BR112020008457A2 - compostos bicíclicos em ponte como moduladores de receptor de farnesoide x - Google Patents

Info

Publication number

BR112020008457A2

BR112020008457A2 BR112020008457-3A BR112020008457A BR112020008457A2 BR 112020008457 A2 BR112020008457 A2 BR 112020008457A2 BR 112020008457 A BR112020008457 A BR 112020008457A BR 112020008457 A2 BR112020008457 A2 BR 112020008457A2

Authority

BR

Brazil

Prior art keywords

independently

heteroaryl

phenyl

alkyl

cyclopropyl

Prior art date

2017-11-01

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002619 bicyclic group Chemical group 0.000 title description 10
• 150000001875 compounds Chemical class 0.000 claims abstract description 329
• 238000000034 method Methods 0.000 claims abstract description 150
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 66
• 150000003839 salts Chemical class 0.000 claims abstract description 60
• 208000035475 disorder Diseases 0.000 claims abstract description 41
• 239000012453 solvate Substances 0.000 claims abstract description 41
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
• 206010016654 Fibrosis Diseases 0.000 claims abstract description 22
• 230000004761 fibrosis Effects 0.000 claims abstract description 21
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
• 201000011510 cancer Diseases 0.000 claims abstract description 12
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 12
• 230000001575 pathological effect Effects 0.000 claims abstract description 6
• -1 cyano, hydroxyl Chemical group 0.000 claims description 261
• 238000002360 preparation method Methods 0.000 claims description 93
• 125000003118 aryl group Chemical group 0.000 claims description 72
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 65
• 125000001072 heteroaryl group Chemical group 0.000 claims description 62
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 59
• 125000000623 heterocyclic group Chemical group 0.000 claims description 57
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
• 229910052757 nitrogen Inorganic materials 0.000 claims description 50
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 48
• 229910052760 oxygen Inorganic materials 0.000 claims description 43
• 229910052717 sulfur Inorganic materials 0.000 claims description 39
• 238000011282 treatment Methods 0.000 claims description 39
• 125000001188 haloalkyl group Chemical group 0.000 claims description 36
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 34
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 34
• 125000004432 carbon atom Chemical group C* 0.000 claims description 33
• 239000003814 drug Substances 0.000 claims description 33
• 229910052799 carbon Inorganic materials 0.000 claims description 32
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 30
• 125000003545 alkoxy group Chemical group 0.000 claims description 29
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 28
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 24
• 125000002947 alkylene group Chemical group 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 23
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 22
• 239000001257 hydrogen Substances 0.000 claims description 22
• 125000004076 pyridyl group Chemical group 0.000 claims description 22
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
• 229910052731 fluorine Inorganic materials 0.000 claims description 21
• 125000005842 heteroatom Chemical group 0.000 claims description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 20
• 229910052801 chlorine Inorganic materials 0.000 claims description 20
• 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 19
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
• 125000004474 heteroalkylene group Chemical group 0.000 claims description 16
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 16
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 15
• 125000002393 azetidinyl group Chemical group 0.000 claims description 15
• 125000004429 atom Chemical group 0.000 claims description 13
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 125000003566 oxetanyl group Chemical group 0.000 claims description 13
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 12
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 11
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 11
• 125000005605 benzo group Chemical group 0.000 claims description 11
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 10
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 10
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
• 125000004043 oxo group Chemical group O=* 0.000 claims description 9
• 238000002560 therapeutic procedure Methods 0.000 claims description 9
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
• 230000008569 process Effects 0.000 claims description 8
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 7
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
• 125000000335 thiazolyl group Chemical group 0.000 claims description 7
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 6
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
• 125000004419 alkynylene group Chemical group 0.000 claims description 6
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 208000010157 sclerosing cholangitis Diseases 0.000 claims description 6
• 125000004450 alkenylene group Chemical group 0.000 claims description 5
• 208000020832 chronic kidney disease Diseases 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000001041 indolyl group Chemical group 0.000 claims description 5
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
• 201000002793 renal fibrosis Diseases 0.000 claims description 5
• 125000005884 carbocyclylalkyl group Chemical group 0.000 claims description 4
• 230000001587 cholestatic effect Effects 0.000 claims description 4
• 125000003147 glycosyl group Chemical group 0.000 claims description 4
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000001425 triazolyl group Chemical group 0.000 claims description 4
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
• 206010004664 Biliary fibrosis Diseases 0.000 claims description 3
• 208000004930 Fatty Liver Diseases 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• 230000001476 alcoholic effect Effects 0.000 claims description 3
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
• 125000005873 benzo[d]thiazolyl group Chemical group 0.000 claims description 3
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 3
• 125000004992 haloalkylamino group Chemical group 0.000 claims description 3
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
• 125000004011 3 membered carbocyclic group Chemical group 0.000 claims description 2
• 125000001845 4 membered carbocyclic group Chemical group 0.000 claims description 2
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 2
• 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 2
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 2
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
• 230000002503 metabolic effect Effects 0.000 claims 2
• 102100036402 DAP3-binding cell death enhancer 1 Human genes 0.000 claims 1
• 101000929221 Homo sapiens DAP3-binding cell death enhancer 1 Proteins 0.000 claims 1
• 125000004659 aryl alkyl thio group Chemical group 0.000 claims 1
• WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 claims 1
• 102100038495 Bile acid receptor Human genes 0.000 abstract description 78
• 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 abstract description 78
• 201000010099 disease Diseases 0.000 abstract description 24
• 230000000694 effects Effects 0.000 abstract description 13
• 239000000556 agonist Substances 0.000 abstract description 5
• 230000008482 dysregulation Effects 0.000 abstract description 2
• 208000001132 Osteoporosis Diseases 0.000 abstract 1
• 206010052779 Transplant rejections Diseases 0.000 abstract 1
• 239000000543 intermediate Substances 0.000 description 227
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
• 238000006243 chemical reaction Methods 0.000 description 151
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 127
• 238000005481 NMR spectroscopy Methods 0.000 description 126
• 229910052796 boron Inorganic materials 0.000 description 123
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 114
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 101
• 235000019439 ethyl acetate Nutrition 0.000 description 95
• 230000015572 biosynthetic process Effects 0.000 description 91
• 239000002253 acid Substances 0.000 description 81
• 238000003786 synthesis reaction Methods 0.000 description 81
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
• 239000000203 mixture Substances 0.000 description 62
• 239000007787 solid Substances 0.000 description 60
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
• 229910001868 water Inorganic materials 0.000 description 48
• 238000004519 manufacturing process Methods 0.000 description 46
• 239000000047 product Substances 0.000 description 46
• 239000012043 crude product Substances 0.000 description 45
• 239000000741 silica gel Substances 0.000 description 45
• 229910002027 silica gel Inorganic materials 0.000 description 45
• 239000002904 solvent Substances 0.000 description 44
• 239000002585 base Substances 0.000 description 42
• 238000003818 flash chromatography Methods 0.000 description 41
• 239000012071 phase Substances 0.000 description 41
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• 239000012267 brine Substances 0.000 description 33
• 239000003153 chemical reaction reagent Substances 0.000 description 33
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
• 239000000243 solution Substances 0.000 description 32
• 239000011541 reaction mixture Substances 0.000 description 31
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000012074 organic phase Substances 0.000 description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 125000005129 aryl carbonyl group Chemical group 0.000 description 23
• 238000002953 preparative HPLC Methods 0.000 description 22
• 150000002148 esters Chemical class 0.000 description 21
• 230000014759 maintenance of location Effects 0.000 description 21
• 239000007858 starting material Substances 0.000 description 21
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 20
• 230000007062 hydrolysis Effects 0.000 description 20
• 238000006460 hydrolysis reaction Methods 0.000 description 20
• 239000002245 particle Substances 0.000 description 20
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 19
• 239000005695 Ammonium acetate Substances 0.000 description 19
• 235000019257 ammonium acetate Nutrition 0.000 description 19
• 229940043376 ammonium acetate Drugs 0.000 description 19
• 229940124597 therapeutic agent Drugs 0.000 description 19
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical group CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 18
• 239000000460 chlorine Substances 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 18
• 239000000651 prodrug Substances 0.000 description 18
• 229940002612 prodrug Drugs 0.000 description 18
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
• 125000001424 substituent group Chemical group 0.000 description 17
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
• 229910052938 sodium sulfate Inorganic materials 0.000 description 16
• 235000011152 sodium sulphate Nutrition 0.000 description 16
• 229910001854 alkali hydroxide Inorganic materials 0.000 description 15
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 15
• 150000001721 carbon Chemical group 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 239000003112 inhibitor Substances 0.000 description 15
• 239000003880 polar aprotic solvent Substances 0.000 description 15
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 14
• 239000003795 chemical substances by application Substances 0.000 description 14
• XXHKQNFPSVYHBJ-UHFFFAOYSA-N 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole Chemical compound C1(CC1)C1=CC(=NO1)C1=C(C=CC=C1Cl)Cl XXHKQNFPSVYHBJ-UHFFFAOYSA-N 0.000 description 13
• 235000015165 citric acid Nutrition 0.000 description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
• 239000011734 sodium Substances 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 239000007832 Na2SO4 Substances 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• 239000003613 bile acid Substances 0.000 description 12
• 238000005859 coupling reaction Methods 0.000 description 12
• 239000000463 material Substances 0.000 description 12
• 239000000126 substance Substances 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 11
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 239000004480 active ingredient Substances 0.000 description 11
• 229910052792 caesium Inorganic materials 0.000 description 11
• 125000002950 monocyclic group Chemical group 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 10
• 238000010168 coupling process Methods 0.000 description 10
• 125000004093 cyano group Chemical group *C#N 0.000 description 10
• 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 10
• 125000004404 heteroalkyl group Chemical group 0.000 description 10
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 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 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 230000008878 coupling Effects 0.000 description 9
• 230000003176 fibrotic effect Effects 0.000 description 9
• 125000002757 morpholinyl group Chemical group 0.000 description 9
• 125000002347 octyl group Chemical group [H]C([*])([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 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• 241000282414 Homo sapiens Species 0.000 description 8
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
• 230000002378 acidificating effect Effects 0.000 description 8
• 239000008186 active pharmaceutical agent Substances 0.000 description 8
• 125000003342 alkenyl group Chemical group 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
• 239000012230 colorless oil Substances 0.000 description 8
• 150000004820 halides Chemical class 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• 230000002062 proliferating effect Effects 0.000 description 8
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
• 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 7
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
• 125000004414 alkyl thio group Chemical group 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• 239000011575 calcium Substances 0.000 description 7
• 239000013058 crude material Substances 0.000 description 7
• 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 7
• 229910052744 lithium Inorganic materials 0.000 description 7
• 150000002825 nitriles Chemical class 0.000 description 7
• AKRYBBWYDSDZHG-UHFFFAOYSA-N nitrosobis(2-oxopropyl)amine Chemical compound CC(=O)CN(N=O)CC(C)=O AKRYBBWYDSDZHG-UHFFFAOYSA-N 0.000 description 7
• 125000004193 piperazinyl group Chemical group 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• 150000003254 radicals Chemical class 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 230000009466 transformation Effects 0.000 description 7
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 6
• 125000000304 alkynyl group Chemical group 0.000 description 6
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
• 230000027455 binding Effects 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 125000002837 carbocyclic group Chemical group 0.000 description 6
• CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 6
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 230000002440 hepatic effect Effects 0.000 description 6
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 6
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 210000004185 liver Anatomy 0.000 description 6
• 150000004702 methyl esters Chemical class 0.000 description 6
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 238000007363 ring formation reaction Methods 0.000 description 6
• 241000894007 species Species 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 125000001544 thienyl group Chemical group 0.000 description 6
• RCMLKQSZCSYLLS-UHFFFAOYSA-N 1-hydroxy-2,3-dihydroindole Chemical compound C1=CC=C2N(O)CCC2=C1 RCMLKQSZCSYLLS-UHFFFAOYSA-N 0.000 description 5
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 5
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
• 238000012512 characterization method Methods 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 150000002367 halogens Chemical class 0.000 description 5
• 210000000936 intestine Anatomy 0.000 description 5
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical group CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 5
• 125000004430 oxygen atom Chemical group O* 0.000 description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• 238000010189 synthetic method Methods 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 238000000844 transformation Methods 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 4
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 4
• GJPIPLPHQGHOOY-UHFFFAOYSA-N 4-(3,5-difluorobenzoyl)oxybicyclo[2.2.2]octane-1-carboxylic acid Chemical compound OC(=O)C12CCC(CC1)(CC2)OC(=O)c1cc(F)cc(F)c1 GJPIPLPHQGHOOY-UHFFFAOYSA-N 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 241001331845 Equus asinus x caballus Species 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• KRGFOUGVZFEEBW-UHFFFAOYSA-N [5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methanol Chemical compound OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl KRGFOUGVZFEEBW-UHFFFAOYSA-N 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 230000010933 acylation Effects 0.000 description 4
• 238000005917 acylation reaction Methods 0.000 description 4
• 125000001931 aliphatic group Chemical group 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 125000004104 aryloxy group Chemical group 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 230000009286 beneficial effect Effects 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 4
• PUNFICOCZAPAJV-UHFFFAOYSA-N bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC2CCC1(C(=O)O)CC2 PUNFICOCZAPAJV-UHFFFAOYSA-N 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 238000001023 centrifugal evaporation Methods 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 125000004122 cyclic group Chemical group 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
• 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 4
• 239000002552 dosage form Substances 0.000 description 4
• MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 208000006454 hepatitis Diseases 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 125000001183 hydrocarbyl group Chemical group 0.000 description 4
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
• 208000002551 irritable bowel syndrome Diseases 0.000 description 4
• 208000032839 leukemia Diseases 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 4
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 4
• 239000004033 plastic Substances 0.000 description 4
• 229920003023 plastic Polymers 0.000 description 4
• 239000011591 potassium Substances 0.000 description 4
• 229910052700 potassium Inorganic materials 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 238000004007 reversed phase HPLC Methods 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 125000004434 sulfur atom Chemical group 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 125000004306 triazinyl group Chemical group 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical class NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 3
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 3
• PNZIYSWKRBYITO-UHFFFAOYSA-N 4-(bromomethyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole Chemical compound ClC1=CC=CC(Cl)=C1C1=NOC(C2CC2)=C1CBr PNZIYSWKRBYITO-UHFFFAOYSA-N 0.000 description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
• GGKHJPORUJLZSZ-UHFFFAOYSA-N 5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazole Chemical compound C1(CC1)C1=CC(=NO1)C1=C(C=CC=C1)OC(F)(F)F GGKHJPORUJLZSZ-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
• 239000004475 Arginine Substances 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• 208000032928 Dyslipidaemia Diseases 0.000 description 3
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 102000003816 Interleukin-13 Human genes 0.000 description 3
• 108090000176 Interleukin-13 Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
• 208000017170 Lipid metabolism disease Diseases 0.000 description 3
• 238000006751 Mitsunobu reaction Methods 0.000 description 3
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241000283984 Rodentia Species 0.000 description 3
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
• YJPRZVHHSVCUIU-UHFFFAOYSA-N [5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methanol Chemical compound OCC1=C(C2CC2)ON=C1C1=CC=CC=C1OC(F)(F)F YJPRZVHHSVCUIU-UHFFFAOYSA-N 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
• 210000000988 bone and bone Anatomy 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 150000003857 carboxamides Chemical class 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 239000011111 cardboard Substances 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 239000010949 copper Substances 0.000 description 3
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 210000000232 gallbladder Anatomy 0.000 description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 125000002632 imidazolidinyl group Chemical group 0.000 description 3
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 208000017169 kidney disease Diseases 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000011572 manganese Substances 0.000 description 3
• YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 239000007800 oxidant agent Substances 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 239000000123 paper Substances 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 208000011317 telomere syndrome Diseases 0.000 description 3
• TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 2
• VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 2
• SQHSJJGGWYIFCD-UHFFFAOYSA-N (e)-1-diazonio-1-dimethoxyphosphorylprop-1-en-2-olate Chemical compound COP(=O)(OC)C(\[N+]#N)=C(\C)[O-] SQHSJJGGWYIFCD-UHFFFAOYSA-N 0.000 description 2
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 2
• MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 2
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
• 125000005955 1H-indazolyl group Chemical group 0.000 description 2
• RAXXELZNTBOGNW-MQIHXRCWSA-N 1h-imidazole Chemical compound C1=C[15NH]C=[15N]1 RAXXELZNTBOGNW-MQIHXRCWSA-N 0.000 description 2
• ZZWWXIBKLBMSCS-FQEVSTJZSA-N 2-[1-[(2r)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanoic acid Chemical compound COC1=CC=CC=C1[C@@H](OC1CCOCC1)CN1C(=O)N(C(C)(C)C(O)=O)C(=O)C2=C1SC(C=1OC=CN=1)=C2C ZZWWXIBKLBMSCS-FQEVSTJZSA-N 0.000 description 2
• CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical class NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
• MSUAFFBEKJQZIC-UHFFFAOYSA-N 2-chloroethanone Chemical compound ClC[C]=O MSUAFFBEKJQZIC-UHFFFAOYSA-N 0.000 description 2
• DEZDVAAAZZONAM-UHFFFAOYSA-N 4-(bromomethyl)-5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazole Chemical compound FC(F)(F)OC1=CC=CC=C1C1=NOC(C2CC2)=C1CBr DEZDVAAAZZONAM-UHFFFAOYSA-N 0.000 description 2
• MXDAYVCCPKGPOE-UHFFFAOYSA-N 4-amino-3-sulfanylbenzonitrile Chemical compound NC1=CC=C(C#N)C=C1S MXDAYVCCPKGPOE-UHFFFAOYSA-N 0.000 description 2
• REIDAMBAPLIATC-UHFFFAOYSA-N 4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1 REIDAMBAPLIATC-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• IKZIMZJLXVLAEB-UHFFFAOYSA-N 5-cyclopropyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound C1(CC1)C1=CC(=NO1)C1=C(C=CC=C1)C(F)(F)F IKZIMZJLXVLAEB-UHFFFAOYSA-N 0.000 description 2
• HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 2
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000937413 Axia Species 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 2
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• 229910052684 Cerium Inorganic materials 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 2
• 206010008635 Cholestasis Diseases 0.000 description 2
• 206010008909 Chronic Hepatitis Diseases 0.000 description 2
• 206010009944 Colon cancer Diseases 0.000 description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 2
• 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
• 239000005977 Ethylene Substances 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 208000010412 Glaucoma Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000007818 Grignard reagent Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• 208000029523 Interstitial Lung disease Diseases 0.000 description 2
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 102100027159 Membrane primary amine oxidase Human genes 0.000 description 2
• 101710132836 Membrane primary amine oxidase Proteins 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• NMMIHXMBOZYNET-UHFFFAOYSA-N Methyl picolinate Chemical compound COC(=O)C1=CC=CC=N1 NMMIHXMBOZYNET-UHFFFAOYSA-N 0.000 description 2
• 102100033127 Mitogen-activated protein kinase kinase kinase 5 Human genes 0.000 description 2
• 101710164337 Mitogen-activated protein kinase kinase kinase 5 Proteins 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 150000001204 N-oxides Chemical class 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
• 208000008589 Obesity Diseases 0.000 description 2
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical group CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
• 206010060862 Prostate cancer Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 102000034527 Retinoid X Receptors Human genes 0.000 description 2
• 108010038912 Retinoid X Receptors Proteins 0.000 description 2
• 206010038934 Retinopathy proliferative Diseases 0.000 description 2
• 229940125907 SJ995973 Drugs 0.000 description 2
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 239000012317 TBTU Substances 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2
• 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 159000000021 acetate salts Chemical class 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 231100000354 acute hepatitis Toxicity 0.000 description 2
• 125000002015 acyclic group Chemical group 0.000 description 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 239000002390 adhesive tape Substances 0.000 description 2
• 206010064930 age-related macular degeneration Diseases 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 150000003973 alkyl amines Chemical class 0.000 description 2
• 150000001351 alkyl iodides Chemical class 0.000 description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 150000003863 ammonium salts Chemical class 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 239000000010 aprotic solvent Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 2
• 125000005110 aryl thio group Chemical group 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
• 125000005512 benztetrazolyl group Chemical group 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 230000009787 cardiac fibrosis Effects 0.000 description 2
• 125000002091 cationic group Chemical group 0.000 description 2
• XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 231100000359 cholestasis Toxicity 0.000 description 2
• 230000007870 cholestasis Effects 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
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• TXWRERCHRDBNLG-UHFFFAOYSA-N cubane Chemical compound C12C3C4C1C1C4C3C12 TXWRERCHRDBNLG-UHFFFAOYSA-N 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
• 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 2
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• NUJBTXFFJUGENN-UHFFFAOYSA-N ethyl 3,4-diaminobenzoate Chemical compound CCOC(=O)C1=CC=C(N)C(N)=C1 NUJBTXFFJUGENN-UHFFFAOYSA-N 0.000 description 2
• 238000013265 extended release Methods 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 206010016629 fibroma Diseases 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 239000003292 glue Substances 0.000 description 2
• 150000004795 grignard reagents Chemical class 0.000 description 2
• 125000005114 heteroarylalkoxy group Chemical group 0.000 description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 description 2
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
• 230000013632 homeostatic process Effects 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 229910052500 inorganic mineral Inorganic materials 0.000 description 2
• 230000010354 integration Effects 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 2
• 125000001786 isothiazolyl group Chemical group 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
• 150000002576 ketones Chemical class 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 239000012280 lithium aluminium hydride Substances 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• 159000000003 magnesium salts Chemical class 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• FXDVFDQQCPJMCJ-UHFFFAOYSA-N methyl 3-(hydrazinecarbonyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)NN)=C1 FXDVFDQQCPJMCJ-UHFFFAOYSA-N 0.000 description 2
• PIXOBZFOAGWQGO-UHFFFAOYSA-N methyl 5-cyano-2-methoxybenzoate Chemical compound COC(=O)C1=CC(C#N)=CC=C1OC PIXOBZFOAGWQGO-UHFFFAOYSA-N 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
• 229960001238 methylnicotinate Drugs 0.000 description 2
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
• 235000001968 nicotinic acid Nutrition 0.000 description 2
• 239000011664 nicotinic acid Substances 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 201000004071 non-specific interstitial pneumonia Diseases 0.000 description 2
• 239000012457 nonaqueous media Substances 0.000 description 2
• XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 230000000414 obstructive effect Effects 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 125000000160 oxazolidinyl group Chemical group 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 229960000649 oxyphenbutazone Drugs 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 238000010647 peptide synthesis reaction Methods 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 150000002989 phenols Chemical class 0.000 description 2
• 150000004714 phosphonium salts Chemical class 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
• 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 150000003140 primary amides Chemical class 0.000 description 2
• 201000000742 primary sclerosing cholangitis Diseases 0.000 description 2
• 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
• 150000003222 pyridines Chemical class 0.000 description 2
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 230000037390 scarring Effects 0.000 description 2
• 238000004683 secondary electrospray ionisation mass spectroscopy Methods 0.000 description 2
• YIDDLAAKOYYGJG-UHFFFAOYSA-N selonsertib Chemical compound CC(C)N1C=NN=C1C1=CC=CC(NC(=O)C=2C(=CC(C)=C(C=2)N2C=C(N=C2)C2CC2)F)=N1 YIDDLAAKOYYGJG-UHFFFAOYSA-N 0.000 description 2
• 229950003181 selonsertib Drugs 0.000 description 2
• BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 229910052709 silver Inorganic materials 0.000 description 2
• 239000004332 silver Substances 0.000 description 2
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
• 210000000813 small intestine Anatomy 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• 230000003595 spectral effect Effects 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 229940124530 sulfonamide Drugs 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 150000003573 thiols Chemical class 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 2
• 238000003828 vacuum filtration Methods 0.000 description 2
• HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
• HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
• SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
• WLNBMPZUVDTASE-HXIISURNSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;sulfuric acid Chemical compound [O-]S([O-])(=O)=O.O=C[C@H]([NH3+])[C@@H](O)[C@H](O)[C@H](O)CO.O=C[C@H]([NH3+])[C@@H](O)[C@H](O)[C@H](O)CO WLNBMPZUVDTASE-HXIISURNSA-N 0.000 description 1
• LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 1
• AEMPUAWUDAMJBV-QFIPXVFZSA-N (2s)-4-(4-methylphenyl)-5-(2h-tetrazol-5-yl)-2-[4-(4,4,4-trifluorobutoxy)phenyl]-2-(trifluoromethyl)-1,3-dihydropyridin-6-one Chemical compound C1=CC(C)=CC=C1C(C[C@](NC1=O)(C=2C=CC(OCCCC(F)(F)F)=CC=2)C(F)(F)F)=C1C1=NN=NN1 AEMPUAWUDAMJBV-QFIPXVFZSA-N 0.000 description 1
• LDQKDRLEMKIYMC-XMMPIXPASA-N (3R)-1'-(9-anthrylcarbonyl)-3-(morpholin-4-ylcarbonyl)-1,4'-bipiperidine Chemical compound O=C([C@H]1CN(CCC1)C1CCN(CC1)C(=O)C=1C2=CC=CC=C2C=C2C=CC=CC2=1)N1CCOCC1 LDQKDRLEMKIYMC-XMMPIXPASA-N 0.000 description 1
• PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
• FOLCUFKJHSQMEL-BIXPGCQOSA-N (4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CCCCC1CCC(CC1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C=O FOLCUFKJHSQMEL-BIXPGCQOSA-N 0.000 description 1
• VIVDIJOFLVCYRY-KOFBORESSA-N (4R,4aR,7S,7aR,12bS)-3-methyl-9-sulfanyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4S VIVDIJOFLVCYRY-KOFBORESSA-N 0.000 description 1
• YCHYFHOSGQABSW-RTBURBONSA-N (6ar,10ar)-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene-9-carboxylic acid Chemical compound C1C(C(O)=O)=CC[C@H]2C(C)(C)OC3=CC(C(C)(C)CCCCCC)=CC(O)=C3[C@@H]21 YCHYFHOSGQABSW-RTBURBONSA-N 0.000 description 1
• QOLHWXNSCZGWHK-BWBORTOCSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecylcarbamoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)NCCCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 QOLHWXNSCZGWHK-BWBORTOCSA-N 0.000 description 1
• VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 1
• 125000006832 (C1-C10) alkylene group Chemical group 0.000 description 1
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WEYFZKRRQZYAJI-SNAWJCMRSA-N (e)-3-(3-cyanophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(C#N)=C1 WEYFZKRRQZYAJI-SNAWJCMRSA-N 0.000 description 1
• COLOHWPRNRVWPI-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound [CH2]C(F)(F)F COLOHWPRNRVWPI-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical class C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
• CPVMAYNPSFMOGK-UHFFFAOYSA-N 1-(hydroxymethyl)bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(CO)CC2 CPVMAYNPSFMOGK-UHFFFAOYSA-N 0.000 description 1
• OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
• GQBRZBHEPUQRPL-LJQANCHMSA-N 1-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GQBRZBHEPUQRPL-LJQANCHMSA-N 0.000 description 1
• KNOCEIYOPWHYEO-UHFFFAOYSA-N 1-[[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-1-bicyclo[2.2.2]octanyl]methyl]pyrazole-4-carboxylic acid Chemical compound C1(CC1)C1=C(C(=NO1)C1=C(C=CC=C1Cl)Cl)COC12CCC(CC1)(CC2)CN1N=CC(=C1)C(=O)O KNOCEIYOPWHYEO-UHFFFAOYSA-N 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• 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
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• JLZVIWSFUPLSOR-UHFFFAOYSA-N 2,3-difluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1F JLZVIWSFUPLSOR-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• NUMXHEUHHRTBQT-AATRIKPKSA-N 2,4-dimethoxy-1-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C(OC)=C1 NUMXHEUHHRTBQT-AATRIKPKSA-N 0.000 description 1
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
• OZMLUMPWPFZWTP-UHFFFAOYSA-N 2-(tributyl-$l^{5}-phosphanylidene)acetonitrile Chemical compound CCCCP(CCCC)(CCCC)=CC#N OZMLUMPWPFZWTP-UHFFFAOYSA-N 0.000 description 1
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• AWLPPBSWOMXWGA-UHFFFAOYSA-N 2-[1,2,2-tris(carboxymethylsulfanyl)ethylsulfanyl]acetic acid Chemical compound OC(=O)CSC(SCC(O)=O)C(SCC(O)=O)SCC(O)=O AWLPPBSWOMXWGA-UHFFFAOYSA-N 0.000 description 1
• MSSQOQPKGAMUSY-LEAFIULHSA-N 2-[1-[2-[(4r,6s)-8-chloro-6-(2,3-dimethoxyphenyl)-4,6-dihydropyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC([C@@H]2C3=CC(Cl)=CC=C3N3C=CC=C3[C@@H](CC(=O)N3CCC(CC(O)=O)CC3)O2)=C1OC MSSQOQPKGAMUSY-LEAFIULHSA-N 0.000 description 1
• KZSKGLFYQAYZCO-UHFFFAOYSA-N 2-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(N2CC(O)(C2)C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)=C1 KZSKGLFYQAYZCO-UHFFFAOYSA-N 0.000 description 1
• RYWCQJDEHXJHRI-XJMXIVSISA-N 2-[3-[5-[6-[3-[3-(carboxymethyl)phenyl]-4-[(2r,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]hexyl]-2-[(2r,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]phenyl]acetic acid Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC(C(=C1)C=2C=C(CC(O)=O)C=CC=2)=CC=C1CCCCCCC(C=C1C=2C=C(CC(O)=O)C=CC=2)=CC=C1O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 RYWCQJDEHXJHRI-XJMXIVSISA-N 0.000 description 1
• WGPXBGGTZUUQQC-UHFFFAOYSA-N 2-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-1-bicyclo[2.2.2]octanyl]quinoline-6-carboxylic acid Chemical compound C1(CC1)C1=C(C(=NO1)C1=C(C=CC=C1Cl)Cl)COC12CCC(CC1)(CC2)C1=NC2=CC=C(C=C2C=C1)C(=O)O WGPXBGGTZUUQQC-UHFFFAOYSA-N 0.000 description 1
• BVAHPPKGOOJSPU-UHFFFAOYSA-N 2-[[5-chloro-2-[(5-methyl-2-propan-2-ylpyrazol-3-yl)amino]pyridin-4-yl]amino]-n-methoxybenzamide Chemical compound CONC(=O)C1=CC=CC=C1NC1=CC(NC=2N(N=C(C)C=2)C(C)C)=NC=C1Cl BVAHPPKGOOJSPU-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• ADSOSINJPNKUJK-UHFFFAOYSA-N 2-butylpyridine Chemical compound CCCCC1=CC=CC=N1 ADSOSINJPNKUJK-UHFFFAOYSA-N 0.000 description 1
• QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical group ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
• AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical class NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 1
• 125000006040 2-hexenyl group Chemical group 0.000 description 1
• MAFJOMAYYKSZOS-UHFFFAOYSA-N 2-methoxycarbonylpyridine-4-carboxylic acid Chemical compound COC(=O)C1=CC(C(O)=O)=CC=N1 MAFJOMAYYKSZOS-UHFFFAOYSA-N 0.000 description 1
• 125000006022 2-methyl-2-propenyl group Chemical group 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
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• KRTGJZMJJVEKRX-UHFFFAOYSA-N 2-phenylethan-1-yl Chemical group [CH2]CC1=CC=CC=C1 KRTGJZMJJVEKRX-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• WPGHPGAUFIJVJF-UHFFFAOYSA-N 3,5-dichloropyridine Chemical compound ClC1=CN=CC(Cl)=C1 WPGHPGAUFIJVJF-UHFFFAOYSA-N 0.000 description 1
• YFJXQKGQZGVBHT-SNAWJCMRSA-N 3-[(E)-2-(4-hydroxy-1-bicyclo[2.2.2]octanyl)ethenyl]benzonitrile Chemical compound OC12CCC(CC1)(CC2)/C=C/C=1C=C(C#N)C=CC=1 YFJXQKGQZGVBHT-SNAWJCMRSA-N 0.000 description 1
• PRRZDZJYSJLDBS-UHFFFAOYSA-N 3-bromo-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CBr PRRZDZJYSJLDBS-UHFFFAOYSA-N 0.000 description 1
• JKCYKISVUIVZCS-UHFFFAOYSA-N 3-bromo-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1Br JKCYKISVUIVZCS-UHFFFAOYSA-N 0.000 description 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• OJCKPWOBQFQMAA-UHFFFAOYSA-N 3-cyano-2,6-difluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC(C#N)=C1F OJCKPWOBQFQMAA-UHFFFAOYSA-N 0.000 description 1
• MTYFJFMXUMMQDL-UHFFFAOYSA-N 3-cyano-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(C#N)=C1F MTYFJFMXUMMQDL-UHFFFAOYSA-N 0.000 description 1
• 125000006041 3-hexenyl group Chemical group 0.000 description 1
• WMZNGTSLFSJHMZ-UHFFFAOYSA-N 3-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=CC(C(O)=O)=C1 WMZNGTSLFSJHMZ-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• MPODTOYFPVYLMR-UHFFFAOYSA-N 4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]bicyclo[2.2.2]octane-1-carbaldehyde Chemical compound C1(CC1)C1=C(C(=NO1)C1=C(C=CC=C1Cl)Cl)COC12CCC(CC1)(CC2)C=O MPODTOYFPVYLMR-UHFFFAOYSA-N 0.000 description 1
• NCZFTTJAPGMQOW-UHFFFAOYSA-N 4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]bicyclo[2.2.2]octane-1-carbonitrile Chemical compound C1(CC1)C1=C(C(=NO1)C1=C(C=CC=C1Cl)Cl)COC12CCC(CC1)(CC2)C#N NCZFTTJAPGMQOW-UHFFFAOYSA-N 0.000 description 1
• QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
• LUUMLYXKTPBTQR-UHFFFAOYSA-N 4-chloro-n-[5-methyl-2-(7h-pyrrolo[2,3-d]pyrimidine-4-carbonyl)pyridin-3-yl]-3-(trifluoromethyl)benzenesulfonamide Chemical compound C=1C(C)=CN=C(C(=O)C=2C=3C=CNC=3N=CN=2)C=1NS(=O)(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 LUUMLYXKTPBTQR-UHFFFAOYSA-N 0.000 description 1
• 125000006042 4-hexenyl group Chemical group 0.000 description 1
• AEMUWTWTDIUOLJ-UHFFFAOYSA-N 4-iodobicyclo[2.2.2]octane-1-carboxylic acid Chemical compound C1CC2(I)CCC1(C(=O)O)CC2 AEMUWTWTDIUOLJ-UHFFFAOYSA-N 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• KBZVAQVEHVGIEI-UHFFFAOYSA-N 4-methoxycarbonylbicyclo[2.2.2]octane-1-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C(=O)OC)CC2 KBZVAQVEHVGIEI-UHFFFAOYSA-N 0.000 description 1
• ZMYKITJYWFYRFJ-UHFFFAOYSA-N 4-oxo-4-(2-phenylethylamino)butanoic acid Chemical compound OC(=O)CCC(=O)NCCC1=CC=CC=C1 ZMYKITJYWFYRFJ-UHFFFAOYSA-N 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• 102100022464 5'-nucleotidase Human genes 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• UQXVUTYCTZULCD-UHFFFAOYSA-N 5-cyano-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC(C#N)=CC=C1F UQXVUTYCTZULCD-UHFFFAOYSA-N 0.000 description 1
• BYAKRZATGHVTEH-UHFFFAOYSA-N 5-cyclopropyl-3-(2,6-dichlorophenyl)-4-methyl-1,2-oxazole Chemical compound CC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl BYAKRZATGHVTEH-UHFFFAOYSA-N 0.000 description 1
• 125000006043 5-hexenyl group Chemical group 0.000 description 1
• 101710179734 6,7-dimethyl-8-ribityllumazine synthase 2 Proteins 0.000 description 1
• VWIOMFMPIVMLIR-UHFFFAOYSA-N 6-methoxycarbonylpyridine-2-carboxylic acid Chemical compound COC(=O)C1=CC=CC(C(O)=O)=N1 VWIOMFMPIVMLIR-UHFFFAOYSA-N 0.000 description 1
• 125000005330 8 membered heterocyclic group Chemical group 0.000 description 1
• 102100022622 Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Human genes 0.000 description 1
• 101000878595 Arabidopsis thaliana Squalene synthase 1 Proteins 0.000 description 1
• CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 206010070545 Bacterial translocation Diseases 0.000 description 1
• 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 206010004659 Biliary cirrhosis Diseases 0.000 description 1
• 241000283725 Bos Species 0.000 description 1
• 241000566113 Branta sandvicensis Species 0.000 description 1
• 102000001902 CC Chemokines Human genes 0.000 description 1
• 108010040471 CC Chemokines Proteins 0.000 description 1
• 101100532679 Caenorhabditis elegans scc-1 gene Proteins 0.000 description 1
• 101100420946 Caenorhabditis elegans sea-2 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• 108010076667 Caspases Proteins 0.000 description 1
• 102000011727 Caspases Human genes 0.000 description 1
• 229930186147 Cephalosporin Natural products 0.000 description 1
• 102400001244 Cerebellin Human genes 0.000 description 1
• 101800001299 Cerebellin Proteins 0.000 description 1
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
• 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
• 102000006383 Chemokine CCL24 Human genes 0.000 description 1
• 108010083647 Chemokine CCL24 Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• AEMZEDNMNLIDSL-YGCVIUNWSA-N Cl.CC(C)(C)NC(=O)C1=CC=C(OC\C(CN)=C\F)C=C1 Chemical compound Cl.CC(C)(C)NC(=O)C1=CC=C(OC\C(CN)=C\F)C=C1 AEMZEDNMNLIDSL-YGCVIUNWSA-N 0.000 description 1
• 229940126559 Compound 4e Drugs 0.000 description 1
• 241000761389 Copa Species 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 241000252210 Cyprinidae Species 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 101710134178 DNA polymerase processivity factor BMRF1 Proteins 0.000 description 1
• JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
• 101150010908 Dcbld2 gene Proteins 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• NTURVSFTOYPGON-UHFFFAOYSA-N Dihydroquinazoline Chemical compound C1=CC=C2C=NCNC2=C1 NTURVSFTOYPGON-UHFFFAOYSA-N 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• 206010072268 Drug-induced liver injury Diseases 0.000 description 1
• 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
• 229940118365 Endothelin receptor antagonist Drugs 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 229940124783 FAK inhibitor Drugs 0.000 description 1
• 229940125634 FPR2 agonist Drugs 0.000 description 1
• 101710153363 Fibroblast growth factor 15 Proteins 0.000 description 1
• 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
• 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
• 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
• 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
• 102000020897 Formins Human genes 0.000 description 1
• 108091022623 Formins Proteins 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 108010001517 Galectin 3 Proteins 0.000 description 1
• 102100039558 Galectin-3 Human genes 0.000 description 1
• 241000726221 Gemma Species 0.000 description 1
• 229930183217 Genin Natural products 0.000 description 1
• 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• 206010019668 Hepatic fibrosis Diseases 0.000 description 1
• 206010019708 Hepatic steatosis Diseases 0.000 description 1
• 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
• 229910052689 Holmium Inorganic materials 0.000 description 1
• 101000972916 Homo sapiens Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Proteins 0.000 description 1
• 101000966782 Homo sapiens Lysophosphatidic acid receptor 1 Proteins 0.000 description 1
• 101001043352 Homo sapiens Lysyl oxidase homolog 2 Proteins 0.000 description 1
• 101001129178 Homo sapiens Patatin-like phospholipase domain-containing protein 6 Proteins 0.000 description 1
• 101001092910 Homo sapiens Serum amyloid P-component Proteins 0.000 description 1
• 101000713575 Homo sapiens Tubulin beta-3 chain Proteins 0.000 description 1
• 101000713585 Homo sapiens Tubulin beta-4A chain Proteins 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 101000618467 Hypocrea jecorina (strain ATCC 56765 / BCRC 32924 / NRRL 11460 / Rut C-30) Endo-1,4-beta-xylanase 2 Proteins 0.000 description 1
• 101150088952 IGF1 gene Proteins 0.000 description 1
• 208000010159 IgA glomerulonephritis Diseases 0.000 description 1
• 206010021263 IgA nephropathy Diseases 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 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
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• IVRXNBXKWIJUQB-UHFFFAOYSA-N LY-2157299 Chemical compound CC1=CC=CC(C=2C(=C3CCCN3N=2)C=2C3=CC(=CC=C3N=CC=2)C(N)=O)=N1 IVRXNBXKWIJUQB-UHFFFAOYSA-N 0.000 description 1
• 108010014552 LY2405319 Proteins 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 241000270322 Lepidosauria Species 0.000 description 1
• 102220498675 Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 2_C28Y_mutation Human genes 0.000 description 1
• 101710186609 Lipoyl synthase 2 Proteins 0.000 description 1
• 101710122908 Lipoyl synthase 2, chloroplastic Proteins 0.000 description 1
• 101710101072 Lipoyl synthase 2, mitochondrial Proteins 0.000 description 1
• YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
• 108010019598 Liraglutide Proteins 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 208000005777 Lupus Nephritis Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 description 1
• 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 description 1
• 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 1
• 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 244000237986 Melia azadirachta Species 0.000 description 1
• 235000013500 Melia azadirachta Nutrition 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 208000001145 Metabolic Syndrome Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101500025412 Mus musculus Processed cyclic AMP-responsive element-binding protein 3-like protein 1 Proteins 0.000 description 1
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
• 201000004458 Myoma Diseases 0.000 description 1
• RATDFIOSZONOPC-UHFFFAOYSA-N N'-hydroxy-4-iodobicyclo[2.2.2]octane-1-carboximidamide Chemical compound O\N=C(/N)\C12CCC(CC1)(CC2)I RATDFIOSZONOPC-UHFFFAOYSA-N 0.000 description 1
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
• 108010082699 NADPH Oxidase 4 Proteins 0.000 description 1
• 102100021872 NADPH oxidase 4 Human genes 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 101150094382 NSS gene Proteins 0.000 description 1
• 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
• 206010029279 Neurogenic bladder Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
• VYLOOGHLKSNNEK-PIIMJCKOSA-N OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 Chemical compound OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 VYLOOGHLKSNNEK-PIIMJCKOSA-N 0.000 description 1
• UXRZLDREKITWRO-UHFFFAOYSA-N P(c1ccccc1)c1ccccc1.CC1(C)c2ccccc2Oc2ccccc12 Chemical compound P(c1ccccc1)c1ccccc1.CC1(C)c2ccccc2Oc2ccccc12 UXRZLDREKITWRO-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 241000282322 Panthera Species 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 108700027412 Pegbelfermin Proteins 0.000 description 1
• 206010034277 Pemphigoid Diseases 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
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• 241000183024 Populus tremula Species 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
• 102100024304 Protachykinin-1 Human genes 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 235000014443 Pyrus communis Nutrition 0.000 description 1
• 229940127472 RNA Synthetase Inhibitors Drugs 0.000 description 1
• 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
• 108091005682 Receptor kinases Proteins 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• GSINGUMRKGRYJP-VZWAGXQNSA-N Remogliflozin Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N(C(C)C)N=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 GSINGUMRKGRYJP-VZWAGXQNSA-N 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 101000930003 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
• 102100036202 Serum amyloid P-component Human genes 0.000 description 1
• 238000006223 Seyferth-Gilbert homologation reaction Methods 0.000 description 1
• 238000005598 Sharpless reaction Methods 0.000 description 1
• BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
• 206010050207 Skin fibrosis Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
• 101000642823 Solanum tuberosum Granule-bound starch synthase 2, chloroplastic/amyloplastic Proteins 0.000 description 1
• 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
• 101800003906 Substance P Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 238000006859 Swern oxidation reaction Methods 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 0.000 description 1
• 108010025037 T140 peptide Proteins 0.000 description 1
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
• 241001582429 Tetracis Species 0.000 description 1
• 241000534944 Thia Species 0.000 description 1
• 241001130469 Tila Species 0.000 description 1
• KPWYNAGOBXLMSE-UHFFFAOYSA-N Tipelukast Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(OCCCC(O)=O)=C1CCC KPWYNAGOBXLMSE-UHFFFAOYSA-N 0.000 description 1
• 241000838698 Togo Species 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 102100036790 Tubulin beta-3 chain Human genes 0.000 description 1
• 102100036788 Tubulin beta-4A chain Human genes 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• NELWQUQCCZMRPB-UBPLGANQSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(4-amino-5-ethenyl-2-oxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1N1C(=O)N=C(N)C(C=C)=C1 NELWQUQCCZMRPB-UBPLGANQSA-N 0.000 description 1
• OZAPTPNKBQTRMG-UHFFFAOYSA-N [5-cyclopropyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazol-4-yl]methanol Chemical compound OCC1=C(C2CC2)ON=C1C1=CC=CC=C1C(F)(F)F OZAPTPNKBQTRMG-UHFFFAOYSA-N 0.000 description 1
• CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical group [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
• YHGYYWQEZUONHC-UHFFFAOYSA-N [Mg].BrCC1=CC=CC(Br)=C1 Chemical compound [Mg].BrCC1=CC=CC(Br)=C1 YHGYYWQEZUONHC-UHFFFAOYSA-N 0.000 description 1
• WMEKSYHDIDMJMC-UHFFFAOYSA-L [Na+].[Na+].[S-]SSS[S-] Chemical compound [Na+].[Na+].[S-]SSS[S-] WMEKSYHDIDMJMC-UHFFFAOYSA-L 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 229950005008 abituzumab Drugs 0.000 description 1
• AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 1
• 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 239000000048 adrenergic agonist Substances 0.000 description 1
• NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
• 208000002353 alcoholic hepatitis Diseases 0.000 description 1
• 229960000548 alemtuzumab Drugs 0.000 description 1
• 150000001337 aliphatic alkines Chemical class 0.000 description 1
• 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
• 125000005236 alkanoylamino group Chemical group 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• 125000006177 alkyl benzyl group Chemical group 0.000 description 1
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000003510 anti-fibrotic effect Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 235000009697 arginine Nutrition 0.000 description 1
• 125000005018 aryl alkenyl group Chemical group 0.000 description 1
• 125000001691 aryl alkyl amino group Chemical group 0.000 description 1
• 125000005100 aryl amino carbonyl group Chemical group 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
• 125000005164 aryl thioalkyl group Chemical group 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 229960003852 atezolizumab Drugs 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000007375 bacterial translocation Effects 0.000 description 1
• 210000004082 barrier epithelial cell Anatomy 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• WGNZRLMOMHJUSP-UHFFFAOYSA-N benzotriazol-1-yloxy(tripyrrolidin-1-yl)phosphanium Chemical compound C1CCCN1[P+](N1CCCC1)(N1CCCC1)ON1C2=CC=CC=C2N=N1 WGNZRLMOMHJUSP-UHFFFAOYSA-N 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 210000000013 bile duct Anatomy 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 125000005997 bromomethyl group Chemical group 0.000 description 1
• 238000009933 burial Methods 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 229950000771 carlumab Drugs 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 1
• 229950011033 cenicriviroc Drugs 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 229940124587 cephalosporin Drugs 0.000 description 1
• 150000001780 cephalosporins Chemical class 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• 208000026106 cerebrovascular disease Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 230000035605 chemotaxis Effects 0.000 description 1
• FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
• 229940106681 chloroacetic acid Drugs 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid group Chemical class C(C=CC1=CC=CC=C1)(=O)O WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000013066 combination product Substances 0.000 description 1
• 229940127555 combination product Drugs 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000013093 comparative effectiveness research Methods 0.000 description 1
• 229940127206 compound 14d Drugs 0.000 description 1
• 229940125876 compound 15a Drugs 0.000 description 1
• 230000001010 compromised effect Effects 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 239000013256 coordination polymer Substances 0.000 description 1
• 238000012936 correction and preventive action Methods 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• NVBIDTXRBMYRGD-UHFFFAOYSA-N cubane-1-carboxylic acid Chemical compound C12C3C4C5(C(=O)O)C3C2C5C41 NVBIDTXRBMYRGD-UHFFFAOYSA-N 0.000 description 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229960003834 dapagliflozin Drugs 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 231100000517 death Toxicity 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 239000012024 dehydrating agents‎ Substances 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical compound [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 1
• 239000012954 diazonium Substances 0.000 description 1
• 238000006193 diazotization reaction Methods 0.000 description 1
• IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
• 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 102000038379 digestive enzymes Human genes 0.000 description 1
• 108091007734 digestive enzymes Proteins 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 125000003438 dodecyl group Chemical group [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])* 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 201000008865 drug-induced hepatitis Diseases 0.000 description 1
• 238000002592 echocardiography Methods 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 235000013601 eggs Nutrition 0.000 description 1
• 238000005430 electron energy loss spectroscopy Methods 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000013931 endocrine signaling Effects 0.000 description 1
• 239000002308 endothelin receptor antagonist Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000004890 epithelial barrier function Effects 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
• 239000004210 ether based solvent Substances 0.000 description 1
• 238000006266 etherification reaction Methods 0.000 description 1
• KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 1
• RDULEYWUGKOCMR-UHFFFAOYSA-N ethyl 2-chloro-3-oxobutanoate Chemical compound CCOC(=O)C(Cl)C(C)=O RDULEYWUGKOCMR-UHFFFAOYSA-N 0.000 description 1
• IRMLOWMIVFRAQC-UHFFFAOYSA-N ethyl 3-azidobenzoate Chemical compound CCOC(=O)C1=CC=CC(N=[N+]=[N-])=C1 IRMLOWMIVFRAQC-UHFFFAOYSA-N 0.000 description 1
• NIHIQNLBUIGNSC-UHFFFAOYSA-N ethyl 3-cyano-2,6-difluorobenzoate Chemical compound CCOC(=O)c1c(F)ccc(C#N)c1F NIHIQNLBUIGNSC-UHFFFAOYSA-N 0.000 description 1
• UMBRXUJIZAPOEQ-UHFFFAOYSA-N ethyl 3-cyano-2-fluorobenzoate Chemical compound CCOC(=O)C1=C(F)C(=CC=C1)C#N UMBRXUJIZAPOEQ-UHFFFAOYSA-N 0.000 description 1
• SPGMDXDPJKEDGC-UHFFFAOYSA-N ethyl 4-amino-3-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(N)C(F)=C1 SPGMDXDPJKEDGC-UHFFFAOYSA-N 0.000 description 1
• YJZQRRZEDGIEFC-UHFFFAOYSA-N ethyl 4-cyanopyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC(C#N)=CC=N1 YJZQRRZEDGIEFC-UHFFFAOYSA-N 0.000 description 1
• BCANRKMLDXLWMP-UHFFFAOYSA-N ethyl 5-cyano-2-fluorobenzoate Chemical compound CCOC(=O)C1=CC(C#N)=CC=C1F BCANRKMLDXLWMP-UHFFFAOYSA-N 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• FQYYIPZPELSLDK-UHFFFAOYSA-N ethyl pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=N1 FQYYIPZPELSLDK-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 208000010706 fatty liver disease Diseases 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• DCCSDBARQIPTGU-HSZRJFAPSA-N fesoterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)OC(=O)C(C)C)=CC=CC=C1 DCCSDBARQIPTGU-HSZRJFAPSA-N 0.000 description 1
• 210000003754 fetus Anatomy 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 229940126374 fipaxalparant Drugs 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 229960002714 fluticasone Drugs 0.000 description 1
• MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
• 201000005206 focal segmental glomerulosclerosis Diseases 0.000 description 1
• 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 229950000456 galunisertib Drugs 0.000 description 1
• 229940044627 gamma-interferon Drugs 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 230000014101 glucose homeostasis Effects 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
• 125000004995 haloalkylthio group Chemical group 0.000 description 1
• 125000001475 halogen functional group Chemical group 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• 150000002390 heteroarenes Chemical class 0.000 description 1
• 125000005368 heteroarylthio group Chemical group 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 238000004896 high resolution mass spectrometry Methods 0.000 description 1
• 239000012456 homogeneous solution Substances 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 150000004680 hydrogen peroxides Chemical class 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
• RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 229940045207 immuno-oncology agent Drugs 0.000 description 1
• 239000002584 immunological anticancer agent Substances 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000010952 in-situ formation Methods 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000004941 influx Effects 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000004347 intestinal mucosa Anatomy 0.000 description 1
• 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 150000002497 iodine compounds Chemical class 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 238000001616 ion spectroscopy Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229960005386 ipilimumab Drugs 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 125000004936 isatinoyl group Chemical group N1(C(=O)C(=O)C2=CC=CC=C12)C(=O)* 0.000 description 1
• OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000005438 isoindazolyl group Chemical group 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 208000011379 keloid formation Diseases 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 201000010260 leiomyoma Diseases 0.000 description 1
• 229940065725 leukotriene receptor antagonists for obstructive airway diseases Drugs 0.000 description 1
• 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229960002701 liraglutide Drugs 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 229910001416 lithium ion Inorganic materials 0.000 description 1
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
• 238000012317 liver biopsy Methods 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 231100000835 liver failure Toxicity 0.000 description 1
• 208000007903 liver failure Diseases 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 235000018977 lysine Nutrition 0.000 description 1
• JGCMEBMXRHSZKX-UHFFFAOYSA-N macitentan Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JGCMEBMXRHSZKX-UHFFFAOYSA-N 0.000 description 1
• 229960001039 macitentan Drugs 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 238000004503 metal oxide affinity chromatography Methods 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
• OXQRLBFDJMSRMM-NKWVEPMBSA-N methyl (1s,3r)-3-hydroxycyclohexane-1-carboxylate Chemical compound COC(=O)[C@H]1CCC[C@@H](O)C1 OXQRLBFDJMSRMM-NKWVEPMBSA-N 0.000 description 1
• BYTLJVZXUYVJKN-UHFFFAOYSA-N methyl 1-(hydroxymethyl)bicyclo[1.1.1]pentane-3-carboxylate Chemical compound C1C2(CO)CC1(C(=O)OC)C2 BYTLJVZXUYVJKN-UHFFFAOYSA-N 0.000 description 1
• IVHLOIKNKUXUNU-UHFFFAOYSA-N methyl 1-methylpyrrolo[2,3-b]pyridine-3-carboxylate Chemical compound COC(=O)C1=CN(C2=NC=CC=C21)C IVHLOIKNKUXUNU-UHFFFAOYSA-N 0.000 description 1
• ORVHMLCJEKDDAX-UHFFFAOYSA-N methyl 2-cyanopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C#N)=C1 ORVHMLCJEKDDAX-UHFFFAOYSA-N 0.000 description 1
• NPXOIGSBRLCOSD-UHFFFAOYSA-N methyl 3-iodobenzoate Chemical compound COC(=O)C1=CC=CC(I)=C1 NPXOIGSBRLCOSD-UHFFFAOYSA-N 0.000 description 1
• SMRMKBCUMBETPV-UHFFFAOYSA-N methyl 4-amino-3-(aminomethyl)benzoate dihydrochloride Chemical compound Cl.Cl.COC(=O)c1ccc(N)c(CN)c1 SMRMKBCUMBETPV-UHFFFAOYSA-N 0.000 description 1
• SXCLQFMOKUHRIA-UHFFFAOYSA-N methyl 4-iodobicyclo[2.2.2]octane-1-carboxylate Chemical compound C1CC2(I)CCC1(C(=O)OC)CC2 SXCLQFMOKUHRIA-UHFFFAOYSA-N 0.000 description 1
• RLUVYUFWNPLVPL-UHFFFAOYSA-N methyl 5-cyanopyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(C#N)=C1 RLUVYUFWNPLVPL-UHFFFAOYSA-N 0.000 description 1
• RWTWEJPTYZWMEY-UHFFFAOYSA-N methyl 6-cyanopyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(C#N)=N1 RWTWEJPTYZWMEY-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• OLXYLDUSSBULGU-UHFFFAOYSA-N methyl pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC=C1 OLXYLDUSSBULGU-UHFFFAOYSA-N 0.000 description 1
• XSRWQTDEIOHXSL-UHFFFAOYSA-N methyl quinoline-6-carboxylate Chemical compound N1=CC=CC2=CC(C(=O)OC)=CC=C21 XSRWQTDEIOHXSL-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 244000005706 microflora Species 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 229960005127 montelukast Drugs 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 210000002200 mouth mucosa Anatomy 0.000 description 1
• 230000004682 mucosal barrier function Effects 0.000 description 1
• 239000003149 muscarinic antagonist Substances 0.000 description 1
• 206010028537 myelofibrosis Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 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
• XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• KCXYZMFPZHYUFO-UHFFFAOYSA-N n-methyl-n-phosphanylmethanamine Chemical compound CN(C)P KCXYZMFPZHYUFO-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
• 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 210000002850 nasal mucosa Anatomy 0.000 description 1
• 210000004237 neck muscle Anatomy 0.000 description 1
• 230000001338 necrotic effect Effects 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
• 101150115538 nero gene Proteins 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 1
• XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
• 229960004378 nintedanib Drugs 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 229960003301 nivolumab Drugs 0.000 description 1
• 231100000706 no observed effect level Toxicity 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• PLZZPPHAMDJOSR-UHFFFAOYSA-N nonanenitrile Chemical compound CCCCCCCCC#N PLZZPPHAMDJOSR-UHFFFAOYSA-N 0.000 description 1
• FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
• 238000005016 nuclear Overhauser enhanced spectroscopy Methods 0.000 description 1
• 102000006255 nuclear receptors Human genes 0.000 description 1
• 108020004017 nuclear receptors Proteins 0.000 description 1
• 102000027507 nuclear receptors type II Human genes 0.000 description 1
• 108091008686 nuclear receptors type II Proteins 0.000 description 1
• 238000011330 nucleic acid test Methods 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• 229960002450 ofatumumab Drugs 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 150000002482 oligosaccharides Chemical class 0.000 description 1
• ACSQLTBPYZSGBA-GMXVVIOVSA-N olorinab Chemical compound C([C@@H]1C[C@@H]1C=12)C=1C(C(=O)N[C@H](CO)C(C)(C)C)=NN2C1=C[N+]([O-])=CC=N1 ACSQLTBPYZSGBA-GMXVVIOVSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 1
• 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
• LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
• CNDQSXOVEQXJOE-UHFFFAOYSA-N oxyphenbutazone hydrate Chemical compound O.O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 CNDQSXOVEQXJOE-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 230000014306 paracrine signaling Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 229960002621 pembrolizumab Drugs 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000006611 pharmacological activation Effects 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
• CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
• LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
• ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
• 229960003073 pirfenidone Drugs 0.000 description 1
• 239000011505 plaster Substances 0.000 description 1
• 229920000548 poly(silane) polymer Polymers 0.000 description 1
• 229920001690 polydopamine Polymers 0.000 description 1
• 125000006684 polyhaloalkyl group Polymers 0.000 description 1
• 150000004032 porphyrins Chemical class 0.000 description 1
• 208000007232 portal hypertension Diseases 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 108010042589 prolyl T RNA synthetase Proteins 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• WWABBFPTGJZEDN-UHFFFAOYSA-N quinazoline-6-carboxylic acid Chemical compound N1=CN=CC2=CC(C(=O)O)=CC=C21 WWABBFPTGJZEDN-UHFFFAOYSA-N 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 238000007347 radical substitution reaction Methods 0.000 description 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
• 230000007420 reactivation Effects 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 108091006082 receptor inhibitors Proteins 0.000 description 1
• 231100000272 reduced body weight Toxicity 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001172 regenerating effect Effects 0.000 description 1
• RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
• 229940126844 remogliflozin Drugs 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 1
• 238000002390 rotary evaporation Methods 0.000 description 1
• 229960002052 salbutamol Drugs 0.000 description 1
• 229960004017 salmeterol Drugs 0.000 description 1
• MRWFZSLZNUJVQW-DEOSSOPVSA-N saroglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCN1C(C=2C=CC(SC)=CC=2)=CC=C1C MRWFZSLZNUJVQW-DEOSSOPVSA-N 0.000 description 1
• 229950006544 saroglitazar Drugs 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 150000003334 secondary amides Chemical class 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 229950011186 semaglutide Drugs 0.000 description 1
• 108010060325 semaglutide Proteins 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• RGYQPQARIQKJKH-UHFFFAOYSA-N setanaxib Chemical compound CN(C)C1=CC=CC(C2=C3C(=O)N(C=4C(=CC=CC=4)Cl)NC3=CC(=O)N2C)=C1 RGYQPQARIQKJKH-UHFFFAOYSA-N 0.000 description 1
• 229910000077 silane Inorganic materials 0.000 description 1
• 229960003310 sildenafil Drugs 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 229910001961 silver nitrate Inorganic materials 0.000 description 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
• 229960002218 sodium chlorite Drugs 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• JEZLFWXSKCTMPN-ILCIQDJASA-M sodium;2-[(2s,3r,4e,6e,10e,12s)-13-(4-fluorophenoxy)-2,3,12-trihydroxytrideca-4,6,10-trien-8-ynoxy]acetate Chemical compound [Na+].[O-]C(=O)COC[C@H](O)[C@H](O)/C=C/C=C/C#C/C=C/[C@H](O)COC1=CC=C(F)C=C1 JEZLFWXSKCTMPN-ILCIQDJASA-M 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 238000007614 solvation Methods 0.000 description 1
• 206010062261 spinal cord neoplasm Diseases 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000002466 tachykinin receptor agonist Substances 0.000 description 1
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
• 229960001967 tacrolimus Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960003080 taurine Drugs 0.000 description 1
• AMTJCHSHZCTCIP-UHFFFAOYSA-N tert-butyl 4-amino-3-fluoro-5-sulfanylbenzoate Chemical compound NC1=C(C=C(C(=O)OC(C)(C)C)C=C1S)F AMTJCHSHZCTCIP-UHFFFAOYSA-N 0.000 description 1
• FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
• RLCSLTZMOWQOAA-UHFFFAOYSA-N tert-butyl n,n-di(propan-2-yl)carbamimidate Chemical compound CC(C)N(C(C)C)C(=N)OC(C)(C)C RLCSLTZMOWQOAA-UHFFFAOYSA-N 0.000 description 1
• 150000003511 tertiary amides Chemical class 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
• 150000003555 thioacetals Chemical class 0.000 description 1
• 125000005309 thioalkoxy group Chemical group 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• 125000005403 thiohaloalkoxy group Chemical group 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
• 229940110309 tiotropium Drugs 0.000 description 1
• 229950004996 tipelukast Drugs 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 229950000835 tralokinumab Drugs 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000012250 transgenic expression Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 229960005294 triamcinolone Drugs 0.000 description 1
• GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical group CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
• ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
• BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
• TVLNGWSWPKIYAO-UHFFFAOYSA-N tris(2-diphenylphosphanylethyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(CCP(C=1C=CC=CC=1)C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 TVLNGWSWPKIYAO-UHFFFAOYSA-N 0.000 description 1
• SCHZCUMIENIQMY-UHFFFAOYSA-N tris(trimethylsilyl)silicon Chemical compound C[Si](C)(C)[Si]([Si](C)(C)C)[Si](C)(C)C SCHZCUMIENIQMY-UHFFFAOYSA-N 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
• REQQVBGILUTQNN-UHFFFAOYSA-N ziritaxestat Chemical compound CCC=1N=C2C(C)=CC(N3CCN(CC(=O)N4CC(O)C4)CC3)=CN2C=1N(C)C(SC=1C#N)=NC=1C1=CC=C(F)C=C1 REQQVBGILUTQNN-UHFFFAOYSA-N 0.000 description 1