description 3
- CVBUKMMMRLOKQR-UHFFFAOYSA-N 1-phenylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1 CVBUKMMMRLOKQR-UHFFFAOYSA-N 0.000 description 3
- JYWHQBLLIBQGCU-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethanol Chemical compound OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JYWHQBLLIBQGCU-UHFFFAOYSA-N 0.000 description 3
- BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000002051 biphasic effect Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 3
- 125000005594 diketone group Chemical group 0.000 description 3
- 229940126904 hypoglycaemic agent Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- IUXVIPGPIFGSEU-INIZCTEOSA-N methyl (2s)-2-amino-3-(4-phenylmethoxyphenyl)propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1OCC1=CC=CC=C1 IUXVIPGPIFGSEU-INIZCTEOSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 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 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 238000003828 vacuum filtration Methods 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- JXHXZEWREZILOO-UHFFFAOYSA-N (2-aminophenyl)-cyclohexylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1CCCCC1 JXHXZEWREZILOO-UHFFFAOYSA-N 0.000 description 2
- UMCVZQMJGFTEHO-UHFFFAOYSA-N (3-aminothiophen-2-yl)-phenylmethanone Chemical compound C1=CSC(C(=O)C=2C=CC=CC=2)=C1N UMCVZQMJGFTEHO-UHFFFAOYSA-N 0.000 description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 2
- VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 2
- GPYKJDYMMUIUFG-UHFFFAOYSA-N 1-(2-Furanyl)-1,3-butanedione Chemical compound CC(=O)CC(=O)C1=CC=CO1 GPYKJDYMMUIUFG-UHFFFAOYSA-N 0.000 description 2
- CZQOKCRFTKTJKQ-UHFFFAOYSA-N 1-(3-iodophenyl)butane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC(I)=C1 CZQOKCRFTKTJKQ-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- HHIWVLZQIJUIPJ-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfanylethanol Chemical compound OCCSC1=CC=C(Cl)C=C1 HHIWVLZQIJUIPJ-UHFFFAOYSA-N 0.000 description 2
- KESQFSZFUCZCEI-UHFFFAOYSA-N 2-(5-nitropyridin-2-yl)oxyethanol Chemical compound OCCOC1=CC=C([N+]([O-])=O)C=N1 KESQFSZFUCZCEI-UHFFFAOYSA-N 0.000 description 2
- AZXMOBBALOXQIU-UHFFFAOYSA-N 2-[2-(cyclohexanecarbonyl)anilino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1CCCCC1 AZXMOBBALOXQIU-UHFFFAOYSA-N 0.000 description 2
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 2
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 2
- UBPDKIDWEADHPP-UHFFFAOYSA-N 2-iodoaniline Chemical compound NC1=CC=CC=C1I UBPDKIDWEADHPP-UHFFFAOYSA-N 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PCIITXGDSHXTSN-UHFFFAOYSA-N Chromone-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(=O)O)=COC2=C1 PCIITXGDSHXTSN-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- QTQMRBZOBKYXCG-MHZLTWQESA-N GW 1929 Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCN(C)C=1N=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 QTQMRBZOBKYXCG-MHZLTWQESA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
- KAFHLONDOVSENM-HNNXBMFYSA-N O-Benzyl-L-tyrosine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1OCC1=CC=CC=C1 KAFHLONDOVSENM-HNNXBMFYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- NORMSRFGHVKNJL-NRFANRHFSA-N methyl (2s)-2-(2-benzoylanilino)-3-(4-hydroxyphenyl)propanoate Chemical compound C([C@@H](C(=O)OC)NC=1C(=CC=CC=1)C(=O)C=1C=CC=CC=1)C1=CC=C(O)C=C1 NORMSRFGHVKNJL-NRFANRHFSA-N 0.000 description 2
- JEENWEAPRWGXSG-UHFFFAOYSA-N methyl 2-oxocyclohexane-1-carboxylate Chemical compound COC(=O)C1CCCCC1=O JEENWEAPRWGXSG-UHFFFAOYSA-N 0.000 description 2
- YGBMHHMGCJNTAL-UHFFFAOYSA-N methyl 3-[4-[1-(1,3-benzoxazol-2-yl)pyrrolidin-3-yl]oxyphenyl]-2-(2-benzoylanilino)propanoate Chemical compound C=1C=C(OC2CN(CC2)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 YGBMHHMGCJNTAL-UHFFFAOYSA-N 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 2
- QACBXWKOMVOZLD-UHFFFAOYSA-N n-cyclohexylcyclohexanamine;3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[(4-oxo-4-phenylbut-2-en-2-yl)amino]propanoic acid Chemical compound C1CCCCC1NC1CCCCC1.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC(C)=CC(=O)C1=CC=CC=C1 QACBXWKOMVOZLD-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229920005990 polystyrene resin Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 210000000229 preadipocyte Anatomy 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000004808 supercritical fluid chromatography Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 229960004441 tyrosine Drugs 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 1
- MZPDVYDLHYUTQS-UHFFFAOYSA-N (2-amino-5-methylphenyl)-phenylmethanone Chemical compound CC1=CC=C(N)C(C(=O)C=2C=CC=CC=2)=C1 MZPDVYDLHYUTQS-UHFFFAOYSA-N 0.000 description 1
- ASDIDCKLLOQMSN-UHFFFAOYSA-N (2-aminophenyl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CC=C1N ASDIDCKLLOQMSN-UHFFFAOYSA-N 0.000 description 1
- RMMJUQSANCPTMV-UHFFFAOYSA-N (2-aminophenyl)-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=CC=C1N RMMJUQSANCPTMV-UHFFFAOYSA-N 0.000 description 1
- UIFFDAJFRQWWAB-UHFFFAOYSA-N (2-aminophenyl)-(4-phenylmethoxyphenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 UIFFDAJFRQWWAB-UHFFFAOYSA-N 0.000 description 1
- TVHNGTPXKLXSCY-UHFFFAOYSA-N (2-aminophenyl)-cycloheptylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1CCCCCC1 TVHNGTPXKLXSCY-UHFFFAOYSA-N 0.000 description 1
- CIBMIYFKYMRDBM-UHFFFAOYSA-N (2-aminophenyl)-cyclopentylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1CCCC1 CIBMIYFKYMRDBM-UHFFFAOYSA-N 0.000 description 1
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
- WWOXRCKQTDZALJ-CYULUMSASA-N (2s)-2-amino-3-methylbutanedioic acid;hydrochloride Chemical compound Cl.OC(=O)C(C)[C@H](N)C(O)=O WWOXRCKQTDZALJ-CYULUMSASA-N 0.000 description 1
- MCRMUCXATQAAMN-HNNXBMFYSA-N (2s)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=C(O)C=C1 MCRMUCXATQAAMN-HNNXBMFYSA-N 0.000 description 1
- GJDHFKPKXFOMGL-PMERELPUSA-N (2s)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-[2-(pyridine-3-carbonyl)anilino]propanoic acid Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CN=C1 GJDHFKPKXFOMGL-PMERELPUSA-N 0.000 description 1
- PDJBKTJBLWHPMV-PMERELPUSA-N (2s)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-[2-(pyridine-4-carbonyl)anilino]propanoic acid Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=NC=C1 PDJBKTJBLWHPMV-PMERELPUSA-N 0.000 description 1
- ZZLLEVLMZDJINU-NDEPHWFRSA-N (2s)-3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-(2-benzoylanilino)propanoic acid Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCN(C)C=1OC2=CC=CC=C2N=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZLLEVLMZDJINU-NDEPHWFRSA-N 0.000 description 1
- XGGMTGVZCUWSQF-QHCPKHFHSA-N (2s)-3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[(4-oxochromene-3-carbonyl)amino]propanoic acid Chemical compound C1=CC=C2OC(N(CCOC=3C=CC(C[C@H](NC(=O)C=4C(C5=CC=CC=C5OC=4)=O)C(O)=O)=CC=3)C)=NC2=C1 XGGMTGVZCUWSQF-QHCPKHFHSA-N 0.000 description 1
- IQYSYNREXOLHBC-GIGWZHCTSA-N (2s)-3-[4-[[(4r)-3-(1,3-benzoxazol-2-yl)-1,3-thiazolidin-4-yl]methoxy]phenyl]-2-(2-benzoylanilino)propanoic acid Chemical compound N([C@@H](CC=1C=CC(OC[C@H]2N(CSC2)C=2OC3=CC=CC=C3N=2)=CC=1)C(=O)O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 IQYSYNREXOLHBC-GIGWZHCTSA-N 0.000 description 1
- HJBGZJMKTOMQRR-UHFFFAOYSA-N (3-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=O)=C1 HJBGZJMKTOMQRR-UHFFFAOYSA-N 0.000 description 1
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- WIJNYNBSPQMJGO-UHFFFAOYSA-N (3-phenylmethoxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 WIJNYNBSPQMJGO-UHFFFAOYSA-N 0.000 description 1
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- YQMXOIAIYXXXEE-NSHDSACASA-N (3s)-1-benzylpyrrolidin-3-ol Chemical compound C1[C@@H](O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-NSHDSACASA-N 0.000 description 1
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 description 1
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- FJWNZTPXVSWUKF-LURJTMIESA-N (4r)-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-thiazolidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CSC[C@H]1C(O)=O FJWNZTPXVSWUKF-LURJTMIESA-N 0.000 description 1
- JIICNFNEXQQZOX-UHFFFAOYSA-N (5-amino-1-methylpyrazol-4-yl)-cyclohexylmethanone Chemical compound CN1N=CC(C(=O)C2CCCCC2)=C1N JIICNFNEXQQZOX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- ZQGWBPQBZHMUFG-UHFFFAOYSA-N 1,1-dimethylthiourea Chemical compound CN(C)C(N)=S ZQGWBPQBZHMUFG-UHFFFAOYSA-N 0.000 description 1
- HXDISUFYLUUTLD-UHFFFAOYSA-N 1-(1,3-benzoxazol-2-yl)pyrrolidin-3-ol Chemical compound C1C(O)CCN1C1=NC2=CC=CC=C2O1 HXDISUFYLUUTLD-UHFFFAOYSA-N 0.000 description 1
- UYUUVEOAFPDCIS-UHFFFAOYSA-N 1-(methoxymethyl)-4-methyl-2-phenylimidazole Chemical compound COCN1C=C(C)N=C1C1=CC=CC=C1 UYUUVEOAFPDCIS-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- LZSYGJNFCREHMD-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)benzene Chemical compound BrCC1=CC=CC=C1Br LZSYGJNFCREHMD-UHFFFAOYSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- GPOFSFLJOIAMSA-UHFFFAOYSA-N 1-chloro-4-ethylbenzene Chemical compound CCC1=CC=C(Cl)C=C1 GPOFSFLJOIAMSA-UHFFFAOYSA-N 0.000 description 1
- OQJQPIWVCBJVAZ-UHFFFAOYSA-N 1-methyl-2-phenylimidazole Chemical compound CN1C=CN=C1C1=CC=CC=C1 OQJQPIWVCBJVAZ-UHFFFAOYSA-N 0.000 description 1
- KTGYDKACJATEDM-UHFFFAOYSA-N 1-methyl-4-phenylimidazole Chemical compound CN1C=NC(C=2C=CC=CC=2)=C1 KTGYDKACJATEDM-UHFFFAOYSA-N 0.000 description 1
- SIRPHJCQZYVEES-UHFFFAOYSA-N 1-methylbenzimidazole-2-carbaldehyde Chemical compound C1=CC=C2N(C)C(C=O)=NC2=C1 SIRPHJCQZYVEES-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- ORTOIUYGGQSINR-UHFFFAOYSA-N 2-(1-methyl-4-phenylimidazol-2-yl)ethanol Chemical compound N1=C(CCO)N(C)C=C1C1=CC=CC=C1 ORTOIUYGGQSINR-UHFFFAOYSA-N 0.000 description 1
- QNBBONUOVHBLSG-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-(4-phenylmethoxyphenyl)propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCC1=CC=CC=C1 QNBBONUOVHBLSG-UHFFFAOYSA-N 0.000 description 1
- PYTSGKKGDQNEEA-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(3-cyanophenoxy)ethoxy]phenyl]propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCCOC1=CC=CC(C#N)=C1 PYTSGKKGDQNEEA-UHFFFAOYSA-N 0.000 description 1
- HMEJFULZHZIJTL-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(3-methyl-6-oxopyridazin-1-yl)ethoxy]phenyl]propanoic acid Chemical compound N1=C(C)C=CC(=O)N1CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 HMEJFULZHZIJTL-UHFFFAOYSA-N 0.000 description 1
- VZQRFGZHAASEKW-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(4-chlorophenyl)ethoxy]phenyl]propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCCC1=CC=C(Cl)C=C1 VZQRFGZHAASEKW-UHFFFAOYSA-N 0.000 description 1
- RLEAWABYZLHNEG-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]phenyl]propanoic acid Chemical compound N1=CSC(CCOC=2C=CC(CC(NC=3C(=CC=CC=3)C(=O)C=3C=CC=CC=3)C(O)=O)=CC=2)=C1C RLEAWABYZLHNEG-UHFFFAOYSA-N 0.000 description 1
- JMDKQXZISRXZRU-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(5-nitropyridin-2-yl)oxyethoxy]phenyl]propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCCOC1=CC=C([N+]([O-])=O)C=N1 JMDKQXZISRXZRU-UHFFFAOYSA-N 0.000 description 1
- SIZIHIQGQOCHRG-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(6-methoxypyridin-2-yl)sulfanylethoxy]phenyl]propanoic acid Chemical compound COC1=CC=CC(SCCOC=2C=CC(CC(NC=3C(=CC=CC=3)C(=O)C=3C=CC=CC=3)C(O)=O)=CC=2)=N1 SIZIHIQGQOCHRG-UHFFFAOYSA-N 0.000 description 1
- VNLOLGBBFUHTBM-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-[4-(dimethylamino)phenyl]ethoxy]phenyl]propanoic acid Chemical compound C1=CC(N(C)C)=CC=C1CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 VNLOLGBBFUHTBM-UHFFFAOYSA-N 0.000 description 1
- QEGRZXUKGARHKH-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[[1-(4-nitrophenyl)pyrrolidin-2-yl]methoxy]phenyl]propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCC1CCCN1C1=CC=C([N+]([O-])=O)C=C1 QEGRZXUKGARHKH-UHFFFAOYSA-N 0.000 description 1
- FJHCPXVSVRSABF-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCC(N=1)=CSC=1C1=CC=C(Cl)C=C1 FJHCPXVSVRSABF-UHFFFAOYSA-N 0.000 description 1
- KEVVLZNNDCEUAB-UHFFFAOYSA-N 2-(2-hydroxyethyl)-6-methylpyridazin-3-one Chemical compound CC=1C=CC(=O)N(CCO)N=1 KEVVLZNNDCEUAB-UHFFFAOYSA-N 0.000 description 1
- UNOADLLIDAEBJH-UHFFFAOYSA-N 2-(2-methoxycarbonylanilino)-3-[4-[(1-phenylpyrrolidin-2-yl)methoxy]phenyl]propanoic acid Chemical compound COC(=O)C1=CC=CC=C1NC(C(O)=O)CC(C=C1)=CC=C1OCC1N(C=2C=CC=CC=2)CCC1 UNOADLLIDAEBJH-UHFFFAOYSA-N 0.000 description 1
- QYIOGYCRGNHDNK-UHFFFAOYSA-N 2-(4-bromophenoxy)ethanol Chemical compound OCCOC1=CC=C(Br)C=C1 QYIOGYCRGNHDNK-UHFFFAOYSA-N 0.000 description 1
- HZFRKZWBVUJYDA-UHFFFAOYSA-N 2-(4-chlorophenyl)ethanol Chemical compound OCCC1=CC=C(Cl)C=C1 HZFRKZWBVUJYDA-UHFFFAOYSA-N 0.000 description 1
- CWHSZHXUFUEFMP-UHFFFAOYSA-N 2-(4-phenylbenzoyl)cyclohexan-1-one Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)C1CCCCC1=O CWHSZHXUFUEFMP-UHFFFAOYSA-N 0.000 description 1
- KLOJLJIHCJJDCT-UHFFFAOYSA-N 2-(5-chloropyridin-2-yl)sulfanylethanol Chemical compound OCCSC1=CC=C(Cl)C=N1 KLOJLJIHCJJDCT-UHFFFAOYSA-N 0.000 description 1
- FSKGAXYBJXKXTM-UHFFFAOYSA-N 2-(5-methyl-2-piperidin-1-yl-1,3-oxazol-4-yl)ethanol Chemical compound OCCC1=C(C)OC(N2CCCCC2)=N1 FSKGAXYBJXKXTM-UHFFFAOYSA-N 0.000 description 1
- YEABVNXPNYBSFD-UHFFFAOYSA-N 2-(5-methyl-2-pyridin-4-yl-1,3-oxazol-4-yl)ethanol Chemical compound OCCC1=C(C)OC(C=2C=CN=CC=2)=N1 YEABVNXPNYBSFD-UHFFFAOYSA-N 0.000 description 1
- BJLJZZUVNDIVAW-UHFFFAOYSA-N 2-(5-methyl-2-pyridin-4-yl-1,3-thiazol-4-yl)ethanol Chemical compound OCCC1=C(C)SC(C=2C=CN=CC=2)=N1 BJLJZZUVNDIVAW-UHFFFAOYSA-N 0.000 description 1
- WSUWPFKLFSRXNX-UHFFFAOYSA-N 2-(5-methyl-3-phenylpyrazol-1-yl)ethanol Chemical compound OCCN1C(C)=CC(C=2C=CC=CC=2)=N1 WSUWPFKLFSRXNX-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- KRNUKKZDGDAWBF-UHFFFAOYSA-N 2-(n-ethyl-n-m-toluidino)ethanol Chemical compound OCCN(CC)C1=CC=CC(C)=C1 KRNUKKZDGDAWBF-UHFFFAOYSA-N 0.000 description 1
- PIUVCKCIXRKVBO-UHFFFAOYSA-N 2-(pyridine-3-carbonyl)cyclohexan-1-one Chemical compound C=1C=CN=CC=1C(=O)C1CCCCC1=O PIUVCKCIXRKVBO-UHFFFAOYSA-N 0.000 description 1
- NSTCBWTUKABFFO-UHFFFAOYSA-N 2-(pyridine-4-carbonyl)cyclohexan-1-one Chemical compound C=1C=NC=CC=1C(=O)C1CCCCC1=O NSTCBWTUKABFFO-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
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
- ROINRXKIPPQGDA-UHFFFAOYSA-N 2-[2-(2-methoxyethylamino)-5-methyl-1,3-thiazol-4-yl]ethanol Chemical compound COCCNC1=NC(CCO)=C(C)S1 ROINRXKIPPQGDA-UHFFFAOYSA-N 0.000 description 1
- ASJZWFBTOCRMDP-UHFFFAOYSA-N 2-[2-(dimethylamino)-5-methyl-1,3-oxazol-4-yl]ethanol Chemical compound CN(C)C1=NC(CCO)=C(C)O1 ASJZWFBTOCRMDP-UHFFFAOYSA-N 0.000 description 1
- JNDJCTRXENWLIY-UHFFFAOYSA-N 2-[2-[3-(methoxycarbonylamino)benzoyl]anilino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound COC(=O)NC1=CC=CC(C(=O)C=2C(=CC=CC=2)NC(CC=2C=CC(OCCC3=C(OC(=N3)C=3C=CC=CC=3)C)=CC=2)C(O)=O)=C1 JNDJCTRXENWLIY-UHFFFAOYSA-N 0.000 description 1
- XULPUEVNKCEDLG-UHFFFAOYSA-N 2-[2-[4-[(dimethylamino)methyl]benzoyl]anilino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid;hydrochloride Chemical compound Cl.C1=CC(CN(C)C)=CC=C1C(=O)C1=CC=CC=C1NC(C(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 XULPUEVNKCEDLG-UHFFFAOYSA-N 0.000 description 1
- OIUHSFKEXYXWSD-UHFFFAOYSA-N 2-[3-(6-methylpyridin-2-yl)propoxy]ethanol Chemical compound CC1=CC=CC(CCCOCCO)=N1 OIUHSFKEXYXWSD-UHFFFAOYSA-N 0.000 description 1
- CZKQOXPBXFKTLI-UHFFFAOYSA-N 2-[3-(furan-2-yl)-5-methylpyrazol-1-yl]ethanol Chemical compound OCCN1C(C)=CC(C=2OC=CC=2)=N1 CZKQOXPBXFKTLI-UHFFFAOYSA-N 0.000 description 1
- WCPQABSSEZSXNB-UHFFFAOYSA-N 2-[3-(methoxymethyl)-5-methyl-2-phenylimidazol-4-yl]ethanol Chemical compound COCN1C(CCO)=C(C)N=C1C1=CC=CC=C1 WCPQABSSEZSXNB-UHFFFAOYSA-N 0.000 description 1
- ZMTIBXQPXBUWPQ-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(OC(F)(F)F)C=C1 ZMTIBXQPXBUWPQ-UHFFFAOYSA-N 0.000 description 1
- KRUVCQLRXNPHIN-UHFFFAOYSA-N 2-[5-methyl-2-(5-methyl-1,2-oxazol-3-yl)-1,3-oxazol-4-yl]ethanol Chemical compound O1C(C)=CC(C=2OC(C)=C(CCO)N=2)=N1 KRUVCQLRXNPHIN-UHFFFAOYSA-N 0.000 description 1
- DCEAWLCKOZHYPD-UHFFFAOYSA-N 2-[5-methyl-2-(5-methylthiophen-2-yl)-1,3-oxazol-4-yl]ethanol Chemical compound S1C(C)=CC=C1C1=NC(CCO)=C(C)O1 DCEAWLCKOZHYPD-UHFFFAOYSA-N 0.000 description 1
- FHUHABKTFRRBQN-UHFFFAOYSA-N 2-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]-3-(2-bromophenyl)propanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)CC1=CC=CC=C1Br FHUHABKTFRRBQN-UHFFFAOYSA-N 0.000 description 1
- HKVVIUMWDFWOJL-UHFFFAOYSA-N 2-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]-3-phenylpropanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)CC1=CC=CC=C1 HKVVIUMWDFWOJL-UHFFFAOYSA-N 0.000 description 1
- COTQFECOGMADPE-UHFFFAOYSA-N 2-amino-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]propanoic acid Chemical compound C=1C=CC=NC=1N(C)CCOC1=CC=C(CC(N)C(O)=O)C=C1 COTQFECOGMADPE-UHFFFAOYSA-N 0.000 description 1
- FDPVTENMNDHFNK-UHFFFAOYSA-N 2-amino-n-phenylbenzamide Chemical compound NC1=CC=CC=C1C(=O)NC1=CC=CC=C1 FDPVTENMNDHFNK-UHFFFAOYSA-N 0.000 description 1
- GRWKNBPOGBTZMN-UHFFFAOYSA-N 2-benzyl-3-phenylpropane-1,2-diamine Chemical compound C=1C=CC=CC=1CC(N)(CN)CC1=CC=CC=C1 GRWKNBPOGBTZMN-UHFFFAOYSA-N 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- RHGSWONXHKQNKK-UHFFFAOYSA-N 2-diazonio-1-methoxy-3-(4-phenylmethoxyphenyl)prop-1-en-1-olate Chemical compound C1=CC(CC(=C([O-])OC)[N+]#N)=CC=C1OCC1=CC=CC=C1 RHGSWONXHKQNKK-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- XLJXJKHWLMYXBE-UHFFFAOYSA-N 2-methoxyethylthiourea Chemical compound COCCNC(N)=S XLJXJKHWLMYXBE-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- GHPUMGIECCOLLL-UHFFFAOYSA-N 3-(2-hydroxyethoxy)benzonitrile Chemical compound OCCOC1=CC=CC(C#N)=C1 GHPUMGIECCOLLL-UHFFFAOYSA-N 0.000 description 1
- NIIDHUCLROLCBU-UHFFFAOYSA-N 3-(4-methoxyphenyl)propan-1-ol Chemical compound COC1=CC=C(CCCO)C=C1 NIIDHUCLROLCBU-UHFFFAOYSA-N 0.000 description 1
- QCGUXRFTJDHKTF-UHFFFAOYSA-N 3-(dimethylamino)propylthiourea Chemical compound CN(C)CCCNC(N)=S QCGUXRFTJDHKTF-UHFFFAOYSA-N 0.000 description 1
- VVSHKLXYBAYORP-UHFFFAOYSA-N 3-(furan-2-yl)-5-methyl-1h-pyrazole Chemical compound N1C(C)=CC(C=2OC=CC=2)=N1 VVSHKLXYBAYORP-UHFFFAOYSA-N 0.000 description 1
- LBVZCSKDTGDAQW-UHFFFAOYSA-N 3-[(2-oxo-1,3-oxazolidin-3-yl)phosphanyl]-1,3-oxazolidin-2-one;hydrochloride Chemical compound [Cl-].O=C1OCCN1[PH2+]N1C(=O)OCC1 LBVZCSKDTGDAQW-UHFFFAOYSA-N 0.000 description 1
- VFMRGCFZOIBVAE-UHFFFAOYSA-N 3-[4-[1-(1,3-benzoxazol-2-yl)pyrrolidin-3-yl]oxyphenyl]-2-(2-benzoylanilino)propanoic acid Chemical compound C=1C=C(OC2CN(CC2)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 VFMRGCFZOIBVAE-UHFFFAOYSA-N 0.000 description 1
- KPKFXYIXCWRXJD-UHFFFAOYSA-N 3-[4-[2-(4-chlorophenyl)sulfanylethoxy]phenyl]-2-(2-methoxycarbonylanilino)propanoic acid Chemical compound COC(=O)C1=CC=CC=C1NC(C(O)=O)CC(C=C1)=CC=C1OCCSC1=CC=C(Cl)C=C1 KPKFXYIXCWRXJD-UHFFFAOYSA-N 0.000 description 1
- RIIAAWSRWXBMIZ-UHFFFAOYSA-N 3-[4-[2-(benzimidazol-1-yl)ethoxy]phenyl]-2-(2-benzoylanilino)propanoic acid Chemical compound C=1C=C(OCCN2C3=CC=CC=C3N=C2)C=CC=1CC(C(=O)O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 RIIAAWSRWXBMIZ-UHFFFAOYSA-N 0.000 description 1
- CLDWIYLTZCNVHQ-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-(2-benzoyl-4-methylanilino)propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=C(C)C=C1C(=O)C1=CC=CC=C1 CLDWIYLTZCNVHQ-UHFFFAOYSA-N 0.000 description 1
- ZZLLEVLMZDJINU-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-(2-benzoylanilino)propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZLLEVLMZDJINU-UHFFFAOYSA-N 0.000 description 1
- FOPNQIAKJLVHHZ-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(3-hydroxybenzoyl)anilino]propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC(O)=C1 FOPNQIAKJLVHHZ-UHFFFAOYSA-N 0.000 description 1
- LGYLPQDCGVFKFX-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(cycloheptanecarbonyl)anilino]propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1CCCCCC1 LGYLPQDCGVFKFX-UHFFFAOYSA-N 0.000 description 1
- VNSBCISODOSQER-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(cyclohexanecarbonyl)-5-fluoroanilino]propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC(F)=CC=C1C(=O)C1CCCCC1 VNSBCISODOSQER-UHFFFAOYSA-N 0.000 description 1
- YQSQUWWQEJSFGZ-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(cyclohexanecarbonyl)anilino]propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1CCCCC1 YQSQUWWQEJSFGZ-UHFFFAOYSA-N 0.000 description 1
- ZIDAAQFLGVRNGM-UHFFFAOYSA-N 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-3-[(4-benzoylthiophen-2-yl)amino]propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1C(CC(O)=O)NC(SC=1)=CC=1C(=O)C1=CC=CC=C1 ZIDAAQFLGVRNGM-UHFFFAOYSA-N 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
- DJQQYMHZVJXALQ-UHFFFAOYSA-N 3-azido-4-oxopentanoic acid Chemical compound OC(=O)CC(C(=O)C)N=[N+]=[N-] DJQQYMHZVJXALQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- UEJQTBKTWJQBRN-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-chlorophenyl)-1,3-thiazole Chemical compound ClCC1=CSC(C=2C=CC(Cl)=CC=2)=N1 UEJQTBKTWJQBRN-UHFFFAOYSA-N 0.000 description 1
- FRMKJZNBTRONBV-UHFFFAOYSA-N 4-[2-[methyl(pyridin-2-yl)amino]ethoxy]benzaldehyde Chemical compound C=1C=CC=NC=1N(C)CCOC1=CC=C(C=O)C=C1 FRMKJZNBTRONBV-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- VNDHYTGVCGVETQ-UHFFFAOYSA-N 4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C=C1 VNDHYTGVCGVETQ-UHFFFAOYSA-N 0.000 description 1
- GUCPYIYFQVTFSI-UHFFFAOYSA-N 4-methoxybenzamide Chemical compound COC1=CC=C(C(N)=O)C=C1 GUCPYIYFQVTFSI-UHFFFAOYSA-N 0.000 description 1
- SJWSGYOCBFJBAX-UHFFFAOYSA-N 4-methylthiadiazole-5-carboxamide Chemical compound CC=1N=NSC=1C(N)=O SJWSGYOCBFJBAX-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- TYOXIFXYEIILLY-UHFFFAOYSA-N 5-methyl-2-phenyl-1h-imidazole Chemical compound N1C(C)=CN=C1C1=CC=CC=C1 TYOXIFXYEIILLY-UHFFFAOYSA-N 0.000 description 1
- IFLKEBSJTZGCJG-UHFFFAOYSA-N 5-methyl-2-thiophenecarboxylic acid Natural products CC=1C=CSC=1C(O)=O IFLKEBSJTZGCJG-UHFFFAOYSA-N 0.000 description 1
- UJCLXNPHJKRLPX-UHFFFAOYSA-N 5-methyl-3-phenyl-1h-1,2,4-triazole Chemical compound N1C(C)=NC(C=2C=CC=CC=2)=N1 UJCLXNPHJKRLPX-UHFFFAOYSA-N 0.000 description 1
- QHRSESMSOJZMCO-UHFFFAOYSA-N 5-methyl-3-phenyl-1h-pyrazole Chemical compound N1C(C)=CC(C=2C=CC=CC=2)=N1 QHRSESMSOJZMCO-UHFFFAOYSA-N 0.000 description 1
- VCNGNQLPFHVODE-UHFFFAOYSA-N 5-methylthiophene-2-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)S1 VCNGNQLPFHVODE-UHFFFAOYSA-N 0.000 description 1
- AYKKNCZWZNXBGY-UHFFFAOYSA-N 7-methoxy-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)COC2=CC(OC)=CC=C21 AYKKNCZWZNXBGY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- RTAUFJNZUXTZAX-UHFFFAOYSA-N 9,9-dimethyl-6-[5-(4-nitrophenyl)furan-2-yl]-5-(2-phenylacetyl)-6,8,10,11-tetrahydrobenzo[b][1,4]benzodiazepin-7-one Chemical compound C1C(C)(C)CC(=O)C2=C1NC1=CC=CC=C1N(C(=O)CC=1C=CC=CC=1)C2C(O1)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 RTAUFJNZUXTZAX-UHFFFAOYSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 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
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 102000003706 Complement factor D Human genes 0.000 description 1
- 108090000059 Complement factor D Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- HVVNJUAVDAZWCB-RXMQYKEDSA-N D-prolinol Chemical compound OC[C@H]1CCCN1 HVVNJUAVDAZWCB-RXMQYKEDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 102000058063 Glucose Transporter Type 1 Human genes 0.000 description 1
- 102000058061 Glucose Transporter Type 4 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 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
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- IPHTZOSHNVGORH-GJFSDDNBSA-N N-ethylethanamine (2R)-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[(4-oxo-4-phenylbut-2-en-2-yl)amino]propanoic acid Chemical compound CCNCC.N([C@H](CC1=CC=C(C=C1)OCCN(C)C=1N=CC=CC=1)C(O)=O)C(C)=CC(=O)C1=CC=CC=C1 IPHTZOSHNVGORH-GJFSDDNBSA-N 0.000 description 1
- IPHTZOSHNVGORH-JIDHJSLPSA-N N-ethylethanamine (2S)-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[(4-oxo-4-phenylbut-2-en-2-yl)amino]propanoic acid Chemical compound CCNCC.N([C@@H](CC1=CC=C(C=C1)OCCN(C)C=1N=CC=CC=1)C(O)=O)C(C)=CC(=O)C1=CC=CC=C1 IPHTZOSHNVGORH-JIDHJSLPSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 108091006296 SLC2A1 Proteins 0.000 description 1
- 108091006300 SLC2A4 Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 206010057362 Underdose Diseases 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- NZIDTDIDEPGKHB-LBPRGKRZSA-N [(3s)-1-benzylpyrrolidin-3-yl] methanesulfonate Chemical compound C1[C@@H](OS(=O)(=O)C)CCN1CC1=CC=CC=C1 NZIDTDIDEPGKHB-LBPRGKRZSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- RSXCJJVBDQSDJF-UHFFFAOYSA-N [1-(1,3-benzoxazol-2-yl)pyrrolidin-3-yl] methanesulfonate Chemical compound C1C(OS(=O)(=O)C)CCN1C1=NC2=CC=CC=C2O1 RSXCJJVBDQSDJF-UHFFFAOYSA-N 0.000 description 1
- JNSBEPKGFVENFS-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC=C1C(F)(F)F JNSBEPKGFVENFS-UHFFFAOYSA-N 0.000 description 1
- KXZCLGBIAGNAGS-UHFFFAOYSA-N [4-(propylsulfamoyl)phenyl]boronic acid Chemical compound CCCNS(=O)(=O)C1=CC=C(B(O)O)C=C1 KXZCLGBIAGNAGS-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000002293 adipogenic effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000004411 aluminium Substances 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- UDLLFLQFQMACJB-UHFFFAOYSA-N azidomethylbenzene Chemical compound [N-]=[N+]=NCC1=CC=CC=C1 UDLLFLQFQMACJB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- HFKZACKOGICGMZ-UHFFFAOYSA-N boric acid;1,3-xylene Chemical compound OB(O)O.CC1=CC=CC(C)=C1 HFKZACKOGICGMZ-UHFFFAOYSA-N 0.000 description 1
- XIXMDRKCCYQJGY-UHFFFAOYSA-N boric acid;trifluoromethylbenzene Chemical compound OB(O)O.FC(F)(F)C1=CC=CC=C1 XIXMDRKCCYQJGY-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 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
- 239000006227 byproduct Substances 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical class [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000009838 combustion analysis Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 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
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000002993 cycloalkylene group Chemical group 0.000 description 1
- 125000005725 cyclohexenylene group Chemical group 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- JSUZLXJGDBCNDB-UHFFFAOYSA-N ethyl 2-(benzhydrylideneamino)-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]propanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)=NC(C(=O)OCC)CC(C=C1)=CC=C1OCCN(C)C1=CC=CC=N1 JSUZLXJGDBCNDB-UHFFFAOYSA-N 0.000 description 1
- QUGJYNGNUBHTNS-UHFFFAOYSA-N ethyl 2-(benzhydrylideneamino)acetate Chemical compound C=1C=CC=CC=1C(=NCC(=O)OCC)C1=CC=CC=C1 QUGJYNGNUBHTNS-UHFFFAOYSA-N 0.000 description 1
- NMHNERYNYIUFMQ-UHFFFAOYSA-N ethyl 2-amino-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]propanoate Chemical compound C1=CC(CC(N)C(=O)OCC)=CC=C1OCCN(C)C1=CC=CC=N1 NMHNERYNYIUFMQ-UHFFFAOYSA-N 0.000 description 1
- POGCXCWRMMXDAQ-UHFFFAOYSA-N ethyl 3-iodobenzoate Chemical compound CCOC(=O)C1=CC=CC(I)=C1 POGCXCWRMMXDAQ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 229940035423 ethyl ether Drugs 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZZCHHVUQYRMYLW-HKBQPEDESA-N farglitazar Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZCHHVUQYRMYLW-HKBQPEDESA-N 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- BNTRVUUJBGBGLZ-UHFFFAOYSA-N hydron;pyridine-4-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=NC=C1 BNTRVUUJBGBGLZ-UHFFFAOYSA-N 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003914 insulin secretion Effects 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
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 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
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 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
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- DDOICUKCJCTMSS-VWLOTQADSA-N methyl (2s)-2-[(4-oxo-4-phenylbut-2-en-2-yl)amino]-3-(4-phenylmethoxyphenyl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(C)=CC(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 DDOICUKCJCTMSS-VWLOTQADSA-N 0.000 description 1
- IQKXGACPIPNLEL-NTISSMGPSA-N methyl (2s)-2-amino-3-(4-phenylmethoxyphenyl)propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OCC1=CC=CC=C1 IQKXGACPIPNLEL-NTISSMGPSA-N 0.000 description 1
- FEETXSMPSPHKSO-HKBQPEDESA-N methyl (2s)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-[2-(pyridine-3-carbonyl)anilino]propanoate Chemical compound C([C@@H](C(=O)OC)NC=1C(=CC=CC=1)C(=O)C=1C=NC=CC=1)C(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 FEETXSMPSPHKSO-HKBQPEDESA-N 0.000 description 1
- XDFARYFKFNSAQE-RNAHPLFWSA-N methyl (2s)-3-[4-[[(4r)-3-(1,3-benzoxazol-2-yl)-1,3-thiazolidin-4-yl]methoxy]phenyl]-2-(2-benzoylanilino)propanoate Chemical compound N([C@@H](CC=1C=CC(OC[C@H]2N(CSC2)C=2OC3=CC=CC=C3N=2)=CC=1)C(=O)OC)C1=CC=CC=C1C(=O)C1=CC=CC=C1 XDFARYFKFNSAQE-RNAHPLFWSA-N 0.000 description 1
- ADYZVTFHEILCHQ-UHFFFAOYSA-N methyl 2-(2-benzoylanilino)-3-[4-(2-hydroxyethoxy)phenyl]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)OC)CC1=CC=C(OCCO)C=C1 ADYZVTFHEILCHQ-UHFFFAOYSA-N 0.000 description 1
- ZTWYRYKDJWUJFE-UHFFFAOYSA-N methyl 2-(2-benzoylanilino)-3-[4-(2-methylsulfonyloxyethoxy)phenyl]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)OC)CC1=CC=C(OCCOS(C)(=O)=O)C=C1 ZTWYRYKDJWUJFE-UHFFFAOYSA-N 0.000 description 1
- KTXOGJVRDGYJEH-UHFFFAOYSA-N methyl 2-(2-iodoanilino)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C=1C=CC=C(I)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 KTXOGJVRDGYJEH-UHFFFAOYSA-N 0.000 description 1
- CVSBEMCXALOBMW-UHFFFAOYSA-N methyl 2-(2-phenylmethoxyanilino)-3-(4-phenylmethoxyphenyl)propanoate Chemical compound C=1C=CC=C(OCC=2C=CC=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCC1=CC=CC=C1 CVSBEMCXALOBMW-UHFFFAOYSA-N 0.000 description 1
- IGRGQWSVDTYHID-UHFFFAOYSA-N methyl 2-(5-methyl-2-phenyl-1,3-thiazol-4-yl)acetate Chemical compound S1C(C)=C(CC(=O)OC)N=C1C1=CC=CC=C1 IGRGQWSVDTYHID-UHFFFAOYSA-N 0.000 description 1
- IJXAUJZALSWCDF-UHFFFAOYSA-N methyl 2-(5-methyl-2-pyridin-4-yl-1,3-oxazol-4-yl)acetate Chemical compound O1C(C)=C(CC(=O)OC)N=C1C1=CC=NC=C1 IJXAUJZALSWCDF-UHFFFAOYSA-N 0.000 description 1
- FDNSJQQRPAUKLJ-UHFFFAOYSA-N methyl 2-[(2-benzoylthiophen-3-yl)amino]-3-(4-phenylmethoxyphenyl)propanoate Chemical compound C1=CSC(C(=O)C=2C=CC=CC=2)=C1NC(C(=O)OC)CC(C=C1)=CC=C1OCC1=CC=CC=C1 FDNSJQQRPAUKLJ-UHFFFAOYSA-N 0.000 description 1
- OSDTUBLUGRYJIM-UHFFFAOYSA-N methyl 2-[(3-benzoylthiophen-2-yl)amino]-3-(4-phenylmethoxyphenyl)propanoate Chemical compound S1C=CC(C(=O)C=2C=CC=CC=2)=C1NC(C(=O)OC)CC(C=C1)=CC=C1OCC1=CC=CC=C1 OSDTUBLUGRYJIM-UHFFFAOYSA-N 0.000 description 1
- AVGBCQDDEIHXBU-UHFFFAOYSA-N methyl 2-[2-(2H-cyclopenta[c]pyridin-4-yl)-5-methyl-1,3-thiazol-4-yl]acetate Chemical compound S1C(C)=C(CC(=O)OC)N=C1C1=CNC=C2C1=CC=C2 AVGBCQDDEIHXBU-UHFFFAOYSA-N 0.000 description 1
- MEMDFGVHURWSPH-UHFFFAOYSA-N methyl 2-[2-(3-hydroxybenzoyl)anilino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=C(O)C=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 MEMDFGVHURWSPH-UHFFFAOYSA-N 0.000 description 1
- YPQQQCVGWVDWIT-UHFFFAOYSA-N methyl 2-[2-(4-formylbenzoyl)anilino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=CC(C=O)=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 YPQQQCVGWVDWIT-UHFFFAOYSA-N 0.000 description 1
- MVAXVLNTNVKGNJ-UHFFFAOYSA-N methyl 2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]acetate Chemical compound O1C(C)=C(CC(=O)OC)N=C1C1=CC=C(OC)C=C1 MVAXVLNTNVKGNJ-UHFFFAOYSA-N 0.000 description 1
- YFVJTLFMRHQJCK-UHFFFAOYSA-N methyl 2-[2-(cyclohexanecarbonyl)anilino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C=1C=CC=C(C(=O)C2CCCCC2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 YFVJTLFMRHQJCK-UHFFFAOYSA-N 0.000 description 1
- VEZXABULTDRBFU-UHFFFAOYSA-N methyl 2-[2-[3-(dimethylamino)propylamino]-5-methyl-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC=1N=C(NCCCN(C)C)SC=1C VEZXABULTDRBFU-UHFFFAOYSA-N 0.000 description 1
- JJHNJIFPFRHUGE-UHFFFAOYSA-N methyl 2-[5-methyl-2-(4-methylthiadiazol-5-yl)-1,3-oxazol-4-yl]acetate Chemical compound O1C(C)=C(CC(=O)OC)N=C1C1=C(C)N=NS1 JJHNJIFPFRHUGE-UHFFFAOYSA-N 0.000 description 1
- PCVLQLQJWTZORF-UHFFFAOYSA-N methyl 2-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]-3-phenylpropanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)CC1=CC=CC=C1 PCVLQLQJWTZORF-UHFFFAOYSA-N 0.000 description 1
- JUKCTOHWTHYRPF-UHFFFAOYSA-N methyl 3,5-dioxohexanoate Chemical compound COC(=O)CC(=O)CC(C)=O JUKCTOHWTHYRPF-UHFFFAOYSA-N 0.000 description 1
- ZBUUPZGUITZZOC-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2-[2-(4-methoxybenzoyl)anilino]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=CC(OC)=CC=2)C=1NC(C(=O)OC)CC1=CC=C(O)C=C1 ZBUUPZGUITZZOC-UHFFFAOYSA-N 0.000 description 1
- DJFGOJXFJMRGBQ-UHFFFAOYSA-N methyl 3-[(5-methylthiophen-2-yl)amino]-4-oxopentanoate Chemical compound COC(=O)CC(C(C)=O)NC1=CC=C(C)S1 DJFGOJXFJMRGBQ-UHFFFAOYSA-N 0.000 description 1
- IPXPWOFRFMLEAV-UHFFFAOYSA-N methyl 3-[4-(1-benzylpyrrolidin-3-yl)oxyphenyl]-2-(2-phenylanilino)propanoate Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OC(C1)CCN1CC1=CC=CC=C1 IPXPWOFRFMLEAV-UHFFFAOYSA-N 0.000 description 1
- CIPDJIXVJPPZSK-UHFFFAOYSA-N methyl 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-[2-(3-phenylmethoxybenzoyl)anilino]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=C(OCC=3C=CC=CC=3)C=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 CIPDJIXVJPPZSK-UHFFFAOYSA-N 0.000 description 1
- JBWJYPAJFBMMNC-UHFFFAOYSA-N methyl 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-[2-[3-(2-oxoethoxy)benzoyl]anilino]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=C(OCC=O)C=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 JBWJYPAJFBMMNC-UHFFFAOYSA-N 0.000 description 1
- FVRDMBHKJHGWNM-UHFFFAOYSA-N methyl 3-[4-[2-(benzimidazol-1-yl)ethoxy]phenyl]-2-(2-benzoylanilino)propanoate Chemical compound C=1C=C(OCCN2C3=CC=CC=C3N=C2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 FVRDMBHKJHGWNM-UHFFFAOYSA-N 0.000 description 1
- MDSZYYGNHYBJLH-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-(2-benzoylanilino)propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MDSZYYGNHYBJLH-UHFFFAOYSA-N 0.000 description 1
- KSTKSRXFCNHFSZ-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(2-methylbenzoyl)anilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=CC=C1C KSTKSRXFCNHFSZ-UHFFFAOYSA-N 0.000 description 1
- ULXRFZIADSTAMB-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(3-hydroxybenzoyl)anilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=CC(O)=C1 ULXRFZIADSTAMB-UHFFFAOYSA-N 0.000 description 1
- ZXNOAWKMDLURRB-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(4-methylbenzoyl)anilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=C(C)C=C1 ZXNOAWKMDLURRB-UHFFFAOYSA-N 0.000 description 1
- NTIDGYCTRXCZRK-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(4-phenylbenzoyl)anilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 NTIDGYCTRXCZRK-UHFFFAOYSA-N 0.000 description 1
- ZFQTUIVCZOSTCD-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(cyclohexanecarbonyl)-5-fluoroanilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC(F)=CC=C1C(=O)C1CCCCC1 ZFQTUIVCZOSTCD-UHFFFAOYSA-N 0.000 description 1
- XJSPXIQZSDCYJN-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(cyclohexanecarbonyl)anilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1CCCCC1 XJSPXIQZSDCYJN-UHFFFAOYSA-N 0.000 description 1
- HLMDWRQUVIXDLV-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-[2-(cyclopentanecarbonyl)anilino]propanoate Chemical compound C=1C=C(OCCN(C)C=2OC3=CC=CC=C3N=2)C=CC=1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1CCCC1 HLMDWRQUVIXDLV-UHFFFAOYSA-N 0.000 description 1
- QLMIUFITFKRIHW-UHFFFAOYSA-N methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1OCCN(C)C1=NC2=CC=CC=C2O1 QLMIUFITFKRIHW-UHFFFAOYSA-N 0.000 description 1
- MKMJBLQCPVFGKN-UHFFFAOYSA-N methyl 3-amino-4-oxopentanoate Chemical compound COC(=O)CC(N)C(C)=O MKMJBLQCPVFGKN-UHFFFAOYSA-N 0.000 description 1
- PYEPIWRQEUGIRK-UHFFFAOYSA-N methyl 3-bromo-4-oxopentanoate Chemical compound COC(=O)CC(Br)C(C)=O PYEPIWRQEUGIRK-UHFFFAOYSA-N 0.000 description 1
- XWDCQYLZSYSBCP-UHFFFAOYSA-N methyl 3-hydroxy-3-phenyl-2-[(4-phenylmethoxyphenyl)methyl]-1h-indole-2-carboxylate Chemical compound N1C2=CC=CC=C2C(C=2C=CC=CC=2)(O)C1(C(=O)OC)CC(C=C1)=CC=C1OCC1=CC=CC=C1 XWDCQYLZSYSBCP-UHFFFAOYSA-N 0.000 description 1
- CBDZTZRCJJFHLL-UHFFFAOYSA-N methyl 4-oxo-3-(pyridine-4-carbonylamino)pentanoate Chemical compound COC(=O)CC(C(C)=O)NC(=O)C1=CC=NC=C1 CBDZTZRCJJFHLL-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- AGCDTYFRBPSPSX-UHFFFAOYSA-N n-[2-[4-(bromomethyl)phenoxy]ethyl]-n-methylpyridin-2-amine Chemical compound C=1C=CC=NC=1N(C)CCOC1=CC=C(CBr)C=C1 AGCDTYFRBPSPSX-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 101150015886 nuc-1 gene Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-N o-aminobenzenecarboxylic acid Natural products NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- OIGWAXDAPKFNCQ-UHFFFAOYSA-N p-Isopropylbenzyl alcohol Natural products CC(C)C1=CC=C(CO)C=C1 OIGWAXDAPKFNCQ-UHFFFAOYSA-N 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- KPIIGXWUNXGGCP-UHFFFAOYSA-N pyridine-4-carbothioamide Chemical compound NC(=S)C1=CC=NC=C1 KPIIGXWUNXGGCP-UHFFFAOYSA-N 0.000 description 1
- VONGYFFEWFJHNP-UHFFFAOYSA-N pyrrolecarboxylic acid methyl ester Natural products COC(=O)C1=CC=CN1 VONGYFFEWFJHNP-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 102000027483 retinoid hormone receptors Human genes 0.000 description 1
- 108091008679 retinoid hormone receptors Proteins 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BFFLLBPMZCIGRM-QMMMGPOBSA-N tert-butyl (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CO BFFLLBPMZCIGRM-QMMMGPOBSA-N 0.000 description 1
- VDVKVJWSONANJF-UHFFFAOYSA-N tert-butyl 4-[4-(2-hydroxyethyl)-5-methyl-1,3-thiazol-2-yl]piperazine-1-carboxylate Chemical compound OCCC1=C(C)SC(N2CCN(CC2)C(=O)OC(C)(C)C)=N1 VDVKVJWSONANJF-UHFFFAOYSA-N 0.000 description 1
- RFDSJHHLGFFVHD-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)-n-methylcarbamate Chemical compound OCCN(C)C(=O)OC(C)(C)C RFDSJHHLGFFVHD-UHFFFAOYSA-N 0.000 description 1
- POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 108010072897 transcription factor Brn-2 Proteins 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/11—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/12—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9604242.9A GB9604242D0 (en) | 1996-02-28 | 1996-02-28 | Chemical compounds |
PCT/EP1997/000916 WO1997031907A1 (en) | 1996-02-28 | 1997-02-26 | Substituted 4-hydroxy-phenylalcanoic acid derivatives with agonist activity to ppar-gamma |
Publications (3)
Publication Number | Publication Date |
---|---|
NO983940D0 NO983940D0 (no) | 1998-08-27 |
NO983940L NO983940L (no) | 1998-10-27 |
NO311516B1 true NO311516B1 (no) | 2001-12-03 |
Family
ID=10789571
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19983940A NO311516B1 (no) | 1996-02-28 | 1998-08-27 | Derivater av substituerte 4-hydroksy-fenylalkanosyrer med agonistisk aktivitet for PPAR-gamma, farmasöytiske preparaterinneholdende dem, anvendelse av dem og fremgangsmåte forfremstilling av dem |
Country Status (41)
Country | Link |
---|---|
US (1) | US6294580B1 (da) |
EP (1) | EP0888317B1 (da) |
JP (1) | JP3255930B2 (da) |
KR (1) | KR100462730B1 (da) |
CN (1) | CN1093124C (da) |
AP (1) | AP780A (da) |
AR (1) | AR011502A1 (da) |
AT (1) | ATE205485T1 (da) |
AU (1) | AU717699B2 (da) |
BG (1) | BG102792A (da) |
BR (1) | BR9707786B1 (da) |
CA (1) | CA2247443C (da) |
CY (1) | CY2319B1 (da) |
CZ (1) | CZ295383B6 (da) |
DE (1) | DE69706658T2 (da) |
DK (1) | DK0888317T3 (da) |
EA (1) | EA001403B1 (da) |
EE (1) | EE9800288A (da) |
ES (1) | ES2163125T3 (da) |
GB (1) | GB9604242D0 (da) |
GE (1) | GEP20012580B (da) |
HK (1) | HK1015369A1 (da) |
HR (1) | HRP970110B1 (da) |
HU (1) | HUP0004845A3 (da) |
ID (1) | ID15985A (da) |
IL (1) | IL125796A (da) |
IS (1) | IS1869B (da) |
MY (1) | MY119425A (da) |
NO (1) | NO311516B1 (da) |
NZ (1) | NZ331381A (da) |
OA (1) | OA10843A (da) |
PE (1) | PE43098A1 (da) |
PL (1) | PL191118B1 (da) |
PT (1) | PT888317E (da) |
RS (1) | RS49586B (da) |
SI (1) | SI0888317T1 (da) |
SK (1) | SK282753B6 (da) |
TR (1) | TR199801707T2 (da) |
UA (1) | UA58502C2 (da) |
WO (1) | WO1997031907A1 (da) |
ZA (1) | ZA971645B (da) |
Families Citing this family (155)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000515133A (ja) * | 1996-07-01 | 2000-11-14 | イーライ・リリー・アンド・カンパニー | 血糖降下性および脂質低下性の化合物 |
CN1233241A (zh) * | 1996-08-19 | 1999-10-27 | 日本烟草产业株式会社 | 丙酸衍生物及其用途 |
JP2001514663A (ja) | 1997-03-12 | 2001-09-11 | エスモンド,ロバート ダブリュー. | アルツハイマー病を処置または予防するための方法 |
DE69815008T2 (de) * | 1997-09-19 | 2004-04-01 | Ssp Co., Ltd. | Alfa-substituierte Phenylpropionsäurederivate und diese enthaltende Arzneimittel |
ID24376A (id) | 1997-10-02 | 2000-07-13 | Sankyo Co | Turunan-turunan asam amidokarboksilat |
US6444816B1 (en) * | 1997-10-27 | 2002-09-03 | Dr. Reddy's Research Foundation | Fused 7-oxo-pyrimidinyl compounds, preparation, composition and use thereof |
US6329372B1 (en) * | 1998-01-27 | 2001-12-11 | Celltech Therapeutics Limited | Phenylalanine derivatives |
JP4253126B2 (ja) | 1998-01-29 | 2009-04-08 | アムジェン インコーポレイテッド | Ppar−ガンマ調節剤 |
US6583157B2 (en) | 1998-01-29 | 2003-06-24 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
US6555562B1 (en) | 1998-02-26 | 2003-04-29 | Celltech R&D Limited | Phenylalanine derivatives |
GB9805655D0 (en) | 1998-03-16 | 1998-05-13 | Celltech Therapeutics Ltd | Chemical compounds |
US6521626B1 (en) | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
IL139470A0 (en) * | 1998-05-11 | 2001-11-25 | Takeda Chemical Industries Ltd | Oxyiminoalkanoic acid derivatives |
GB9811159D0 (en) | 1998-05-22 | 1998-07-22 | Celltech Therapeutics Ltd | Chemical compounds |
GB9811969D0 (en) * | 1998-06-03 | 1998-07-29 | Celltech Therapeutics Ltd | Chemical compounds |
SE9801990D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl propionic acid derivatives and analogs |
SE9801992D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
MA26634A1 (fr) * | 1998-06-04 | 2004-12-20 | Astra Ab | Nouveaux derives de l'acide 3-aryl propionique et analogues |
JP4533534B2 (ja) * | 1998-06-19 | 2010-09-01 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | グリコーゲンシンターゼキナーゼ3のインヒビター |
GB9814414D0 (en) | 1998-07-03 | 1998-09-02 | Celltech Therapeutics Ltd | Chemical compounds |
GB9817118D0 (en) * | 1998-08-07 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
GB9821061D0 (en) * | 1998-09-28 | 1998-11-18 | Celltech Therapeutics Ltd | Chemical compounds |
GB9821222D0 (en) | 1998-09-30 | 1998-11-25 | Celltech Therapeutics Ltd | Chemical compounds |
US6589969B1 (en) | 1998-10-16 | 2003-07-08 | Ono Pharmaceutical Co., Ltd. | Carboxylic acid derivatives and drugs containing the same as the active ingredient |
GB9825652D0 (en) | 1998-11-23 | 1999-01-13 | Celltech Therapeutics Ltd | Chemical compounds |
GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
CA2355645A1 (en) * | 1998-12-17 | 2000-06-22 | Mindset Biopharmaceuticals (Usa), Inc. | Increasing brain glucose utilization |
US6127394A (en) * | 1999-03-08 | 2000-10-03 | The University Of Mississippi | 1,2-Dithiolane derivatives |
US6204288B1 (en) | 1999-03-08 | 2001-03-20 | The University Of Mississippi | 1,2-dithiolane derivatives |
AU760163B2 (en) | 1999-04-06 | 2003-05-08 | Sankyo Company Limited | Alpha-substituted carboxylic acid derivatives |
EP1171430A1 (en) * | 1999-04-16 | 2002-01-16 | Dr. Reddy's Research Foundation | Novel polymorphic forms of an antidiabetic agent: process for their preparation and pharmaceutical compositions containing them |
US6528507B1 (en) | 1999-04-16 | 2003-03-04 | Dr. Reddy's Laboratories Limited | Polymorphic forms of an antidiabetic agent: process for their preparation and a pharmaceutical composition containing them |
WO2000063189A1 (en) * | 1999-04-16 | 2000-10-26 | Novo Nordisk A/S | Crystalline r- guanidines, arginine or (l) -arginine (2s) -2- ethoxy -3-{4- [2-(10h -phenoxazin -10-yl)ethoxy]phenyl}propanoate |
AU4250200A (en) * | 1999-04-19 | 2000-11-02 | Coelacanth Corporation | Ppar-(gamma) agonists as agents for the treatment of type ii diabetes |
EP1171438A1 (en) * | 1999-04-20 | 2002-01-16 | Novo Nordisk A/S | Compounds, their preparation and use |
JP2002542237A (ja) * | 1999-04-20 | 2002-12-10 | ノボ ノルディスク アクティーゼルスカブ | 新規な化合物、それらの製造及び使用 |
US6369055B1 (en) | 1999-04-20 | 2002-04-09 | Novo Nordisk A/S | Compounds, their preparation and use |
US7414128B2 (en) | 1999-04-20 | 2008-08-19 | Dr. Reddy's Laboratories, Limited | Crystalline R-guanidines, Arginine or (L)-Arginine (2S)-2-Ethoxy-3-{4-[2-(10H -phenoxazin-10-yl)ethoxy]phenyl}propanoate |
AU3958000A (en) * | 1999-04-20 | 2000-11-02 | Novo Nordisk A/S | New compounds, their preparation and use |
US6972294B1 (en) | 1999-04-20 | 2005-12-06 | Novo Nordisk, A/S | Compounds, their preparation and use |
US6274608B1 (en) | 1999-04-20 | 2001-08-14 | Novo Nordisk A/S | Compounds, their preparation and use |
JP2002543065A (ja) * | 1999-04-28 | 2002-12-17 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Ppap受容体リガンドとしてのトリアリール酸誘導体 |
IL146104A0 (en) | 1999-04-28 | 2002-07-25 | Reddy Research Foundation | Substituted bicyclic heterocyclic compounds, processes for their preparation and pharmaceutical compositions containing the same |
US6518283B1 (en) | 1999-05-28 | 2003-02-11 | Celltech R&D Limited | Squaric acid derivatives |
JP4618845B2 (ja) * | 1999-06-09 | 2011-01-26 | 杏林製薬株式会社 | ヒトペルオキシゾーム増殖薬活性化受容体(PPAR)αアゴニストとしての置換フェニルプロピオン酸誘導体 |
GB9913782D0 (en) * | 1999-06-14 | 1999-08-11 | Smithkline Beecham Plc | Novel compounds |
GB9914977D0 (en) * | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
ES2437103T3 (es) * | 1999-06-30 | 2014-01-08 | Amgen Inc. | Compuestos para la modulacion de la actividad de PPAR gamma |
US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
JP2003508389A (ja) | 1999-08-27 | 2003-03-04 | エリ リリー アンド カンパニー | ビアリール−オキサ(チア)ゾール誘導体およびそのpparモジュレーターとしての使用 |
HUP0202731A3 (en) | 1999-09-17 | 2003-10-28 | Kyorin Seiyaku Kk | O-anisamide derivatives, process for their preparation and pharmaceutical compositions containing them |
TWI302149B (en) * | 1999-09-22 | 2008-10-21 | Bristol Myers Squibb Co | Substituted acid derivatives useful as antiodiabetic and antiobesity agents and method |
US6414002B1 (en) | 1999-09-22 | 2002-07-02 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
EP1939188A1 (en) * | 1999-09-22 | 2008-07-02 | Bristol-Myers Squibb Company | Oxa-and thiazole derivatives useful as antidiabetic and antiobesity agents |
US6534513B1 (en) | 1999-09-29 | 2003-03-18 | Celltech R&D Limited | Phenylalkanoic acid derivatives |
SE9904415D0 (sv) * | 1999-12-03 | 1999-12-03 | Astra Ab | New process |
PL356769A1 (en) * | 1999-12-03 | 2004-07-12 | Kyoto Pharmaceutical Industries, Ltd. | Novel heterocyclic compounds and salts thereof and medicinal use of the same |
US6455539B2 (en) | 1999-12-23 | 2002-09-24 | Celltech R&D Limited | Squaric acid derivates |
JP4316787B2 (ja) * | 2000-01-11 | 2009-08-19 | 壽製薬株式会社 | エーテル又はアミド誘導体、その製法並びにそれを含有する糖尿病治療剤、 |
JP2001261674A (ja) * | 2000-03-22 | 2001-09-26 | Mitsui Chemicals Inc | ベンゾチオフェン誘導体およびそれを有効成分として含有する核内レセプター作動薬 |
WO2001079173A2 (en) | 2000-04-17 | 2001-10-25 | Celltech R & D Limited | Enamine derivatives as cell adhesion molecules |
US6653332B2 (en) | 2000-05-03 | 2003-11-25 | Tularik Inc. | Combination therapeutic compositions and method of use |
FR2808798A1 (fr) * | 2000-05-09 | 2001-11-16 | Hoechst Marion Roussel Inc | Nouveaux derives antagonistes du recepteur de la vitronectine |
US6403608B1 (en) | 2000-05-30 | 2002-06-11 | Celltech R&D, Ltd. | 3-Substituted isoquinolin-1-yl derivatives |
US6545013B2 (en) | 2000-05-30 | 2003-04-08 | Celltech R&D Limited | 2,7-naphthyridine derivatives |
GB0014969D0 (en) | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
EP1301488A1 (en) | 2000-07-07 | 2003-04-16 | Celltech R&D Limited | Squaric acid derivatives containing a bicyclic heteroaromatic ring as integrin antagonists |
CA2417059A1 (en) | 2000-08-02 | 2002-02-07 | Celltech R&D Limited | 3-substituted isoquinolin-1-yl derivatives |
WO2002013864A1 (fr) * | 2000-08-16 | 2002-02-21 | Sankyo Company, Limited | Preparation medicinale de prevention et traitement du cancer |
SK1872003A3 (en) | 2000-08-23 | 2003-07-01 | Lilly Co Eli | Oxazolyl-arylpropionic acid derivatives and their use as PPAR agonists |
AU2001284660A1 (en) | 2000-08-23 | 2002-03-04 | Eli Lilly And Company | Oxazolyl-arylpropionic acid derivatives and their use as ppar agonists |
ES2288982T3 (es) | 2000-08-23 | 2008-02-01 | Eli Lilly And Company | Derivados de acido oxazolil-ariloxiacetico y su uso como agonistas ppar. |
GB0030845D0 (en) * | 2000-12-18 | 2001-01-31 | Smithkline Beecham Plc | Novel treatment |
PL207798B1 (pl) * | 2000-12-25 | 2011-02-28 | Ono Pharmaceutical Co | Pochodne dihydronaftalenu i zawierające je regulatory receptorów aktywowanych przez proliferatory peroksysomów, takie jak agonista PPAR, środek hipoglikemiczny i/lub hipolipidemiczny, środek do podwyższania poziomu cholesterolu HDL i/lub obniżania poziomu LDL i/lub VLDL oraz środki do zapobiegania i/lub leczenia chorób związanych z zaburzeniami metabolicznymi |
WO2002051441A1 (fr) | 2000-12-26 | 2002-07-04 | Sankyo Company, Limited | Compositions medicinales contenant un diuretique et un agent renforçant la resistance a l'insuline |
EP1911462A3 (en) | 2001-01-26 | 2011-11-30 | Schering Corporation | Compositions comprising a sterol absorption inhibitor |
CA2440680C (en) | 2001-03-12 | 2010-06-01 | Roberto Pellicciari | Steroids as agonists for fxr |
WO2002087580A1 (fr) * | 2001-04-25 | 2002-11-07 | Takeda Chemical Industries, Ltd. | Promoteurs d'expression d'abc |
KR100654516B1 (ko) * | 2001-05-15 | 2006-12-05 | 에프. 호프만-라 로슈 아게 | 당뇨병 치료에서 ppar-알파 및 -감마 활성제로서사용하기 위한 카복실산 치환된 옥사졸 유도체 |
EP1398313A4 (en) | 2001-05-29 | 2005-11-16 | Kyoto Pharma Ind | NEW HETEROCYCLIC DERIVATIVES AND THEIR MEDICAL USE |
PL367639A1 (en) | 2001-05-29 | 2005-03-07 | Kyoto Pharmaceutical Industries, Ltd. | Novel heterocyclic compound and medicinal use thereof |
DE10127126A1 (de) * | 2001-06-05 | 2002-12-19 | Forschungszentrum Juelich Gmbh | Geschützte Tyrosinderivate, Verfahren zu deren Herstellung und deren Verwendung zur Herstellung von O-(2-[·18·F]-Fluorethyl)-L-tyrosin |
US7282501B2 (en) | 2001-06-07 | 2007-10-16 | Eli Lilly And Company | Modulators of peroxisome proliferator activated receptors (PPAR) |
EP1392637A2 (en) * | 2001-06-07 | 2004-03-03 | Eli Lilly And Company | Modulators of peroxisome proliferator activated receptors |
US7067530B2 (en) | 2001-07-30 | 2006-06-27 | Novo Nordisk A/S | Compounds, their preparation and use |
EP1414785A1 (en) * | 2001-07-30 | 2004-05-06 | Novo Nordisk A/S | Novel vinyl n-(2-benzoylphenyl)-l-tyrosine derivatives and their use as antidiabetics etc |
EP1414806A1 (en) * | 2001-07-30 | 2004-05-06 | Novo Nordisk A/S | Novel vinyl n-(2-benzoylphenyl)-l-tyrosine derivatives and their use as antidiabetics etc |
US20030171377A1 (en) * | 2001-08-29 | 2003-09-11 | Bigge Christopher Franklin | Antidiabetic agents |
TW200300681A (en) | 2001-11-12 | 2003-06-16 | Ono Pharmaceutical Co | Carboxylic acid derivative compound and medicament containing same as active ingredient |
MXPA04005123A (es) * | 2001-11-30 | 2005-02-17 | Lilly Co Eli | Agonistas del receptor activado por proliferador de peroxisoma. |
TW200300677A (en) * | 2001-12-11 | 2003-06-16 | Sankyo Co | A pharmaceutical composition |
DE60209824T2 (de) * | 2001-12-21 | 2006-10-19 | Smithkline Beecham Corp. | Dosierschema für ppar-gamma-aktivatoren |
CA2473207A1 (en) | 2002-01-17 | 2003-07-24 | Toa Eiyo Ltd. | Halogenobenzylaminopropionic acid derivatives |
US20050084840A1 (en) * | 2002-01-23 | 2005-04-21 | Hideki Endoh | Method for screening drug for improving insulin resistance |
US6716842B2 (en) | 2002-04-05 | 2004-04-06 | Warner-Lambert Company, Llc | Antidiabetic agents |
EP1513817A1 (en) * | 2002-05-24 | 2005-03-16 | Takeda Pharmaceutical Company Limited | 1, 2-azole derivatives with hypoglycemic and hypolipidemic activity |
JP2004277397A (ja) * | 2002-05-24 | 2004-10-07 | Takeda Chem Ind Ltd | 1,2−アゾール誘導体 |
GB0214149D0 (en) * | 2002-06-19 | 2002-07-31 | Glaxo Group Ltd | Chemical compounds |
NZ537251A (en) * | 2002-07-09 | 2007-02-23 | Bristol Myers Squibb Co | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
PL374860A1 (en) | 2002-07-09 | 2005-11-14 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
WO2004037248A2 (en) * | 2002-10-24 | 2004-05-06 | Carex Sa | Modulation of peroxisome proliferator activated receptors activity |
US7960369B2 (en) | 2002-11-08 | 2011-06-14 | Takeda Pharmaceutical Company Limited | Receptor function regulator |
US7268157B2 (en) * | 2002-11-26 | 2007-09-11 | Shenzhen Chipscreen Biosciences, Ltd. | Substituted arylalcanoic acid derivatives as PPAR pan agonists with potent antihyperglycemic and antihyperlipidemic activity |
US6653334B1 (en) | 2002-12-27 | 2003-11-25 | Kowa Co., Ltd. | Benzoxazole compound and pharmaceutical composition containing the same |
JP2006520755A (ja) | 2003-02-14 | 2006-09-14 | イーライ リリー アンド カンパニー | Pparモジュレータとしてのスルホンアミド誘導体 |
US20060142356A1 (en) * | 2003-02-17 | 2006-06-29 | Davis Adrian F | Novel therapeutic method and compositions for topical administration |
GB0303600D0 (en) * | 2003-02-17 | 2003-03-19 | Glaxo Group Ltd | Novel therapeutic method and compositions |
US20050059708A1 (en) * | 2003-05-13 | 2005-03-17 | Karel Pospisilik | Processes for making thiazolidinedione derivatives and compounds thereof |
WO2005005423A1 (en) | 2003-07-02 | 2005-01-20 | F. Hoffmann-La Roche Ag | Indolyl derivatives substituted with a thiazole ring and their use as ppar modulators |
MXPA06001916A (es) * | 2003-08-20 | 2006-05-17 | Lilly Co Eli | Compuestos, metodos y formulaciones para el suministro oral de un compuesto peptidico similar a glucagona (glp)-i o un peptido agonista del receptor de melanocortina 4 (mc4). |
DE602004004156T2 (de) * | 2003-08-20 | 2007-10-11 | Eli Lilly And Co., Indianapolis | Verbindungen, verfahren und formulierungen zur oralen verabreichung einer glucagon like peptide (glp)-1-verbindung oder eines am melanocortin-4-rezeptor (mc4) als agonist wirkenden peptids |
US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
TW200526588A (en) * | 2003-11-17 | 2005-08-16 | Smithkline Beecham Corp | Chemical compounds |
JP4922615B2 (ja) | 2003-11-26 | 2012-04-25 | 武田薬品工業株式会社 | 受容体機能調節剤 |
BRPI0417401A (pt) * | 2003-12-15 | 2007-05-08 | Lilly Co Eli | composto, composição farmacêutica, métodos para modular um receptor ativado por proliferador de peroxissomo, para tratar doença ou condição, para abaixar glicose sanguìnea em um mamìfero, para tratar diabetes mellitus em um mamìfero, para tratar doença cardiovascular em um mamìfero, para tratar sìndrome x em um mamìfero, e, uso de composto |
RU2006126978A (ru) | 2003-12-25 | 2008-01-27 | Такеда Фармасьютикал Компани Лимитед (Jp) | Производные 3-(4-бензилоксифенил)пропановой кислоты |
JP4855777B2 (ja) | 2003-12-26 | 2012-01-18 | 武田薬品工業株式会社 | フェニルプロパン酸誘導体 |
WO2005085235A1 (en) * | 2004-03-09 | 2005-09-15 | F. Hoffmann-La Roche Ag | Pyrazolyl indolyl derivatives as ppar activators |
US10987362B2 (en) | 2004-03-12 | 2021-04-27 | Intercept Pharmaceuticals, Inc. | Treatment of fibrosis using FXR ligands |
SI1734970T1 (sl) | 2004-03-12 | 2015-04-30 | Intercept Pharmaceuticals, Inc. | Zdravljenje fibroze z uporabo FXR ligandov |
KR20070058471A (ko) | 2004-07-30 | 2007-06-08 | 라보라토리오스 살바트, 에스.에이. | Ppar-감마-조절자로서의 티로신 유도체 |
MX2007001634A (es) * | 2004-08-11 | 2007-04-23 | Kyorin Seiyaku Kk | Nuevo derivado de acido amino benzoico ciclico. |
US7622491B2 (en) * | 2004-08-13 | 2009-11-24 | Metabolex Inc. | Modulators of PPAR and methods of their preparation |
PL371841A1 (pl) | 2004-12-20 | 2006-06-26 | ADAMED Sp.z o.o. | Nowe związki pochodne kwasu 3-fenylopropionowego |
PL372332A1 (pl) * | 2005-01-19 | 2006-07-24 | ADAMED Sp.z o.o. | Nowe związki, pochodne kwasu 3-fenylopropionowego |
PL372356A1 (pl) | 2005-01-20 | 2006-07-24 | ADAMED Sp.z o.o. | Nowe związki, pochodne kwasu 3-fenylopropionowego |
WO2006082495A1 (en) * | 2005-02-02 | 2006-08-10 | Ranbaxy Laboratories Limited | Peroxisome proliferator activated receptor modulators |
ITMI20050912A1 (it) | 2005-05-19 | 2006-11-20 | Erregierre Spa | Processo di preparazione di acidi 3-a-ya(b)-diidrossi-6-a(b)-alchil-5b-colanici |
US8097610B2 (en) | 2005-08-26 | 2012-01-17 | Shionogi & Co., Ltd. | Derivative having PPAR agonistic activity |
WO2007147336A1 (en) * | 2006-06-13 | 2007-12-27 | Shanghai Institue Of Materia Medica, Chinese Academy Of Sciences | Heterocyclic non-nucleoside compounds, their peparation, pharmaceutical composition and their use as antiviral agents |
NZ574710A (en) | 2006-09-07 | 2012-02-24 | Nycomed Gmbh | Combination treatment comprising the PDE4 inhibitor Compound A ((2R,4aR, 10bR)6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1 ,2,3,4,4a,10b-hexahydrophenanthridin-2-ol) for diabetes mellitus |
US9308198B2 (en) | 2006-09-08 | 2016-04-12 | Rhode Island Hospital | Treatment, prevention, and reversal of alcohol-induced brain disease |
EA017714B1 (ru) | 2007-01-19 | 2013-02-28 | Интерсепт Фармасьютикалз, Инк. | Модуляторы tgr5 и способы их применения |
JP2008239616A (ja) * | 2007-02-28 | 2008-10-09 | Iyaku Bunshi Sekkei Kenkyusho:Kk | Hdl上昇剤 |
WO2008117982A1 (en) * | 2007-03-28 | 2008-10-02 | Crystal Genomics, Inc. | Heterocyclic carboxylic acid derivatives and pharmaceutical composition for inhibiting lipid accumulation containing same |
EP3053440B1 (en) | 2007-04-11 | 2020-08-12 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
US11241420B2 (en) | 2007-04-11 | 2022-02-08 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
US20160331729A9 (en) | 2007-04-11 | 2016-11-17 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
WO2008139879A1 (ja) * | 2007-04-26 | 2008-11-20 | Pharmafrontier, Co., Ltd. | G蛋白質共役型レセプター抑制剤および医薬 |
CA2690004C (en) | 2007-06-04 | 2018-01-23 | Ben-Gurion University Of The Negev Research And Development Authority | Tri-aryl compounds and compositions comprising the same |
BRPI0916735B8 (pt) | 2008-07-30 | 2021-05-25 | Intercept Pharmaceuticals Inc | compostos moduladores de tgr5, composições farmacêuticas compreendendo os mesmos e seus usos |
DK2698375T3 (da) | 2008-11-19 | 2018-05-28 | Intercept Pharmaceuticals Inc | TGR5-modulatorer og fremgangsmåde til anvendelse deraf |
BRPI1009141A2 (pt) | 2009-03-11 | 2016-03-08 | Omeros Corp | composições e métodos para profilaxia e tratamento de vícios |
US8581001B2 (en) | 2010-04-16 | 2013-11-12 | Codman & Shurtleff | Metformin-cysteine prodrug |
US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
RU2695383C2 (ru) * | 2012-06-19 | 2019-07-23 | Синбиас Фарма АГ | Производные бендамустина, родственные соединения и их медицинское применение для лечения рака |
KR101881245B1 (ko) | 2012-06-19 | 2018-07-23 | 인터셉트 파마슈티컬즈, 인크. | 오베티콜산의 제조법, 용도 및 고체 형태 |
US9982008B2 (en) | 2012-06-19 | 2018-05-29 | Intercept Pharmaceuticals, Inc. | Preparation and uses of obeticholic acid |
WO2014184104A1 (en) * | 2013-05-17 | 2014-11-20 | Boehringer Ingelheim International Gmbh | Pyrrolidine derivatives, pharmaceutical compositions and uses thereof |
KR20160094956A (ko) | 2013-11-05 | 2016-08-10 | 벤-구리온 유니버시티 오브 더 네게브 리서치 앤드 디벨럽먼트 어쏘러티 | 당뇨병 및 당뇨병으로부터 발생하는 합병증 질환의 치료를 위한 화합물 |
WO2016071727A1 (en) | 2014-11-04 | 2016-05-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the prevention and the treatment of rapidly progressive glomerulonephritis |
US9987255B2 (en) | 2014-12-19 | 2018-06-05 | Merck Sharp & Dohme Corp. | 5,5-bicyclic oxazole orexin receptor antagonists |
CN104744282A (zh) * | 2015-02-17 | 2015-07-01 | 南通恒盛精细化工有限公司 | 一种胰岛素增敏剂的制备工艺 |
WO2019224393A1 (en) * | 2018-05-25 | 2019-11-28 | University Of Copenhagen | Fenofibrate for reducing hypoglycemia in type 1 diabetes/lada |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5522636A (en) | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
US4342771A (en) | 1981-01-02 | 1982-08-03 | Pfizer Inc. | Hypoglycemic 5-substituted oxazolidine-2,4-diones |
US4367234A (en) | 1980-07-28 | 1983-01-04 | Pfizer Inc. | Hypoglycemic 5-substituted oxazolidine-2,4-diones |
RU1473300C (ru) | 1987-06-01 | 1995-02-09 | Научно-производственное объединение "Витамины" | Способ получения 4-бензоиламино-3-оксотетрагидротиофена |
US5220023A (en) | 1989-07-18 | 1993-06-15 | Janssen Pharmaceutica N.V. | Glycine derivatives |
DE3941438A1 (de) | 1989-12-15 | 1991-06-20 | Hoechst Ag | Neue 2-substituierte 4-(3-alkyl-5-tert.-butyl-4-hydroxy-phenyl)-thiazole, verfahren zu ihrer herstellung, die sie enthaltenden arzneimittel und ihre verwendung |
US5089514A (en) | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
JPH07505647A (ja) | 1992-04-10 | 1995-06-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 複素環化合物および2型糖尿病の治療におけるそれらの使用 |
RU2134686C1 (ru) | 1992-07-03 | 1999-08-20 | Смитклайн Бичам П.Л.С. | Гетероциклическое соединение, или его таутомерная форма, и/или фармацевтически приемлемая соль, и/или фармацевтически приемлемый сольват, фармацевтическая композиция, снижающая содержание глюкозы в крови, способ лечения и/или профилактики гипергликемии |
US5232945A (en) | 1992-07-20 | 1993-08-03 | Pfizer Inc. | 3-aryl-2-hydroxypropionic acid derivatives and analogs as antihypertensives |
GB9225386D0 (en) | 1992-12-04 | 1993-01-27 | Smithkline Beecham Plc | Novel compounds |
GB9311661D0 (en) | 1993-06-05 | 1993-07-21 | Smithkline Beecham Plc | Novel compounds |
GB9311644D0 (en) | 1993-06-05 | 1993-07-21 | Smithkline Beecham Plc | Novel compounds |
SE9302332D0 (sv) | 1993-07-06 | 1993-07-06 | Ab Astra | New compounds |
GB9315148D0 (en) | 1993-07-22 | 1993-09-08 | Smithkline Beecham Plc | Novel compounds |
JPH08325264A (ja) * | 1995-05-31 | 1996-12-10 | Sumitomo Metal Ind Ltd | 新規2−芳香環置換−3−フェニルプロピオン酸またはアクリル酸誘導体 |
JPH08325263A (ja) | 1995-05-31 | 1996-12-10 | Sumitomo Metal Ind Ltd | 新規2−アミノ−3−フェニルプロピオン酸誘導体 |
JPH08325564A (ja) | 1995-06-05 | 1996-12-10 | Nec Corp | 有機薄膜el素子 |
JP2000515133A (ja) * | 1996-07-01 | 2000-11-14 | イーライ・リリー・アンド・カンパニー | 血糖降下性および脂質低下性の化合物 |
-
1996
- 1996-02-28 GB GBGB9604242.9A patent/GB9604242D0/en active Pending
-
1997
- 1997-02-25 MY MYPI97000725A patent/MY119425A/en unknown
- 1997-02-26 ZA ZA9701645A patent/ZA971645B/xx unknown
- 1997-02-26 WO PCT/EP1997/000916 patent/WO1997031907A1/en active IP Right Grant
- 1997-02-26 KR KR10-1998-0706730A patent/KR100462730B1/ko not_active IP Right Cessation
- 1997-02-26 CZ CZ19982750A patent/CZ295383B6/cs not_active IP Right Cessation
- 1997-02-26 HU HU0004845A patent/HUP0004845A3/hu unknown
- 1997-02-26 GE GEAP19974466A patent/GEP20012580B/en unknown
- 1997-02-26 DE DE69706658T patent/DE69706658T2/de not_active Expired - Lifetime
- 1997-02-26 PL PL328871A patent/PL191118B1/pl not_active IP Right Cessation
- 1997-02-26 JP JP53058697A patent/JP3255930B2/ja not_active Expired - Fee Related
- 1997-02-26 BR BRPI9707786-0A patent/BR9707786B1/pt not_active IP Right Cessation
- 1997-02-26 CN CN97193988A patent/CN1093124C/zh not_active Expired - Fee Related
- 1997-02-26 PE PE1997000137A patent/PE43098A1/es not_active Application Discontinuation
- 1997-02-26 DK DK97906130T patent/DK0888317T3/da active
- 1997-02-26 AT AT97906130T patent/ATE205485T1/de not_active IP Right Cessation
- 1997-02-26 SI SI9730233T patent/SI0888317T1/xx unknown
- 1997-02-26 EP EP97906130A patent/EP0888317B1/en not_active Expired - Lifetime
- 1997-02-26 EE EE9800288A patent/EE9800288A/xx unknown
- 1997-02-26 IL IL12579697A patent/IL125796A/en not_active IP Right Cessation
- 1997-02-26 TR TR1998/01707T patent/TR199801707T2/xx unknown
- 1997-02-26 SK SK1163-98A patent/SK282753B6/sk not_active IP Right Cessation
- 1997-02-26 AU AU20935/97A patent/AU717699B2/en not_active Ceased
- 1997-02-26 US US09/125,750 patent/US6294580B1/en not_active Expired - Fee Related
- 1997-02-26 UA UA98084544A patent/UA58502C2/uk unknown
- 1997-02-26 EA EA199800664A patent/EA001403B1/ru not_active IP Right Cessation
- 1997-02-26 CA CA002247443A patent/CA2247443C/en not_active Expired - Fee Related
- 1997-02-26 HR HR970110A patent/HRP970110B1/xx not_active IP Right Cessation
- 1997-02-26 ES ES97906130T patent/ES2163125T3/es not_active Expired - Lifetime
- 1997-02-26 PT PT97906130T patent/PT888317E/pt unknown
- 1997-02-26 NZ NZ331381A patent/NZ331381A/en not_active IP Right Cessation
- 1997-02-27 AR ARP970100771A patent/AR011502A1/es active IP Right Grant
- 1997-02-27 ID IDP970584A patent/ID15985A/id unknown
- 1997-02-27 AP APAP/P/1997/000935A patent/AP780A/en active
-
1998
- 1998-08-12 IS IS4822A patent/IS1869B/is unknown
- 1998-08-25 OA OA9800148A patent/OA10843A/en unknown
- 1998-08-27 NO NO19983940A patent/NO311516B1/no not_active IP Right Cessation
- 1998-08-28 RS YUP-369/98A patent/RS49586B/sr unknown
- 1998-09-24 BG BG102792A patent/BG102792A/xx unknown
-
1999
- 1999-02-05 HK HK99100498A patent/HK1015369A1/xx not_active IP Right Cessation
-
2003
- 2003-03-12 CY CY0300026A patent/CY2319B1/xx unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO311516B1 (no) | Derivater av substituerte 4-hydroksy-fenylalkanosyrer med agonistisk aktivitet for PPAR-gamma, farmasöytiske preparaterinneholdende dem, anvendelse av dem og fremgangsmåte forfremstilling av dem | |
US7625938B2 (en) | Substituted pyrazoles, compositions containing such compounds and methods of use | |
DE60216094T2 (de) | Modulatoren der peroxisom-proliferator-aktivierten rezeptoren (ppar) | |
US7238716B2 (en) | Alkanoic acid derivatives process for their production and use thereof | |
JP3997491B2 (ja) | カルバゾール誘導体、その溶媒和物、又は薬学的に許容されるその塩 | |
WO2008044700A1 (fr) | INHIBITEUR DE LA GSK-3β | |
NO323643B1 (no) | Diarylsyrederivater, farmasoytisk preparat omfattende disse og deres anvendelse for fremstilling av farmasoytiske preparater | |
KR20130124524A (ko) | 폴리시클릭 lpa₁ 길항제 및 그의 용도 | |
JP2009533410A (ja) | Gタンパク質共役型受容体(gpr119)アゴニストとしてのアゼチジン誘導体 | |
JP2011500659A (ja) | アゼチジニルgタンパク質共役受容体アゴニスト | |
US7714004B2 (en) | Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation | |
JP2010539152A (ja) | 代謝障害の治療のための化合物 | |
EP1394154A1 (en) | Five-membered heterocyclic alkanoic acid derivative | |
GB2356197A (en) | Amide derivatives as beta 3 agonists | |
RU2296759C2 (ru) | N-замещенные 1н-индол-5-пропионовые кислоты, фармацевтическая композиция, содержащая эти соединения, и их применение (варианты) | |
US20080207685A1 (en) | Heterocyclic Compounds As Modulators Of Peroxisome Proliferator Activated Receptors, Useful For The Treatment And/Or Prevention Of Disorders Modulated By A Ppar | |
JP7385852B2 (ja) | P2x3受容体のアンタゴニストとしてのn-カルボキサミドピラゾリン系誘導体及びその使用 | |
WO2005040127A1 (en) | Novel compounds as agonist for ppar gamma and ppar alpha, method for preparation of the same, and pharmaceutical composition containing the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |