AU2009221722B2 - Oxadiazoanthracene compounds for the treatment of diabetes - Google Patents
Oxadiazoanthracene compounds for the treatment of diabetes Download PDFInfo
- Publication number
- AU2009221722B2 AU2009221722B2 AU2009221722A AU2009221722A AU2009221722B2 AU 2009221722 B2 AU2009221722 B2 AU 2009221722B2 AU 2009221722 A AU2009221722 A AU 2009221722A AU 2009221722 A AU2009221722 A AU 2009221722A AU 2009221722 B2 AU2009221722 B2 AU 2009221722B2
- Authority
- AU
- Australia
- Prior art keywords
- phenyl
- oxo
- diaza
- hexahydro
- oxa
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims description 322
- 238000011282 treatment Methods 0.000 title claims description 21
- 206010012601 diabetes mellitus Diseases 0.000 title claims description 17
- 238000000034 method Methods 0.000 claims description 253
- 239000000203 mixture Substances 0.000 claims description 189
- -1 2 -n-hexyl Chemical group 0.000 claims description 125
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 89
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000001424 substituent group Chemical group 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- 239000003795 chemical substances by application Substances 0.000 claims description 30
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 24
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- 239000003085 diluting agent Substances 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 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 12
- 102000004877 Insulin Human genes 0.000 claims description 12
- 108090001061 Insulin Proteins 0.000 claims description 12
- 229940125396 insulin Drugs 0.000 claims description 11
- 239000008103 glucose Substances 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 8
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 7
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 208000017442 Retinal disease Diseases 0.000 claims description 6
- 206010038923 Retinopathy Diseases 0.000 claims description 6
- 229940030600 antihypertensive agent Drugs 0.000 claims description 6
- 239000002220 antihypertensive agent Substances 0.000 claims description 6
- 201000001421 hyperglycemia Diseases 0.000 claims description 6
- 230000001771 impaired effect Effects 0.000 claims description 6
- 208000017169 kidney disease Diseases 0.000 claims description 6
- 208000030159 metabolic disease Diseases 0.000 claims description 6
- 201000001119 neuropathy Diseases 0.000 claims description 6
- 230000007823 neuropathy Effects 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 230000029663 wound healing Effects 0.000 claims description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 5
- 230000008991 intestinal motility Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 4
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 4
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 4
- 239000000883 anti-obesity agent Substances 0.000 claims description 4
- 229940125710 antiobesity agent Drugs 0.000 claims description 4
- 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 claims description 4
- 230000003178 anti-diabetic effect Effects 0.000 claims description 3
- 230000000879 anti-atherosclerotic effect Effects 0.000 claims description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical group CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 2
- 229960003105 metformin Drugs 0.000 claims description 2
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 230000000052 comparative effect Effects 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 188
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 110
- 239000000243 solution Substances 0.000 description 106
- 239000000543 intermediate Substances 0.000 description 96
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
- 239000012044 organic layer Substances 0.000 description 57
- 125000003118 aryl group Chemical group 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
- 125000000753 cycloalkyl group Chemical group 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- 229910052796 boron Inorganic materials 0.000 description 43
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 42
- 229910052938 sodium sulfate Inorganic materials 0.000 description 42
- 235000011152 sodium sulphate Nutrition 0.000 description 42
- 125000000623 heterocyclic group Chemical group 0.000 description 40
- 125000001072 heteroaryl group Chemical group 0.000 description 39
- 150000002148 esters Chemical class 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 36
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
- 239000002904 solvent Substances 0.000 description 34
- 235000002639 sodium chloride Nutrition 0.000 description 33
- 125000000304 alkynyl group Chemical group 0.000 description 31
- 125000003342 alkenyl group Chemical group 0.000 description 30
- 229910052731 fluorine Inorganic materials 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 238000006467 substitution reaction Methods 0.000 description 29
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 25
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 23
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 23
- 239000002253 acid Substances 0.000 description 23
- 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 22
- 238000009472 formulation Methods 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 19
- 125000004429 atom Chemical group 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 125000005842 heteroatom Chemical group 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 229910052717 sulfur Chemical group 0.000 description 15
- 239000011593 sulfur Chemical group 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 14
- 101100337060 Caenorhabditis elegans glp-1 gene Proteins 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 229910000029 sodium carbonate Inorganic materials 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 239000001301 oxygen Chemical group 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 125000004350 aryl cycloalkyl group Chemical group 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 11
- 150000002431 hydrogen Chemical group 0.000 description 11
- 150000004702 methyl esters Chemical class 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229960001866 silicon dioxide Drugs 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000005275 alkylenearyl group Chemical group 0.000 description 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000003755 preservative agent Substances 0.000 description 9
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 8
- XLWSBDFQAJXCQX-UHFFFAOYSA-N 4-(bromomethyl)-1,2-dichlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1Cl XLWSBDFQAJXCQX-UHFFFAOYSA-N 0.000 description 8
- 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 description 8
- 239000000556 agonist Substances 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 125000004367 cycloalkylaryl group Chemical group 0.000 description 8
- 125000005215 cycloalkylheteroaryl group Chemical group 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- HBQCWQTZQIEOKT-UHFFFAOYSA-N 1H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound N1C=COC2=CC3=CN=C(C=C3C=C12)C(=O)O HBQCWQTZQIEOKT-UHFFFAOYSA-N 0.000 description 7
- ZQHMWEHUJDILSQ-LBPRGKRZSA-N 3-o-methyl 2-o-propan-2-yl (3s)-7-hydroxy-6-nitro-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylate Chemical compound [O-][N+](=O)C1=C(O)C=C2CN(C(=O)OC(C)C)[C@H](C(=O)OC)CC2=C1 ZQHMWEHUJDILSQ-LBPRGKRZSA-N 0.000 description 7
- 239000004215 Carbon black (E152) Substances 0.000 description 7
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- BTPGQGHBPMYLIT-FRJFGJRTSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound O=C([C@@H]1CC2=CC=3N(C)C(=O)[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C BTPGQGHBPMYLIT-FRJFGJRTSA-N 0.000 description 7
- 125000004419 alkynylene group Chemical group 0.000 description 7
- 239000003086 colorant Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229930195733 hydrocarbon Natural products 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000003765 sweetening agent Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- XJSUFXFSUACKAT-UHFFFAOYSA-N 1-bromopropylbenzene Chemical compound CCC(Br)C1=CC=CC=C1 XJSUFXFSUACKAT-UHFFFAOYSA-N 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000004450 alkenylene group Chemical group 0.000 description 6
- 125000005218 alkyleneheteroaryl group Chemical group 0.000 description 6
- 239000003524 antilipemic agent Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 229920000728 polyester Polymers 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- NUCASUNWFGZWMC-JKGBFCRXSA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN(C(CC4=CC=3NC2=O)C(O)=O)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 NUCASUNWFGZWMC-JKGBFCRXSA-N 0.000 description 5
- IEYVTXNDBGMIHA-GVUKDKGQSA-N (3s,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@@H](CC)C=2C=CC=CC=2)=CC=C(O)C=C1 IEYVTXNDBGMIHA-GVUKDKGQSA-N 0.000 description 5
- URKJLRXNIAYEJA-UHFFFAOYSA-N 2-chloro-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]acetyl chloride Chemical compound C1=CC(C(C(Cl)=O)Cl)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 URKJLRXNIAYEJA-UHFFFAOYSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- YVUUJVUIWAWCKN-TWZYKFNQSA-N 7-o-tert-butyl 8-o-[(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@H]1N(C(=O)OC(C)(C)C)CC2=CC(O[C@H](C(=O)N3)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 YVUUJVUIWAWCKN-TWZYKFNQSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 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 5
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 5
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 5
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 239000002270 dispersing agent Substances 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- IVDOIYGHPJPXFO-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 IVDOIYGHPJPXFO-NTISSMGPSA-N 0.000 description 5
- KDHNRZAQCGZYRA-UHFFFAOYSA-N methyl 2,3,6,7,8,9-hexahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound N1CCOC2=C1C=C1CC(C(=O)OC)NCC1=C2 KDHNRZAQCGZYRA-UHFFFAOYSA-N 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000000600 sorbitol Substances 0.000 description 5
- 235000010356 sorbitol Nutrition 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 239000000375 suspending agent Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 5
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 4
- NQZCDMOTQDDJBF-UHFFFAOYSA-N 2,3,4a,5,5a,6-hexahydro-1H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound N1CCOC2CC3CN=C(C=C3C=C12)C(=O)O NQZCDMOTQDDJBF-UHFFFAOYSA-N 0.000 description 4
- JZYYDSXUCPMSDQ-LBPRGKRZSA-N 3-o-methyl 2-o-propan-2-yl (3s)-6-amino-7-hydroxy-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylate Chemical compound NC1=C(O)C=C2CN(C(=O)OC(C)C)[C@H](C(=O)OC)CC2=C1 JZYYDSXUCPMSDQ-LBPRGKRZSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 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 4
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 4
- 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 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- ZPQOILXQXPJURH-FDRRKANLSA-N [(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] 2,3,4a,5,5a,6-hexahydro-1H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate hydrochloride Chemical compound Cl.C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1=NCC2CC3OCCNC3=CC2=C1 ZPQOILXQXPJURH-FDRRKANLSA-N 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 235000013877 carbamide Nutrition 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 229960004873 levomenthol Drugs 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 235000015424 sodium Nutrition 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 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 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- QKSGEZAPDKRYGI-GPNIZQGCSA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@H]2C(=O)N(C3=CC=4CC(N(CC=4C=C3O2)C(=O)OC(C)(C)C)C(O)=O)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 QKSGEZAPDKRYGI-GPNIZQGCSA-N 0.000 description 3
- ADHVLZYRJIOUNA-JKGBFCRXSA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-7-propan-2-yloxycarbonyl-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN(C(CC4=CC=3NC2=O)C(O)=O)C(=O)OC(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 ADHVLZYRJIOUNA-JKGBFCRXSA-N 0.000 description 3
- MIWHMOODQMFHOY-RZVDFNOWSA-N (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-7-carboxylic acid Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)N(C)C=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(O)=O)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 MIWHMOODQMFHOY-RZVDFNOWSA-N 0.000 description 3
- NUCASUNWFGZWMC-AHWVRZQESA-N (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3NC2=O)C(O)=O)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 NUCASUNWFGZWMC-AHWVRZQESA-N 0.000 description 3
- PUDPGVZTTKAMBN-LBPRGKRZSA-N 2-o-tert-butyl 3-o-methyl (3s)-7-hydroxy-6-nitro-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylate Chemical compound [O-][N+](=O)C1=C(O)C=C2CN(C(=O)OC(C)(C)C)[C@H](C(=O)OC)CC2=C1 PUDPGVZTTKAMBN-LBPRGKRZSA-N 0.000 description 3
- HFQXXZMZMZAGJZ-UHFFFAOYSA-N 3H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound N1=CCOC2=CC3=CN=C(C=C3C=C12)C(=O)O HFQXXZMZMZAGJZ-UHFFFAOYSA-N 0.000 description 3
- SUGZPSIGVCAQSR-XCZPVHLTSA-N 7-o-tert-butyl 8-o-methyl (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@H]2C(=O)N(C)C=3C=C4C[C@H](N(CC4=CC=3O2)C(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 SUGZPSIGVCAQSR-XCZPVHLTSA-N 0.000 description 3
- OYRDFYQSNAVOCY-GPNIZQGCSA-N 8-o-methyl 7-o-propan-2-yl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@H]2C(=O)NC=3C=C4CC(N(CC4=CC=3O2)C(=O)OC(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 OYRDFYQSNAVOCY-GPNIZQGCSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000006751 Mitsunobu reaction Methods 0.000 description 3
- WPBAHUDDSZJLIS-UHFFFAOYSA-N N1=NC=CC2=CC3=CC=C(C=C3C=C12)C(=O)O Chemical compound N1=NC=CC2=CC3=CC=C(C=C3C=C12)C(=O)O WPBAHUDDSZJLIS-UHFFFAOYSA-N 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000002877 alkyl aryl group Chemical group 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- 239000000164 antipsychotic agent Substances 0.000 description 3
- 125000000732 arylene group Chemical group 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000010931 ester hydrolysis Methods 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 3
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 description 3
- 125000005549 heteroarylene group Chemical group 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 3
- OAURIXDOYOTCSJ-XJRLVATOSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 OAURIXDOYOTCSJ-XJRLVATOSA-N 0.000 description 3
- GCBCSGFKXLPAEP-UDQMMGIDSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@@H](OC=3C=C2CN1[C@H](CC)C=1C=CC=CC=1)C=1C=CC(O)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 GCBCSGFKXLPAEP-UDQMMGIDSA-N 0.000 description 3
- AKTIEANZOSAGOH-TXDWVUBVSA-N methyl (3s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound O([C@H](C(=O)NC=1C=C2CC3C(=O)OC)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)C=1C=C2CN3C(=O)C1=CC=CC=C1 AKTIEANZOSAGOH-TXDWVUBVSA-N 0.000 description 3
- BPJQKEYAFMJRCT-PPHPATTJSA-N methyl (3s)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate;hydrochloride Chemical compound Cl.C1=C(O)C=C2CN[C@H](C(=O)OC)CC2=C1 BPJQKEYAFMJRCT-PPHPATTJSA-N 0.000 description 3
- GXGPHFVGRDJMNL-DHLKQENFSA-N methyl (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-6,7,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound C1=CC([C@H]2C(=O)N(C)C=3C=C4C[C@H](NCC4=CC=3O2)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 GXGPHFVGRDJMNL-DHLKQENFSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000008227 sterile water for injection Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- KQMVOUMISGSBGA-OFWCELHQSA-N tert-butyl (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-(4-hydroxyphenyl)-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(O)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 KQMVOUMISGSBGA-OFWCELHQSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- FAUNAKACKIAHCD-UHFFFAOYSA-N (3,4-dichlorophenyl)methyl 2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-hydroxyacetate Chemical compound C=1C=C(OCC=2C=C(Cl)C(Cl)=CC=2)C=CC=1C(O)C(=O)OCC1=CC=C(Cl)C(Cl)=C1 FAUNAKACKIAHCD-UHFFFAOYSA-N 0.000 description 2
- QKSGEZAPDKRYGI-AHKZPQOWSA-N (3R,8S)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-8,9-dihydro-6H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2C(=O)N(C3=CC=4C[C@H](N(CC=4C=C3O2)C(=O)OC(C)(C)C)C(O)=O)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 QKSGEZAPDKRYGI-AHKZPQOWSA-N 0.000 description 2
- QKSGEZAPDKRYGI-BDYUSTAISA-N (3S,8S)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-8,9-dihydro-6H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@H]2C(=O)N(C3=CC=4C[C@H](N(CC=4C=C3O2)C(=O)OC(C)(C)C)C(O)=O)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 QKSGEZAPDKRYGI-BDYUSTAISA-N 0.000 description 2
- IEYVTXNDBGMIHA-LLZJGCNPSA-N (3r,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@@H](CC)C=2C=CC=CC=2)=CC=C(O)C=C1 IEYVTXNDBGMIHA-LLZJGCNPSA-N 0.000 description 2
- CADSDLSKDZVATC-FXFVSWTPSA-N (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 CADSDLSKDZVATC-FXFVSWTPSA-N 0.000 description 2
- IEYVTXNDBGMIHA-CWDLOFLHSA-N (3s,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@H](CC)C=2C=CC=CC=2)=CC=C(O)C=C1 IEYVTXNDBGMIHA-CWDLOFLHSA-N 0.000 description 2
- CADSDLSKDZVATC-WXWREJFYSA-N (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 CADSDLSKDZVATC-WXWREJFYSA-N 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical class OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 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 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- HEKUNBNASAOLHK-UHFFFAOYSA-N 2,3,6,7,8,9-hexahydro-1H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound N1CCOC2=CC=3CNC(CC=3C=C12)C(=O)O HEKUNBNASAOLHK-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- JSNVYAVXHOJLBL-UHFFFAOYSA-N 2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-hydroxyacetic acid Chemical compound C1=CC(C(C(O)=O)O)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 JSNVYAVXHOJLBL-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- ATPBHLAWGXOMOR-UHFFFAOYSA-N 2-hydroxy-2-(4-hydroxyphenyl)acetic acid;hydrate Chemical compound O.OC(=O)C(O)C1=CC=C(O)C=C1 ATPBHLAWGXOMOR-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- RKNCIBMWPVZEAJ-UHFFFAOYSA-N 3-bromoprop-1-ynylbenzene Chemical compound BrCC#CC1=CC=CC=C1 RKNCIBMWPVZEAJ-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- JBWMLCHGBNGGLO-UHFFFAOYSA-N 7-[(2-methylpropan-2-yl)oxycarbonyl]-1,2,3,4a,5,5a,6,8-octahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1CC2CC3OCCNC3=CC2=CC1C(=O)O JBWMLCHGBNGGLO-UHFFFAOYSA-N 0.000 description 2
- QKVJGANXOMUEAW-UHFFFAOYSA-N 7-[(2-methylpropan-2-yl)oxycarbonyl]benzo[g]cinnoline-8-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)C=1C=C2C=C3C=CN=NC3=CC2=CC=1C(=O)O QKVJGANXOMUEAW-UHFFFAOYSA-N 0.000 description 2
- SUGZPSIGVCAQSR-RXBHZZDJSA-N 7-o-tert-butyl 8-o-methyl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@H]2C(=O)N(C)C=3C=C4CC(N(CC4=CC=3O2)C(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 SUGZPSIGVCAQSR-RXBHZZDJSA-N 0.000 description 2
- BEBOFGPCIPAFMF-PVCWFJFTSA-N 7-o-tert-butyl 8-o-methyl (8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C([C@H](N(CC1=CC=2O3)C(=O)OC(C)(C)C)C(=O)OC)C1=CC=2NC(=O)C3C(C=C1)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 BEBOFGPCIPAFMF-PVCWFJFTSA-N 0.000 description 2
- CYJXDRNSHXKUGH-RXBHZZDJSA-N 8-o-methyl 7-o-propan-2-yl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@H]2C(=O)N(C)C=3C=C4CC(N(CC4=CC=3O2)C(=O)OC(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 CYJXDRNSHXKUGH-RXBHZZDJSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010011459 Exenatide Proteins 0.000 description 2
- PUFQLBBNKMYCHS-VCZPCNJUSA-N FC1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 Chemical compound FC1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 PUFQLBBNKMYCHS-VCZPCNJUSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 2
- NHTGHBARYWONDQ-JTQLQIEISA-N L-α-methyl-Tyrosine Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C=C1 NHTGHBARYWONDQ-JTQLQIEISA-N 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 102000003729 Neprilysin Human genes 0.000 description 2
- 108090000028 Neprilysin Proteins 0.000 description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 150000003931 anilides Chemical class 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 229940125708 antidiabetic agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 230000001593 cAMP accumulation Effects 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000002993 cycloalkylene group Chemical group 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- SYZWSSNHPZXGML-UHFFFAOYSA-N dichloromethane;oxolane Chemical compound ClCCl.C1CCOC1 SYZWSSNHPZXGML-UHFFFAOYSA-N 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 229960001519 exenatide Drugs 0.000 description 2
- 229940125753 fibrate Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229960004580 glibenclamide Drugs 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 230000002641 glycemic effect Effects 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 230000000055 hyoplipidemic effect Effects 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- LTCNMAXNNIYTLU-OAHLLOKOSA-N methyl (2r)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-hydroxyacetate Chemical compound C1=CC([C@@H](O)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 LTCNMAXNNIYTLU-OAHLLOKOSA-N 0.000 description 2
- WNJMQFWABBSJAR-WVZLRYJISA-N methyl (2s)-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-methylphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C)C=C1 WNJMQFWABBSJAR-WVZLRYJISA-N 0.000 description 2
- XVWNPJLPYBSCFI-IKABJYOBSA-N methyl (2s)-2-[[(3s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-chlorophenyl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 XVWNPJLPYBSCFI-IKABJYOBSA-N 0.000 description 2
- GLGPKPQQVWBNHT-UTLKBRERSA-N methyl (2s)-2-amino-3-(4-pyridin-4-yloxyphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=CC=NC=C1 GLGPKPQQVWBNHT-UTLKBRERSA-N 0.000 description 2
- YJEMPXNNDQRUNK-TUYUPMGOSA-N methyl (2s)-2-amino-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-4-methyl-3-oxo-1,4-benzoxazin-6-yl]propanoate;hydrochloride Chemical compound Cl.C1=CC([C@@H]2OC3=CC=C(C=C3N(C)C2=O)C[C@H](N)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 YJEMPXNNDQRUNK-TUYUPMGOSA-N 0.000 description 2
- ZPGYXIVFYCKLQK-SFHVURJKSA-N methyl (2s)-2-amino-3-[4-(4-cyanophenyl)phenyl]-2-methylpropanoate Chemical compound C1=CC(C[C@](C)(N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 ZPGYXIVFYCKLQK-SFHVURJKSA-N 0.000 description 2
- SEXYDEKFJLXIME-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(4-cyanophenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 SEXYDEKFJLXIME-INIZCTEOSA-N 0.000 description 2
- FDFQRJWLHKSHPZ-LBPRGKRZSA-N methyl (2s)-3-(4-bromophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(Br)C=C1 FDFQRJWLHKSHPZ-LBPRGKRZSA-N 0.000 description 2
- NQIFXJSLCUJHBB-LBPRGKRZSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C=C1 NQIFXJSLCUJHBB-LBPRGKRZSA-N 0.000 description 2
- AGWKPQQUZAALHO-IBGZPJMESA-N methyl (2s)-3-(4-hydroxyphenyl)-2-methyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@](C)(C(=O)OC)NC(=O)OCC=1C=CC=CC=1)C1=CC=C(O)C=C1 AGWKPQQUZAALHO-IBGZPJMESA-N 0.000 description 2
- IHOFASRDFCCYKZ-AHWVRZQESA-N methyl (2s)-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-3-oxo-4h-1,4-benzoxazin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3NC2=O)C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 IHOFASRDFCCYKZ-AHWVRZQESA-N 0.000 description 2
- GCBCSGFKXLPAEP-KTRJPECLSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3r,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@H](OC=3C=C2CN1[C@H](CC)C=1C=CC=CC=1)C=1C=CC(O)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 GCBCSGFKXLPAEP-KTRJPECLSA-N 0.000 description 2
- GCBCSGFKXLPAEP-LOQWQTBXSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3r,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(O)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 GCBCSGFKXLPAEP-LOQWQTBXSA-N 0.000 description 2
- OXWPBBYANQPGAI-HOUSFYCTSA-N methyl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate;hydrochloride Chemical compound Cl.C1=CC([C@H]2C(=O)NC=3C=C4CC(NCC4=CC=3O2)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 OXWPBBYANQPGAI-HOUSFYCTSA-N 0.000 description 2
- IVDOIYGHPJPXFO-UHFFFAOYSA-N methyl 2-amino-3-[4-(4-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CC(N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 IVDOIYGHPJPXFO-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- GNZCSGYHILBXLL-UHFFFAOYSA-N n-tert-butyl-6,7-dichloro-3-methylsulfonylquinoxalin-2-amine Chemical compound ClC1=C(Cl)C=C2N=C(S(C)(=O)=O)C(NC(C)(C)C)=NC2=C1 GNZCSGYHILBXLL-UHFFFAOYSA-N 0.000 description 2
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 231100000344 non-irritating Toxicity 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000003186 pharmaceutical solution Substances 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000002504 physiological saline solution Substances 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
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- QQWGOGVWXSSPTC-PZKPWUIHSA-N propan-2-yl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-8-[[(2s)-1-methoxy-1-oxo-3-(4-phenylphenyl)propan-2-yl]carbamoyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC(C)C)C(C=C1)=CC=C1C1=CC=CC=C1 QQWGOGVWXSSPTC-PZKPWUIHSA-N 0.000 description 2
- GIPZKQHUTFZRKK-NWUFIKPXSA-N propan-2-yl (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 GIPZKQHUTFZRKK-NWUFIKPXSA-N 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical group CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 238000001525 receptor binding assay Methods 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000009491 slugging Methods 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 2
- 229910052815 sulfur oxide Inorganic materials 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- KBYAAYQENIGWKX-SVBPBHIXSA-N tert-butyl (3s)-6-amino-3-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-7-hydroxy-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC(O)=C(N)C=C2C1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 KBYAAYQENIGWKX-SVBPBHIXSA-N 0.000 description 2
- HRPXENJCOSNQGJ-UHFFFAOYSA-N tert-butyl 2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound N1C(=O)COC2=C1C=C1CCN(C(=O)OC(C)(C)C)CC1=C2 HRPXENJCOSNQGJ-UHFFFAOYSA-N 0.000 description 2
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 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 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- WJMWSPUOZRYMJD-UHFFFAOYSA-N (1-phenylcyclopentyl)methanol Chemical compound C=1C=CC=CC=1C1(CO)CCCC1 WJMWSPUOZRYMJD-UHFFFAOYSA-N 0.000 description 1
- QFCQNAHLDRETJC-UHFFFAOYSA-N (2,6-dichlorophenyl)methyl 2-[4-[(2,6-dichlorophenyl)methoxy]phenyl]-2-hydroxyacetate Chemical compound C=1C=C(OCC=2C(=CC=CC=2Cl)Cl)C=CC=1C(O)C(=O)OCC1=C(Cl)C=CC=C1Cl QFCQNAHLDRETJC-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- MYBPLVRYJIXETB-POUGLEAXSA-N (2S)-2-[[(3S)-3-[4-[[4-chloro-3-(trifluoromethyl)phenyl]methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1H-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid Chemical compound ClC1=C(C=C(COC2=CC=C(C=C2)[C@H]2C(NC3=CC=4CC(NCC4C=C3O2)C(=O)N[C@H](C(=O)O)CC2=CC=C(C=C2)C2=CC=C(C=C2)C#N)=O)C=C1)C(F)(F)F MYBPLVRYJIXETB-POUGLEAXSA-N 0.000 description 1
- FJVGGQKSFLFMDJ-UDVBZZPGSA-N (2S)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3S,8S)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-7-(2-phenylethyl)-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoic acid Chemical compound OC(=O)[C@H](CC1=CC=C(C=C1)C1=CC=C(C=C1)C#N)NC(=O)[C@@H]1CC2=C(CN1CCC1=CC=CC=C1)C=C1O[C@H](C(=O)NC1=C2)C1=CC=C(OCC2=CC(Cl)=C(Cl)C=C2)C=C1 FJVGGQKSFLFMDJ-UDVBZZPGSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NVXFXLSOGLFXKQ-JMSVASOKSA-N (2s)-1-[(2r,4r)-5-ethoxy-2,4-dimethyl-5-oxopentanoyl]-2,3-dihydroindole-2-carboxylic acid Chemical compound C1=CC=C2N(C(=O)[C@H](C)C[C@@H](C)C(=O)OCC)[C@H](C(O)=O)CC2=C1 NVXFXLSOGLFXKQ-JMSVASOKSA-N 0.000 description 1
- YNAJOMWNXOKORZ-AWEZNQCLSA-N (2s)-2-amino-3-[4-(4-chlorophenyl)phenyl]propanoic acid Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C1=CC=C(Cl)C=C1 YNAJOMWNXOKORZ-AWEZNQCLSA-N 0.000 description 1
- ULNOXUAEIPUJMK-NSHDSACASA-N (2s)-3-(4-bromophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(Br)C=C1 ULNOXUAEIPUJMK-NSHDSACASA-N 0.000 description 1
- CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- NUCASUNWFGZWMC-AZGAKELHSA-N (3R,8S)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3NC2=O)C(O)=O)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 NUCASUNWFGZWMC-AZGAKELHSA-N 0.000 description 1
- LDMUFKQPYCVWEK-HAWHYNLDSA-N (3S)-8-[[(2S)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(5,6-dichloropyridin-3-yl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylic acid Chemical compound C(#N)C1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)OC)NC(=O)C1N(CC=2C=C3O[C@H](C(NC3=CC2C1)=O)C1=CC=C(C=C1)OCC=1C=NC(=C(C1)Cl)Cl)C(=O)O LDMUFKQPYCVWEK-HAWHYNLDSA-N 0.000 description 1
- IEYVTXNDBGMIHA-KTIWRFAQSA-N (3r,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@H](CC)C=2C=CC=CC=2)=CC=C(O)C=C1 IEYVTXNDBGMIHA-KTIWRFAQSA-N 0.000 description 1
- HWCGPSKDYLOKTO-XUZZJYLKSA-N (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-6,7,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2C(=O)N(C3=CC=4C[C@H](NCC=4C=C3O2)C(O)=O)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 HWCGPSKDYLOKTO-XUZZJYLKSA-N 0.000 description 1
- CADSDLSKDZVATC-GZNLZADCSA-N (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 CADSDLSKDZVATC-GZNLZADCSA-N 0.000 description 1
- GJPUZWQLOIFGOF-NNBQYGFHSA-N (3s)-3-(4-hydroxyphenyl)-7-[(2-methylpropan-2-yl)oxycarbonyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1([C@@H]2OC=3C=C4CN(C(CC4=CC=3NC2=O)C(O)=O)C(=O)OC(C)(C)C)=CC=C(O)C=C1 GJPUZWQLOIFGOF-NNBQYGFHSA-N 0.000 description 1
- SKXJAPTXPIEIAI-VYMYHHRLSA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-(1-phenylethyl)-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN(C(CC4=CC=3N(C)C2=O)C(O)=O)C(C)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 SKXJAPTXPIEIAI-VYMYHHRLSA-N 0.000 description 1
- XFAWFWGNZTVBMJ-YANBTOMASA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylic acid Chemical compound C1=CC([C@H]2C(=O)NC=3C=C4CC(N(CC4=CC=3O2)C(O)=O)C(=O)O)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 XFAWFWGNZTVBMJ-YANBTOMASA-N 0.000 description 1
- MYLXQYITMMUMDL-STJUJJKNSA-N (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-(2,3-dihydro-1h-inden-2-yl)-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@H]2C(=O)N(C3=CC=4CC(N(C5CC6=CC=CC=C6C5)CC=4C=C3O2)C(O)=O)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 MYLXQYITMMUMDL-STJUJJKNSA-N 0.000 description 1
- UTFBGCLEKBUODW-QMMMGPOBSA-N (3s)-6-amino-7-hydroxy-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(O)=O)CC2=C1C=C(N)C(O)=C2 UTFBGCLEKBUODW-QMMMGPOBSA-N 0.000 description 1
- ITDVKTHYQBAZNL-ACEFPKFPSA-N (3s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound O([C@H](C(=O)NC=1C=C2CC3C(=O)O)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)C=1C=C2CN3C(=O)C1=CC=CC=C1 ITDVKTHYQBAZNL-ACEFPKFPSA-N 0.000 description 1
- CDRWAEOGMDPSDU-ACEFPKFPSA-N (3s)-7-cyclopentyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound O([C@H](C(=O)N(C1=CC=2CC3C(O)=O)C)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)C1=CC=2CN3C1CCCC1 CDRWAEOGMDPSDU-ACEFPKFPSA-N 0.000 description 1
- HIKCRLDSCSWXML-VIFPVBQESA-N (3s)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=C(O)C=C2CN[C@H](C(=O)O)CC2=C1 HIKCRLDSCSWXML-VIFPVBQESA-N 0.000 description 1
- UMNZVUSQSPPFIC-NSHDSACASA-N (3s)-7-hydroxy-6-nitro-2-propan-2-yloxycarbonyl-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound OC1=C([N+]([O-])=O)C=C2C[C@@H](C(O)=O)N(C(=O)OC(C)C)CC2=C1 UMNZVUSQSPPFIC-NSHDSACASA-N 0.000 description 1
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 description 1
- CADSDLSKDZVATC-QBACOJCQSA-N (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C1=CC([C@@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(O)=O)[C@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 CADSDLSKDZVATC-QBACOJCQSA-N 0.000 description 1
- XFAWFWGNZTVBMJ-GMAHTHKFSA-N (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylic acid Chemical compound C1=CC([C@H]2C(=O)NC=3C=C4C[C@H](N(CC4=CC=3O2)C(O)=O)C(=O)O)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 XFAWFWGNZTVBMJ-GMAHTHKFSA-N 0.000 description 1
- ZZXVGVQYAYMQML-UHFFFAOYSA-N (4-chlorophenyl)methyl 2-[4-[(4-chlorophenyl)methoxy]phenyl]-2-hydroxyacetate Chemical compound C=1C=C(OCC=2C=CC(Cl)=CC=2)C=CC=1C(O)C(=O)OCC1=CC=C(Cl)C=C1 ZZXVGVQYAYMQML-UHFFFAOYSA-N 0.000 description 1
- CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical class COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- KZCVVVIPPHGCOH-UHFFFAOYSA-N 1-phenylcyclopentane-1-carbaldehyde Chemical compound C=1C=CC=CC=1C1(C=O)CCCC1 KZCVVVIPPHGCOH-UHFFFAOYSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- CEFMXIYQJCGCNH-UHFFFAOYSA-N 2-(3-bromoprop-1-ynyl)pyrimidine Chemical compound BrCC#CC1=NC=CC=N1 CEFMXIYQJCGCNH-UHFFFAOYSA-N 0.000 description 1
- NXGKPRKPUCSEIL-UHFFFAOYSA-N 2-acetamido-4-methyl-1,3-thiazole-5-sulfonyl chloride Chemical compound CC(=O)NC1=NC(C)=C(S(Cl)(=O)=O)S1 NXGKPRKPUCSEIL-UHFFFAOYSA-N 0.000 description 1
- RZRJYURCNBXIST-UHFFFAOYSA-N 2-anthroic acid Chemical compound C1=CC=CC2=CC3=CC(C(=O)O)=CC=C3C=C21 RZRJYURCNBXIST-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- XRKPZHXBFXMAAN-LBPRGKRZSA-N 2-o-tert-butyl 3-o-methyl (3s)-6-amino-7-hydroxy-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylate Chemical compound NC1=C(O)C=C2CN(C(=O)OC(C)(C)C)[C@H](C(=O)OC)CC2=C1 XRKPZHXBFXMAAN-LBPRGKRZSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- HSUWKKYVMLNZMB-NSHDSACASA-N 3-O-methyl 2-O-propan-2-yl (3S)-7-hydroxy-8-nitro-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate Chemical compound C1=C(O)C([N+]([O-])=O)=C2CN(C(=O)OC(C)C)[C@H](C(=O)OC)CC2=C1 HSUWKKYVMLNZMB-NSHDSACASA-N 0.000 description 1
- OJFZASGMWBZUDJ-UHFFFAOYSA-N 3-O-tert-butyl 2-O-methyl anthracene-2,3-dicarboxylate Chemical compound COC(=O)C1=C(C=C2C=C3C=CC=CC3=CC2=C1)C(=O)OC(C)(C)C OJFZASGMWBZUDJ-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- NITUNGCLDSFVDL-UHFFFAOYSA-N 3-phenylprop-2-yn-1-ol Chemical compound OCC#CC1=CC=CC=C1 NITUNGCLDSFVDL-UHFFFAOYSA-N 0.000 description 1
- FQDFCZIYPKOIIF-UHFFFAOYSA-N 3-pyrimidin-2-ylprop-2-yn-1-ol Chemical compound OCC#CC1=NC=CC=N1 FQDFCZIYPKOIIF-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- 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 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- VTDOEFXTVHCAAM-UHFFFAOYSA-N 4-methylpent-3-ene-1,2,3-triol Chemical compound CC(C)=C(O)C(O)CO VTDOEFXTVHCAAM-UHFFFAOYSA-N 0.000 description 1
- HCEQQASHRRPQFE-UHFFFAOYSA-N 5-chloro-n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide;3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N.COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 HCEQQASHRRPQFE-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- UTFBGCLEKBUODW-UHFFFAOYSA-N 6-amino-7-hydroxy-3,4-dihydro-1h-isoquinoline-2,3-dicarboxylic acid Chemical compound C1C(C(O)=O)N(C(O)=O)CC2=C1C=C(N)C(O)=C2 UTFBGCLEKBUODW-UHFFFAOYSA-N 0.000 description 1
- WOHXPNHYAUIZAJ-JKRVXOIWSA-N 7-O-tert-butyl 8-O-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] 1,2,3,4a,5,5a,6,8-octahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1N(CC2CC3OCCNC3=CC2=C1)C(=O)OC(C)(C)C WOHXPNHYAUIZAJ-JKRVXOIWSA-N 0.000 description 1
- LDLAAZNPEQJXDG-FTGWLVSGSA-N 7-O-tert-butyl 8-O-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] benzo[g]cinnoline-7,8-dicarboxylate Chemical compound C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1=C(C=C2C=C3C=CN=NC3=CC2=C1)C(=O)OC(C)(C)C LDLAAZNPEQJXDG-FTGWLVSGSA-N 0.000 description 1
- RQFNYVOQCYBUJQ-UHFFFAOYSA-N 7-O-tert-butyl 8-O-methyl 1,2,3,4a,5,5a,6,8-octahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound COC(=O)C1N(CC2CC3OCCNC3=CC2=C1)C(=O)OC(C)(C)C RQFNYVOQCYBUJQ-UHFFFAOYSA-N 0.000 description 1
- CFCFBGAMAQVSCV-UHFFFAOYSA-N 7-O-tert-butyl 8-O-methyl 1,2,3,6,8,9-hexahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound COC(=O)C1N(CC=2C=C3OCCNC3=CC=2C1)C(=O)OC(C)(C)C CFCFBGAMAQVSCV-UHFFFAOYSA-N 0.000 description 1
- QNTBCXLCJNZKFH-UHFFFAOYSA-N 7-O-tert-butyl 8-O-methyl benzo[g]cinnoline-7,8-dicarboxylate Chemical compound COC(=O)C1=C(C=C2C=C3C=CN=NC3=CC2=C1)C(=O)OC(C)(C)C QNTBCXLCJNZKFH-UHFFFAOYSA-N 0.000 description 1
- PIHIPQXWNQVLRR-UHFFFAOYSA-N 7-[(2-methylpropan-2-yl)oxycarbonyl]-1,2,3,6,8,9-hexahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1CC=2C=C3OCCNC3=CC=2CC1C(=O)O PIHIPQXWNQVLRR-UHFFFAOYSA-N 0.000 description 1
- SUGZPSIGVCAQSR-XTEPFMGCSA-N 7-o-tert-butyl 8-o-methyl (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@@H]2C(=O)N(C)C=3C=C4C[C@H](N(CC4=CC=3O2)C(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 SUGZPSIGVCAQSR-XTEPFMGCSA-N 0.000 description 1
- BEBOFGPCIPAFMF-AHKZPQOWSA-N 7-o-tert-butyl 8-o-methyl (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@@H]2C(=O)NC=3C=C4C[C@H](N(CC4=CC=3O2)C(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 BEBOFGPCIPAFMF-AHKZPQOWSA-N 0.000 description 1
- BEBOFGPCIPAFMF-GPNIZQGCSA-N 7-o-tert-butyl 8-o-methyl (3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@H]2C(=O)NC=3C=C4CC(N(CC4=CC=3O2)C(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 BEBOFGPCIPAFMF-GPNIZQGCSA-N 0.000 description 1
- BEBOFGPCIPAFMF-BDYUSTAISA-N 7-o-tert-butyl 8-o-methyl (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C1=CC([C@H]2C(=O)NC=3C=C4C[C@H](N(CC4=CC=3O2)C(=O)OC(C)(C)C)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 BEBOFGPCIPAFMF-BDYUSTAISA-N 0.000 description 1
- DGAQNIRQJWZWTA-PVCWFJFTSA-N 7-o-tert-butyl 8-o-methyl (8s)-3-[4-[(2,5-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C([C@H](N(CC1=CC=2O3)C(=O)OC(C)(C)C)C(=O)OC)C1=CC=2NC(=O)C3C(C=C1)=CC=C1OCC1=CC(Cl)=CC=C1Cl DGAQNIRQJWZWTA-PVCWFJFTSA-N 0.000 description 1
- MDYSTQREJBMVMF-PVCWFJFTSA-N 7-o-tert-butyl 8-o-methyl (8s)-3-[4-[(2,6-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C([C@H](N(CC1=CC=2O3)C(=O)OC(C)(C)C)C(=O)OC)C1=CC=2NC(=O)C3C(C=C1)=CC=C1OCC1=C(Cl)C=CC=C1Cl MDYSTQREJBMVMF-PVCWFJFTSA-N 0.000 description 1
- VZSJKUMXFGSSDF-PVCWFJFTSA-N 7-o-tert-butyl 8-o-methyl (8s)-3-[4-[(4-chlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7,8-dicarboxylate Chemical compound C([C@H](N(CC1=CC=2O3)C(=O)OC(C)(C)C)C(=O)OC)C1=CC=2NC(=O)C3C(C=C1)=CC=C1OCC1=CC=C(Cl)C=C1 VZSJKUMXFGSSDF-PVCWFJFTSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- XOANJDROOKSIFR-FQZVVGDXSA-N C(#N)C1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 Chemical compound C(#N)C1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 XOANJDROOKSIFR-FQZVVGDXSA-N 0.000 description 1
- DFAZSTYHUSGNNC-HAWHYNLDSA-N C(#N)C1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)OC)NC(=O)C1N(CC=2C=C3O[C@H](C(NC3=CC2C1)=O)C1=CC=C(C=C1)OCC1=NC(=C(C=C1)Cl)Cl)C(=O)O Chemical compound C(#N)C1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)OC)NC(=O)C1N(CC=2C=C3O[C@H](C(NC3=CC2C1)=O)C1=CC=C(C=C1)OCC1=NC(=C(C=C1)Cl)Cl)C(=O)O DFAZSTYHUSGNNC-HAWHYNLDSA-N 0.000 description 1
- IRRPJXMHSLMOHH-MHZLTWQESA-N C(C)(C)(C)OC(=O)N1CC=2C=C3OCC(N(C3=CC2CC1)C(N[C@@H](CC1=CC=C(C=C1)C1=CC=C(C=C1)C#N)C(=O)OC)=O)=O Chemical compound C(C)(C)(C)OC(=O)N1CC=2C=C3OCC(N(C3=CC2CC1)C(N[C@@H](CC1=CC=C(C=C1)C1=CC=C(C=C1)C#N)C(=O)OC)=O)=O IRRPJXMHSLMOHH-MHZLTWQESA-N 0.000 description 1
- QJCWATCIIVVACC-UPKQVVFYSA-N C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1=CC=C2C=C3C=CN=NC3=CC2=C1 Chemical compound C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1=CC=C2C=C3C=CN=NC3=CC2=C1 QJCWATCIIVVACC-UPKQVVFYSA-N 0.000 description 1
- XDELRCXZRZSPAW-GRXFUPECSA-N C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1N(CC=2C=C3OC(C(N(C3=CC2C1)C)=O)C1=CC=C(C=C1)OCC1=CC(=C(C=C1)Cl)Cl)C(=O)OC(C)(C)C Chemical compound C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1N(CC=2C=C3OC(C(N(C3=CC2C1)C)=O)C1=CC=C(C=C1)OCC1=CC(=C(C=C1)Cl)Cl)C(=O)OC(C)(C)C XDELRCXZRZSPAW-GRXFUPECSA-N 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
- GIKYQFGFBMGONT-UHFFFAOYSA-N Cl.COC(=O)C1=CC=C2C=C3C=CN=NC3=CC2=C1 Chemical compound Cl.COC(=O)C1=CC=C2C=C3C=CN=NC3=CC2=C1 GIKYQFGFBMGONT-UHFFFAOYSA-N 0.000 description 1
- PVFDPEZUUMRXQX-UHFFFAOYSA-N Cl.COC(=O)C1=NC=C2C=C3OC=CNC3=CC2=C1 Chemical compound Cl.COC(=O)C1=NC=C2C=C3OC=CNC3=CC2=C1 PVFDPEZUUMRXQX-UHFFFAOYSA-N 0.000 description 1
- GQLBBPNKJVGRTL-IJLZXJCXSA-N ClC1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 Chemical compound ClC1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 GQLBBPNKJVGRTL-IJLZXJCXSA-N 0.000 description 1
- FHNHYAITUNBPBN-QHCPKHFHSA-N ClC=1C=C(COC2=CC=C(C=C2)[C@H]2C(NC3=CC=4CCNCC4C=C3O2)=O)C=CC1Cl Chemical compound ClC=1C=C(COC2=CC=C(C=C2)[C@H]2C(NC3=CC=4CCNCC4C=C3O2)=O)C=CC1Cl FHNHYAITUNBPBN-QHCPKHFHSA-N 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- BMOVQUBVGICXQN-UHFFFAOYSA-N Clinofibrate Chemical compound C1=CC(OC(C)(CC)C(O)=O)=CC=C1C1(C=2C=CC(OC(C)(CC)C(O)=O)=CC=2)CCCCC1 BMOVQUBVGICXQN-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 102000034534 Cotransporters Human genes 0.000 description 1
- 108020003264 Cotransporters Proteins 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PUFQLBBNKMYCHS-IJLZXJCXSA-N FC1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 Chemical compound FC1=CC=C(C=C1)C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)O)[C@@H](CC)C1=CC=CC=C1 PUFQLBBNKMYCHS-IJLZXJCXSA-N 0.000 description 1
- 102000030914 Fatty Acid-Binding Human genes 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000036119 Frailty Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 108010016122 Ghrelin Receptors Proteins 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 101800004295 Glucagon-like peptide 1(7-36) Proteins 0.000 description 1
- 102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 102100039256 Growth hormone secretagogue receptor type 1 Human genes 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 206010021518 Impaired gastric emptying Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 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
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229940086609 Lipase inhibitor Drugs 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CESYKOGBSMNBPD-UHFFFAOYSA-N Methyclothiazide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CCl)NC2=C1 CESYKOGBSMNBPD-UHFFFAOYSA-N 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 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
- 229910002651 NO3 Inorganic materials 0.000 description 1
- BAKDEJPTGHRTTC-HNNXBMFYSA-N N[C@H](C(=O)O)CC1=CC=C(C=C1)C1=CC=C(C=C1)C#N Chemical compound N[C@H](C(=O)O)CC1=CC=C(C=C1)C1=CC=C(C=C1)C#N BAKDEJPTGHRTTC-HNNXBMFYSA-N 0.000 description 1
- 102400000064 Neuropeptide Y Human genes 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- CYLWJCABXYDINA-UHFFFAOYSA-N Polythiazide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HSIJBPOQWNCLRO-NBHCPLFVSA-N [(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] 2,3,6,7,8,9-hexahydro-1H-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound C(C)(C)[C@H]1[C@@H](C[C@@H](CC1)C)OC(=O)C1NCC=2C=C3OCCNC3=CC=2C1 HSIJBPOQWNCLRO-NBHCPLFVSA-N 0.000 description 1
- JZNMYRWUEUXJLI-GAEHKXHXSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-6,7,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylate;hydrochloride Chemical compound Cl.CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@H]1NCC2=CC(O[C@@H](C(=O)N3C)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 JZNMYRWUEUXJLI-GAEHKXHXSA-N 0.000 description 1
- BTPGQGHBPMYLIT-NSSRGBRASA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound O=C([C@@H]1CC2=CC=3N(C)C(=O)[C@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C BTPGQGHBPMYLIT-NSSRGBRASA-N 0.000 description 1
- QTJXKFQJNDFPLC-JJEVKXTASA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@H]1NCC2=CC(O[C@@H](C(=O)N3)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 QTJXKFQJNDFPLC-JJEVKXTASA-N 0.000 description 1
- JZNMYRWUEUXJLI-GZYRLLMRSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-6,7,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylate;hydrochloride Chemical compound Cl.CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@H]1NCC2=CC(O[C@H](C(=O)N3C)C=4C=CC(OCC=5C=C(Cl)C(Cl)=CC=5)=CC=4)=C3C=C2C1 JZNMYRWUEUXJLI-GZYRLLMRSA-N 0.000 description 1
- BTPGQGHBPMYLIT-VRSNKBDTSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound O=C([C@@H]1CC2=CC=3N(C)C(=O)[C@@H](OC=3C=C2CN1[C@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C BTPGQGHBPMYLIT-VRSNKBDTSA-N 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000005136 alkenylsulfinyl group Chemical group 0.000 description 1
- 125000005137 alkenylsulfonyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 125000005134 alkynylsulfinyl group Chemical group 0.000 description 1
- 125000005139 alkynylsulfonyl group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- PAZJSJFMUHDSTF-UHFFFAOYSA-N alprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1CC=C PAZJSJFMUHDSTF-UHFFFAOYSA-N 0.000 description 1
- 229960002213 alprenolol Drugs 0.000 description 1
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 1
- 229940125709 anorectic agent Drugs 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000005333 aroyloxy group Chemical group 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 108010014210 axokine Proteins 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 229960003515 bendroflumethiazide Drugs 0.000 description 1
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- NDTSRXAMMQDVSW-UHFFFAOYSA-N benzthiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1N=C2CSCC1=CC=CC=C1 NDTSRXAMMQDVSW-UHFFFAOYSA-N 0.000 description 1
- 229960001541 benzthiazide Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- NRIMHVFWRMABGJ-UHFFFAOYSA-N bicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylic acid Chemical compound C1C2C(C(=O)O)=C(C(O)=O)C1C=C2 NRIMHVFWRMABGJ-UHFFFAOYSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- JCZLABDVDPYLRZ-AWEZNQCLSA-N biphenylalanine Chemical class C1=CC(C[C@H](N)C(O)=O)=CC=C1C1=CC=CC=C1 JCZLABDVDPYLRZ-AWEZNQCLSA-N 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-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
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
- 229960004064 bumetanide Drugs 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 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
- 229940084891 byetta Drugs 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical compound [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
- 229960005110 cerivastatin Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229960002174 ciprofibrate Drugs 0.000 description 1
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 229950003072 clinofibrate Drugs 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004976 cyclobutylene group Chemical group 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004977 cycloheptylene group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004980 cyclopropylene group Chemical group 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
- 229960005227 delapril Drugs 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 150000004862 dioxolanes Chemical class 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- 229960003199 etacrynic acid Drugs 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 108091022862 fatty acid binding Proteins 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 239000002871 fertility agent Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229960003028 flumethiazide Drugs 0.000 description 1
- RGUQWGXAYZNLMI-UHFFFAOYSA-N flumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O RGUQWGXAYZNLMI-UHFFFAOYSA-N 0.000 description 1
- 125000005567 fluorenylene group Chemical group 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 125000001543 furan-2,5-diyl group Chemical group O1C(=CC=C1*)* 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- YRSVDSQRGBYVIY-GJZGRUSLSA-N gemopatrilat Chemical compound O=C1N(CC(O)=O)C(C)(C)CCC[C@@H]1NC(=O)[C@@H](S)CC1=CC=CC=C1 YRSVDSQRGBYVIY-GJZGRUSLSA-N 0.000 description 1
- 229950006480 gemopatrilat Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229940112611 glucovance Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- DMDGGSIALPNSEE-UHFFFAOYSA-N hydroflumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O DMDGGSIALPNSEE-UHFFFAOYSA-N 0.000 description 1
- 229960003313 hydroflumethiazide Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 description 1
- UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical compound C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229940125699 infertility agent Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910001504 inorganic chloride Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 229960000299 mazindol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 230000009988 metabolic benefit Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- SEXYDEKFJLXIME-MRXNPFEDSA-N methyl (2r)-2-amino-3-[4-(4-cyanophenyl)phenyl]propanoate Chemical compound C1=CC(C[C@@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 SEXYDEKFJLXIME-MRXNPFEDSA-N 0.000 description 1
- IVDOIYGHPJPXFO-PKLMIRHRSA-N methyl (2r)-2-amino-3-[4-(4-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@@H](N)C(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 IVDOIYGHPJPXFO-PKLMIRHRSA-N 0.000 description 1
- XJZIQTAVMDFWDN-KRWDZBQOSA-N methyl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-pyridin-4-yloxyphenyl)propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OC1=CC=NC=C1 XJZIQTAVMDFWDN-KRWDZBQOSA-N 0.000 description 1
- PEKXBSREBMOTQU-XJRLVATOSA-N methyl (2s)-2-[[(3s)-3-[4-[(4-chlorophenyl)methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=CC(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 PEKXBSREBMOTQU-XJRLVATOSA-N 0.000 description 1
- UHAKCBFRDNNXCW-QGONPRBCSA-N methyl (2s)-2-[[(3s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-(4-pyridin-4-yloxyphenyl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1OC1=CC=NC=C1 UHAKCBFRDNNXCW-QGONPRBCSA-N 0.000 description 1
- QBUJULDFKRVZBW-QGONPRBCSA-N methyl (2s)-2-[[(3s)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-(4-pyridin-4-ylphenyl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=NC=C1 QBUJULDFKRVZBW-QGONPRBCSA-N 0.000 description 1
- KUYHWWRTSRRQBZ-AWEZNQCLSA-N methyl (2s)-2-amino-3-(4-pyridin-4-ylphenyl)propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1 KUYHWWRTSRRQBZ-AWEZNQCLSA-N 0.000 description 1
- RHZGSWPGNNKTAM-UTLKBRERSA-N methyl (2s)-2-amino-3-(4-pyridin-4-ylphenyl)propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=NC=C1 RHZGSWPGNNKTAM-UTLKBRERSA-N 0.000 description 1
- SWJBPEXDUCZVHQ-HNNXBMFYSA-N methyl (2s)-2-amino-3-[4-(4-chlorophenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(Cl)C=C1 SWJBPEXDUCZVHQ-HNNXBMFYSA-N 0.000 description 1
- QWJMMNXUOBFQLN-RSAXXLAASA-N methyl (2s)-2-amino-3-[4-(4-chlorophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(Cl)C=C1 QWJMMNXUOBFQLN-RSAXXLAASA-N 0.000 description 1
- NMCROLOVMHXPSL-HNNXBMFYSA-N methyl (2s)-2-amino-3-[4-(4-fluorophenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(F)C=C1 NMCROLOVMHXPSL-HNNXBMFYSA-N 0.000 description 1
- VRRRLQSVWDNHDW-RSAXXLAASA-N methyl (2s)-2-amino-3-[4-(4-fluorophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(F)C=C1 VRRRLQSVWDNHDW-RSAXXLAASA-N 0.000 description 1
- HNAUTRSQBWZHGJ-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-methoxyphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(OC)C=C1 HNAUTRSQBWZHGJ-NTISSMGPSA-N 0.000 description 1
- BOZVHPFMZPKTRE-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(4-methylphenyl)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C)C=C1 BOZVHPFMZPKTRE-INIZCTEOSA-N 0.000 description 1
- NCIPTOKUHQWFBY-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(4-methylphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=C(C)C=C1 NCIPTOKUHQWFBY-NTISSMGPSA-N 0.000 description 1
- NAFOVHMALJGPPY-JTQLQIEISA-N methyl (2s)-3-(4-hydroxy-3-nitrophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C([N+]([O-])=O)=C1 NAFOVHMALJGPPY-JTQLQIEISA-N 0.000 description 1
- LPZBAKRLDQQOJI-IGKIAQTJSA-N methyl (2s)-3-[(2s)-2-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-4-methyl-3-oxo-1,4-benzoxazin-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC([C@@H]2OC3=CC=C(C=C3N(C)C2=O)C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 LPZBAKRLDQQOJI-IGKIAQTJSA-N 0.000 description 1
- UVFURMMSZMNWRX-CVLAXDPASA-N methyl (2s)-3-[4-(4-chlorophenyl)phenyl]-2-[[(3r,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(O)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 UVFURMMSZMNWRX-CVLAXDPASA-N 0.000 description 1
- GOUWLKGRUODXDV-IBGZPJMESA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1C1=CC=C(C#N)C=C1 GOUWLKGRUODXDV-IBGZPJMESA-N 0.000 description 1
- UQYVUBICGBEPLT-AWQJWTIYSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UQYVUBICGBEPLT-AWQJWTIYSA-N 0.000 description 1
- HDQVEDOGEABLJA-XJRLVATOSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(2,6-dichlorophenyl)methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C(=CC=CC=2Cl)Cl)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 HDQVEDOGEABLJA-XJRLVATOSA-N 0.000 description 1
- QEADFMDCECLBCY-FBTNJIQESA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-6,7,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](C(=O)N(C)C=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 QEADFMDCECLBCY-FBTNJIQESA-N 0.000 description 1
- CVNPMWPNHWCMAU-FBTNJIQESA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s)-3-[4-[[4-methoxy-3-(trifluoromethyl)phenyl]methoxy]phenyl]-2-oxo-6,7,8,9-tetrahydro-1h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1NCC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(C(OC)=CC=2)C(F)(F)F)=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 CVNPMWPNHWCMAU-FBTNJIQESA-N 0.000 description 1
- GCBCSGFKXLPAEP-RZUTUZSPSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s,8s)-3-(4-hydroxyphenyl)-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(O)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 GCBCSGFKXLPAEP-RZUTUZSPSA-N 0.000 description 1
- UQYVUBICGBEPLT-BELRPRRISA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1r)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@@H](OC=3C=C2CN1[C@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UQYVUBICGBEPLT-BELRPRRISA-N 0.000 description 1
- UQYVUBICGBEPLT-SFXRUFGHSA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-[[(3s,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound C([C@H](NC(=O)[C@@H]1CC2=CC=3N(C)C(=O)[C@@H](OC=3C=C2CN1[C@@H](CC)C=1C=CC=CC=1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UQYVUBICGBEPLT-SFXRUFGHSA-N 0.000 description 1
- SFBFOJAPSYMOEM-SANMLTNESA-N methyl (2s)-3-[4-(4-cyanophenyl)phenyl]-2-methyl-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C([C@@](C)(C(=O)OC)NC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 SFBFOJAPSYMOEM-SANMLTNESA-N 0.000 description 1
- GXGPHFVGRDJMNL-WIOPSUGQSA-N methyl (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-6,7,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound C1=CC([C@@H]2C(=O)N(C)C=3C=C4C[C@H](NCC4=CC=3O2)C(=O)OC)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 GXGPHFVGRDJMNL-WIOPSUGQSA-N 0.000 description 1
- DJUBCSBWUPPQQI-LEEDBYTESA-N methyl (3r,8s)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1s)-1-phenylpropyl]-8,9-dihydro-6h-pyrido[4,3-g][1,4]benzoxazine-8-carboxylate Chemical compound C1=CC([C@H]2OC=3C=C4CN([C@@H](CC4=CC=3N(C)C2=O)C(=O)OC)[C@@H](CC)C=2C=CC=CC=2)=CC=C1OCC1=CC=C(Cl)C(Cl)=C1 DJUBCSBWUPPQQI-LEEDBYTESA-N 0.000 description 1
- OEXCOILCVVMABT-QMMMGPOBSA-N methyl (3s)-7-hydroxy-6-nitro-1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound [O-][N+](=O)C1=C(O)C=C2CN[C@H](C(=O)OC)CC2=C1 OEXCOILCVVMABT-QMMMGPOBSA-N 0.000 description 1
- YTNGWXICCHJHKA-UHFFFAOYSA-N methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound C1=CC=C2CNC(C(=O)OC)CC2=C1 YTNGWXICCHJHKA-UHFFFAOYSA-N 0.000 description 1
- ISYLQYOQVUWLEI-UHFFFAOYSA-N methyl 2-[4-[(5,6-dichloropyridin-3-yl)methoxy]phenyl]-2-hydroxyacetate Chemical compound C1=CC(C(O)C(=O)OC)=CC=C1OCC1=CN=C(Cl)C(Cl)=C1 ISYLQYOQVUWLEI-UHFFFAOYSA-N 0.000 description 1
- VDINVGSNZKKPBY-LLGZSRGJSA-N methyl 2-[[(3S,8S)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-1-methyl-2-oxo-7-[(1S)-1-phenylpropyl]-8,9-dihydro-6H-pyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]propanoate Chemical compound COC(C(C)NC(=O)[C@H]1N(CC=2C=C3O[C@H](C(N(C3=CC=2C1)C)=O)C1=CC=C(C=C1)OCC1=CC(=C(C=C1)Cl)Cl)[C@@H](CC)C1=CC=CC=C1)=O VDINVGSNZKKPBY-LLGZSRGJSA-N 0.000 description 1
- RYYDMSMPNITDHP-UHFFFAOYSA-N methyl 2-amino-3-(4-phenylphenyl)propanoate;hydrochloride Chemical compound [Cl-].C1=CC(CC([NH3+])C(=O)OC)=CC=C1C1=CC=CC=C1 RYYDMSMPNITDHP-UHFFFAOYSA-N 0.000 description 1
- ZXBQZVMJOHLRPQ-UHFFFAOYSA-N methyl 2-amino-3-[4-(4-methoxyphenyl)phenyl]propanoate Chemical compound C1=CC(CC(N)C(=O)OC)=CC=C1C1=CC=C(OC)C=C1 ZXBQZVMJOHLRPQ-UHFFFAOYSA-N 0.000 description 1
- DHPYYPJMQRYNLX-UHFFFAOYSA-N methyl 2-hydroxy-2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)C(O)C1=CC=C(O)C=C1 DHPYYPJMQRYNLX-UHFFFAOYSA-N 0.000 description 1
- MUASODGGMBZJGK-UHFFFAOYSA-N methyl benzo[g]cinnoline-8-carboxylate Chemical compound COC(=O)C1=CC=C2C=C3C=CN=NC3=CC2=C1 MUASODGGMBZJGK-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical compound COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
- 229950009116 mevastatin Drugs 0.000 description 1
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-O morpholinium Chemical compound [H+].C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-O 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- BFYLULHOYZNWPC-UHFFFAOYSA-N n-[[4,5-dimethyl-1-[(2-methylphenyl)methyl]imidazol-2-yl]methyl]-2,4-dimethoxy-n-(3-methylbutyl)benzamide Chemical compound COC1=CC(OC)=CC=C1C(=O)N(CCC(C)C)CC1=NC(C)=C(C)N1CC1=CC=CC=C1C BFYLULHOYZNWPC-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229940127264 non-peptide agonist Drugs 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- LVRLSYPNFFBYCZ-VGWMRTNUSA-N omapatrilat Chemical compound C([C@H](S)C(=O)N[C@H]1CCS[C@H]2CCC[C@H](N2C1=O)C(=O)O)C1=CC=CC=C1 LVRLSYPNFFBYCZ-VGWMRTNUSA-N 0.000 description 1
- 229950000973 omapatrilat Drugs 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229950008492 pentopril Drugs 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 125000006551 perfluoro alkylene group Chemical group 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000002856 peripheral neuron Anatomy 0.000 description 1
- 229940083256 peripheral vasodilators nicotinic acid and derivative Drugs 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000012071 phase Substances 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
- 229960003562 phentermine Drugs 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Chemical class 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229960005483 polythiazide Drugs 0.000 description 1
- 229920000046 polythiazide Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- KBOOFQCJRVAUOQ-BDYUSTAISA-N propan-2-yl (3s)-3-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-7-hydroxy-6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC(O)=C(C=C2C1)[N+]([O-])=O)C(=O)OC(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 KBOOFQCJRVAUOQ-BDYUSTAISA-N 0.000 description 1
- BPYHSXYXZHOPJO-UHFFFAOYSA-N propan-2-yl 2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound N1C(=O)COC2=C1C=C1CCN(C(=O)OC(C)C)CC1=C2 BPYHSXYXZHOPJO-UHFFFAOYSA-N 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- VEMKTZHHVJILDY-UHFFFAOYSA-N resmethrin Chemical compound CC1(C)C(C=C(C)C)C1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UHFFFAOYSA-N 0.000 description 1
- 230000003979 response to food Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011257 shell material Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 1
- 229960002578 sitaxentan Drugs 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 239000004059 squalene synthase inhibitor Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- ORWNYERLOQDYHX-NWUFIKPXSA-N tert-butyl (3s)-3-[4-[(4-chlorophenyl)methoxy]phenyl]-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=CC(Cl)=CC=2)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 ORWNYERLOQDYHX-NWUFIKPXSA-N 0.000 description 1
- UTFBATQAEYCLMO-BDYUSTAISA-N tert-butyl (3s)-3-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-7-hydroxy-6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1N(CC2=CC(O)=C(C=C2C1)[N+]([O-])=O)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UTFBATQAEYCLMO-BDYUSTAISA-N 0.000 description 1
- MEHGPXXMGBMFOE-NWUFIKPXSA-N tert-butyl (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(2,5-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C(=CC=C(Cl)C=2)Cl)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 MEHGPXXMGBMFOE-NWUFIKPXSA-N 0.000 description 1
- OEURQZDPWFOKMU-NWUFIKPXSA-N tert-butyl (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(2,6-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C(=CC=CC=2Cl)Cl)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 OEURQZDPWFOKMU-NWUFIKPXSA-N 0.000 description 1
- BBXNSYFJQDPWJL-NWUFIKPXSA-N tert-butyl (3s)-8-[[(2s)-3-[4-(4-cyanophenyl)phenyl]-1-methoxy-1-oxopropan-2-yl]carbamoyl]-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound C([C@@H](C(=O)OC)NC(=O)C1N(CC2=CC=3O[C@H](C(=O)NC=3C=C2C1)C=1C=CC(OCC=2C=C(Cl)C(Cl)=CC=2)=CC=1)C(=O)OC(C)(C)C)C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 BBXNSYFJQDPWJL-NWUFIKPXSA-N 0.000 description 1
- YYOUAAZOTHZOLN-UHFFFAOYSA-N tert-butyl 1,2,3,6,8,9-hexahydropyrido[4,3-g][1,4]benzoxazine-7-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC2=CC3=C(OCCN3)C=C2C1 YYOUAAZOTHZOLN-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 229960004813 trichlormethiazide Drugs 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- IAIDUHCBNLFXEF-MNEFBYGVSA-N zofenopril Chemical compound C([C@@H](C)C(=O)N1[C@@H](C[C@@H](C1)SC=1C=CC=CC=1)C(O)=O)SC(=O)C1=CC=CC=C1 IAIDUHCBNLFXEF-MNEFBYGVSA-N 0.000 description 1
- 229960002769 zofenopril Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3459908P | 2008-03-07 | 2008-03-07 | |
| US61/034,599 | 2008-03-07 | ||
| PCT/US2009/036333 WO2009111700A2 (en) | 2008-03-07 | 2009-03-06 | Oxadiazoanthracene compounds for the treatment of diabetes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2009221722A1 AU2009221722A1 (en) | 2009-09-11 |
| AU2009221722B2 true AU2009221722B2 (en) | 2014-12-18 |
Family
ID=41056666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2009221722A Active AU2009221722B2 (en) | 2008-03-07 | 2009-03-06 | Oxadiazoanthracene compounds for the treatment of diabetes |
Country Status (17)
| Country | Link |
|---|---|
| US (7) | US7727983B2 (enExample) |
| EP (1) | EP2262364B1 (enExample) |
| JP (1) | JP5382952B2 (enExample) |
| KR (1) | KR101616737B1 (enExample) |
| CN (1) | CN101959405B (enExample) |
| AU (1) | AU2009221722B2 (enExample) |
| BR (1) | BRPI0910282A2 (enExample) |
| CA (1) | CA2716664C (enExample) |
| DK (1) | DK2262364T3 (enExample) |
| EA (1) | EA018225B1 (enExample) |
| ES (1) | ES2567451T3 (enExample) |
| IL (1) | IL207570A (enExample) |
| MA (1) | MA32175B1 (enExample) |
| MX (1) | MX2010009752A (enExample) |
| NZ (1) | NZ587343A (enExample) |
| WO (1) | WO2009111700A2 (enExample) |
| ZA (1) | ZA201006367B (enExample) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0910282A2 (pt) * | 2008-03-07 | 2015-09-01 | Transtech Pharma Inc | Composto oxadiazo-antraceno para o tratamento de diabetes |
| JP5755217B2 (ja) | 2009-03-30 | 2015-07-29 | トランステック・ファーマ，エルエルシー | 置換アゾアントラセン誘導体、その医薬組成物とその使用の方法 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| DE102010015123A1 (de) | 2010-04-16 | 2011-10-20 | Sanofi-Aventis Deutschland Gmbh | Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| CA2822017C (en) | 2010-12-23 | 2015-04-07 | Pfizer Inc. | Glucagon receptor modulators |
| WO2012096824A1 (en) * | 2011-01-12 | 2012-07-19 | Transtech Pharma, Inc. | Phenylglyoxylic acid derivatives and their preparation and use |
| GEP20156351B (en) | 2011-02-08 | 2015-08-25 | Pfizer | Glucagon receptor modulator |
| CN103732578B (zh) | 2011-07-22 | 2015-08-12 | 辉瑞大药厂 | 喹啉基胰高血糖素受体调节剂 |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| CN104202977A (zh) * | 2012-03-22 | 2014-12-10 | 转化技术制药有限责任公司 | 小分子glp1r激动剂的三(羟甲基)氨基甲烷盐及其药物组合物和用途 |
| US20150297573A1 (en) | 2012-10-24 | 2015-10-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | TPL2 KINASE INHIBITORS FOR PREVENTING OR TREATING DIABETES AND FOR PROMOTING Beta-CELL SURVIVAL |
| ES2687083T3 (es) * | 2013-01-17 | 2018-10-23 | Vtv Therapeutics Llc | Combinaciones de un agonista del GLPR1 y metformina y el uso de estos para el tratamiento de la diabetes tipo 2 y otros trastornos |
| CN112457301A (zh) * | 2014-07-25 | 2021-03-09 | 赛尔基因第二国际有限公司 | 新的glp-1受体调节剂 |
| US10426818B2 (en) | 2015-03-24 | 2019-10-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Method and pharmaceutical composition for use in the treatment of diabetes |
| JOP20190060A1 (ar) | 2016-09-26 | 2019-03-26 | Chugai Pharmaceutical Co Ltd | مشتق بيرازولو بيريدين له تأثير مساعد لمستقبل glp-1 |
| WO2019103060A1 (ja) * | 2017-11-22 | 2019-05-31 | 第一三共株式会社 | 縮合三環化合物 |
| MX2020008387A (es) | 2018-05-08 | 2020-12-11 | Vtv Therapeutics Llc | Usos terapeuticos de agonistas glp1r. |
| MA54555A (fr) | 2018-11-22 | 2021-09-29 | Qilu Regor Therapeutics Inc | Agonistes de glp-1r et leurs utilisations |
| MA55627A (fr) * | 2019-04-12 | 2022-02-16 | Qilu Regor Therapeutics Inc | Agonistes de glp-1r et leurs utilisations |
| EP4048664A1 (en) | 2019-10-25 | 2022-08-31 | Gilead Sciences, Inc. | Glp-1r modulating compounds |
| CN115461344B (zh) | 2020-04-01 | 2024-01-12 | 杭州中美华东制药有限公司 | 一种glp-1受体激动剂的晶型a及其制备方法 |
| JP2023528726A (ja) | 2020-04-01 | 2023-07-06 | ハンジョウ ジョンメイ フアドン ファーマシューティカル シーオー．，エルティーディー． | Ｇｌｐ１ｒアゴニスト遊離塩基の薬学的に許容される酸塩類およびその調製法 |
| TW202144340A (zh) | 2020-04-03 | 2021-12-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 稠合咪唑類衍生物、其製備方法及其在醫藥上的應用 |
| US20230348483A1 (en) * | 2020-05-28 | 2023-11-02 | Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd. | Preparation method for (s)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)methyl propionate diacid salt |
| EP4159737A4 (en) * | 2020-05-28 | 2024-10-09 | Hangzhou Zhongmeihuadong Pharmaceutical Co., Ltd. | METHOD FOR PREPARING A GLP-1 RECEPTOR AGONIST-FREE BASE |
| CA3188891A1 (en) | 2020-09-01 | 2022-01-13 | Fanglong Yang | Fused imidazole derivative, preparation method therefor, and medical use thereof |
| EP4227299A4 (en) | 2020-10-12 | 2025-04-09 | Hangzhou Zhongmeihuadong Pharmaceutical Co., Ltd. | GLP-1 RECEPTOR AGONIST, BENZIMIDAZOLONE AND ITS USE |
| ES3041328T3 (en) * | 2020-10-14 | 2025-11-11 | Qilu Regor Therapeutics Inc | Crystal forms of glp-1r agonists and uses thereof |
| EP4247804A1 (en) | 2020-11-20 | 2023-09-27 | Gilead Sciences, Inc. | Polyheterocyclic glp-1 r modulating compounds |
| CN115461334B (zh) | 2020-11-27 | 2024-06-21 | 深圳信立泰药业股份有限公司 | 一种苯并咪唑类衍生物及其制备方法和医药用途 |
| WO2022199458A1 (zh) | 2021-03-22 | 2022-09-29 | 杭州中美华东制药有限公司 | 噻吩类glp-1受体激动剂及其用途 |
| US20240217966A1 (en) | 2021-03-24 | 2024-07-04 | Shionogi & Co., Ltd. | Pharmaceutical composition containing glp-1 receptor agonist having fused ring |
| WO2022262615A1 (zh) * | 2021-06-17 | 2022-12-22 | 杭州中美华东制药有限公司 | 蒽类化合物、其制备方法和医药用途 |
| JP2024523525A (ja) | 2021-06-24 | 2024-06-28 | 杭州中美華東製薬有限公司 | Ｇｌｐ－１受容体アゴニストならびにその組成物および使用 |
| CN115521320B (zh) * | 2021-06-25 | 2023-09-05 | 沈阳兴齐眼药股份有限公司 | 一种制备普拉洛芬的方法 |
| CN119907794A (zh) | 2022-09-22 | 2025-04-29 | 盐野义制药株式会社 | 具有glp-1受体激动剂作用的稠环化合物 |
| CN120981457A (zh) | 2023-09-14 | 2025-11-18 | 歌礼制药(中国)有限公司 | Glp-1r激动剂及其治疗方法 |
| US12291530B1 (en) | 2023-11-24 | 2025-05-06 | Ascletis Pharma (China) Co., Limited | GLP-1R agonist and therapeutic method thereof |
| WO2025158275A1 (en) | 2024-01-24 | 2025-07-31 | Pfizer Inc. | Combination therapy using glucose-dependent insulinotropic polypeptide receptor antagonist compounds and glp-1 receptor agonist compounds |
| WO2025189141A1 (en) | 2024-03-08 | 2025-09-12 | Annapurna Bio, Inc. | Methods for treating obesity and increasing weight loss |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4789675A (en) * | 1986-02-11 | 1988-12-06 | Takeda Chemical Industries, Ltd. | 1,4-benzoxazine derivatives and pharmaceutical use |
| US20040019072A1 (en) * | 1995-10-06 | 2004-01-29 | Stacie Canan-Koch | Dimer-selective RXR modulators and methods for their use |
| WO2004085403A1 (en) * | 2003-03-26 | 2004-10-07 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6345270A (ja) * | 1986-02-11 | 1988-02-26 | Takeda Chem Ind Ltd | １，４−ベンゾオキサジン誘導体，その製造法およびそれを含有する医薬用組成物 |
| JP2002534512A (ja) * | 1999-01-15 | 2002-10-15 | ノボ ノルディスク アクティーゼルスカブ | 非ペプチドｇｌｐ−１アゴニスト |
| CZ20021911A3 (cs) * | 1999-12-03 | 2002-10-16 | Kyoto Pharmaceutical Industries, Ltd. | Nové heterocyklické sloučeniny a jejich soli a jejich vyuľití v lékařství |
| EP1125925A1 (en) | 2000-02-15 | 2001-08-22 | Applied Research Systems ARS Holding N.V. | Amine derivatives for the treatment of apoptosis |
| US20050222036A1 (en) | 2000-08-24 | 2005-10-06 | Thomas Jefferson University | Peptide compositions with effects on blood glucose |
| BRPI0910282A2 (pt) * | 2008-03-07 | 2015-09-01 | Transtech Pharma Inc | Composto oxadiazo-antraceno para o tratamento de diabetes |
| WO2011156655A2 (en) | 2010-06-09 | 2011-12-15 | Receptos, Inc. | Novel glp-1 receptor stabilizers and modulators |
-
2009
- 2009-03-06 BR BRPI0910282-5A patent/BRPI0910282A2/pt not_active Application Discontinuation
- 2009-03-06 EA EA201071045A patent/EA018225B1/ru not_active IP Right Cessation
- 2009-03-06 DK DK09718287.7T patent/DK2262364T3/en active
- 2009-03-06 JP JP2010549910A patent/JP5382952B2/ja active Active
- 2009-03-06 MX MX2010009752A patent/MX2010009752A/es active IP Right Grant
- 2009-03-06 CA CA2716664A patent/CA2716664C/en active Active
- 2009-03-06 NZ NZ587343A patent/NZ587343A/en not_active IP Right Cessation
- 2009-03-06 EP EP09718287.7A patent/EP2262364B1/en active Active
- 2009-03-06 ES ES09718287T patent/ES2567451T3/es active Active
- 2009-03-06 CN CN200980108115.XA patent/CN101959405B/zh active Active
- 2009-03-06 KR KR1020107020688A patent/KR101616737B1/ko not_active Expired - Fee Related
- 2009-03-06 WO PCT/US2009/036333 patent/WO2009111700A2/en not_active Ceased
- 2009-03-06 US US12/399,504 patent/US7727983B2/en active Active
- 2009-03-06 AU AU2009221722A patent/AU2009221722B2/en active Active
-
2010
- 2010-04-13 US US12/759,010 patent/US7790714B2/en active Active
- 2010-08-03 US US12/849,225 patent/US7906507B2/en active Active
- 2010-08-12 IL IL207570A patent/IL207570A/en active IP Right Grant
- 2010-08-31 US US12/872,580 patent/US8524708B2/en not_active Expired - Fee Related
- 2010-09-10 ZA ZA2010/06367A patent/ZA201006367B/en unknown
- 2010-09-30 MA MA33212A patent/MA32175B1/fr unknown
-
2013
- 2013-08-01 US US13/956,578 patent/US8703766B2/en not_active Expired - Fee Related
-
2014
- 2014-03-05 US US14/197,771 patent/US8933222B2/en active Active
- 2014-12-01 US US14/556,837 patent/US9120813B2/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4789675A (en) * | 1986-02-11 | 1988-12-06 | Takeda Chemical Industries, Ltd. | 1,4-benzoxazine derivatives and pharmaceutical use |
| US20040019072A1 (en) * | 1995-10-06 | 2004-01-29 | Stacie Canan-Koch | Dimer-selective RXR modulators and methods for their use |
| WO2004085403A1 (en) * | 2003-03-26 | 2004-10-07 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009221722B2 (en) | Oxadiazoanthracene compounds for the treatment of diabetes | |
| JP5755217B2 (ja) | 置換アゾアントラセン誘導体、その医薬組成物とその使用の方法 | |
| HK1148435B (en) | Oxadiazoanthracene compounds for the treatment of diabetes | |
| CN118908937B (zh) | 一种具有sting蛋白降解作用的化合物及其制备方法和用途 | |
| HK1164050B (en) | Substituted azoanthracene derivatives, pharmaceutical compositions, and methods of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC1 | Assignment before grant (sect. 113) |
Owner name: TRANSTECH PHARMA, LLC. Free format text: FORMER APPLICANT(S): TRANSTECH PHARMA, INC. |
|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO READ GUZEL, MUSTAFA; DAVIS, STEPHEN THOMAS; YOKUM, THOMAS SCOTT; MJALLI, ADNAN M. M.; KALPATHY,SANTHOSH CHIDAMBARESWARAN; BEHME, CHRISTOPHER AND POLISETTI, DHARMA RAO |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| PC | Assignment registered |
Owner name: VTV THERAPEUTICS LLC Free format text: FORMER OWNER WAS: VTV THERAPEUTICS LLC |