WO2004058164A2 - Asthma and allergic inflammation modulators - Google Patents
Asthma and allergic inflammation modulators Download PDFInfo
- Publication number
- WO2004058164A2 WO2004058164A2 PCT/US2003/040617 US0340617W WO2004058164A2 WO 2004058164 A2 WO2004058164 A2 WO 2004058164A2 US 0340617 W US0340617 W US 0340617W WO 2004058164 A2 WO2004058164 A2 WO 2004058164A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- group
- aryl
- nrr
- compound
- Prior art date
Links
- 208000006673 asthma Diseases 0.000 title claims description 25
- 230000009285 allergic inflammation Effects 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 93
- 238000000034 method Methods 0.000 claims abstract description 72
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 15
- 201000011510 cancer Diseases 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 298
- 125000003118 aryl group Chemical group 0.000 claims description 150
- 125000005842 heteroatom Chemical group 0.000 claims description 122
- -1 -NRR" Chemical group 0.000 claims description 105
- 108050000258 Prostaglandin D receptors Proteins 0.000 claims description 97
- 102000009389 Prostaglandin D receptors Human genes 0.000 claims description 97
- 229910052739 hydrogen Inorganic materials 0.000 claims description 83
- 239000001257 hydrogen Substances 0.000 claims description 82
- 125000001072 heteroaryl group Chemical group 0.000 claims description 76
- 102000005962 receptors Human genes 0.000 claims description 72
- 108020003175 receptors Proteins 0.000 claims description 72
- 229910052717 sulfur Inorganic materials 0.000 claims description 63
- 229910052760 oxygen Inorganic materials 0.000 claims description 62
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 47
- 125000001153 fluoro group Chemical group F* 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000002947 alkylene group Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 229940002612 prodrug Drugs 0.000 claims description 23
- 239000000651 prodrug Substances 0.000 claims description 23
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 claims description 23
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 13
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 12
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 12
- 230000004054 inflammatory process Effects 0.000 claims description 12
- 229910052701 rubidium Inorganic materials 0.000 claims description 12
- 201000004624 Dermatitis Diseases 0.000 claims description 11
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 11
- 206010037660 Pyrexia Diseases 0.000 claims description 11
- 206010052779 Transplant rejections Diseases 0.000 claims description 11
- 208000036142 Viral infection Diseases 0.000 claims description 11
- 201000008937 atopic dermatitis Diseases 0.000 claims description 11
- 208000010668 atopic eczema Diseases 0.000 claims description 11
- 201000006417 multiple sclerosis Diseases 0.000 claims description 11
- 230000036407 pain Effects 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 230000009385 viral infection Effects 0.000 claims description 11
- 201000001320 Atherosclerosis Diseases 0.000 claims description 10
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 10
- 208000011231 Crohn disease Diseases 0.000 claims description 10
- 206010016654 Fibrosis Diseases 0.000 claims description 10
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 10
- 206010028735 Nasal congestion Diseases 0.000 claims description 10
- 201000004681 Psoriasis Diseases 0.000 claims description 10
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 10
- 206010040047 Sepsis Diseases 0.000 claims description 10
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 10
- 201000010105 allergic rhinitis Diseases 0.000 claims description 10
- 230000004761 fibrosis Effects 0.000 claims description 10
- 238000011010 flushing procedure Methods 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 10
- 206010010741 Conjunctivitis Diseases 0.000 claims description 9
- 208000007536 Thrombosis Diseases 0.000 claims description 9
- 239000005557 antagonist Substances 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 229940124597 therapeutic agent Drugs 0.000 claims description 9
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 208000000094 Chronic Pain Diseases 0.000 claims description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 7
- 206010052568 Urticaria chronic Diseases 0.000 claims description 7
- 201000005547 chronic conjunctivitis Diseases 0.000 claims description 7
- 208000037976 chronic inflammation Diseases 0.000 claims description 7
- 208000024376 chronic urticaria Diseases 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000003003 spiro group Chemical group 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 239000003246 corticosteroid Substances 0.000 claims description 5
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 4
- 208000024780 Urticaria Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- 229940124003 CRTH2 antagonist Drugs 0.000 claims description 3
- 208000019693 Lung disease Diseases 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229960000265 cromoglicic acid Drugs 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 2
- 229940124748 beta 2 agonist Drugs 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 2
- 150000001555 benzenes Chemical group 0.000 claims 6
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 230000001387 anti-histamine Effects 0.000 claims 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 abstract description 14
- 102000004169 proteins and genes Human genes 0.000 abstract description 13
- 230000002757 inflammatory effect Effects 0.000 abstract description 12
- 230000004968 inflammatory condition Effects 0.000 abstract description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 2
- 208000012657 Atopic disease Diseases 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 79
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- 238000005481 NMR spectroscopy Methods 0.000 description 64
- 238000005160 1H NMR spectroscopy Methods 0.000 description 59
- 208000035475 disorder Diseases 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 43
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- 230000001404 mediated effect Effects 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 25
- 239000000243 solution Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 18
- 0 CS(NC(*)=O)(=O)=O Chemical compound CS(NC(*)=O)(=O)=O 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 208000026935 allergic disease Diseases 0.000 description 13
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000004913 activation Effects 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 125000004404 heteroalkyl group Chemical group 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000005714 functional activity Effects 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 230000003834 intracellular effect Effects 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000000132 electrospray ionisation Methods 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 229960003424 phenylacetic acid Drugs 0.000 description 8
- 239000003279 phenylacetic acid Substances 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- VDLXOPFPGXYGKI-UHFFFAOYSA-N 2-[4-[2-[(4-methylphenyl)sulfonylamino]-4-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC(C(F)(F)F)=CC=C1OC1=CC=C(CC(O)=O)C=C1 VDLXOPFPGXYGKI-UHFFFAOYSA-N 0.000 description 7
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 210000001772 blood platelet Anatomy 0.000 description 7
- 238000000423 cell based assay Methods 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- FDTPBIKNYWQLAE-UHFFFAOYSA-N 2,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C(Cl)=C1 FDTPBIKNYWQLAE-UHFFFAOYSA-N 0.000 description 6
- TZHCBFDHJDEEOS-UHFFFAOYSA-N 2-[3-hydroxy-5-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC(O)=CC(C(F)(F)F)=C1 TZHCBFDHJDEEOS-UHFFFAOYSA-N 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 210000003979 eosinophil Anatomy 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 208000026278 immune system disease Diseases 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 230000036642 wellbeing Effects 0.000 description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 5
- 210000004241 Th2 cell Anatomy 0.000 description 5
- 210000003651 basophil Anatomy 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- NPXHLFIFZGWRKS-UHFFFAOYSA-N 2-[3-chloro-5-[4-(ethylcarbamoyl)-2-nitrophenoxy]phenyl]acetic acid Chemical compound [O-][N+](=O)C1=CC(C(=O)NCC)=CC=C1OC1=CC(Cl)=CC(CC(O)=O)=C1 NPXHLFIFZGWRKS-UHFFFAOYSA-N 0.000 description 4
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- 238000010256 biochemical assay Methods 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- ZQYLDVNTWDEAJI-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C=C1 ZQYLDVNTWDEAJI-UHFFFAOYSA-N 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- FJSAJUXIHJIAMD-UHFFFAOYSA-N 2,4-difluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C(F)=C1 FJSAJUXIHJIAMD-UHFFFAOYSA-N 0.000 description 3
- YVKIWFSALXZQGO-UHFFFAOYSA-N 2-[3-[2-(benzenesulfonamido)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC=2C(=CC=CC=2)NS(=O)(=O)C=2C=CC=CC=2)=C1 YVKIWFSALXZQGO-UHFFFAOYSA-N 0.000 description 3
- BVUKSULCIKOIED-UHFFFAOYSA-N 2-[3-[2-[(4-chlorophenyl)sulfonylamino]-4-(ethylcarbamoyl)phenoxy]-5-(trifluoromethyl)phenyl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC(CC(O)=O)=CC(C(F)(F)F)=C1 BVUKSULCIKOIED-UHFFFAOYSA-N 0.000 description 3
- GHPDDKBYMSSDNI-IBGZPJMESA-N 2-[3-[2-[(4-chlorophenyl)sulfonylamino]-4-[[(1s)-1-phenylethyl]carbamoylamino]phenoxy]phenyl]acetic acid Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)NC(C=C1NS(=O)(=O)C=2C=CC(Cl)=CC=2)=CC=C1OC1=CC=CC(CC(O)=O)=C1 GHPDDKBYMSSDNI-IBGZPJMESA-N 0.000 description 3
- MLJXSSQLUGGNKC-UHFFFAOYSA-N 2-[3-[2-[[benzyl(methyl)carbamoyl]amino]-4-(ethylcarbamoyl)phenoxy]-4-methoxyphenyl]acetic acid Chemical compound C=1C=CC=CC=1CN(C)C(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC(CC(O)=O)=CC=C1OC MLJXSSQLUGGNKC-UHFFFAOYSA-N 0.000 description 3
- MPZYHKMDSLEXKK-UHFFFAOYSA-N 2-[3-[4-(carbamoylamino)-2-[(4-chlorophenyl)sulfonylamino]phenoxy]phenyl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)NC1=CC(NC(=O)N)=CC=C1OC1=CC=CC(CC(O)=O)=C1 MPZYHKMDSLEXKK-UHFFFAOYSA-N 0.000 description 3
- KGARLEPVGMQGIW-UHFFFAOYSA-N 2-[3-[4-(ethylcarbamoyl)-2-[(4-methoxyphenyl)sulfonylamino]phenoxy]-5-(trifluoromethyl)phenyl]acetic acid Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC(CC(O)=O)=CC(C(F)(F)F)=C1 KGARLEPVGMQGIW-UHFFFAOYSA-N 0.000 description 3
- SMYWRLYBUQQURL-UHFFFAOYSA-N 2-[3-[4-(ethylcarbamoyl)-2-[(4-methylphenyl)sulfonylamino]phenoxy]-5-(trifluoromethyl)phenyl]acetic acid Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC(CC(O)=O)=CC(C(F)(F)F)=C1 SMYWRLYBUQQURL-UHFFFAOYSA-N 0.000 description 3
- SGGGHTSFSWEZKS-UHFFFAOYSA-N 2-[3-[4-acetyl-2-(benzenesulfonamido)phenoxy]phenyl]acetic acid Chemical compound C=1C=CC=CC=1S(=O)(=O)NC1=CC(C(=O)C)=CC=C1OC1=CC=CC(CC(O)=O)=C1 SGGGHTSFSWEZKS-UHFFFAOYSA-N 0.000 description 3
- KJAGTNQZIYPSQP-UHFFFAOYSA-N 2-[3-[4-amino-2-[(4-chlorophenyl)sulfonylamino]phenoxy]phenyl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)NC1=CC(N)=CC=C1OC1=CC=CC(CC(O)=O)=C1 KJAGTNQZIYPSQP-UHFFFAOYSA-N 0.000 description 3
- RADNEWAUYSBPJJ-UHFFFAOYSA-N 2-[3-chloro-4-[4-(ethylcarbamoyl)-2-[(4-methoxyphenyl)sulfonylamino]phenoxy]phenyl]acetic acid Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC=C(CC(O)=O)C=C1Cl RADNEWAUYSBPJJ-UHFFFAOYSA-N 0.000 description 3
- ANDJCIHHMAGZBQ-UHFFFAOYSA-N 2-[4-[2-(naphthalen-1-ylsulfonylamino)-4-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC1=CC=C(C(F)(F)F)C=C1NS(=O)(=O)C1=CC=CC2=CC=CC=C12 ANDJCIHHMAGZBQ-UHFFFAOYSA-N 0.000 description 3
- NDSIIQAYWBAQIS-UHFFFAOYSA-N 2-[4-[2-[(2,4-dichlorophenyl)sulfonyl-methylamino]-4-(ethylcarbamoyl)phenoxy]phenyl]acetic acid Chemical compound C=1C=C(Cl)C=C(Cl)C=1S(=O)(=O)N(C)C1=CC(C(=O)NCC)=CC=C1OC1=CC=C(CC(O)=O)C=C1 NDSIIQAYWBAQIS-UHFFFAOYSA-N 0.000 description 3
- PHVAWXPVFMKPON-UHFFFAOYSA-N 2-[4-[2-[(2,4-dichlorophenyl)sulfonylamino]-4-(ethylcarbamoyl)phenoxy]-3-methoxyphenyl]acetic acid Chemical compound C=1C=C(Cl)C=C(Cl)C=1S(=O)(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC=C(CC(O)=O)C=C1OC PHVAWXPVFMKPON-UHFFFAOYSA-N 0.000 description 3
- KZNRDJGCOWVIGD-UHFFFAOYSA-N 2-[4-[2-benzamido-4-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC1=CC=C(C(F)(F)F)C=C1NC(=O)C1=CC=CC=C1 KZNRDJGCOWVIGD-UHFFFAOYSA-N 0.000 description 3
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 3
- JSMPMXPYSGMTCO-UHFFFAOYSA-N 3-(benzenesulfonamido)-4-[4-(carboxymethyl)phenoxy]benzoic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC1=CC=C(C(O)=O)C=C1NS(=O)(=O)C1=CC=CC=C1 JSMPMXPYSGMTCO-UHFFFAOYSA-N 0.000 description 3
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- 108090000467 Interferon-beta Proteins 0.000 description 3
- 102000003996 Interferon-beta Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100024218 Prostaglandin D2 receptor 2 Human genes 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical compound C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- XOSOWNTVRUKHIZ-UHFFFAOYSA-N ethyl 2-[3-(2-nitrophenoxy)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(OC=2C(=CC=CC=2)[N+]([O-])=O)=C1 XOSOWNTVRUKHIZ-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 210000003630 histaminocyte Anatomy 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 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 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 102000017953 prostanoid receptors Human genes 0.000 description 3
- 108050007059 prostanoid receptors Proteins 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 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 3
- 210000003491 skin Anatomy 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 229960001967 tacrolimus Drugs 0.000 description 3
- 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 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- 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 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- VSRXYLYXIXYEST-KZTWKYQFSA-N 13,14-dihydro-15-ketoprostaglandin D2 Chemical compound CCCCCC(=O)CC[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O VSRXYLYXIXYEST-KZTWKYQFSA-N 0.000 description 2
- BDIRHVVIIRHCHB-UHFFFAOYSA-N 2-[3-(2-amino-4-nitrophenoxy)phenyl]acetic acid Chemical compound NC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC(CC(O)=O)=C1 BDIRHVVIIRHCHB-UHFFFAOYSA-N 0.000 description 2
- YGAIRJMNDPNYCC-UHFFFAOYSA-N 2-[3-[2-[(4-chlorophenyl)sulfonylamino]-4-nitrophenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC=2C(=CC(=CC=2)[N+]([O-])=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 YGAIRJMNDPNYCC-UHFFFAOYSA-N 0.000 description 2
- UCCIMWFNUYIQRI-UHFFFAOYSA-N 2-[3-[4-(ethylcarbamoyl)-2-nitrophenoxy]phenyl]acetic acid Chemical compound [O-][N+](=O)C1=CC(C(=O)NCC)=CC=C1OC1=CC=CC(CC(O)=O)=C1 UCCIMWFNUYIQRI-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FVMDYYGIDFPZAX-UHFFFAOYSA-N 3-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=CC(O)=C1 FVMDYYGIDFPZAX-UHFFFAOYSA-N 0.000 description 2
- IWLGXPWQZDOMSB-UHFFFAOYSA-N 4-chloro-3-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC(C(Cl)=O)=CC=C1Cl IWLGXPWQZDOMSB-UHFFFAOYSA-N 0.000 description 2
- NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 2
- BPMFPOGUJAAYHL-UHFFFAOYSA-N 9H-Pyrido[2,3-b]indole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=N1 BPMFPOGUJAAYHL-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 108010008165 Etanercept Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- 239000000006 Nitroglycerin Substances 0.000 description 2
- MITFXPHMIHQXPI-UHFFFAOYSA-N Oraflex Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 229910002666 PdCl2 Inorganic materials 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 229910006124 SOCl2 Inorganic materials 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 2
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- ZZHLYYDVIOPZBE-UHFFFAOYSA-N Trimeprazine Chemical compound C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 ZZHLYYDVIOPZBE-UHFFFAOYSA-N 0.000 description 2
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 208000037883 airway inflammation Diseases 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003491 cAMP production Effects 0.000 description 2
- 230000001275 ca(2+)-mobilization Effects 0.000 description 2
- 229960002882 calcipotriol Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 229940095074 cyclic amp Drugs 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- NSQBADKMIYCCSC-UHFFFAOYSA-N ethyl 2-(3-hydroxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(O)=C1 NSQBADKMIYCCSC-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- HQMNCQVAMBCHCO-DJRRULDNSA-N etretinate Chemical compound CCOC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C=C(OC)C(C)=C1C HQMNCQVAMBCHCO-DJRRULDNSA-N 0.000 description 2
- 229960002199 etretinate Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 2
- 101710108492 fMet-Leu-Phe receptor Proteins 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229960003711 glyceryl trinitrate Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000013537 high throughput screening Methods 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 210000001821 langerhans cell Anatomy 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- CYTXEYOPTVLMHF-UHFFFAOYSA-N methyl 2-[4-[2-[(4-methylphenyl)sulfonylamino]-4-(trifluoromethyl)phenoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OC1=CC=C(C(F)(F)F)C=C1NS(=O)(=O)C1=CC=C(C)C=C1 CYTXEYOPTVLMHF-UHFFFAOYSA-N 0.000 description 2
- ZZINCNMJRZHIMH-UHFFFAOYSA-N methyl 2-[4-[2-amino-4-(trifluoromethyl)phenoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OC1=CC=C(C(F)(F)F)C=C1N ZZINCNMJRZHIMH-UHFFFAOYSA-N 0.000 description 2
- HDLMKVVRSHLRIX-UHFFFAOYSA-N methyl 2-[4-[2-nitro-4-(trifluoromethyl)phenoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OC1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O HDLMKVVRSHLRIX-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 229960005127 montelukast Drugs 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
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 125000001151 peptidyl group Chemical group 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 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 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229910052702 rhenium Inorganic materials 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003746 solid phase reaction Methods 0.000 description 2
- 238000010671 solid-state reaction Methods 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 2
- 229960001641 troglitazone Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- GUHPRPJDBZHYCJ-SECBINFHSA-N (2s)-2-(5-benzoylthiophen-2-yl)propanoic acid Chemical compound S1C([C@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CC=C1 GUHPRPJDBZHYCJ-SECBINFHSA-N 0.000 description 1
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- PZIFPMYXXCAOCC-JWQCQUIFSA-N (2s,3r)-3-(2-carboxyethylsulfanyl)-2-hydroxy-3-[2-(8-phenyloctyl)phenyl]propanoic acid Chemical compound OC(=O)CCS[C@@H]([C@@H](O)C(O)=O)C1=CC=CC=C1CCCCCCCCC1=CC=CC=C1 PZIFPMYXXCAOCC-JWQCQUIFSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 1
- LENAVORGWBTPJR-UHFFFAOYSA-N (5-pyridin-3-ylfuran-2-yl)methanamine Chemical compound O1C(CN)=CC=C1C1=CC=CN=C1 LENAVORGWBTPJR-UHFFFAOYSA-N 0.000 description 1
- RWIUTHWKQHRQNP-ZDVGBALWSA-N (9e,12e)-n-(1-phenylethyl)octadeca-9,12-dienamide Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)NC(C)C1=CC=CC=C1 RWIUTHWKQHRQNP-ZDVGBALWSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- QUGBPWLPAUHDTI-PLGLXCLHSA-N (z)-7-[(1r,2e,5s)-5-hydroxy-2-[(e)-oct-2-enylidene]-3-oxocyclopentyl]hept-5-enoic acid Chemical compound CCCCC\C=C\C=C1/[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O QUGBPWLPAUHDTI-PLGLXCLHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- HLDFCCHSOZWKAA-UHFFFAOYSA-N 1-fluoro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1F HLDFCCHSOZWKAA-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 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
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- WGGKQIKICKLWGN-UHFFFAOYSA-N 2,6-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC(Cl)=C1S(Cl)(=O)=O WGGKQIKICKLWGN-UHFFFAOYSA-N 0.000 description 1
- KLIVRBFRQSOGQI-UHFFFAOYSA-N 2-(11-oxo-6h-benzo[c][1]benzothiepin-3-yl)acetic acid Chemical compound S1CC2=CC=CC=C2C(=O)C2=CC=C(CC(=O)O)C=C12 KLIVRBFRQSOGQI-UHFFFAOYSA-N 0.000 description 1
- MYQXHLQMZLTSDB-UHFFFAOYSA-N 2-(2-ethyl-2,3-dihydro-1-benzofuran-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2OC(CC)CC2=C1 MYQXHLQMZLTSDB-UHFFFAOYSA-N 0.000 description 1
- OKNQVVFOZSGKGQ-UHFFFAOYSA-N 2-(3-chloro-5-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC(O)=CC(Cl)=C1 OKNQVVFOZSGKGQ-UHFFFAOYSA-N 0.000 description 1
- NREQDYYHKLEOPH-UHFFFAOYSA-N 2-(3-chloro-5-methoxyphenyl)acetonitrile Chemical compound COC1=CC(Cl)=CC(CC#N)=C1 NREQDYYHKLEOPH-UHFFFAOYSA-N 0.000 description 1
- DCXHLPGLBYHNMU-UHFFFAOYSA-N 2-[1-(4-azidobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(N=[N+]=[N-])C=C1 DCXHLPGLBYHNMU-UHFFFAOYSA-N 0.000 description 1
- APBSKHYXXKHJFK-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(C=2C=CC(Cl)=CC=2)=N1 APBSKHYXXKHJFK-UHFFFAOYSA-N 0.000 description 1
- ZLGFSUNYGJVNQU-UHFFFAOYSA-N 2-[3-[2-(benzenesulfonamido)-4-benzoylphenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC=2C(=CC(=CC=2)C(=O)C=2C=CC=CC=2)NS(=O)(=O)C=2C=CC=CC=2)=C1 ZLGFSUNYGJVNQU-UHFFFAOYSA-N 0.000 description 1
- MYRIXKLAPMTTFW-UHFFFAOYSA-N 2-[3-[2-(benzenesulfonamido)-4-carbamoylphenoxy]phenyl]acetic acid Chemical compound C=1C=CC=CC=1S(=O)(=O)NC1=CC(C(=O)N)=CC=C1OC1=CC=CC(CC(O)=O)=C1 MYRIXKLAPMTTFW-UHFFFAOYSA-N 0.000 description 1
- SBVYTWNHKAGTKI-UHFFFAOYSA-N 2-[3-[2-(benzenesulfonamido)-4-methoxyphenoxy]phenyl]acetic acid Chemical compound C=1C=CC=CC=1S(=O)(=O)NC1=CC(OC)=CC=C1OC1=CC=CC(CC(O)=O)=C1 SBVYTWNHKAGTKI-UHFFFAOYSA-N 0.000 description 1
- MOPXRLKDQNFEHT-UHFFFAOYSA-N 2-[3-[2-[(2,4-dichlorophenyl)sulfonylamino]phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC=2C(=CC=CC=2)NS(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1 MOPXRLKDQNFEHT-UHFFFAOYSA-N 0.000 description 1
- HEWKSTAYEJUQTF-UHFFFAOYSA-N 2-[3-[2-amino-4-(ethylcarbamoyl)phenoxy]phenyl]acetic acid Chemical compound NC1=CC(C(=O)NCC)=CC=C1OC1=CC=CC(CC(O)=O)=C1 HEWKSTAYEJUQTF-UHFFFAOYSA-N 0.000 description 1
- DTYXSDFGSKPRCZ-UHFFFAOYSA-N 2-[3-[4-(ethylcarbamoyl)-2-(propan-2-yloxycarbonylamino)phenoxy]-4-methoxyphenyl]acetic acid Chemical compound CC(C)OC(=O)NC1=CC(C(=O)NCC)=CC=C1OC1=CC(CC(O)=O)=CC=C1OC DTYXSDFGSKPRCZ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- TYCOFFBAZNSQOJ-UHFFFAOYSA-N 2-[4-(3-fluorophenyl)phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC(F)=C1 TYCOFFBAZNSQOJ-UHFFFAOYSA-N 0.000 description 1
- JIEKMACRVQTPRC-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-2-phenyl-5-thiazolyl]acetic acid Chemical compound OC(=O)CC=1SC(C=2C=CC=CC=2)=NC=1C1=CC=C(Cl)C=C1 JIEKMACRVQTPRC-UHFFFAOYSA-N 0.000 description 1
- WGDADRBTCPGSDG-UHFFFAOYSA-N 2-[[4,5-bis(4-chlorophenyl)-1,3-oxazol-2-yl]sulfanyl]propanoic acid Chemical compound O1C(SC(C)C(O)=O)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=C(Cl)C=C1 WGDADRBTCPGSDG-UHFFFAOYSA-N 0.000 description 1
- BCSHRERPHLTPEE-NRFANRHFSA-N 2-[[5-chloro-2-[[(6s)-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methoxy-6,7,8,9-tetrahydro-5h-benzo[7]annulen-2-yl]amino]pyrimidin-4-yl]amino]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NC1=NC(NC=2C(=C3CCC[C@@H](CC3=CC=2)N2CCN(CCO)CC2)OC)=NC=C1Cl BCSHRERPHLTPEE-NRFANRHFSA-N 0.000 description 1
- XKSAJZSJKURQRX-UHFFFAOYSA-N 2-acetyloxy-5-(4-fluorophenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC(=O)C)=CC=C1C1=CC=C(F)C=C1 XKSAJZSJKURQRX-UHFFFAOYSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- KMVZDSQHLDGKGV-UHFFFAOYSA-N 2-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC=C1S(Cl)(=O)=O KMVZDSQHLDGKGV-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical class OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=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
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- VRGCYEIGVVTZCC-UHFFFAOYSA-N 3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione Chemical compound ClC1=C(Cl)C(=O)C(=O)C(Cl)=C1Cl VRGCYEIGVVTZCC-UHFFFAOYSA-N 0.000 description 1
- NYIBPWGZGSXURD-UHFFFAOYSA-N 3,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1Cl NYIBPWGZGSXURD-UHFFFAOYSA-N 0.000 description 1
- CXKCZFDUOYMOOP-UHFFFAOYSA-N 3,5-dichlorobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC(Cl)=C1 CXKCZFDUOYMOOP-UHFFFAOYSA-N 0.000 description 1
- GZLPFEYTAAXJCP-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-sulfonyl chloride Chemical group CC1=NOC(C)=C1S(Cl)(=O)=O GZLPFEYTAAXJCP-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- OINWZUJVEXUHCC-UHFFFAOYSA-N 3-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC(S(Cl)(=O)=O)=C1 OINWZUJVEXUHCC-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])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
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- SYCHUQUJURZQMO-UHFFFAOYSA-N 4-hydroxy-2-methyl-1,1-dioxo-n-(1,3-thiazol-2-yl)-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 SYCHUQUJURZQMO-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 1
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- RDMFHRSPDKWERA-UHFFFAOYSA-N 5H-Pyrido[4,3-b]indole Chemical compound C1=NC=C2C3=CC=CC=C3NC2=C1 RDMFHRSPDKWERA-UHFFFAOYSA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- IXJCHVMUTFCRBH-SDUHDBOFSA-N 7-[(1r,2s,3e,5z)-10-(4-acetyl-3-hydroxy-2-propylphenoxy)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]deca-3,5-dien-2-yl]sulfanyl-4-oxochromene-2-carboxylic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCC\C=C/C=C/[C@@H]([C@H](O)C=1C=C(C=CC=1)C(F)(F)F)SC1=CC=C2C(=O)C=C(C(O)=O)OC2=C1 IXJCHVMUTFCRBH-SDUHDBOFSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 206010058284 Allergy to arthropod sting Diseases 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 108010058207 Anistreplase Proteins 0.000 description 1
- 241000952610 Aphis glycines Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- XHVAWZZCDCWGBK-WYRLRVFGSA-M Aurothioglucose Chemical compound OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O XHVAWZZCDCWGBK-WYRLRVFGSA-M 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 208000027496 Behcet disease Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- ZBJJDYGJCNTNTH-UHFFFAOYSA-N Betahistine mesilate Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.CNCCC1=CC=CC=N1 ZBJJDYGJCNTNTH-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 206010048396 Bone marrow transplant rejection Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- PJFHZKIDENOSJB-UHFFFAOYSA-N Budesonide/formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1.C1CC2=CC(=O)C=CC2(C)C2C1C1CC3OC(CCC)OC3(C(=O)CO)C1(C)CC2O PJFHZKIDENOSJB-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- VMAQYKGITHDWKL-UHFFFAOYSA-N CC(C(N1)=O)NC1=O Chemical compound CC(C(N1)=O)NC1=O VMAQYKGITHDWKL-UHFFFAOYSA-N 0.000 description 1
- PTXFGUVCXVEZET-UHFFFAOYSA-N CC(C(N1)=O)SC1=O Chemical compound CC(C(N1)=O)SC1=O PTXFGUVCXVEZET-UHFFFAOYSA-N 0.000 description 1
- XGTDJPMYWQNDCS-UHFFFAOYSA-N CCCc1n[s]nc1O Chemical compound CCCc1n[s]nc1O XGTDJPMYWQNDCS-UHFFFAOYSA-N 0.000 description 1
- MRZQXGKQQGJPHO-UHFFFAOYSA-N CCNC(C(C1)C=CC(OC2C=CC=C(CC(O)O)C2)=C1NC(c1c2NCC=Cc2ccc1)=O)=O Chemical compound CCNC(C(C1)C=CC(OC2C=CC=C(CC(O)O)C2)=C1NC(c1c2NCC=Cc2ccc1)=O)=O MRZQXGKQQGJPHO-UHFFFAOYSA-N 0.000 description 1
- JRLPEMVDPFPYPJ-UHFFFAOYSA-N CCc1ccc(C)cc1 Chemical compound CCc1ccc(C)cc1 JRLPEMVDPFPYPJ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N Cc1c(C)cccc1 Chemical compound Cc1c(C)cccc1 CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- KGVPNLBXJKTABS-UHFFFAOYSA-N Cc1cc(O)n[o]1 Chemical compound Cc1cc(O)n[o]1 KGVPNLBXJKTABS-UHFFFAOYSA-N 0.000 description 1
- WGVHNCAJPFIFCR-UHFFFAOYSA-N Cc1n[nH]c(O)c1 Chemical compound Cc1n[nH]c(O)c1 WGVHNCAJPFIFCR-UHFFFAOYSA-N 0.000 description 1
- CPWLODRXTMANAL-UHFFFAOYSA-N Cc1n[o]c(O)c1 Chemical compound Cc1n[o]c(O)c1 CPWLODRXTMANAL-UHFFFAOYSA-N 0.000 description 1
- PZKFSRWSQOQYNR-UHFFFAOYSA-N Cc1ncn[nH]1 Chemical compound Cc1ncn[nH]1 PZKFSRWSQOQYNR-UHFFFAOYSA-N 0.000 description 1
- XZGLNCKSNVGDNX-UHFFFAOYSA-N Cc1nnn[nH]1 Chemical compound Cc1nnn[nH]1 XZGLNCKSNVGDNX-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- OIRAEJWYWSAQNG-UHFFFAOYSA-N Clidanac Chemical compound ClC=1C=C2C(C(=O)O)CCC2=CC=1C1CCCCC1 OIRAEJWYWSAQNG-UHFFFAOYSA-N 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010056489 Coronary artery restenosis Diseases 0.000 description 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 230000000970 DNA cross-linking effect Effects 0.000 description 1
- 239000012625 DNA intercalator Substances 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010013700 Drug hypersensitivity Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- HUDBDWIQSIGUDI-UHFFFAOYSA-N Ethyl 3-indoleacetate Chemical compound C1=CC=C2C(CC(=O)OCC)=CNC2=C1 HUDBDWIQSIGUDI-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- RBBWCVQDXDFISW-UHFFFAOYSA-N Feprazone Chemical compound O=C1C(CC=C(C)C)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 RBBWCVQDXDFISW-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229940123414 Folate antagonist Drugs 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 108010072051 Glatiramer Acetate Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 101001117314 Homo sapiens Prostaglandin D2 receptor 2 Proteins 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 102000002284 Hydroxymethylglutaryl-CoA Synthase Human genes 0.000 description 1
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 108010005716 Interferon beta-1a Proteins 0.000 description 1
- 108010005714 Interferon beta-1b Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- HUYWAWARQUIQLE-UHFFFAOYSA-N Isoetharine Chemical compound CC(C)NC(CC)C(O)C1=CC=C(O)C(O)=C1 HUYWAWARQUIQLE-UHFFFAOYSA-N 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- RTGDFNSFWBGLEC-UHFFFAOYSA-N Mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1CC=C(C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-UHFFFAOYSA-N 0.000 description 1
- IJHNSHDBIRRJRN-UHFFFAOYSA-N N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=CC=C1 IJHNSHDBIRRJRN-UHFFFAOYSA-N 0.000 description 1
- LYAVXWPXKIFHBU-UHFFFAOYSA-N N-{2-[(1,2-diphenylhydrazinyl)carbonyl]-2-hydroxyhexanoyl}-6-aminohexanoic acid Chemical compound C=1C=CC=CC=1N(C(=O)C(O)(C(=O)NCCCCCC(O)=O)CCCC)NC1=CC=CC=C1 LYAVXWPXKIFHBU-UHFFFAOYSA-N 0.000 description 1
- 229910020889 NaBH3 Inorganic materials 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 1
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710201263 Prostaglandin D2 receptor 2 Proteins 0.000 description 1
- 101150034985 Ptgdr2 gene Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 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
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010058141 Skin graft rejection Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000005782 Squalene Monooxygenase Human genes 0.000 description 1
- 108020003891 Squalene monooxygenase Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 230000027029 T-helper 2 cell chemotaxis Effects 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- UFLGIAIHIAPJJC-UHFFFAOYSA-N Tripelennamine Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 UFLGIAIHIAPJJC-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010057469 Vascular stenosis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- JJSCUXAFAJEQGB-QMMMGPOBSA-N [(1s)-1-isocyanatoethyl]benzene Chemical compound O=C=N[C@@H](C)C1=CC=CC=C1 JJSCUXAFAJEQGB-QMMMGPOBSA-N 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- YYAZJTUGSQOFHG-IAVNQIGZSA-N [(6s,8s,10s,11s,13s,14s,16r,17r)-6,9-difluoro-17-(fluoromethylsulfanylcarbonyl)-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate;2-(hydroxymethyl)-4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]eth Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)C1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O YYAZJTUGSQOFHG-IAVNQIGZSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 229960004892 acemetacin Drugs 0.000 description 1
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 229940062328 actos Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 229940090167 advair Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 230000036428 airway hyperreactivity Effects 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
- 229960005142 alclofenac Drugs 0.000 description 1
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229960003790 alimemazine Drugs 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000005237 alkyleneamino group Chemical group 0.000 description 1
- 125000005238 alkylenediamino group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 208000002029 allergic contact dermatitis Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- FPHLBGOJWPEVME-UHFFFAOYSA-N alminoprofen Chemical compound OC(=O)C(C)C1=CC=C(NCC(C)=C)C=C1 FPHLBGOJWPEVME-UHFFFAOYSA-N 0.000 description 1
- 229960004663 alminoprofen Drugs 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229960003318 alteplase Drugs 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940051880 analgesics and antipyretics pyrazolones Drugs 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 229960000983 anistreplase Drugs 0.000 description 1
- 229960002469 antazoline Drugs 0.000 description 1
- REYFJDPCWQRWAA-UHFFFAOYSA-N antazoline Chemical compound N=1CCNC=1CN(C=1C=CC=CC=1)CC1=CC=CC=C1 REYFJDPCWQRWAA-UHFFFAOYSA-N 0.000 description 1
- NUZWLKWWNNJHPT-UHFFFAOYSA-N anthralin Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 description 1
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000005165 aryl thioxy group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
- 229960005207 auranofin Drugs 0.000 description 1
- 229960001799 aurothioglucose Drugs 0.000 description 1
- 229940062310 avandia Drugs 0.000 description 1
- 229940003504 avonex Drugs 0.000 description 1
- 229960001671 azapropazone Drugs 0.000 description 1
- WOIIIUDZSOLAIW-NSHDSACASA-N azapropazone Chemical compound C1=C(C)C=C2N3C(=O)[C@H](CC=C)C(=O)N3C(N(C)C)=NC2=C1 WOIIIUDZSOLAIW-NSHDSACASA-N 0.000 description 1
- 229960000383 azatadine Drugs 0.000 description 1
- SEBMTIQKRHYNIT-UHFFFAOYSA-N azatadine Chemical compound C1CN(C)CCC1=C1C2=NC=CC=C2CCC2=CC=CC=C21 SEBMTIQKRHYNIT-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229960005430 benoxaprofen Drugs 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 1
- 229940021459 betaseron Drugs 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 229960004620 bitolterol Drugs 0.000 description 1
- FZGVEKPRDOIXJY-UHFFFAOYSA-N bitolterol Chemical compound C1=CC(C)=CC=C1C(=O)OC1=CC=C(C(O)CNC(C)(C)C)C=C1OC(=O)C1=CC=C(C)C=C1 FZGVEKPRDOIXJY-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229960000725 brompheniramine Drugs 0.000 description 1
- ZDIGNSYAACHWNL-UHFFFAOYSA-N brompheniramine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 ZDIGNSYAACHWNL-UHFFFAOYSA-N 0.000 description 1
- IJTPQQVCKPZIMV-UHFFFAOYSA-N bucloxic acid Chemical compound ClC1=CC(C(=O)CCC(=O)O)=CC=C1C1CCCCC1 IJTPQQVCKPZIMV-UHFFFAOYSA-N 0.000 description 1
- 229950005608 bucloxic acid Drugs 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 229940107810 cellcept Drugs 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960003291 chlorphenamine Drugs 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002881 clemastine Drugs 0.000 description 1
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 description 1
- 229950010886 clidanac Drugs 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229960001140 cyproheptadine Drugs 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 229960001271 desloratadine Drugs 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
- 229960001882 dexchlorpheniramine Drugs 0.000 description 1
- SOYKEARSMXGVTM-HNNXBMFYSA-N dexchlorpheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 SOYKEARSMXGVTM-HNNXBMFYSA-N 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- 229960003461 dezocine Drugs 0.000 description 1
- VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 229960000879 diphenylpyraline Drugs 0.000 description 1
- OWQUZNMMYNAXSL-UHFFFAOYSA-N diphenylpyraline Chemical compound C1CN(C)CCC1OC(C=1C=CC=CC=1)C1=CC=CC=C1 OWQUZNMMYNAXSL-UHFFFAOYSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 1
- 229960002311 dithranol Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940075049 dovonex Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 229950002375 englitazone Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- DTSRJUYUJHDFEN-UHFFFAOYSA-N ethyl 2-(2,3-dihydro-1h-indol-3-yl)acetate Chemical compound C1=CC=C2C(CC(=O)OCC)CNC2=C1 DTSRJUYUJHDFEN-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- 229950006236 fenclofenac Drugs 0.000 description 1
- IDKAXRLETRCXKS-UHFFFAOYSA-N fenclofenac Chemical compound OC(=O)CC1=CC=CC=C1OC1=CC=C(Cl)C=C1Cl IDKAXRLETRCXKS-UHFFFAOYSA-N 0.000 description 1
- 229950011481 fenclozic acid Drugs 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 229960001022 fenoterol Drugs 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 1
- 229960002679 fentiazac Drugs 0.000 description 1
- 229960000489 feprazone Drugs 0.000 description 1
- 229960003592 fexofenadine Drugs 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 229950007979 flufenisal Drugs 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229950001284 fluprofen Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 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
- 229960003765 fluvastatin Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229950010931 furofenac Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229960003776 glatiramer acetate Drugs 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229940095884 glucophage Drugs 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000002344 gold compounds Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229960000930 hydroxyzine Drugs 0.000 description 1
- ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 description 1
- 230000035874 hyperreactivity Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 229950009183 ibufenac Drugs 0.000 description 1
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 208000009326 ileitis Diseases 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 229940073062 imuran Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 229960004187 indoprofen Drugs 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 229950000831 iralukast Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960001268 isoetarine Drugs 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229950011455 isoxepac Drugs 0.000 description 1
- QFGMXJOBTNZHEL-UHFFFAOYSA-N isoxepac Chemical compound O1CC2=CC=CC=C2C(=O)C2=CC(CC(=O)O)=CC=C21 QFGMXJOBTNZHEL-UHFFFAOYSA-N 0.000 description 1
- 229950002252 isoxicam Drugs 0.000 description 1
- YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000003410 keratolytic agent Substances 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 229960003406 levorphanol Drugs 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- 229950008446 melinamide Drugs 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229960004056 methdilazine Drugs 0.000 description 1
- HTMIBDQKFHUPSX-UHFFFAOYSA-N methdilazine Chemical compound C1N(C)CCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 HTMIBDQKFHUPSX-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- PKMDIVSLKFUBIS-UHFFFAOYSA-N methyl 2-(3-fluoro-5-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC(O)=CC(F)=C1 PKMDIVSLKFUBIS-UHFFFAOYSA-N 0.000 description 1
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
- QOHGMEYPUKSMST-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(O)C=C1 QOHGMEYPUKSMST-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- OJGQFYYLKNCIJD-UHFFFAOYSA-N miroprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CN(C=CC=C2)C2=N1 OJGQFYYLKNCIJD-UHFFFAOYSA-N 0.000 description 1
- 229950006616 miroprofen Drugs 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960005285 mofebutazone Drugs 0.000 description 1
- REOJLIXKJWXUGB-UHFFFAOYSA-N mofebutazone Chemical compound O=C1C(CCCC)C(=O)NN1C1=CC=CC=C1 REOJLIXKJWXUGB-UHFFFAOYSA-N 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- LBFBRXGCXUHRJY-HKHDRNBDSA-M montelukast sodium Chemical compound [Na+].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 LBFBRXGCXUHRJY-HKHDRNBDSA-M 0.000 description 1
- 229960001951 montelukast sodium Drugs 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 208000010125 myocardial infarction Diseases 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
- 125000003136 n-heptyl 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])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
- 229960000805 nalbuphine Drugs 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- AIKVCUNQWYTVTO-UHFFFAOYSA-N nicardipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 AIKVCUNQWYTVTO-UHFFFAOYSA-N 0.000 description 1
- 229960002289 nicardipine hydrochloride Drugs 0.000 description 1
- 229960000916 niflumic acid Drugs 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229950006344 nocodazole Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000003865 nucleic acid synthesis inhibitor Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229960002657 orciprenaline Drugs 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960005118 oxymorphone Drugs 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- HFHZKZSRXITVMK-UHFFFAOYSA-N oxyphenbutazone Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 HFHZKZSRXITVMK-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229960001190 pheniramine Drugs 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 229960005414 pirbuterol Drugs 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960000851 pirprofen Drugs 0.000 description 1
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229950011515 pobilukast Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 1
- 229960004583 pranlukast Drugs 0.000 description 1
- 229960003101 pranoprofen Drugs 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 229940072288 prograf Drugs 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- SXYFKXOFMCIXQW-UHFFFAOYSA-N propanedioyl dichloride Chemical compound ClC(=O)CC(Cl)=O SXYFKXOFMCIXQW-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000005599 propionic acid derivatives Chemical class 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 239000003790 pyrimidine antagonist Substances 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 238000011002 quantification Methods 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
- 229940099538 rapamune Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000033904 relaxation of vascular smooth muscle Effects 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000027272 reproductive process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960002917 reteplase Drugs 0.000 description 1
- 108010051412 reteplase Proteins 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 229940127100 salmeterol-fluticasone Drugs 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 1
- 229940115586 simulect Drugs 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 229940083618 sodium nitroprusside Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000004059 squalene synthase inhibitor Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229950005175 sudoxicam Drugs 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940035073 symbicort Drugs 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229960001312 tiaprofenic acid Drugs 0.000 description 1
- 229950002345 tiopinac Drugs 0.000 description 1
- 229950006150 tioxaprofen Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 description 1
- 229960002905 tolfenamic acid Drugs 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000009529 traumatic brain injury 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
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 229960003223 tripelennamine Drugs 0.000 description 1
- 229960001128 triprolidine Drugs 0.000 description 1
- CBEQULMOCCWAQT-WOJGMQOQSA-N triprolidine Chemical compound C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C/CN1CCCC1 CBEQULMOCCWAQT-WOJGMQOQSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000025102 vascular smooth muscle contraction Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229940087652 vioxx Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 150000003704 vitamin D3 derivatives Chemical class 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical class OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
- 229950007802 zidometacin Drugs 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/36—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- C07C205/37—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/75—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Definitions
- G-protein coupled receptors play important roles in diverse signaling processes, including those involved in host defense mechanisms. Immune responses to infectious diseases, injury, tumors and organ transplantation and in diseases and conditions such as asthma, allergy, rheumatoid arthritis and neoplasia have been linked to GPCR regulation. Exaggerated or misdirected immune responses are responsible for many inflammatory and hypersensitivity diseases which, left untreated, can result in tissue or organ damage, pain and/or loss of function. Tissue inflammation is largely implicated in the pathogenesis of such diseases, of which asthma and allergic diseases are among the most well characterized. The mechanisms underlying airway inflammation and hyperreactivity are similar to those underlying allergic inflammation in other tissues, such as the skin and gut.
- Prostaglandins are lipid-derived inflammatory mediators that recruit macrophages, T cells, eosinophils, basophils and neutrophils from peripheral blood to damaged or inflamed tissues.
- prostaglandins can, depending on the target cell type, induce or inhibit intracellular Ca 2+ mobilization, cAMP production, platelet aggregation, leukocyte aggregation, T cell proliferation, lymphocyte migration, and Th2 cell chemotaxis, IL-la and IL-2 secretion and vascular and non-vascular smooth muscle contraction in responsive cells.
- Prostaglandins have been implicated in fever, various allergic diseases, vascular and non-vascular smooth muscle relaxation, pain perception, sleep, platelet aggregation and reproductive processes.
- Prostaglandins exert their effects by interacting with specific GPCRs.
- Prostaglandin D 2 (PGD 2 ) is the major inflammatory mediator released by activated mast cells, typically found near skin surfaces, mucous membranes and blood vessels, upon immunological challenge (Lewis et al. (1982) J. Immunol. 129:1627-1631). During asthma and allergic responses, PGD is released in large amounts. The role of PGD 2 in the initiation and maintenance of allergic inflammation has been well established in mouse models of asthma. For example, it has been demonstrated that overproduction of PGD 2 in vivo by PGD 2 synthase exacerbates airway inflammation in a mouse model of asthma (Fujitani et al. (2002) J Immunol. 168:443-449).
- DP PGD 2 -selective receptor
- DP 7 mice exhibited reduced asthma symptoms, e.g., reduced cellular infiltration of eosinophils and lymphocytes in BAL fluid, reduced Th2 cytokine levels in BAL fluid and reduced airway hyperreactivity to acetylcholine (Matsuoka et al. (2002) Science 287:2013- 2019).
- the increased cellular infiltration in lung tissue and mucus secretion by airway epithelial cells characteristic of asthma in humans and observed in wild-type mice was not observed in DP-deficient mice.
- chemoattractant receptor-homologous molecule expressed on Th2 cells has been identified (Hirai et al. (2001J J. Exp. Med. 193(2):255-261).
- the receptor was previously referred to as GPR44 or DL1R.
- human CRTH2 is selectively expressed on Th2 cells, and is highly expressed on cell types associated with allergic inflammation such as eosinophils, basophils and Th2 cells. It has been shown that CRTH2 activation induces intracellular Ca 2+ mobilization and infiltration of Th2 cells, eosinophils and basophils.
- CRTH2 has no significant homology to DP, but rather, is related to members of the N-formyl peptide receptor (FPR) subfamily (Nagata et al. (1999) J. Immunol. 162:1278-1286). In contrast to DP, CRTH2 has been shown to couple primarily to G ⁇ i protein. These observations suggest that CRTH2 and DP may function independently to regulate aspects of allergic inflammation.
- FPR N-formyl peptide receptor
- the invention provides compounds, pharmaceutical compositions and methods useful for treating or preventing conditions and disorders associated with inflammation processes.
- the invention provides compounds, pharmaceutical compositions and methods useful for treating or preventing asthma, allergic diseases, inflammatory conditions, cancer and viral infection.
- the compounds of the invention have the general formula (I):
- A' is C(R 3 ) or N;
- X is a divalent linkage selected from the group consisting of-O- - S(O) k - -CR a R b - -C(O)-, -NR 8 - and -C(NR 9 )-;
- Y is a divalent linkage selected from the group consisting of a single bond, -S(O) k NR 10 -, -C(O)NR 10 -, (C ⁇ -C 4 )alkylene, hetero(C 2 -C 4 )alkylene, - N(R 11 )C(O)NR 10 -, -N(R ⁇ )S(O) k NR 10 -, -N(R n )CO 2 - -NR 11 -, -O- and -S(O) k -; optionally, X and Y are combined to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from the group consisting of N, O and S;
- Z is selected from the group consisting of -CO 2 R 12 , -C(O)NR 12 R 13 and heteroaryl;
- L is a divalent linkage selected from the group consisting of a single bond, (C ⁇ -C 6 )alkylene and (C 2 -C 4 )heteroalkylene;
- R is selected from the group consisting of hydrogen, -OR', (Cj- C 8 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl and aryl(Cj-C )alkyl;
- R 3 , R 4 , R 5 and R 6 are independently selected from the group consisting of hydrogen, halogen, (Cj-C 8 )alkyl, fluoro(C ⁇ -C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C C 4 )alkyl, -NR'R", -OR', -NO 2 , -CN, -C(O)R', -CO 2 R', -
- R is selected from the group consisting of hydrogen, halogen, (Ci- C 8 )alkyl, fluoro(C ⁇ -C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C ⁇ -C 4 )alkyl, - NR'R", -OR', -C(O)R', -CO 2 R', -C(O)NR'R", -S(O) m R' and -S(O) k NR'R";
- R a and R b are independently selected from the group consisting of hydrogen, (Cj-C 6 )alkyl, hetero(C 2 -C 6 )alkyl, aryl(C ⁇ -C 4 )alkyl, -OR' and -NR'R"; optionally, R a and R b are combined to form a 5-, 6-, 7- or 8-membered spiro ring containing from 0 to 3 heteroatoms selected from the group consisting of N, O and S;
- R 8 , R 10 and R 11 are independently selected from the group consisting of hydrogen, (Cj-C 8 )alkyl, fluoro(Cj-C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, -aryl(C,-C 4 )alkyl, -C(O)R', -CO 2 R', -C(O)NR'R", -S(O) m R' and -S(O) k NR'R"; R 9 is selected from the group consisting of (Cj-C 6 )alkyl, hetero(C 2 - C 6 )alkyl, aryl(C,-C 4 )alkyl, -OR' and -NR'R"; optionally, R 8 or R 9 is combined with W to form a 5-, 6-, 7- or 8- membered fused ring containing from 0 to 3 heteroatoms selected from the group consisting of N, O and S;
- -Y-R 2 is -NHSO 2 -heterocyclo(C 3 -C 8 )alkyl, -NHSO 2 -phenyl or -NHSO 2 -heteroaryl;
- a 2 is other than C(O- substituted (C 2 -C 4 )alkyl) or C(S- substituted (C 2 -C )alkyl).
- the invention also provides pharmaceutical compositions comprising a compound of formula I and a pharmaceutically acceptable carrier, excipient or diluent.
- the invention also provides methods for treating or preventing inflammatory conditions, immune disorders, asthma, allergic rhinitis, eczema, psoriasis, atopic dermatitis, fever, sepsis, systemic lupus erythematosus, diabetes, rheumatoid arthritis, multiple sclerosis, atherosclerosis, transplant rejection, inflammatory bowel disease, cancer, viral infection, thrombosis, fibrosis, flushing, Crohn's disease, ulcerative colitis, chronic obstructive pulmonary disease, inflammation, pain, conjunctivitis, nasal congestion and urticaria, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I.
- the invention also provides methods for treating or preventing a condition or disorder mediated, regulated or influenced by Th2 cells, eosinophils, basophils, platelets, Langerhans cells, dendritic cells or mast cells, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I.
- the invention also provides methods for treating or preventing a condition or disorder mediated, regulated or influenced by PGD 2 and metabolites thereof, such as 13,14-dihydro-15-keto-PGD 2 and 15-deoxy- ⁇ 1 ' ,4 -PGD 2 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I.
- the invention further provides methods for treating or preventing a condition or disorder responsive to modulation of CRTH2 and/or one or more other PGD 2 receptors, e.g., DP, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I.
- the invention also provides methods for treating or preventing a condition or disorder mediated by CRTH2 and/or one or more other PGD receptors, e.g., DP, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I.
- the invention also provides methods for modulating CRTH2 and/or one or more other PGD 2 receptors, e.g., DP, comprising contacting a cell with a compound of formula I.
- treat are meant to include alleviating or abrogating a disease and/or its attendant symptoms and alleviating or eradicating the cause of the disease itself.
- prevent refers to a method of delaying or precluding the onset of a disease and/or its attendant symptoms, barring a subject from acquiring a disease or reducing a subject's risk of acquiring a disease.
- therapeutically effective amount refers to the amount of the subject compound that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinician.
- therapeutically effective amount includes that amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more of the symptoms of the condition or disorder being treated.
- the therapeutically effective amount will vary depending on the compound, the disease and its severity and the age, weight, etc., of the mammal to be treated.
- the "subject” is defined herein to include animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In preferred embodiments, the subject is a human.
- the term "CRTH2" refers to a CRTH2 protein (RefSeq
- CRTH2 variants include proteins substantially homologous to native CRTH2, i.e., proteins having one or more naturally or non- naturally occurring amino acid deletions, insertions or substitutions (e.g., CRTH2 derivatives, homologs and fragments).
- the amino acid sequence of CRTH2 variant preferably is at least about 80% identical to a native CRTH2, more preferably at least about 90%) identical, and most preferably at least about 95% identical.
- other PGD 2 receptor refers to a prostanoid receptor protein other than CRTH2, or variant thereof, that is capable of mediating a cellular response to PGD 2 in vitro or in vivo.
- Another PGD 2 receptor may be selective for PGD 2 , e.g., DP (RefSeq Accession No. NP 000944), or other one or more other prostanoids (e.g., EPi, EP 2 , EP 3 and EP 4 , FP, LP and TP).
- PGD 2 receptor variants include proteins substantially homologous to a corresponding native prostanoid receptor other than CRTH2, i.e., proteins having one or more naturally or non-naturally occurring amino acid deletions, insertions or substitutions (e.g., derivatives, homologs and fragments of another PGD 2 receptor).
- the amino acid sequence of other PGD receptor variants preferably is at least about 80% identical to the corresponding native other PGD 2 receptors, more preferably at least about 90% identical, and most preferably at least about 95 % identical.
- another PGD 2 receptor is DP.
- DP refers to a DP protein (RefSeq Accession No. NP_000944) or variant thereof that is capable of mediating a cellular response to PGD 2 in vitro or in vivo.
- DP variants include proteins substantially homologous to native DP, i.e., proteins having one or more naturally or non-naturally occurring amino acid deletions, insertions or substitutions (e.g., DP derivatives, homologs and fragments).
- the amino acid sequence of DP variant preferably is at least about 80% identical to a native DP, more preferably at least about 90% identical, and most preferably at least about 95% identical.
- modulate refers to the ability of a compound to increase or decrease the function and/or expression of CRTH2 and/or one or more other PGD 2 receptors, e.g., DP, where such function may include transcription regulatory activity and/or protein-binding. Modulation may occur in vitro or in vivo. Modulation, as described herein, includes the inhibition, antagonism, partial antagonism, activation, agonism or partial agonism of a function or characteristic associated with CRTH2 and/or one or more other PGD 2 receptors, either directly or indirectly, and/or the upregulation or downregulation of the expression of CRTH2 and/or one or more other PGD 2 receptors, either directly or indirectly.
- the modulation is direct.
- Inhibitors or antagonists are compounds that, e.g., bind to, partially or totally block stimulation, decrease, prevent, inhibit, delay activation, inactivate, desensitize, or downregulate signal transduction.
- Activators or agonists are compounds that, e.g., bind to, stimulate, increase, open, activate, facilitate, enhance activation, activate, sensitize or upregulate signal transduction.
- the ability of a compound to inhibit the function of CRTH2 and/or one or more other PGD 2 receptors can be demonstrated in a biochemical assay, e.g., binding assay, or a cell-based assay, e.g., a transient transfection assay.
- CRTH2 -modulating amount refers to that amount of a compound that is needed to produce a desired effect in any one of the cell-based assays, biochemical assays or animal models described herein or otherwise known to the skilled artisan.
- a CRTH2 -modulating amount of a compound will be at least that amount which exhibits an EC 50 in a reporter-gene cell-based assay (relative to an untreated control).
- CRTH2 -responsive condition or disorder refers to a condition or disorder associated with inappropriate, e.g., less than or greater than normal, CRTH2 activity and at least partially responsive to or affected by CRTH2 modulation (e.g., a CRTH2 antagonist or agonist results in some improvement in patient well-being in at least some patients).
- CRTH2 functional activity might arise as the result of CRTH2 expression in cells which normally do not express CRTH2, increased CRTH2 expression or degree of intracellular activation (leading to, e.g., inflammatory and immune-related disorders and diseases) or decreased CRTH2 expression.
- a CRTH2-associated condition or disorder may include a CRTH2- mediated condition or disorder.
- CRTH2-mediated condition or disorder refers to a condition or disorder characterized by inappropriate, e.g., less than or greater than normal, CRTH2 activity. Inappropriate CRTH2 functional activity might arise as the result of CRTH2 expression in cells which normally do not express CRTH2, increased CRTH2 expression or degree of intracellular activation (leading to, e.g., inflammatory and immune-related disorders and diseases) or decreased CRTH2 expression.
- a CRTH2 -mediated condition or disorder may be completely or partially mediated by inappropriate CRTH2 functional activity.
- a CRTH2 -mediated condition or disorder is one in which modulation of CRTH2 results in some effect on the underlying condition or disorder (e.g., an CRTH2 antagonist or agonist results in some improvement in patient well-being in at least some patients).
- PGD 2 receptor-modulating amount refers to that amount of a compound that is needed to produce a desired effect in any one of the cell-based assays, biochemical assays or animal models described herein or otherwise known to the skilled artisan.
- a PGD 2 receptor-modulating amount of a compound will be at least that amount which exhibits an EC 50 in a reporter-gene cell-based assay (relative to an untreated control).
- condition or disorder responsive to another PGD 2 receptor refers to a condition or disorder associated with inappropriate, e.g., less than or greater than normal, activity of another PGD 2 receptor and at least partially responsive to or affected by modulation of another PGD receptor (e.g., another PGD 2 receptor antagonist or agonist results in some improvement in patient well-being in at least some patients).
- another PGD 2 receptor antagonist or agonist results in some improvement in patient well-being in at least some patients.
- Inappropriate functional activity of another PGD 2 receptor might arise as the result of expression of another PGD 2 receptor in cells which normally do not express the receptor, increased expression of another PGD receptor or degree of intracellular activation (leading to, e.g., inflammatory and immune-related disorders and diseases) or decreased expression of another PGD 2 receptor.
- a condition or disorder associated with another PGD 2 receptor may include a condition or disorder mediated by another PGD 2 receptor.
- condition or disorder mediated by another PGD 2 receptor refers to a condition or disorder characterized by inappropriate, e.g., less than or greater than normal, activity of another PGD 2 receptor. Inappropriate functional activity of another PGD 2 receptor might arise as the result of expression of another PGD 2 receptor in cells which normally do not express the receptor, increased expression of another PGD 2 receptor or degree of intracellular activation (leading to, e.g., inflammatory and immune-related disorders and diseases) or decreased expression of another PGD 2 receptor.
- a condition or disorder mediated by another PGD 2 receptor may be completely or partially mediated by inappropriate functional activity of another PGD 2 receptor.
- a condition or disorder mediated by of another PGD 2 receptor is one in which modulation of another PGD 2 receptor results in some effect on the underlying condition or disorder (e.g., another PGD 2 receptor antagonist or agonist results in some improvement in patient well-being in at least some patients).
- DP-modulating amount refers to that amount of a compound that is needed to produce a desired effect in any one of the cell-based assays, biochemical assays or animal models described herein or otherwise known to the skilled artisan.
- a DP-modulating amount of a compound will be at least that amount which exhibits an EC 50 in a reporter-gene cell-based assay (relative to an untreated control).
- DP -responsive condition or disorder refers to a condition or disorder associated with inappropriate, e.g., less than or greater than normal, DP activity and at least partially responsive to or affected by DP modulation (e.g., a DP antagonist or agonist results in some improvement in patient well-being in at least some patients).
- Inappropriate DP functional activity might arise as the result of DP expression in cells which normally do not express DP, increased DP expression or degree of intracellular activation (leading to, e.g., inflammatory and immune-related disorders and diseases) or decreased DP expression.
- a DP-associated condition or disorder may include a DP-mediated condition or disorder.
- DP-mediated condition or disorder refers to a condition or disorder characterized by inappropriate, e.g., less than or greater than normal, DP activity. Inappropriate DP functional activity might arise as the result of DP expression in cells which normally do not express DP, increased DP expression or degree of intracellular activation (leading to, e.g., inflammatory and immune-related disorders and diseases) or decreased DP expression.
- a DP-mediated condition or disorder may be completely or partially mediated by inappropriate DP functional activity.
- a DP-mediated condition or disorder is one in which modulation of DP results in some effect on the underlying condition or disorder (e.g., an DP antagonist or agonist results in some improvement in patient well-being in at least some patients).
- alkyl by itself or as part of another substituent, means, unless otherwise stated, a straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which is fully saturated, having the number of carbon atoms designated (i.e., -Cg means one to eight carbons).
- alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n- pentyl, n-hexyl, n-heptyl, n-octyl and the like.
- alkenyl by itself or as part of another substituent, means a straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which may be mono- or polyunsaturated, having the number of carbon atoms designated (i.e., C 2 -C 8 means two to eight carbons) and one or more double bonds.
- alkenyl groups include vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-
- alkynyl by itself or as part of another substituent, means a straight or branched chain hydrocarbon radical, or combination thereof, which may be mono- or polyunsaturated, having the number of carbon atoms designated (i.e., C 2 -C 8 means two to eight carbons) and one or more triple bonds.
- alkynyl groups include ethynyl, 1- and 3-propynyl, 3-butynyl and higher homologs and isomers thereof.
- alkylene by itself or as part of another substituent means a divalent radical derived from alkyl, as exemplified by -CH 2 CH 2 CH 2 CH 2 -.
- an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in the present invention.
- a “lower alkyl” or “lower alkylene” is a shorter chain alkyl or alkylene group, generally having eight or fewer carbon atoms.
- alkoxy alkylamino and “alkylthio” (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups attached to the remainder of the molecule via an oxygen atom, an amino group, or a sulfur atom, respectively.
- dialkylamino refers to an amino group having two attached alkyl groups that can be the same or different.
- heteroalkyl by itself or in combination with another term, means, unless otherwise stated, a stable straight or branched chain, or cyclic hydrocarbon radical, or combinations thereof, consisting of the stated number of carbon atoms and from one to three heteroatoms selected from O, N, Si and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized.
- the heteroatom(s) O, N and S may be placed at any interior position of the heteroalkyl group.
- the heteroatom Si may be placed at any position of the heteroalkyl group, including the position at which the alkyl group is attached to the remainder of the molecule.
- Up to two heteroatoms may be consecutive, such as, for example, -CH 2 -NH-OCH 3 and - CH 2 -O-Si(CH 3 ) 3 .
- a prefix such as (C 2 -C 8 ) is used to refer to a heteroalkyl group, the number of carbons (2-8, in this example) is meant to include the heteroatoms as well.
- a C 2 -heteroalkyl group is meant to include, for example, -CH 2 OH (one carbon atom and one heteroatom replacing a carbon atom) and -CH 2 SH.
- heteroalkylene by itself or as part of another substituent means a divalent radical derived from heteroalkyl, as exemplified by -CH 2 -CH 2 -S-CH 2 CH 2 - and -CH 2 -S-CH 2 - CH 2 -NH-CH 2 -.
- heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied.
- cycloalkyl and heterocycloalkyl represent, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl”, respectively.
- cycloalkyl and heterocycloalkyl are meant to be included in the terms “alkyl” and “heteroalkyl”, respectively.
- a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of cycloalkyl include cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like.
- heterocycloalkyl examples include 1 -(1,2, 5,6- tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3- morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1 -piperazinyl, 2-piperazinyl, and the like.
- halo or halogen
- substituents mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom.
- terms such as “haloalkyl” are meant to include alkyl substituted with halogen atoms which can be the same or different, in a number ranging from one to (2m'+l), where m' is the total number of carbon atoms in the alkyl group.
- halo(C ⁇ -C 4 )alkyl is meant to include trifluoromethyl, 2,2,2- trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like.
- haloalkyl includes monohaloalkyl (alkyl substituted with one halogen atom) and polyhaloalkyl (alkyl substituted with halogen atoms in a number ranging from two to (2m'+l) halogen atoms).
- perhaloalkyl means, unless otherwise stated, alkyl substituted with (2m'+l) halogen atoms, where m' is the total number of carbon atoms in the alkyl group.
- perhalo(C ⁇ -C )alkyl is meant to include trifluoromethyl, pentachloroethyl, l,l,l-trifluoro-2-bromo-2-chloroethyl, and the like.
- aryl means, unless otherwise stated, a polyunsaturated, typically aromatic, hydrocarbon substituent which can be a single ring or multiple rings (up to three rings) which are fused together or linked covalently.
- heteroaryl refers to aryl groups (or rings) that contain from one to four heteroatoms selected from the group consisting of N, O and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized.
- a heteroaryl group can be attached to the remainder of the molecule through a heteroatom.
- Non- limiting examples of aryl and heteroaryl groups include phenyl, 1 -naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4- isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 2-pyrimidinyl, 4- pyrimidinyl, 5- pyrimidinyl, 3-pyridaziny
- aryl refers to a phenyl or naphthyl group which is unsubstituted or substituted.
- heteroaryl refers to a pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, purinyl, benzimidazolyl, indolyl, isoquinolyl, quinoxalinyl or quinolyl group which is unsubstituted or substituted.
- aryl when used in combination with other terms (e.g., aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroaryl rings as defined above.
- arylalkyl is meant to include those radicals in which an aryl group is attached to an alkyl group (e.g., benzyl, phenethyl, pyridylmethyl and the like) including those alkyl groups in which a carbon atom (e.g., a methylene group) has been replaced by, for example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(l-naphthyloxy)propyl, and the like).
- alkyl group e.g., benzyl, phenethyl, pyridylmethyl and the like
- an oxygen atom e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(l-naph
- R', R" and R'" each independently refer to hydrogen, unsubstituted (C ⁇ -C 8 )alkyl and heteroalkyl, unsubstituted aryl, aryl substituted with one to three halogens, unsubstituted alkyl, alkoxy or thioalkoxy groups, or aryl-(C ⁇ -C 4 )alkyl groups.
- R' and R" When R' and R" are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5-, 6- or 7-membered ring.
- -NR'R is meant to include 1-pyrrolidinyl and 4-morpholinyl.
- an alkyl or heteroalkyl group will have from zero to three substituents, with those groups having two or fewer substituents being preferred in the present invention. More preferably, an alkyl or heteroalkyl radical will be unsubstituted or monosubstituted. Most preferably, an alkyl or heteroalkyl radical will be unsubstituted. From the above discussion of substituents, one of skill in the art will understand that the term "alkyl" is meant to include groups such as trihaloalkyl (e.g., -CF 3 and -CH 2 CF 3 ).
- Two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -T-C(O)-(CH 2 ) q -U-, wherein T and U are independently -NH-, -O-, -CH 2 - or a single bond, and q is an integer of from 0 to 2.
- two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -A- (CH 2 ) r -B-, wherein A and B are independently -CH 2 -, -O-, -NH-, -S-, -S(O)-, -S(O) 2 -, - S(O) 2 NR'- or a single bond, and r is an integer of from 1 to 3.
- One of the single bonds of the new ring so formed may optionally be replaced with a double bond.
- two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -(CH ) s -X-(CH 2 ) t -, where s and t are independently integers of from 0 to 3, and X is -O-, -NR'-, -S-, -S(O)-, - S(O) 2 -, or -S(O) 2 NR'-.
- the substituent R' in -NR'- and -S(O) 2 NR'- is selected from hydrogen or unsubstituted (C ⁇ -C 6 )alkyl. Otherwise, R' is as defined above.
- the term "heteroatom” is meant to include oxygen (O), nitrogen (N), sulfur (S) and silicon (Si).
- salts are meant to include salts of the active compounds which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein.
- base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent.
- pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt.
- acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent.
- Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like.
- inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like,
- salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galacturonic acids and the like (see, for example, Berge et al. (1977) J. Pharm. Sci. 66:1-19).
- Certain specific compounds of the invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.
- the neutral forms of the compounds may be regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner.
- the parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents, but otherwise the salts are equivalent to the parent form of the compound for the purposes of the invention.
- the invention provides compounds which are in a prodrug form.
- Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the invention.
- prodrugs can be converted to the compounds of the invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent.
- Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not.
- the prodrug may also have improved solubility in pharmaceutical compositions over the parent drug.
- prodrug derivatives are known in the art, such as those that rely on hydrolytic cleavage or oxidative activation of the prodrug.
- An example, without limitation, of a prodrug would be a compound of the invention which is administered as an ester (the "prodrug"), but then is metabolically hydrolyzed to the carboxylic acid, the active entity.
- Additional examples include peptidyl derivatives of a compound of the invention.
- Certain compounds of the invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are intended to be encompassed within the scope of the invention. Certain compounds of the invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the invention and are intended to be within the scope of the invention. Certain compounds of the invention possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, enantiomers, diastereomers, geometric isomers and individual isomers are all intended to be encompassed within the scope of the invention.
- isomers can be resolved or asymmetrically synthesized using conventional methods to render the isomers "optically pure", i.e., substantially free of its other isomers. If, for instance, a particular enantiomer of a compound of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivation with a chrial auxilliary, where the resulting diastereomeric mixture is separated and the auxilliary group cleaved to provide the pure desired enantiomers.
- the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl
- diastereomeric salts are formed with an appropriate optically- active acid or base, followed by resolution of the diasteromers thus formed by fractional crystallization or chromatagraphic means well known in the art, and subsequent recovery of the pure enantiomers.
- the compounds of the invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds.
- the compounds may be radiolabeled with radioactive isotopes, such as for example tritium ( 3 H), iodine-125 ( 125 I) or carbon-14 ( 1 C).
- Radiolabled compounds are useful as therapeutic or prophylactic agents, e.g., cancer therapeutic agents, research reagents, e.g., CRTH2 assay reagents, and diagnostic agents, e.g., in vivo imaging agents. All isotopic variations of the compounds of the invention, whether radioactive or not, are intended to be encompassed within the scope of the invention.
- a class of compounds that modulate CRTH2 and/or DP and/or one or more other PGD 2 receptors has been discovered. Depending on the biological environment (e.g., cell type, pathological condition of the host, etc.), these compounds can activate or inhibit the actions of CRTH2 and/or one or more other PGD 2 receptors (e.g., ligand binding). By activating or inhibiting CRTH2 and/or one or more other PGD 2 receptors, the compounds will find use as therapeutic agents capable of modulating diseases and conditions responsive to modulation of CRTH2 and/or one or more other PGD 2 receptors and/or mediated by CRTH2 and/or one or more other PGD 2 receptors.
- PGD 2 receptors e.g., ligand binding
- diseases and conditions include inflammatory conditions, immune disorders, asthma, allergic rhinitis, eczema, psoriasis, atopic dermatitis, fever, sepsis, systemic lupus erythematosus, diabetes, rheumatoid arthritis, multiple sclerosis, atherosclerosis, transplant rejection, inflammatory bowel disease, cancer, viral infection, thrombosis, fibrosis, flushing, Crohn's disease, ulcerative colitis, chronic obstructive pulmonary disease, inflammation, pain, conjunctivitis, nasal congestion and urticaria. Additionally, the compounds are useful for the treatment and/or prevention of complications of these diseases and disorders (e.g., cardiovascular disease).
- cardiovascular disease e.g., cardiovascular disease
- While the compounds of the invention are believed to exert their effects by interacting with CRTH2, the mechanism of action by which the compounds act is not a limiting embodiment of the invention.
- compounds of the invention may interact with PGD 2 receptor subtypes other than CRTH2, e.g., DP receptor, and/or other prostanoid receptors, e.g., thromboxane A 2 (TXA 2 ) receptor.
- PGD 2 receptor subtypes other than CRTH2 e.g., DP receptor
- TXA 2 thromboxane A 2
- the present invention specifically contemplates the use of the disclosed compounds to modulate one or more PGD 2 receptors other than CRTH2.
- the invention provides compounds of formula (I):
- a 1 represents C(R 3 ) or N and the symbol A 2 represents C(R 6 ) or N.
- a 1 is C(R 3 ) and
- a 1 , A 2 , the carbon atoms to which A 1 and A 2 are attached and D 1 combine to form a 5- or 6- membered ring, e.g.,
- Exemplary combinations of A 1 , A A 2 , the carbon atoms to which A and A are attached and D are:
- W represents a divalent group selected from a single bond, an aromatic ring, a heteroaromatic ring, a cyclo(C 3 -C )alkane ring and a heterocyclo(C 3 - C 8 )alkane ring.
- Exemplary W groups are:
- the letter X represents a divalent linkage selected from -O-, -S(O) k - - CR «a a ⁇ R)b D -, -C(O)-, -NR 8 - and -C(NR 9 )-.
- Exemplary X groups are -O-, -SO 2 - -CH 2 - -C(O)-, -CH(OH)- and -NH-.
- the letter Y represents a divalent linkage selected from a single bond, -
- Exemplary Y groups are -SO 2 NH- -SO 2 NMe- -C(O)NH-, -NH-, -NHCO 2 - and -NHC(O)NMe-.
- the letter Z represents -CO 2 R 12 , -C(O)NR i2 R 13 or heteroaryl.
- Exemplary Z groups are -CO 2 H, -C(O)NHEt, -C(O)NH 2 , -CO 2 Et, -CO 2 Me, -CO 2 CH 2 S(O)Me, 5-tetrazolyl and -C(O)NHOH.
- the letter L represents a divalent linkage selected from a single bond, (Cj-C 6 )alkylene and (C 2 -C 4 )heteroalkylene.
- Exemplary L groups are methylene, ethylene, chloromethylene, hydroxymethylene and methylmethylene.
- the substituent R 2 is hydrogen, -OR', (Cj-C 8 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl or aryl(Cj-C 4 )alkyl.
- R 2 groups are 4-tolyl, 2-naphthyl, methyl, phenyl, 2,4-dichlorophenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 2- chlorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2,4-dichloro-5-methylphenyl, 4-n- pentylphenyl, 4-cyanophenyl, 4-M-butoxyphenyl, 2-cyano-3-chlorophenyl, 3-chloro-4- methylphenyl, 2-methoxy-5-bromophenyl, 5-trifluoromethoxy-2-pyridyl, 8-quinolyl, 2- thieneyl, 3-methyl-7-chlorobenzothienyl, l-methyl-4-imidazolyl, benzyl and 2,4- di fluorophenyl.
- R 3 , R 4 , R 5 and R 6 are independently hydrogen, halogen, (C]-C 8 )alkyl, fluoro(Cj-C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C ⁇ -C 4 )alkyl, -NR'R", -OR', -NO 2 , -CN, -C(O)R', -CO 2 R', -C(O)NR'R", (C,-C 4 )alkylene-C(O)NR'R", - S(O) m R', -S(O) k NR'R", -OC(O)OR', -OC(O)R', -OC(O)NR'R", - N(R'")C(O)NR'R", -N(R")C(O)R' or -N(R")C(O)OR'.
- R 7 is hydrogen, halogen, (C ⁇ -C 8 )alkyl, fluoro(C ⁇ -C 4 )alkyl, hetero(C 2 - C 8 )alkyl, aryl, heteroaryl, aryl(Cj-C 4 )alkyl, -NR'R", -OR', -C(O)R', -CO 2 R ⁇ - C(O)NR'R", -S(O) m R' or -S(O) k NR'R".
- R a and R b are independently hydrogen, (Cj-C 6 )alkyl, hetero(C 2 -C 6 )alkyl, aryl(Cj-C 4 )alkyl, -OR' or -NR'R".
- R 8 , R 10 and R 11 are independently hydrogen, (Cj-C 8 )alkyl, fluoro(C ⁇ - C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C,-C 4 )alkyl, -C(O)R', -CO 2 R', - C(O)NR'R", -S(O) m R' or -S(O) k NR'R".
- R 9 is (C,-C 6 )alkyl, hetero(C 2 -C 6 )alkyl, aryl(Cj-C 4 )alkyl, -OR' or - NR'R".
- R 12 and R 13 are independently hydrogen, (C ⁇ -C 6 )alkyl, hetero(C 2 - C 6 )alkyl, aryl, aryl(C ⁇ -C 4 )alkyl or heteroaryl.
- Each R', R" and R'" is independently hydrogen, (Cj-C 6 )alkyl, cyclo(C 3 -
- Each subscript k is 0, 1 or 2.
- a and W are combined to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S;
- X and Y are combined to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S;
- R a and R b are combined to form a 5-, 6-, 7- or 8-membered spiro ring containing from 0 to 3 heteroatoms selected from N, O and S;
- R 8 or R 9 is combined with W to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S;
- R a , R b , R 8 or R 9 is combined with Y to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S;
- a 1 is C(R 3 )
- a 2 is C(R 6 ) and D 1 is
- R 3 , R 4 , R 5 and R 6 are independently hydrogen, halogen, (Cj-C 8 )alkyl, fluoro(C C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C C 4 )alkyl, -NR'R", -OR', -NO 2 , -CN, -C(O)R', -CO 2 R', -C(O)NR'R", (C,-C 4 )alkylene-C(O)NR'R", - S(O) m R', -S(O) k NR'R", -OC(O)OR', -OC(O)R', -OC(O)NR'R", - N(R'")C(O)NR'R", -N(R")C(O)R' or -N(R")C(O)OR'.
- R 6 may be combined with W to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S.
- R 6 is -O-substituted (C 2 -C 4 )alkyl or -S-substituted (C 2 -C 4 )alkyl; W is a benzene ring; X is -O- or -S-; and -Y-R 2 is -NHSO 2 -heterocyclo(C 3 -C 8 )alkyl, -NHSO 2 -phenyl or -NHSO 2 -heteroaryl are excluded.
- R 6 is hydrogen, halogen, (Cj-C 8 )alkyl, fluoro(C ⁇ -C 4 )alkyl, aryl, heteroaryl, aryl(C ⁇ -C 4 )alkyl, -NR'R", -NO 2 , -CN, -C(O)R', - CO 2 R', -C(O)NR'R", -S(O) m R', -S(O) k NR'R", -OC(O)OR', -OC(O)R', - OC(O)NR'R", -N(R'")C(O)NR'R", -N(R")C(O)R' or -N(R")C(O)OR'.
- R 3 , R 4 and R 5 are independently hydrogen, halogen, (C,-C 8 )alkyl, fluoro(C,-C 4 )alkyl, -OR', -NR'R", -NO 2 , -CN, - C(O)R', -CO 2 R', -C(O)NR'R", (Cj-C 4 )alkylene-C(O)NR'R", -N(R")C(O)R', - N(R'")C(O)NR'R” or heteroaryl.
- R 6 is hydrogen, halogen, (Cj- C 8 )alkyl, fluoro ⁇ rC ⁇ alkyl, -NR'R", -NO 2 , -CN, -C(O)R', -CO 2 R', -C(O)NR'R", (C,-C 4 )alkylene-C(O)NR'R", -N(R")C(O)R', -N(R'")C(O)NR'R" or heteroaryl.
- R 6 is hydrogen
- R , R and R are hydrogen.
- R 4 is halogen, (C ⁇ -C 8 )alkyl, fluoro(Cj-C 4 )alkyl, -OR', -NO 2 , -C(O)R', -CO 2 R', -C(O)NR'R", (C ⁇ -C 4 )alkylene- C(O)NR'R", -N(R")C(O)R', -N(R'")C(O)NR'R" or heteroaryl.
- R 3 , R 5 and R 6 are hydrogen and R 4 is halogen, (C r C 8 )alkyl, fluoro(C,-C 4 )alkyl, -OR', -NO 2 , -C(O)R', -CO 2 R', - C(O)NR'R", (C ⁇ -C 4 )alkylene-C(O)NR'R", -N(R")C(O)R', -N(R'"C(O)NR'R” or heteroaryl.
- R may be combined with W to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from
- W is an aromatic ring, a heteroaromatic ring or a cyclo(C 3 -C 8 )alkane ring.
- W is benzene, indole, benzofuran, benzothiazole, indoline, dihydrobenzofuran, dihydrobenzothiazole, benzimidazole, benzoxazole, benzthiazole or cyclohexane.
- W is benzene
- each R . 14 is independently halogen, (C ⁇ -C 8 )alkyl, fluoro(C ⁇ -C )alkyl, -OR', - NR'R", -NO 2 , -CN, -C(O)R' or aryl and the subscript n is 0, 1, 2, 3 or 4.
- any two adjacent R 14 groups may be combined to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S.
- the variables X, Y, Z, L, R 2 , R 3 , R 4 , R 5 , R 6 , R' and R" have the meanings and groupings provided above.
- the R 14 group may be combined with R 6 to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S.
- n 0.
- n 1, 2 or 3.
- n 1
- each R 14 is independently halogen, (C,-C 8 )alkyl, fluoro(C,-C 4 )alkyl, -OR', -C(O)R' or aryl.
- R 14 is halogen, fluoro(Cj-C 4 )alkyl or -OR' and n is 1.
- each R 14 is independently (Ci- C 6 )alkyl, halogen, fluoro(C ⁇ -C )alkyl, -C(O)R', aryl or -OR' and n is 2 or 3.
- an R 14 group adjacent to X is combined with R 6 to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from the group consisting of N, O and S.
- D 2 is O, S(O) k , CR a R b , C(O) or NR 8 and the subscript p is 0, 1, 2 or 3.
- the variables X, Y, Z, L, R 2 , R 3 , R 4 , R 5 , R 6 , R a , ,R b , R 8 and R 14 and the subscript k have the meanings and groupings provided above.
- q is 0, 1, 2, 3, 4, 5 or 6.
- the variables X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 14 , R' and R" and the subscript n have the meanings and groupings provided above.
- q is 0, 1, 2 or 3.
- q is 1 or 2.
- q is 1.
- X is -O-,-CR a R b - -C(O)- or -NR 8 - .
- X is -O-.
- X is -CR a R b -
- X is -NR -.
- Y is -S(O) k NR 10 -, -C(O)NR 10 -, -
- Y is - S(O) k NR 10 -.
- X and Y are combined to form a 5-, 6-, 7- or 8-membered fused ring containing from 0 to 3 heteroatoms selected from N, O and S.
- the variables Z, L, R 2 , R 3 , R 4 , R 5 , R 6 , R 14 , R' and R" and the subscript n have the meanings and groupings provided above.
- the variables Z, L, R 2 , R 3 , R 4 , R 5 , R 6 , R 14 , R', R", R c and R d and the subscript n have the meanings and groupings provided above.
- Z is CO 2 R 12 , -C(O)NR 12 R 13 , imidazolyl or tetrazolyl, wherein R 12 and R 13 are as defined above.
- Z is CO 2 R 12 , or -C(O)NR 12 R 13 In another embodiment, Z is CO 2 H.
- group -CO 2 H includes bioisosteric replacements therefor, such as:
- L a single bond or (C ⁇ -C 6 )alkylene. In one embodiment, L is (Cj-C 6 )alkylene.
- R is phenyl or naphthyl.
- W is benzofuran, benzothiazole, indoline, dihydrobenzofliran, dihydrobenzothiazole, benzimidazole, benzoxazole or benzthiazole.
- B' is N(R , 1 1 6 0 ), N, O or S
- R 16 is hydrogen, halogen, (Cj-C 8 )alkyl, fluoro(Cj-C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(Cj-C 4 )alkyl, -NR'R", -OR', -C(O)R', -CO 2 R', -C(O)NR'R", -S(O) m R' or -S(O) k NR'R",
- R 15 is hydrogen or (C ⁇ -Cg)alkyl and the dotted line indicates an optional bond.
- B 2 is C(R 17 ) or N and R 17 is hydrogen, halogen, (C ⁇ -C 8 )alkyl, fluoro(C ⁇ - C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C,-C 4 )alkyl, -NR'R", -OR', - C(O)R', -CO 2 R', -C(O)NR'R", -S(O) m R' or -S(O) k NR'R".
- XVI or a pharmaceutically acceptable salt or prodrug thereof.
- the letter X represents a divalent linkage selected from -O- and -S(O) k - Exemplary X groups are
- the letter Y represents a divalent linkage selected from a single bond, -S(O) k - -C(O)-, (C 2 -C )alkylene, hetero(C 2 -C 4 )alkylene, and -O-.
- Exemplary Y groups are -SO 2 - -S-, and -C(O)-.
- R 2 is a substituted or unsubstituted benzene ring.
- a substituted benzene ring will have from one to five substituents. Typically, a substituted benzene ring will have from one to three substituents.
- Substituents for the benzene ring are varied will include the prefened substituents for the aryl and heteroaryl groups as provided above.
- R is an unsubstituted benzene ring.
- R is a substituted benzene ring and at least one substituent on the benzene ring is selected from the group consisting of halogen, -OCF 3 , -OCH 3 , -(Cj-C 5 )alkyl, -CN, and -NO 2 .
- R 2 is a benzene ring substituted with at least one halogen.
- R is a benzene ring substituted with at least one chlorine.
- R 3 and R 5 are independently selected from the group consisting of hydrogen, halogen, (C ⁇ -C 8 )alkyl, fluoro(Cj-C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(Cj-C 4 )alkyl, -NRR", -OR', -NO 2 , -CN, -C(O)R', -CO 2 R', -C(O)NRR", -(C,-C 4 )alkylene-C(O)NR'R", -S(O) m R', -S(O) NRR", -OC(O)OR', -OC(O)R', -OC(O)NRR", -N(R'")C(O)NRR", -N(R")C(O)R' and -N(R")C(O)OR', where variables R', R", and R'" have the meanings provided
- R 4 is -NC(O)-cyclo(C 5 -C )alkyl.
- R 4 is -C(O)NH-(C]-C 4 )alkyl.
- R 6 is selected from the group consisting of hydrogen, halogen,
- (C ⁇ .Cg)alkyl fluoro(Cj-C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C ⁇ -C 4 )alkyl, -NR'R", -NO 2 , -CN, -C(O)R', -CO 2 R', -C(O)NRR", -(C,-C 4 )alkylene-C(O)NRR", -S(O) m R', -S(O) k NRR", -OC(O)OR', -OC(O)R', -OC(O)NRR", -N(R'")C(O)NR'R", -N(R")C(O)R' and -N(R")C(O)OR'.
- R 6 is selected from the group consisting of hydrogen, halogen, (Cj.C 8 )alkyl, fluoro(C]-C 4 )alkyl, aryl, heteroaryl, aryl(C ⁇ -C 4 )alkyl, -NR'R", -NO 2 , -CN, -C(O)R', -CO 2 R', -C(O)NRR", -(C,-C 4 )alkylene-C(O)NRR", -OC(O)OR', -OC(O)R', -OC(O)NR'R", -N(R'")C(O)NR'R", -N(R")C(O)R' and -N(R")C(O)OR'.
- R 10 is selected from the group consisting of hydrogen, (C ⁇ -C 8 )alkyl, fluoro(Cj-C 4 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, heteroaryl, aryl(C C 4 )alkyl, -C(O)R', -CO 2 R', -C(O)NRR", -S(O) m R' and -S(O) k NR'R".
- L is a divalent linkage selected from the group consisting of a single bond, (C ⁇ -C 6 )alkylene and (C 2 -C 4 )heteroalkylene.
- Z is selected from the group consisting of -CO 2 R 12 , -C(O)NR 12 R 13 and heteroaryl.
- R and R are independently selected from the group consisting of hydrogen, (Cj-C 8 )alkyl, hetero(C 2 -C 8 )alkyl, aryl, aryl(C ⁇ -C 4 )alkyl and heteroaryl.
- Each R 14 is independently selected from the group consisting of halogen, (d-C 8 )alkyl, fluoro(C,-C 4 )alkyl, -OR', -NR'R", -NO 2 , -CN, -C(O)R' and aryl.
- Each R', R" and R'" is independently selected from the group consisting of hydrogen, (Cj-C 6 )alkyl, cyclo(C 3 -C 8 )alkyl, aryl and aryl(C ⁇ -C 4 )alkyl.
- Each subscript k is independently 0, 1 or 2.
- the subscript m is independently 0, 1, 2 or 3.
- the subscript n is 0, 1, 2, 3 or 4.
- Y is -SO 2 -
- X is -O-
- R 10 is hydrogen.
- R 4 is -C(O)NH-(C ⁇ -C )alkyl
- R 6 is hydrogen.
- R is a benzene ring substituted with 1, 2, or 3 chlorine atoms.
- -L-Z taken together are -CH 2 COOH.
- the subscript n is 1 or 2.
- R 14 is -OCH 2 CH 3 or -OCH 3 .
- R , R and R are each hydrogen.
- Another group of embodiments within formula (XVII) is represented by formula (XVIII):
- each R 14 is independently selected from the group consisting of (C ⁇ -C 6 )alkyl, halogen, fluoro(C ⁇ -C 4 )alkyl, -C(O)R', aryl and -OR' and subscript n is 2 or 3.
- formula (XVI) one prefened group of embodiments are
- the invention encompasses novel compounds, novel pharmaceutical compositions and/or novel methods of use. While some compounds disclosed herein are available from commercial sources, the pharmaceutical compositions or methods of using these compounds are novel. Unless otherwise indicated, it is to be understood that the invention includes those compounds that are novel, as well as pharmaceutical compositions, various methods (e.g., methods of treating or preventing certain conditions and diseases mediated by CRTH2 and/or one or more other PGD receptors), and the like which include both the novel compounds of the invention and compounds that are commercially available.
- Synthesis routes to the compounds provided herein are described in the Examples.
- One of skill in the art will understand that the synthetic routes can be modified to use different starting materials and/or alternate reagents to accomplish the desired transformations.
- protecting groups may be necessary for the preparation of certain compounds and will be aware of those conditions compatible with a selected protecting group. Accordingly, the methods and reagents described herein are all expressed as non-limiting embodiments.
- compositions suitable for pharmaceutical use comprising one or more compounds of the invention and a pharmaceutically acceptable carrier, excipient or diluent.
- composition as used herein is intended to encompass a product comprising the specified ingredients (and in the specified amounts, if indicated), as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.
- pharmaceutically acceptable it is meant that the earner or excipient is compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
- Formulation may improve one or more pharmacokinetic properties (e.g., oral bioavailabilty, membrane permeability) of a compound of the invention (herein refened to as the active ingredient).
- pharmacokinetic properties e.g., oral bioavailabilty, membrane permeability
- compositions for the administration of the compounds of this invention may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art. All methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more accessory ingredients.
- the pharmaceutical compositions are prepared by uniformly and intimately bringing the active ingredient into association with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, shaping the product into the desired formulation.
- the active object compound is included in an amount sufficient to produce the desired effect upon the process or condition of diseases.
- compositions containing the active ingredient may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs.
- Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions. Such compositions may contain one or more agents selected from sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with other non-toxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets.
- excipients may be, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc.
- the tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period.
- a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by the techniques described in U.S. Patent Nos. 4,256,108; 4,166,452 and 4,265,874 to form osmotic therapeutic tablets for control release.
- Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin, or olive oil.
- an inert solid diluent for example, calcium carbonate, calcium phosphate or kaolin
- water or an oil medium for example peanut oil, liquid paraffin, or olive oil.
- Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions.
- excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydroxy-propylmethylcellulose, sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide, for example lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxy-ethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan mono
- the aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl, p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin.
- Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin.
- the oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid.
- Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives.
- a dispersing or wetting agent e.g., glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerin, glycerin, glycerin, glycerin, glycerin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerol, glycerol
- the pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions.
- the oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures of these.
- Suitable emulsifying agents may be naturally-occu ing gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate.
- the emulsions may also contain sweetening and flavoring agents.
- Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and flavoring and coloring agents.
- the pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleagenous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above.
- the sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butane diol.
- Suitable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution.
- sterile, fixed oils are conventionally employed as a solvent or suspending medium.
- any bland fixed oil may be employed including synthetic mono- or diglycerides.
- fatty acids such as oleic acid find use in the preparation of injectables.
- compositions may also be administered in the form of suppositories for rectal administration of the drug.
- These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
- suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
- suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
- Such materials are cocoa butter and polyethylene glycols.
- topical application For topical use, creams, ointments, jellies, solutions or suspensions, etc., containing the compounds of the invention are employed. As used herein, topical application is also meant to include the use of mouthwashes and gargles.
- compositions and methods of the invention may further comprise other therapeutically active compounds, as noted herein, useful in the treatment of asthma, allergic diseases, inflammatory conditions and cancer and pathologies associated therewith (e.g., cardiovascular disease) or other adjuvant.
- compositions which include a compounds of the invention and an alternative agent have additive or synergistic effects when administered.
- the invention provides methods of treating or preventing a disease or condition associated with CRTH2 and/or one or more other PGD 2 receptors by administering to a subject having such a condition or disease, a therapeutically effective amount of a compound or composition of the invention.
- diseases and conditions including chronic diseases of humans or other species, can be treated with modulators, or antagonists, of CRTH2 and/or one or more other PGD 2 receptors.
- These diseases and conditions include (1) inflammatory or allergic diseases such as systemic anaphylaxis and hypersensitivity disorders, atopic dermatitis, urticaria, drug allergies, insect sting allergies, food allergies (including celiac disease and the like) and mastocytosis, (2) inflammatory bowel diseases such as Crohn's disease, ulcerative colitis, ileitis and enteritis, (3) vasculitis, Behcet's syndrome, (4) psoriasis and inflammatory dermatoses such as dermatitis, eczema, atopic dermatitis, allergic contact dermatitis, urticaria, viral cutaneous pathologies such as those derived from human papillomavirus, HIV or RLV infection, bacterial, fungal and other parasital cutaneous pathologies, and cutaneous lupus erythematosus, (5) asthma and respiratory allergic diseases such as allergic asthma, allergic rhinitis, otitis media, allergic conjunctivitis, hypersensitivity lung diseases, chronic
- the invention provides methods of treating or preventing a disease or disorder mediated, regulated or influenced by Th2 cells, eosinophils, basophils, platelets, Langerhans cells, dendritic cells or mast cells, comprising administering to a subject having such as disease or disorder a therapeutically effective amount of one or more of the subject compounds or compositions.
- the invention provides methods of treating or preventing a condition or disorder mediated, regulated or influenced by PGD 2 and metabolites thereof, such as 13,14-dihydro-15-keto-PGD 2 and 15-deoxy- ⁇ 12,14 -PGD 2 , comprising administering to a subject having such as disease or disorder a therapeutically effective amount of one or more of the subject compounds or compositions.
- the invention provides methods of treating or preventing a disease or disorder responsive to modulation of CRTH2 and/or one or more other PGD 2 receptors comprising administering to a subject having such a disease or disorder, a therapeutically effective amount of one or more of the subject compounds or compositions.
- the invention provides methods of treating or preventing a disease or disorder mediated by CRTH2 and/or one or more other PGD 2 receptors comprising administering to a subject having such a condition or disease, a therapeutically effective amount of one or more of the subject compounds or compositions.
- the invention provides methods of modulating CRTH2 and/or one or more other PGD 2 receptors comprising contacting a cell with one or more of the subject compounds or compositions.
- the compounds of the invention may be administered by oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous, ICV, intracisternal injection or infusion, subcutaneous injection or implant), inhalation, nasal, vaginal, rectal, sublingual, or topical (e.g., transdermal, local) routes of administration and may be formulated, alone or together, in suitable dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles appropriate for each route of administration.
- the invention also contemplates administration of the compounds of the invention in a depot formulation, in which the active ingredient is released over a defined time period.
- an appropriate dosage level will generally be about 0.001 to 100 mg per kg patient body weight per day which can be administered in single or multiple doses.
- the dosage level will be about 0.01 to about 25 mg/kg per day; more preferably about 0.05 to about 10 mg/kg per day.
- a suitable dosage level may be about 0.01 to 25 mg/kg per day, about 0.05 to 10 mg/kg per day, or about 0.1 to 5 mg/kg per day. Within this range the dosage may be 0.005 to 0.05, 0.05 to 0.5 or 0.5 to 5.0 mg/kg per day.
- the compositions are preferably provided in the form of tablets containing 1.0 to 1000 milligrams of the active ingredient, particularly 1.0, 5.0, 10.0, 15.0.
- the compounds may be administered on a regimen of 1 to 4 times per day, preferably once or twice per day.
- the compounds of the invention can be combined or used in combination with other agents useful in the treatment, prevention, suppression or amelioration of the diseases or conditions for which compounds of the invention are useful, including inflammatory conditions, immune disorders, asthma, allergic rhinitis, eczema, psoriasis, atopic dermatitis, fever, sepsis, systemic lupus erythematosus, diabetes, rheumatoid arthritis, multiple sclerosis, atherosclerosis, transplant rejection, inflammatory bowel disease, cancer, viral infection, thrombosis, fibrosis, flushing, Crohn's disease, ulcerative colitis, chronic obstructive pulmonary disease, inflammation, pain, conjunctivitis, nasal congestion, urticaria and those pathologies noted above.
- agents useful in the treatment, prevention, suppression or amelioration of the diseases or conditions for which compounds of the invention are useful including inflammatory conditions, immune disorders, asthma, allergic rhinitis, eczema, psoria
- Such other agents, or drugs may be administered, by a route and in an amount commonly used therefor, simultaneously or sequentially with a compound of the invention.
- a pharmaceutical composition containing such other drugs in addition to the compound of the invention is prefened.
- the pharmaceutical compositions of the invention include those that also contain one or more other active ingredients or therapeutic agents, in addition to a compound of the invention.
- Examples of other therapeutic agents that may be combined with a compound of the invention, either administered separately or in the same pharmaceutical compositions, include, but are not limited to: (a) VLA-4 antagonists, (b) corticosteroids, such as beclomethasone, methylprednisolone, betamethasone, prednisone, prenisolone, triamcinolone, dexamethasone, fluticasone, flunisolide and hydrocortisone, and corticosteroid analogs such as budesonide; (c) immunosuppressants such as cyclosporine (cyclosporine A, Sandimmune ® , Neorat ® ), tacrolimus (FK-506, Prograf ® ), rapamycin (sirolimus, Rapamune ® ) and other FK-506 type immunosuppressants, and mycophenolate, e.g., mycophenolate mofetil (CellCept ® ); (d) antihistamines (HI
- lubricants or emollients such as petrolatum and lanolin, keratolytic agents, vitamin D 3 derivatives (e.g., calcipotriene and calcipotriol (Dovonex ® )), PUVA, anthralin (Drithrocreme ® ), etretinate (Tegison ® ) and isotretinoin;
- multiple sclerosis therapeutic agents such as interferon ⁇ -l ⁇ (Betaseron ® ), interferon ⁇ -l ⁇ (Avonex ® ), azathioprine (Imurek ® , Imuran ® ), glatiramer acetate (Capoxone ), a glucocorticoid (e.g., prednisolone) and cycl
- the weight ratio of the compound of the invention to the second active ingredient may be varied and will depend upon the effective dose of each ingredient. Generally, an effective dose of each will be used. Thus, for example, when a compound of the invention is combined with an NSAID, the weight ratio of the compound of the invention to the NSAID will generally range from about 1000:1 to about 1:1000, preferably about 200:1 to about 1 :200. Combinations of a compound of the invention and other active ingredients will generally also be within the aforementioned range, but in each case, an effective dose of each active ingredient should be used.
- the invention includes methods to evaluate putative specific agonists or antagonists of CRTH2 and/or one or more other PGD receptors. Accordingly, the invention is directed to the use of these compounds in the preparation and execution of screening assays for compounds which modulate the function of CRTH2 and/or one or more other PGD 2 receptors.
- the compounds of this invention are useful for CRTH2 mutants and/or one or more other PGD 2 receptor mutants, which are excellent screening tools for potent compounds.
- the compounds of this invention are useful in establishing or determining the binding site of other compounds to CRTH2 and/or one or more other PGD 2 receptors, e.g., by competitive inhibition.
- the compounds of the instant invention are also useful for the evaluation of putative specific modulators of CRTH2 and/or one or more other PGD 2 receptors.
- putative specific modulators of CRTH2 and/or one or more other PGD 2 receptors One of skill in the art will appreciate that thorough evaluation of specific agonists and antagonists of PGD 2 receptors has been hampered by the lack of availability of non-peptidyl (metabolically resistant) compounds with high binding affinity for these receptors.
- the compounds provided herein are particularly useful in this context.
- High throughput assays for the presence, absence, quantification, or other properties of particular compounds may be used to test a combinatorial library that contains a large number of potential therapeutic compounds (potential modulator compounds).
- the assays are typically designed to screen large chemical libraries by automating the assay steps and providing compounds from any convenient source to the assays, which are typically run in parallel (e.g., in microtiter formats on microtiter plates in robotic assays).
- Prefened assays detect enhancement or inhibition of CRTH2 and/or one or more other PGD 2 receptors function.
- High throughput screening systems are commercially available (see e.g., Zymark Corp., Hopkinton MA; Air Technical Industries, Mentor OH; Beckman Instruments, Inc., Fullerton CA; Precision Systems, Inc., Natick MA; etc.). These systems typically automate entire procedures, including all sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the assay.
- These configurable systems provide high throughput and rapid start-up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems.
- Zymark Corp. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.
- Reagents and solvents used below can be obtained from commercial sources such as Aldrich Chemical Co. (Milwaukee, Wisconsin, USA).
- 1H-NMR spectra were recorded on a Varian Gemini 400 MHz NMR spectrometer. Sigmficant peaks are tabulated in the order: multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br s, broad singlet), coupling constant(s) in Hertz (Hz) and number of protons.
- Electron Ionization (El) mass spectra were recorded on a Hewlett Packard 5989A mass spectrometer.
- Mass spectrometry results are reported as the ratio of mass over charge, followed by the relative abundance of each ion (in parentheses) or a single m/z value for the M+H (or, as noted, M-H) ion containing the most common atomic isotopes. Isotope patterns conespond to the expected formula in all cases.
- Electrospray ionization (ESI) mass spectrometry analysis was conducted on a Hewlett- Packard 1100 MSD electrospray mass spectrometer using the HP1 100 HPLC for sample delivery.
- the analyte was dissolved in methanol at 0.1 mg/mL and 1 microliter was infused with the delivery solvent into the mass spectrometer, which scanned from 100 to 1500 daltons. All compounds could be analyzed in the positive ESI mode, using 1 : 1 acetonitrile/water with 1 % acetic acid as the delivery solvent. The compounds provided below could also be analyzed in the negative ESI mode, using 2mM NH OAc in acetonitrile/water as delivery solvent.
- 38a 3-Chloro-5-methoxybenoic acid (38a).
- 3,5- dichlorobenzoic acid (1.91 g, 10 mmol, 1.0 equiv.) in 10 mL of HMPA was added NaOMe (1.62 g, 30 mmol, 3.0 equiv.).
- the mixture was heated in a 170 °C oil bath for 72 h. After cooling to room temperature, the mixture was poured into 50 mL of 1 M aqueous HCl. The precipitates were collected by filtration, and washed twice with 20 mL of water. The white solid was dried under vacuum to give 1.4 g of 38a.
- the mixture was warmed to 0 °C. After stirring at 0 °C for another 2 h, the mixture was poured into 200 mL of 1 M aqueous HCl. The mixture was evaporated in vacuo to remove organic solvents. The residue was extracted with 400 mL of ether. The ether layer was washed with 150 mL of saturated NaHCO 3 , 150 mL of brine, dried over Na 2 SO 4 , and evaporated in vacuo to give a light tan oil, which was dissolved in 100 mL of DMSO. NaCN (4.15 g, 85 mmol, 1.1 equiv.) was added to the solution. The mixture was stined vigorously for 14 h.
- Example 47 Example
- Example 47 was prepared in similar fashion as 27. 1H-NMR (CDCI 3 ): ⁇
- Example 51 was prepared in similar fashion as 27. 1H-NMR (CDC1 3 ): ⁇ 7.76-7.77 (m, IH), 7.55-7.60 (m, IH), 7.52-7.57 (m, 2H), 7.05 (m, IH), 7.02-7.04 (m, IH), 6.72-6.74 (m, 2H), 6.55-6.60 (m, IH), 6.10 (m, IH), 3.65 (s, 2H), 3.52-3.54 (m, 2H), 2.42 (s, 3H), 0.89-0.91 (m, 3H). MS (ES+) 503.1 (M+H).
- Scheme 8 a. 4-Toluenesulfonyl chloride, Na 2 CO 3 /H 2 O, 70 °C, 1 h (Org. Synth. Coll. Vol. IV, (1963) 34:35). b. SOCl 2 /DCM, room temperature, 4 days. c. 4- Methoxyphenylacetic acid, AICI 3 /DCE, 50 °C, 3 h.
- Example 58 was prepared according to Scheme 8. ⁇ NMR (CDCI 3 ): ⁇ 11.15 (s, IH), 7.76 (m, 3H), 7.38 (m, 3H), 7.22 (d, 2H), 7.04 (s, IH), 6.93 (m, 2H), 3.63 (s, 3H), 3.59 (s, 2H), 2.36 (s, 3H). MS (ESf) 440.1 [MH] + .
- Example 59 was prepared according to Scheme 9. 1H NMR (CDCI 3 ): ⁇ 11.68 (s, IH), 8.15 (d, IH), 7.62 (d, IH), 7.47 (s, IH), 7.38 (m, 4H), 7.20 (s, IH), 6.97 (d, 2H), 3.67 (s, 3H), 3.64 (s, 2H). MS (ESf) 494.0 [MH] + .
- 61a 61b 61c 61 Scheme 11 a. Ethyl 3 -indoleacetate, tBuOK/DMF, room temperature, overnight, b. H, Pd/C in ethanol, room temperature, 3 h. c. 4-Toluenesulfonyl chloride, DMAP/pyridine. d. LiOH/THF, MeOH and water, room temperature, overnight.
- Example 61 was prepared according to Scheme 11. ] H NMR (CDCI 3 ): ⁇ 7.59 (m, 2H), 7.25 (m, IH), 7.12 (m, 6H), 6.98 (m,lH), 6.73 (m, IH), 6.60 (s, IH), 5.17 (s, 2H), 3.82 (s, 2H), 2.44 (s, 3H). MS (ESf ) 435.1 [MH] + .
- Example 62 was prepared according to Scheme 12. ⁇ NMR (CDCI 3 ): ⁇ 8.65 (m, IH), 8.58 (m, IH), 7.20 (m, 7H), 7.04 (m, 4H), 6.85 (s, IH), 6.80 (s, IH), 5.08 (s, 2H), 3.75 (s, 2H), 3.40 (s, 2H). MS (ESf ) 399.2 [MH] + .
- Example 63 was prepared according to Scheme 13. 1H NMR (CDCI 3 ): ⁇ 7.63 (m,lH), 7.35 (m, IH), 7.21 (m, 6H), 7.06 (m, 3H), 6.98 (s, IH), 6.75 (m, IH), 6.68 (m, IH), 5.17 (s, 2H), 4.23 (s, 2H), 3.76 (s, 2H). MS (ESf ) 371.2 [MH] + .
- Example 64 Example 64
- Example 64 was prepared according to Scheme 14. ⁇ NMR (CDCI 3 ): ⁇ 7.52 (m, 2H), 7.36 (m, IH), 7.20 (m, 7H), 6.95 (m, IH), 6.26 (m, IH), 3.64 (s, 2H), 3.61 (s, 2H), 2.41 (s, 3H). MS (ESf) 396.1 [MH] + .
- Example 65 was prepared according to Scheme 15. ⁇ NMR (CDCI 3 ): ⁇ 8.80 (br s, IH), 7.87 (s, IH), 7.61 (m, 3H), 7.24 (d, 2H), 7.20 (d, IH), 7.15 (d, IH), 7.10 (t, IH), 6.89 (t, IH), 6.34 (d, IH), 6.24 (br s, IH), 3.78 (dd, 2H), 3.65 (m, IH), 3.52 (m, 2H), 3.30 (t, IH), 2.85 (m, 2H), 2.59 (m, IH), 2.42 (s, 3H), 1.28 (m, 3H). MS (ESf ) 508.2 [MH] + .
- Example 66 was prepared according to Scheme 16. H NMR (CDCI 3 ): ⁇ 7.56 (m, 3H), 7.39 (s, IH), 7.36 (m, IH), 7.21 (d, 2H), 7.07 (m, 2H), 6.84 (s, IH), 6.78 (d, IH), 6.55 (d, IH), 6.16 (br s, IH), 5.05 (s, 2H), 3.77 (s, 2H), 3.38 (m, 2H), 2.40 (s, 3H), 1.67 (t, 3H). MS (ESf ) 506.2 [MH] + .
- Example 67 was prepared according to Scheme 17. 1H NMR (CDCI 3 with drops of CD 3 OD) ⁇ 7.37 (m, 3H), 7.18 (m, 6H), 7.08 (d, IH), 7.04 (m, 2H), 6.80 (d, IH), 5.39 (d, IH), 4.93 (d, IH), 4.77 (d, IH), 3.86 (d, IH), 3.53 (s, 2H), 3.29 (s, 3H). MS (ESf) 433.2 [MH] + .
- Scheme 18 a. NEt 3 /EtOH, 100°C, 5days; b. EtNH 2 , EDC, HOBt, NMM/DCM, r.t., 4h; c. H 2 , Pd/C, EtOH, r.t., lh; d. Malonyl dichloride/THF, r.t., 2 days; e. 4-Chlorobenzyl chloride, tBuOK DMF, r.t., overnight; f. LiOH/THF, MeOH, and water, r.t., overnight.
- Example 68 was prepared according to Scheme 18. 1H NMR (CDC1 3 with drops of CD 3 OD) ⁇ 8.05 (s, IH), 7.38 (d, IH), 7.20 (m, 4H), 7.12 (d, 2H), 6.86 (d, IH), 6.59 (d, 2H), 5.86 (d, IH), 4.69 (d, IH), 3.58 (s, 2H), 3.51 (s, 2H), 3.46 (q, 2H), 1.24 (t, 3H). MS (ESf) 506.1 [MHf.
- Example 69 was prepared according to Scheme 19. 1H NMR (CDC1 3 with drops of CD 3 OD) ⁇ 7.54 (d, 2H), 7.35 (m, IH), 7.14 (m, 6H), 6.83 (d, 2H), 3.51 (s, 2H), 3.34 (q, 2H), 2.30 (s, 3H), 1.16 (t, 3H). MS (ESf ) 468.2 [MHf.
- Example 70 was prepared according to Scheme 20. 1H NMR (CDCI 3 ) ⁇ 10.96 (s, IH), 8.00 (s, IH), 7.74 (d, 2H), 7.40 (m, 3H), 7.22 (d, 2H), 7.07 (s, IH), 6.91 (d, IH), 6.18 (br s, IH), 3.61 (s, 2H), 3.59 (s, 3H), 3.50 (m, 2H), 2.35 (s, 3H), 1.27 (t, 3H). MS (ESf) 511.2 [MHf.
- Example 71 was prepared according to Scheme 21. ⁇ NMR (CDC1 3 ) ⁇ 8.11 (s, IH), 7.73 (s, IH), 7.56 (d, IH), 7.50 (d, 2H), 7.30 (d, IH), 7.17 (m, 3H), 7.00 (s, IH), 6.86 (d, IH), 6.15 (br s, IH), 3.99 (s, 3H), 3.52 (s, 2H), 3.47 (m, 4H), 2.35 (s, 3H), 1.27 (t, 3H). MS (ESf ) 497.2 [MH] + .
- Example 72 was prepared according to Scheme 22. ⁇ NMR (CDCI 3 ) ⁇ 8.42 (s, IH), 7.76 (s, IH), 7.61 (d, 2H), 7.50 (d, IH), 7.21 (m, 3H), 7.06 (d, IH), 6.97 (s, IH), 6.86 (d, IH), 6.15 (br s, IH), 5.58 (s, IH), 3.82 (s, 3H), 3.53 (s, 2H), 3.47 (m, 2H), 2.39 (s, 3H), 1.24 (t, 3H). MS (ESf) 513.2 [MH] + .
- Example 73 2,4-Dichlorobenzenesulfonyl chloride (112 g, 455 mmol) was added to a mixture of 73d (135 g, 350 mmol) and 2,6-lutidine (57 mL, 490 mmol) in THF (500 mL) at r.t. The mixture was heated to 60° C and stirred for 12 h. After cooling to r.t., water (300 mL) and ION NaOH (180 mL) were added. The mixture was stined at r.t. for 2 h, acidified to pH 2 with concentrated HCl, and extracted with EtOAc (1 L).
- Example 74 was prepared from Example 12 according to Scheme 24.
- Example 84 was prepared according to Scheme 32.
- Example 85 was prepared from 2-(4-hydroxyphenyl)propionic acid methyl ester following the procedure described for 84.
- Example 86 was prepared according to Scheme 33.
- Example 87 was prepared according to Scheme 34. ⁇ NMR (CDCI 3 ) ⁇
- Scheme 35 a. K 2 CO 3 , DMSO, 60 °C, overnight; b. LiOH/THF, MeOH, and water, r.t., 2 h; c. thionyl chloride, 80 °C, 6 h; d. TMSCHN2, TEA, THF/CH 3 CN; e. silver benzoate, MeOH, r.t., 2 h; f. Fe, AcOH, 60 °C, 3 h; g. 4-Chlorobenzenesulfonyl chloride, 2,6-lutidine, CH 2 C1 2 , overnight.
- Example 89 was prepared according to Scheme 35.
- 2,4-Difluorobenzenesulfonyl chloride 2,6-lutidine, CH 2 C1 2 , overnight; d. LiOH/THF, MeOH, and water, r.t., 2 h; e. Br 2 , AcOH, r.t., overnight; f. Pd(PPh 3 ) 4 , tributyl(vinyl)tin, toluene, reflux, 6 h; g. H 2j Pd/C, EtOH, r.t., 2h.
- Example 92 was prepared according to Scheme 37.
- Full-length human CRTH2 cDNA was generated by polymerase chain reaction (PCR) using human genomic DNA as template and subsequently cloned into pCDNA3.1 (+) (Invitrogen), generating a CRTH2 expression plasmid pHLT 124.
- the plasmid was transfected into 293 cells, which normally express CRTH2, using LipofectAMINETM reagents (Gibco/BRL).
- G418 800mg/mL was added to the culture 48 h after transfection and cells were maintained under selection for 3 weeks to ensure that all surviving cells stably expressed CRTH2. These cells are labeled as 293(124) hereafter.
- 3 H-PGD 2 binding assay was performed using 293(124) cells. In brief, cells were washed and suspended in RPMI containing 0.5% BSA and 20mM HEPES. Each assay contained 25,000 cells, appropriate amount of test compound when necessary and a mixture of lnM 3 H-PGD 2 (Amersham Pharmacia Biotech) and 30nM of unlabeled PGD 2 (Cayman Chemicals) in 200 mL final volume. The cell mixture was incubated at room temperature for 2.5 h with shaking and the cells were separated from free 3 H-PGD 2 and transfened onto a filter plate using a cell harvester. Radioactivity bound to the cells was measured on a liquid scintillation counter. Nonspecific binding was determined in the presence of lOmM of unlabeled PGD 2 .
- Modulation of CRTH2 and/or one or more other PGD 2 receptors by test compounds can be assessed by other in vitro and in vivo assays.
- assays include measuring second messenger (e.g., cAMP, IP 3 or Ca 2+ ) levels, ion flux, phosphorylation levels, transcription levels, and the like.
- second messenger e.g., cAMP, IP 3 or Ca 2+
- Recombinant or naturally occurring CRTH2 polypeptides and/or other PGD 2 receptor peptides can be used and the protein can be isolated, expressed in a cell, expressed in a membrane derived from a cell, expressed in tissue or in an animal.
- Signal transduction can also be examined in vitro with soluble or solid state reactions, using a chimeric molecule such as an extracellular domain of a receptor covalently linked to a heterologous signal transduction domain, or a heterologous extracellular domain covalently linked to the transmembrane and/or cytoplasmic domain of a receptor. Gene amplification can also be examined. Furthermore, ligand-binding domains of the protein of interest can be used in vitro in soluble or solid state reactions to assay for ligand binding.
- CRTH2-G-protein or another PGD 2 receptor-G-protein interactions can also be examined, by, for example, analysis of binding of the G-protein to the receptor or its release from the receptor.
- Exemplary compounds of the invention displayed IC 50 values as shown in Table I in the above-described ligand binding assay.
- Cyclic AMP assays on human DP function are performed using human platelets (AllCells, Berkeley, CA) and the 96-well Tropix cAMP ELISA System (Applied Biosystems) following the manufacturer's manual. Briefly, the human platelets rich plasma (PRP) is diluted 1 :3 with human plasma and incubated with ImM of the phosphodiesterases inhibitor 3-isobutyl-l-methylxanthine (IBMX, Sigma) at 37 °C for 20 min, to prevent hydrolysis of cAMP. 20 ⁇ l of the above PRP sample is mixed 1:1:1 with the test compound and PGD (both prepared in the assay buffer with DMSO concentration ⁇ 1%) in a 96-well plate.
- PRP human platelets rich plasma
- IBMX 3-isobutyl-l-methylxanthine
- the assay buffer can be OPTI-free medium (Gibco BRL). After 20 min incubation at 37 °C, 20 ⁇ l of lysis buffer from the kit is added to each well of the mixture and the plate then incubated at room temperature for 10 min with moderate shaking and at 37 °C for 10 min. After the cell lysis, 60 ⁇ l of the cell lysate together with 30 ⁇ l of diluted cAMP-AP conjugate and 60 ⁇ l anti-cAMP antibody is then transferred into a kit assay plate and the plate incubated at room temperature for 30 min with shaking. The plate is then washed with wash buffer and incubated with 100 ⁇ l per well of substrate/enhancer solution at room temperature for 60 min.
- OPTI-free medium Gibco BRL
- Light signal intensity which is inversely proportional to the cAMP level in each sample, is measured in a luminometer (CLIPR, Dynamic Devices).
- the final human plasma concentration in the assay described above is about 33%.
- the assays are also performed using washed platelets (prepared by centrifuging the PRP at 2000 rpm for 15 min and resuspending the platelets in the assay buffer), or in the presence of higher than about 33% of human plasma by also preparing the test compound and/or PGD solution in human plasma.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Virology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Transplantation (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03814219A EP1585511B1 (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
NZ541234A NZ541234A (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
MXPA05006701A MXPA05006701A (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators. |
EA200501017A EA011087B1 (en) | 2002-12-20 | 2003-12-19 | Compounds and pharmaceutical compositions for treating inflammation diseases |
BR0317591-0A BR0317591A (en) | 2002-12-20 | 2003-12-19 | Pharmaceutically acceptable compound, salt or prodrug, pharmaceutical composition, and methods for treating a disease or condition, for modulating the function of crth2 and / or one or more other pgd2 receptors in a cell and for modulating crth2 and / or a or more other pgd2 receptors |
JP2004563827A JP4457017B2 (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
AU2003297398A AU2003297398B2 (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
ES03814219T ES2401079T3 (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
CA2511214A CA2511214C (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
IS7907A IS7907A (en) | 2002-12-20 | 2005-06-22 | Asthma and adjusts allergic inflammation |
NO20053114A NO20053114L (en) | 2002-12-20 | 2005-06-24 | Asthma and allergic inflammatory modulators. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43536602P | 2002-12-20 | 2002-12-20 | |
US60/435,366 | 2002-12-20 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2004058164A2 true WO2004058164A2 (en) | 2004-07-15 |
WO2004058164A3 WO2004058164A3 (en) | 2004-08-26 |
Family
ID=32682226
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2003/040617 WO2004058164A2 (en) | 2002-12-20 | 2003-12-19 | Asthma and allergic inflammation modulators |
Country Status (17)
Country | Link |
---|---|
US (2) | US7321001B2 (en) |
EP (1) | EP1585511B1 (en) |
JP (1) | JP4457017B2 (en) |
KR (1) | KR20050111314A (en) |
CN (1) | CN100406007C (en) |
AU (1) | AU2003297398B2 (en) |
BR (1) | BR0317591A (en) |
CA (1) | CA2511214C (en) |
EA (1) | EA011087B1 (en) |
ES (1) | ES2401079T3 (en) |
IS (1) | IS7907A (en) |
MX (1) | MXPA05006701A (en) |
NO (1) | NO20053114L (en) |
NZ (1) | NZ541234A (en) |
PL (1) | PL377314A1 (en) |
WO (1) | WO2004058164A2 (en) |
ZA (1) | ZA200505523B (en) |
Cited By (88)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005073234A3 (en) * | 2004-01-31 | 2005-10-06 | Bayer Healthcare Ag | Imidazo[1,2-c]pyrimidinylacetic acid derivatives |
WO2006037982A2 (en) * | 2004-10-05 | 2006-04-13 | Astrazeneca Ab | Modulators of crth2 receptor activity for the treatment of prostaglandin d2 mediated diseases |
WO2007014008A2 (en) * | 2005-07-22 | 2007-02-01 | Glaxo Group Limted | Benzenesulfonamide inhibitor of ccr2 chemokine receptor |
WO2007039736A1 (en) | 2005-10-06 | 2007-04-12 | Astrazeneca Ab | Novel compounds |
WO2007110876A2 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Novel sulfonanilide derivatives, pharmaceutical compositions comprising the same and process thereof |
WO2008008374A2 (en) * | 2006-07-14 | 2008-01-17 | Chemocentryx, Inc. | Ccr2 inhibitors and methods of use thereof |
US7321001B2 (en) | 2002-12-20 | 2008-01-22 | Amgen Inc. | Asthma and allergic inflammation modulators |
WO2008024746A1 (en) | 2006-08-21 | 2008-02-28 | Array Biopharma, Inc. | 4-substituted phenoxyphenylacetic acid derivatives |
WO2007146838A3 (en) * | 2006-06-09 | 2008-03-13 | Icos Corp | Substituted phenyl acetic acids as dp-2 antagonists |
WO2007143745A3 (en) * | 2006-06-09 | 2008-04-17 | Icos Corp | Substituted phenyl acetic acids as dp-2 antagonists |
WO2008137027A2 (en) * | 2007-05-02 | 2008-11-13 | Amgen Inc. | Compounds as crth2 and/or pgd2 receptors modulators and their use for treating asthma and allergic inflammation |
JP2008542217A (en) * | 2005-05-24 | 2008-11-27 | ノバルティス アクチエンゲゼルシャフト | Organic compounds for the treatment of inflammation or allergic conditions |
JP2009518344A (en) * | 2005-12-09 | 2009-05-07 | ノバルティス アクチエンゲゼルシャフト | Bicyclic heterocyclic compounds as anti-inflammatory or anti-allergic agents |
US7531568B2 (en) | 2004-11-30 | 2009-05-12 | Plexxikon, Inc. | PPAR active compounds |
EP2060258A1 (en) | 2003-10-23 | 2009-05-20 | Oxagen Limited | Use of CRTH2 antagonist compounds in therapy |
WO2009085177A1 (en) | 2007-12-19 | 2009-07-09 | Amgen Inc. | Phenyl acetic acid derivatives as inflammation modulators |
WO2009090414A1 (en) | 2008-01-18 | 2009-07-23 | Oxagen Limited | Compounds having crth2 antagonist activity |
WO2009090399A1 (en) * | 2008-01-18 | 2009-07-23 | Argenta Discovery Limited | Indoles active on crth2 receptor |
WO2009093026A1 (en) | 2008-01-22 | 2009-07-30 | Oxagen Limited | Compounds having crth2 antagonist activity |
WO2009099902A1 (en) | 2008-02-01 | 2009-08-13 | Amira Pharmaceuticals, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
US7622583B2 (en) | 2005-01-14 | 2009-11-24 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
WO2009158426A1 (en) | 2008-06-25 | 2009-12-30 | Array Biopharma Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
US7714132B2 (en) | 2004-03-11 | 2010-05-11 | Actelion Pharmaceuticals, Ltd. | Tetrahydropyridoindole derivatives |
US7737135B2 (en) | 2004-08-24 | 2010-06-15 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
WO2010075200A1 (en) | 2008-12-22 | 2010-07-01 | Array Biopharma Inc. | 7-phenoxychroman carboxylic acid derivatives |
US7812160B2 (en) | 2003-04-25 | 2010-10-12 | Actimis Pharmaceuticals, Inc. | Pyrimidine derivatives useful for the treatment of diseases mediated by CRTH2 |
EP2245002A1 (en) * | 2008-02-01 | 2010-11-03 | Amira Pharmaceuticals, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
US7884110B2 (en) | 2007-07-12 | 2011-02-08 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
WO2011002814A3 (en) * | 2009-06-30 | 2011-05-26 | Ligand Pharmaceuticals Inc. | Sulfonamido - biphenyloxyacetic acid compounds |
EP2327693A1 (en) | 2007-12-14 | 2011-06-01 | Pulmagen Therapeutics (Asthma) Limited | Indoles and their therapeutic use |
US7964732B2 (en) | 2006-11-17 | 2011-06-21 | Pfizer Inc. | Substituted bicyclocarboxyamide compounds |
WO2011079007A1 (en) | 2009-12-23 | 2011-06-30 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
US7999109B2 (en) | 2002-05-24 | 2011-08-16 | Millennium Pharmaceuticals, Inc. | CCR9 inhibitors and methods of use thereof |
US8003703B2 (en) | 2003-08-21 | 2011-08-23 | Astrazeneca Ab | Phenoxiacetic acid derivatives |
US8008350B2 (en) | 2005-10-06 | 2011-08-30 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
US8022248B2 (en) | 2004-07-08 | 2011-09-20 | Astrazeneca Ab | Substituted acids for the treatment of respiratory diseases |
WO2011115804A1 (en) | 2010-03-17 | 2011-09-22 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
US8034826B2 (en) | 2008-11-06 | 2011-10-11 | Panmira Pharmaceuticals, Llc | Cycloalkane[B]azaindole antagonists of prostaglandin D2 receptors |
US8049015B2 (en) | 2008-09-29 | 2011-11-01 | Panmira Pharmaceuticals, Llc | Heteroaryl antagonists of prostaglandin D2 receptors |
US8053463B2 (en) | 2007-03-08 | 2011-11-08 | Plexxikon Inc. | PPAR active compounds |
US8071807B2 (en) | 2008-07-03 | 2011-12-06 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
WO2012003405A1 (en) | 2010-06-30 | 2012-01-05 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2012009137A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
WO2012009134A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
US8158820B2 (en) | 2003-04-07 | 2012-04-17 | Astrazeneca Ab | Compounds |
US8168673B2 (en) | 2008-01-22 | 2012-05-01 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
WO2012061926A1 (en) * | 2010-11-08 | 2012-05-18 | Zalicus Pharmaceuticals Ltd. | Bisarylsulfone and dialkylarylsulfone compounds as calcium channel blockers |
WO2012064559A1 (en) | 2010-11-09 | 2012-05-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
EP2462110A2 (en) * | 2009-08-05 | 2012-06-13 | Panmira Pharmaceuticals, LLC | Dp2 antagonist and uses thereof |
EP2480225A2 (en) * | 2009-07-31 | 2012-08-01 | Panmira Pharmaceuticals, LLC | Dermal formulations of dp2 receptor antagonists |
US8242145B2 (en) | 2008-02-14 | 2012-08-14 | Panmira Pharmaceuticals, Llc | Cyclic diaryl ether compounds as antagonists of prostaglandin D2 receptors |
EP2492268A1 (en) | 2006-07-22 | 2012-08-29 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
US8314116B2 (en) | 2007-09-25 | 2012-11-20 | Actimis Pharmaceuticals, Inc. | 2-S-benzyl substituted pyrimidines as CRTH2 antagonists |
EP2526945A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | New CRTH2 Antagonists |
US8324229B2 (en) | 2007-09-25 | 2012-12-04 | Actimis Pharmaceuticals, Inc. | Alkylthio pyrimidines as CRTH2 antagonists |
EP2548863A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists. |
EP2548876A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists |
US8378107B2 (en) | 2008-10-01 | 2013-02-19 | Panmira Pharmaceuticals, Llc | Heteroaryl antagonists of prostaglandin D2 receptors |
US8383654B2 (en) | 2008-11-17 | 2013-02-26 | Panmira Pharmaceuticals, Llc | Heterocyclic antagonists of prostaglandin D2 receptors |
US8426449B2 (en) | 2008-04-02 | 2013-04-23 | Panmira Pharmaceuticals, Llc | Aminoalkylphenyl antagonists of prostaglandin D2 receptors |
WO2013088109A1 (en) | 2011-12-16 | 2013-06-20 | Oxagen Limited | Combination of crth2 antagonist and a proton pump inhibitor for the treatment of eosinophilic esophagitis |
WO2013101830A1 (en) | 2011-12-27 | 2013-07-04 | Ironwood Pharmaceuticals, Inc. | 2 - benzyl, 3 - (pyrimidin- 2 -yl) substituted pyrazoles useful as sgc stimulators |
US8497381B2 (en) | 2008-02-25 | 2013-07-30 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
US8501959B2 (en) | 2008-06-24 | 2013-08-06 | Panmira Pharmaceuticals, Llc | Cycloalkane[B]indole antagonists of prostaglandin D2 receptors |
US8507544B2 (en) | 2007-07-05 | 2013-08-13 | Astrazeneca Ab | Bi-aryl amide compounds as CRTh2 receptor modulators |
US8519135B2 (en) | 2006-07-14 | 2013-08-27 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
US8524715B2 (en) | 2004-11-23 | 2013-09-03 | Astrazeneca Ab | Phenoxyacetic acid derivatives useful for treating respiratory diseases |
US8524748B2 (en) | 2008-10-08 | 2013-09-03 | Panmira Pharmaceuticals, Llc | Heteroalkyl biphenyl antagonists of prostaglandin D2 receptors |
US8575158B2 (en) | 2010-07-05 | 2013-11-05 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
US8642629B2 (en) | 2008-11-17 | 2014-02-04 | Hoffmann-La Roche Inc. | Naphthylacetic acids |
WO2014047111A1 (en) | 2012-09-18 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2014047325A1 (en) | 2012-09-19 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
US8785393B2 (en) | 2009-07-31 | 2014-07-22 | Panmira Pharmaceuticals, Llc | Ophthalmic pharmaceutical compositions of DP2 receptor antagonists |
WO2014144100A2 (en) | 2013-03-15 | 2014-09-18 | Takashi Nakai | Sgc stimulators |
WO2015089182A1 (en) | 2013-12-11 | 2015-06-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2015106268A1 (en) | 2014-01-13 | 2015-07-16 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
WO2016044446A2 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2016044447A1 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | Pyrazole derivatives as sgc stimulators |
WO2016044445A2 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
US9688624B2 (en) | 2010-01-06 | 2017-06-27 | Brickell Biotech, Inc. | DP2 antagonist and uses thereof |
US9828359B2 (en) | 2013-12-17 | 2017-11-28 | Atopix Therapeutics Limited | Process for the preparation of 3-substituted (indol-1-yl)-acetic acid esters |
WO2018009596A1 (en) | 2016-07-07 | 2018-01-11 | Ironwood Pharmaceuticals, Inc. | Phosphorus prodrugs of sgc stimulators |
WO2018009609A1 (en) | 2016-07-07 | 2018-01-11 | Ironwood Pharmaceuticals, Inc. | Solid forms of an sgc stimulator |
US10758540B2 (en) | 2017-10-11 | 2020-09-01 | Chemocentryx, Inc. | Treatment of focal segmental glomerulosclerosis with CCR2 antagonists |
US10973809B2 (en) | 2016-11-23 | 2021-04-13 | Chemocentryx, Inc. | Method of treating focal segmental glomerulosclerosis |
US11191747B2 (en) | 2019-04-03 | 2021-12-07 | Aligos Therapeutics, Inc. | Pyrrole compounds |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7420055B2 (en) | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
CN1511828A (en) * | 2002-12-31 | 2004-07-14 | �й������ž�����ҽѧ��ѧԺ����ҽ | Sufonic aniline derivatives and their medicinal use |
US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
GB0307428D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
SE0301009D0 (en) * | 2003-04-07 | 2003-04-07 | Astrazeneca Ab | Novel compounds |
US20080254053A1 (en) * | 2003-04-09 | 2008-10-16 | Mullally John P | Protocol for treatment of diabetes |
ES2299906T3 (en) * | 2003-11-25 | 2008-06-01 | Eli Lilly And Company | RECEIVER MODULATORS ACTIVATED BY PEROXISOM PROLIFERATORS. |
EP1701940B1 (en) * | 2003-12-23 | 2008-05-28 | H.Lundbeck A/S | 2-(1h-indolylsulfanyl)-benzyl amine derivatives as ssri |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
AR052308A1 (en) * | 2004-07-16 | 2007-03-14 | Lundbeck & Co As H | DERIVATIVES OF 2- (1H-INDOLILSULFANIL) -ARILAMINE AND A PHARMACEUTICAL COMPOSITION CONTAINING THE COMPOUND |
US7968287B2 (en) | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
US8426475B2 (en) | 2005-04-13 | 2013-04-23 | Astion Development A/S | Treatment of connective tissue diseases of the skin |
BRPI0610035A2 (en) * | 2005-04-21 | 2010-05-18 | Serono Lab | substituted pyrazine sulfonamides 2,3 |
AR054393A1 (en) * | 2005-06-17 | 2007-06-20 | Lundbeck & Co As H | DERIVATIVES OF BENZO (B) FURANO AND BENZO (B) THIOPHEN, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE IN THE MANUFACTURE OF A MEDICINAL PRODUCT FOR THE TREATMENT OF DISEASES MEDIATED BY THE INHIBITION OF THE REINFORCEMENT OF AMINA BOSS NEUTRANTS. |
US7629473B2 (en) * | 2005-06-17 | 2009-12-08 | H. Lundbeck A/S | 2-(1H-indolylsulfanyl)-aryl amine derivatives |
EP1948630A2 (en) * | 2005-11-05 | 2008-07-30 | AstraZeneca AB | Novel compounds |
JP2009519308A (en) * | 2005-12-15 | 2009-05-14 | アストラゼネカ・アクチエボラーグ | Substituted diphenyl ethers, amines, sulfides and methane for the treatment of respiratory diseases |
US20100137163A1 (en) | 2006-01-11 | 2010-06-03 | Link Darren R | Microfluidic Devices and Methods of Use in The Formation and Control of Nanoreactors |
WO2007133710A2 (en) * | 2006-05-11 | 2007-11-22 | Raindance Technologies, Inc. | Microfluidic devices and methods of use thereof |
US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
WO2008021123A1 (en) | 2006-08-07 | 2008-02-21 | President And Fellows Of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
US8772046B2 (en) | 2007-02-06 | 2014-07-08 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
US20100305074A1 (en) * | 2007-04-04 | 2010-12-02 | Hight H Thomas | Niacin-based pharmaceutical compositions |
WO2008130623A1 (en) | 2007-04-19 | 2008-10-30 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
WO2009061681A2 (en) * | 2007-11-06 | 2009-05-14 | Amira Pharmaceuticals, Inc | Antagonists of pgd2 receptors |
WO2009061676A2 (en) * | 2007-11-06 | 2009-05-14 | Amira Pharmaceuticals, Inc. | Antagonists of pgd2 receptors |
US7750027B2 (en) * | 2008-01-18 | 2010-07-06 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
US8338406B2 (en) | 2008-02-22 | 2012-12-25 | Otsuka Pharmaceutical Co., Ltd. | Benzodiazepine compound and pharmaceutical composition |
EP2315629B1 (en) | 2008-07-18 | 2021-12-15 | Bio-Rad Laboratories, Inc. | Droplet libraries |
EP2411148B1 (en) | 2009-03-23 | 2018-02-21 | Raindance Technologies, Inc. | Manipulation of microfluidic droplets |
CN102639512B (en) | 2009-08-21 | 2015-12-09 | 大塚制药株式会社 | The preparation method of benzo [b] [Isosorbide-5-Nitrae] diaza *-2,4-dione compounds |
TWI481601B (en) * | 2009-08-21 | 2015-04-21 | Otsuka Pharma Co Ltd | Nitrogen-containing compound and pharmaceutical composition |
EP2486409A1 (en) | 2009-10-09 | 2012-08-15 | Universite De Strasbourg | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
US10837883B2 (en) | 2009-12-23 | 2020-11-17 | Bio-Rad Laboratories, Inc. | Microfluidic systems and methods for reducing the exchange of molecules between droplets |
US9399797B2 (en) | 2010-02-12 | 2016-07-26 | Raindance Technologies, Inc. | Digital analyte analysis |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US8535889B2 (en) | 2010-02-12 | 2013-09-17 | Raindance Technologies, Inc. | Digital analyte analysis |
US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
EP3447155A1 (en) | 2010-09-30 | 2019-02-27 | Raindance Technologies, Inc. | Sandwich assays in droplets |
EP3859011A1 (en) | 2011-02-11 | 2021-08-04 | Bio-Rad Laboratories, Inc. | Methods for forming mixed droplets |
WO2012112804A1 (en) | 2011-02-18 | 2012-08-23 | Raindance Technoligies, Inc. | Compositions and methods for molecular labeling |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
EP3216872B1 (en) | 2011-06-02 | 2020-04-01 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US8658430B2 (en) | 2011-07-20 | 2014-02-25 | Raindance Technologies, Inc. | Manipulating droplet size |
CN104011021B (en) | 2011-12-21 | 2016-08-24 | 埃科特莱茵药品有限公司 | Hete rocyclic derivatives and the purposes as prostaglandin D 2 receptor conditioning agent thereof |
CN104341307B (en) * | 2013-08-05 | 2016-12-28 | 北京京朋汇药业研究发展有限公司 | Phenylacetic acid derivatives and anticancer usage thereof |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US9944977B2 (en) | 2013-12-12 | 2018-04-17 | Raindance Technologies, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
WO2015103367A1 (en) | 2013-12-31 | 2015-07-09 | Raindance Technologies, Inc. | System and method for detection of rna species |
GB201407807D0 (en) | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
GB201407820D0 (en) | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
CN112500281A (en) * | 2020-12-07 | 2021-03-16 | 唐山师范学院 | Preparation method of syringic acid |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995033461A1 (en) | 1994-06-02 | 1995-12-14 | Smithkline Beecham Corporation | Anti-inflammatory compounds |
EP0947500A1 (en) | 1996-12-18 | 1999-10-06 | Ono Pharmaceutical Co., Ltd. | Sulfonamide and carboxamide derivatives and drugs containing the same as the active ingredient |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8704158D0 (en) | 1987-02-23 | 1987-04-01 | Wellcome Found | Substituted hydantoin compounds |
DE4041780A1 (en) * | 1990-12-24 | 1992-06-25 | Boehringer Mannheim Gmbh | NEW AMINES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS |
CA2166413A1 (en) | 1993-06-30 | 1995-01-12 | Richard James Arrowsmith | Anti-atherosclerotic diaryl compounds |
GB9420557D0 (en) * | 1994-10-12 | 1994-11-30 | Zeneca Ltd | Aromatic compounds |
ES2180664T3 (en) | 1994-12-20 | 2003-02-16 | Hoffmann La Roche | DERIVATIVES OF ARIL- AND HETEROARILSULFONAMIDE, OBTAINING AND USE OF THE SAME IN QUALITY OF ENDOTHELINE ANTAGONISTS. |
PT929547E (en) | 1996-09-12 | 2003-03-31 | Schering Ag | BENZAMIDINE DERIVATIVES SUBSTITUTED BY CYCLIC AMINO ACIDS AND CYCLIC HYDROXIACID DERIVATIVES AND ITS USE AS ANTICOAGULANTS |
US6008234A (en) | 1996-09-12 | 1999-12-28 | Berlex Laboratories, Inc. | Benzamidine derivatives substituted by cyclic amino acid and cyclic hydroxy acid derivatives and their use as anti-coagulants |
JPH11202458A (en) | 1998-01-16 | 1999-07-30 | Fuji Photo Film Co Ltd | Silver halide photographic sensitive material |
EP1076641A1 (en) | 1998-04-29 | 2001-02-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of impdh enzyme |
JP2000007646A (en) * | 1998-06-16 | 2000-01-11 | Ono Pharmaceut Co Ltd | Sulfonamide derivative and agent containing the derivative as active component |
AR023659A1 (en) | 1998-09-18 | 2002-09-04 | Vertex Pharma | AN INHIBITOR COMPOUND OF P38, A PHARMACEUTICAL COMPOSITION THAT INCLUDES IT AND THE USE OF SUCH COMPOSITION IN THE TREATMENT AND PREVENTION OF PATHOLOGICAL STATES |
US6248739B1 (en) | 1999-01-08 | 2001-06-19 | Pharmacia & Upjohn Company | Quinolinecarboxamides as antiviral agents |
WO2000053573A1 (en) | 1999-03-10 | 2000-09-14 | Shionogi & Co., Ltd. | Medicinal compositions with [2.2.1] and [3.1.1] bicycloskeleton antagonistic to both of pgd2/txa2 receptors |
EP1211513B1 (en) | 1999-08-23 | 2006-01-04 | BML, Inc. | Method of identifying modulators of prostaglandin d2 receptors |
US6531291B1 (en) * | 1999-11-10 | 2003-03-11 | The Trustees Of Columbia University In The City Of New York | Antimicrobial activity of gemfibrozil and related compounds and derivatives and metabolites thereof |
US20010047027A1 (en) | 2000-04-12 | 2001-11-29 | Marc Labelle | Prostaglandin D2 receptor antagonists |
JPWO2001094309A1 (en) | 2000-06-02 | 2004-02-05 | 塩野義製薬株式会社 | PGD2 / TXA2 receptor antagonist pharmaceutical composition |
US6878522B2 (en) | 2000-07-07 | 2005-04-12 | Baiyong Li | Methods for the identification of compounds useful for the treatment of disease states mediated by prostaglandin D2 |
AU2002229611A1 (en) | 2000-12-08 | 2002-06-18 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Use of active compounds capable of modulating the intracellular pathway triggered by the dp receptor in langerhans cells |
EP1395590B1 (en) | 2001-05-23 | 2006-09-27 | Merck Frosst Canada & Co. | Dihydropyrrolo¬1,2-a|indole and tetrahydropyrido¬1,2-a|indole derivatives as prostaglandin d2 receptor antagonists |
CN1551866A (en) | 2001-08-09 | 2004-12-01 | СҰҩƷ��ҵ��ʽ���� | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
SE0200356D0 (en) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
SE0200411D0 (en) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
ATE516277T1 (en) | 2002-03-19 | 2011-07-15 | Ono Pharmaceutical Co | CARBOXYLIC ACID COMPOUNDS AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS AS ACTIVE INGREDIENTS |
AU2003231509A1 (en) | 2002-05-16 | 2003-12-02 | Shionogi And Co., Ltd. | Compound exhibiting pgd 2 receptor antagonism |
WO2003097042A1 (en) | 2002-05-16 | 2003-11-27 | Shionogi & Co., Ltd. | Pgd2 receptor antagonist |
GB2388540A (en) | 2002-05-17 | 2003-11-19 | Bayer Ag | New use of Ramatroban |
TW200307542A (en) | 2002-05-30 | 2003-12-16 | Astrazeneca Ab | Novel compounds |
SE0201635D0 (en) | 2002-05-30 | 2002-05-30 | Astrazeneca Ab | Novel compounds |
ZA200505523B (en) | 2002-12-20 | 2006-09-27 | Amgen Inc | Asthma and allergic inflammation modulators |
-
2003
- 2003-12-19 ZA ZA200505523A patent/ZA200505523B/en unknown
- 2003-12-19 US US10/742,281 patent/US7321001B2/en active Active
- 2003-12-19 PL PL377314A patent/PL377314A1/en not_active Application Discontinuation
- 2003-12-19 ES ES03814219T patent/ES2401079T3/en not_active Expired - Lifetime
- 2003-12-19 WO PCT/US2003/040617 patent/WO2004058164A2/en active Application Filing
- 2003-12-19 CN CNB2003801097235A patent/CN100406007C/en not_active Expired - Fee Related
- 2003-12-19 NZ NZ541234A patent/NZ541234A/en not_active IP Right Cessation
- 2003-12-19 CA CA2511214A patent/CA2511214C/en not_active Expired - Fee Related
- 2003-12-19 EA EA200501017A patent/EA011087B1/en not_active IP Right Cessation
- 2003-12-19 KR KR1020057011677A patent/KR20050111314A/en active IP Right Grant
- 2003-12-19 AU AU2003297398A patent/AU2003297398B2/en not_active Ceased
- 2003-12-19 MX MXPA05006701A patent/MXPA05006701A/en active IP Right Grant
- 2003-12-19 JP JP2004563827A patent/JP4457017B2/en not_active Expired - Fee Related
- 2003-12-19 BR BR0317591-0A patent/BR0317591A/en not_active IP Right Cessation
- 2003-12-19 EP EP03814219A patent/EP1585511B1/en not_active Expired - Lifetime
-
2005
- 2005-06-22 IS IS7907A patent/IS7907A/en unknown
- 2005-06-24 NO NO20053114A patent/NO20053114L/en not_active Application Discontinuation
-
2007
- 2007-11-26 US US11/986,863 patent/US7541383B2/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995033461A1 (en) | 1994-06-02 | 1995-12-14 | Smithkline Beecham Corporation | Anti-inflammatory compounds |
EP0947500A1 (en) | 1996-12-18 | 1999-10-06 | Ono Pharmaceutical Co., Ltd. | Sulfonamide and carboxamide derivatives and drugs containing the same as the active ingredient |
Non-Patent Citations (3)
Title |
---|
"The Practice of Medicinal Chemistry", 1996, ACADEMIC PRESS, pages: 203 |
BERGE ET AL., J. PHARM. SCI., vol. 66, 1977, pages 1 - 19 |
See also references of EP1585511A4 |
Cited By (162)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9035096B2 (en) | 2002-05-24 | 2015-05-19 | Millennium Pharmaceuticals, Inc. | CCR9 inhibitors and methods of use thereof |
US8030517B2 (en) | 2002-05-24 | 2011-10-04 | Millennium Pharmaceuticals, Inc. | CCR9 inhibitors and methods of use thereof |
US7999109B2 (en) | 2002-05-24 | 2011-08-16 | Millennium Pharmaceuticals, Inc. | CCR9 inhibitors and methods of use thereof |
US7321001B2 (en) | 2002-12-20 | 2008-01-22 | Amgen Inc. | Asthma and allergic inflammation modulators |
US8158820B2 (en) | 2003-04-07 | 2012-04-17 | Astrazeneca Ab | Compounds |
US7960393B2 (en) | 2003-04-25 | 2011-06-14 | Actimis Pharmaceuticals, Inc. | Pyrimidine derivatives useful for the treatment of diseases mediated by CRTH2 |
US7812160B2 (en) | 2003-04-25 | 2010-10-12 | Actimis Pharmaceuticals, Inc. | Pyrimidine derivatives useful for the treatment of diseases mediated by CRTH2 |
US8394986B2 (en) | 2003-08-21 | 2013-03-12 | Astrazeneca Ab | Phenoxiacetic acid derivatives |
US8003703B2 (en) | 2003-08-21 | 2011-08-23 | Astrazeneca Ab | Phenoxiacetic acid derivatives |
US8198314B2 (en) | 2003-10-23 | 2012-06-12 | Oxagen Limited | Treatment of CRTH2-mediated diseases and conditions |
EP2060258A1 (en) | 2003-10-23 | 2009-05-20 | Oxagen Limited | Use of CRTH2 antagonist compounds in therapy |
US7582672B2 (en) | 2003-10-23 | 2009-09-01 | Oxagen Limited | Compounds for the treatment of CRTH2-mediated diseases and conditions |
US8163936B2 (en) | 2003-10-23 | 2012-04-24 | Oxagen Limited | Treatment of CRTH2-mediated diseases and conditions |
US8314257B2 (en) | 2003-10-23 | 2012-11-20 | Oxagen Limited | Treatment of CRTH2-mediated diseases and conditions |
US8163931B2 (en) | 2003-10-23 | 2012-04-24 | Oxagen Limited | Treatment of CRTH2-mediated diseases and conditions |
US7750014B2 (en) | 2004-01-31 | 2010-07-06 | Actimis Pharmaceuticals, Inc. | Imidazo[1,2-C]pyrimidinylacetic acid derivatives |
WO2005073234A3 (en) * | 2004-01-31 | 2005-10-06 | Bayer Healthcare Ag | Imidazo[1,2-c]pyrimidinylacetic acid derivatives |
US7714132B2 (en) | 2004-03-11 | 2010-05-11 | Actelion Pharmaceuticals, Ltd. | Tetrahydropyridoindole derivatives |
US8022248B2 (en) | 2004-07-08 | 2011-09-20 | Astrazeneca Ab | Substituted acids for the treatment of respiratory diseases |
US7737135B2 (en) | 2004-08-24 | 2010-06-15 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
US8163727B2 (en) | 2004-08-24 | 2012-04-24 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
US8722741B2 (en) | 2004-08-24 | 2014-05-13 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
WO2006037982A2 (en) * | 2004-10-05 | 2006-04-13 | Astrazeneca Ab | Modulators of crth2 receptor activity for the treatment of prostaglandin d2 mediated diseases |
WO2006037982A3 (en) * | 2004-10-05 | 2006-08-17 | Astrazeneca Ab | Modulators of crth2 receptor activity for the treatment of prostaglandin d2 mediated diseases |
JP2008515866A (en) * | 2004-10-05 | 2008-05-15 | アストラゼネカ・アクチエボラーグ | CRTh2 receptor modulators for treating diseases mediated by prostaglandin D2 |
US8524715B2 (en) | 2004-11-23 | 2013-09-03 | Astrazeneca Ab | Phenoxyacetic acid derivatives useful for treating respiratory diseases |
US7531568B2 (en) | 2004-11-30 | 2009-05-12 | Plexxikon, Inc. | PPAR active compounds |
US8093247B2 (en) | 2005-01-14 | 2012-01-10 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
US7622583B2 (en) | 2005-01-14 | 2009-11-24 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
JP2008542217A (en) * | 2005-05-24 | 2008-11-27 | ノバルティス アクチエンゲゼルシャフト | Organic compounds for the treatment of inflammation or allergic conditions |
WO2007014008A3 (en) * | 2005-07-22 | 2007-07-12 | Glaxo Group Limted | Benzenesulfonamide inhibitor of ccr2 chemokine receptor |
WO2007014008A2 (en) * | 2005-07-22 | 2007-02-01 | Glaxo Group Limted | Benzenesulfonamide inhibitor of ccr2 chemokine receptor |
US8148572B2 (en) | 2005-10-06 | 2012-04-03 | Astrazeneca Ab | Compounds |
US8415394B2 (en) | 2005-10-06 | 2013-04-09 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
WO2007039736A1 (en) | 2005-10-06 | 2007-04-12 | Astrazeneca Ab | Novel compounds |
US8349897B2 (en) | 2005-10-06 | 2013-01-08 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
US8008350B2 (en) | 2005-10-06 | 2011-08-30 | Astrazeneca Ab | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease |
JP2009518344A (en) * | 2005-12-09 | 2009-05-07 | ノバルティス アクチエンゲゼルシャフト | Bicyclic heterocyclic compounds as anti-inflammatory or anti-allergic agents |
WO2007110876A2 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Novel sulfonanilide derivatives, pharmaceutical compositions comprising the same and process thereof |
WO2007110876A3 (en) * | 2006-03-24 | 2010-02-18 | Panacea Biotec Ltd. | Novel sulfonanilide derivatives, pharmaceutical compositions comprising the same and process thereof |
WO2007146838A3 (en) * | 2006-06-09 | 2008-03-13 | Icos Corp | Substituted phenyl acetic acids as dp-2 antagonists |
WO2007143745A3 (en) * | 2006-06-09 | 2008-04-17 | Icos Corp | Substituted phenyl acetic acids as dp-2 antagonists |
US11433061B2 (en) | 2006-07-14 | 2022-09-06 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
US10206912B2 (en) | 2006-07-14 | 2019-02-19 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
WO2008008374A2 (en) * | 2006-07-14 | 2008-01-17 | Chemocentryx, Inc. | Ccr2 inhibitors and methods of use thereof |
WO2008008374A3 (en) * | 2006-07-14 | 2008-12-11 | Chemocentryx Inc | Ccr2 inhibitors and methods of use thereof |
US8519135B2 (en) | 2006-07-14 | 2013-08-27 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
US10532044B2 (en) | 2006-07-14 | 2020-01-14 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
EP2492268A1 (en) | 2006-07-22 | 2012-08-29 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
US8492437B2 (en) | 2006-08-21 | 2013-07-23 | Array Biopharma Inc. | 4-substituted phenoxyphenylacetic acid derivatives |
KR101397352B1 (en) * | 2006-08-21 | 2014-05-19 | 어레이 바이오파마 인크. | 4-Substituted Phenoxyphenylacetic Acid Derivatives |
TWI409247B (en) * | 2006-08-21 | 2013-09-21 | Array Biopharma Inc | 4-substituted phenoxyphenylacetic acid derivatives |
AU2007286829B2 (en) * | 2006-08-21 | 2013-05-02 | Array Biopharma, Inc. | 4-substituted phenoxyphenylacetic acid derivatives |
WO2008024746A1 (en) | 2006-08-21 | 2008-02-28 | Array Biopharma, Inc. | 4-substituted phenoxyphenylacetic acid derivatives |
US7964732B2 (en) | 2006-11-17 | 2011-06-21 | Pfizer Inc. | Substituted bicyclocarboxyamide compounds |
US8053463B2 (en) | 2007-03-08 | 2011-11-08 | Plexxikon Inc. | PPAR active compounds |
US7960567B2 (en) | 2007-05-02 | 2011-06-14 | Amgen Inc. | Compounds and methods useful for treating asthma and allergic inflammation |
AU2008248201B2 (en) * | 2007-05-02 | 2013-10-24 | Amgen Inc. | Compounds as CRTH2 and/or PGD2 receptors modulators and their use for treating asthma and allergic inflammation |
WO2008137027A2 (en) * | 2007-05-02 | 2008-11-13 | Amgen Inc. | Compounds as crth2 and/or pgd2 receptors modulators and their use for treating asthma and allergic inflammation |
WO2008137027A3 (en) * | 2007-05-02 | 2009-01-15 | Amgen Inc | Compounds as crth2 and/or pgd2 receptors modulators and their use for treating asthma and allergic inflammation |
US8507544B2 (en) | 2007-07-05 | 2013-08-13 | Astrazeneca Ab | Bi-aryl amide compounds as CRTh2 receptor modulators |
US10899765B2 (en) | 2007-07-12 | 2021-01-26 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
US8546408B2 (en) | 2007-07-12 | 2013-10-01 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
US10208050B2 (en) | 2007-07-12 | 2019-02-19 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
US7884110B2 (en) | 2007-07-12 | 2011-02-08 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
US9745312B2 (en) | 2007-07-12 | 2017-08-29 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
US9394307B2 (en) | 2007-07-12 | 2016-07-19 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation |
US8324229B2 (en) | 2007-09-25 | 2012-12-04 | Actimis Pharmaceuticals, Inc. | Alkylthio pyrimidines as CRTH2 antagonists |
US8314116B2 (en) | 2007-09-25 | 2012-11-20 | Actimis Pharmaceuticals, Inc. | 2-S-benzyl substituted pyrimidines as CRTH2 antagonists |
EP2327693A1 (en) | 2007-12-14 | 2011-06-01 | Pulmagen Therapeutics (Asthma) Limited | Indoles and their therapeutic use |
WO2009085177A1 (en) | 2007-12-19 | 2009-07-09 | Amgen Inc. | Phenyl acetic acid derivatives as inflammation modulators |
US8183293B2 (en) | 2007-12-19 | 2012-05-22 | Amgen Inc. | Phenyl acetic acid derivatives |
AU2008343924B2 (en) * | 2007-12-19 | 2013-01-17 | Amgen Inc. | Phenyl acetic acid derivatives as inflammation modulators |
WO2009090399A1 (en) * | 2008-01-18 | 2009-07-23 | Argenta Discovery Limited | Indoles active on crth2 receptor |
WO2009090414A1 (en) | 2008-01-18 | 2009-07-23 | Oxagen Limited | Compounds having crth2 antagonist activity |
WO2009093026A1 (en) | 2008-01-22 | 2009-07-30 | Oxagen Limited | Compounds having crth2 antagonist activity |
US8168673B2 (en) | 2008-01-22 | 2012-05-01 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
AU2009210446B2 (en) * | 2008-02-01 | 2012-07-26 | Brickell Biotech, Inc. | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
AU2009210446C1 (en) * | 2008-02-01 | 2013-01-10 | Brickell Biotech, Inc. | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
WO2009099902A1 (en) | 2008-02-01 | 2009-08-13 | Amira Pharmaceuticals, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
EP2245002A4 (en) * | 2008-02-01 | 2011-08-17 | Amira Pharmaceuticals Inc | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
CN101952244B (en) * | 2008-02-01 | 2014-11-05 | 潘米拉制药公司 | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
US8168678B2 (en) | 2008-02-01 | 2012-05-01 | Panmira Pharmaceuticals, Inc. | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
EP2257524A4 (en) * | 2008-02-01 | 2011-08-17 | Amira Pharmaceuticals Inc | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
US8338484B2 (en) | 2008-02-01 | 2012-12-25 | Panmira Pharmaceuticals, Llc | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
CN101952244A (en) * | 2008-02-01 | 2011-01-19 | 艾米拉制药公司 | PGD 2The N of acceptor, N-disubstituted amido alkyl biphenyl antagonist |
US8362044B2 (en) | 2008-02-01 | 2013-01-29 | Panmira Pharmaceuticals, Llc | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
US8067445B2 (en) | 2008-02-01 | 2011-11-29 | Panmira Pharmaceuticals, Llc | N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors |
EP2257524A1 (en) * | 2008-02-01 | 2010-12-08 | Amira Pharmaceuticals, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
EP2245002A1 (en) * | 2008-02-01 | 2010-11-03 | Amira Pharmaceuticals, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
US8242145B2 (en) | 2008-02-14 | 2012-08-14 | Panmira Pharmaceuticals, Llc | Cyclic diaryl ether compounds as antagonists of prostaglandin D2 receptors |
US8497381B2 (en) | 2008-02-25 | 2013-07-30 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
US8426449B2 (en) | 2008-04-02 | 2013-04-23 | Panmira Pharmaceuticals, Llc | Aminoalkylphenyl antagonists of prostaglandin D2 receptors |
US8501959B2 (en) | 2008-06-24 | 2013-08-06 | Panmira Pharmaceuticals, Llc | Cycloalkane[B]indole antagonists of prostaglandin D2 receptors |
WO2009158426A1 (en) | 2008-06-25 | 2009-12-30 | Array Biopharma Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
EP3144303A1 (en) * | 2008-06-25 | 2017-03-22 | Array Biopharma, Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
US8716498B2 (en) | 2008-06-25 | 2014-05-06 | Array Biopharma, Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
US9096567B2 (en) | 2008-06-25 | 2015-08-04 | Array Biopharma Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
US9556139B2 (en) | 2008-06-25 | 2017-01-31 | Array Biopharma Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
RU2507200C2 (en) * | 2008-06-25 | 2014-02-20 | Эррэй Биофарма Инк. | Position six-substituted phenoxychromanecarboxylic acid derivatives |
US8569522B2 (en) | 2008-06-25 | 2013-10-29 | Array Biopharma Inc. | 6-substituted phenoxychroman carboxylic acid derivatives |
CN103450138A (en) * | 2008-06-25 | 2013-12-18 | 阵列生物制药公司 | Preparation of intermidiates of 6-substituted phenoxychroman carboxylic acid derivatives |
EP2826774A1 (en) | 2008-06-25 | 2015-01-21 | Array Biopharma, Inc. | Intermediates for 6-substituted phenoxychroman carboxylic acid derivatives |
KR101728175B1 (en) | 2008-06-25 | 2017-04-18 | 어레이 바이오파마 인크. | 6-substituted phenoxychroman carboxylic acid derivatives |
CN102131794B (en) * | 2008-06-25 | 2013-09-25 | 阵列生物制药公司 | 6-substituted phenoxychroman carboxylic acid derivatives |
US8071807B2 (en) | 2008-07-03 | 2011-12-06 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
US8247602B2 (en) | 2008-07-03 | 2012-08-21 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
US8049015B2 (en) | 2008-09-29 | 2011-11-01 | Panmira Pharmaceuticals, Llc | Heteroaryl antagonists of prostaglandin D2 receptors |
US8378107B2 (en) | 2008-10-01 | 2013-02-19 | Panmira Pharmaceuticals, Llc | Heteroaryl antagonists of prostaglandin D2 receptors |
US8524748B2 (en) | 2008-10-08 | 2013-09-03 | Panmira Pharmaceuticals, Llc | Heteroalkyl biphenyl antagonists of prostaglandin D2 receptors |
US8034826B2 (en) | 2008-11-06 | 2011-10-11 | Panmira Pharmaceuticals, Llc | Cycloalkane[B]azaindole antagonists of prostaglandin D2 receptors |
US8642629B2 (en) | 2008-11-17 | 2014-02-04 | Hoffmann-La Roche Inc. | Naphthylacetic acids |
US8383654B2 (en) | 2008-11-17 | 2013-02-26 | Panmira Pharmaceuticals, Llc | Heterocyclic antagonists of prostaglandin D2 receptors |
US8785445B2 (en) | 2008-12-22 | 2014-07-22 | Array Biopharma Inc. | 7-phenoxychroman carboxylic acid derivatives |
WO2010075200A1 (en) | 2008-12-22 | 2010-07-01 | Array Biopharma Inc. | 7-phenoxychroman carboxylic acid derivatives |
WO2011002814A3 (en) * | 2009-06-30 | 2011-05-26 | Ligand Pharmaceuticals Inc. | Sulfonamido - biphenyloxyacetic acid compounds |
EP2480225A2 (en) * | 2009-07-31 | 2012-08-01 | Panmira Pharmaceuticals, LLC | Dermal formulations of dp2 receptor antagonists |
EP2480225A4 (en) * | 2009-07-31 | 2013-05-01 | Panmira Pharmaceuticals Llc | Dermal formulations of dp2 receptor antagonists |
US8785393B2 (en) | 2009-07-31 | 2014-07-22 | Panmira Pharmaceuticals, Llc | Ophthalmic pharmaceutical compositions of DP2 receptor antagonists |
US8815917B2 (en) | 2009-08-05 | 2014-08-26 | Panmira Pharmaceuticals, Llc | DP2 antagonist and uses thereof |
EP2462110A4 (en) * | 2009-08-05 | 2013-04-03 | Panmira Pharmaceuticals Llc | Dp2 antagonist and uses thereof |
EP2462110A2 (en) * | 2009-08-05 | 2012-06-13 | Panmira Pharmaceuticals, LLC | Dp2 antagonist and uses thereof |
WO2011079007A1 (en) | 2009-12-23 | 2011-06-30 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
US9688624B2 (en) | 2010-01-06 | 2017-06-27 | Brickell Biotech, Inc. | DP2 antagonist and uses thereof |
WO2011115804A1 (en) | 2010-03-17 | 2011-09-22 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
EP3173407A1 (en) | 2010-06-30 | 2017-05-31 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2012003405A1 (en) | 2010-06-30 | 2012-01-05 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
US8575158B2 (en) | 2010-07-05 | 2013-11-05 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
WO2012009134A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
WO2012009137A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
WO2012061926A1 (en) * | 2010-11-08 | 2012-05-18 | Zalicus Pharmaceuticals Ltd. | Bisarylsulfone and dialkylarylsulfone compounds as calcium channel blockers |
WO2012064559A1 (en) | 2010-11-09 | 2012-05-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2012069175A1 (en) | 2010-11-25 | 2012-05-31 | Almirall, S.A. | New pyrazole derivatives having crth2 antagonistic behaviour |
EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
EP2526945A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | New CRTH2 Antagonists |
WO2013010881A1 (en) | 2011-07-18 | 2013-01-24 | Almirall, S.A. | NEW CRTh2 ANTAGONISTS |
WO2013010880A1 (en) | 2011-07-18 | 2013-01-24 | Almirall, S.A. | New crth2 antagonists |
EP2548876A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists |
EP2548863A1 (en) | 2011-07-18 | 2013-01-23 | Almirall, S.A. | New CRTh2 antagonists. |
WO2013088109A1 (en) | 2011-12-16 | 2013-06-20 | Oxagen Limited | Combination of crth2 antagonist and a proton pump inhibitor for the treatment of eosinophilic esophagitis |
WO2013101830A1 (en) | 2011-12-27 | 2013-07-04 | Ironwood Pharmaceuticals, Inc. | 2 - benzyl, 3 - (pyrimidin- 2 -yl) substituted pyrazoles useful as sgc stimulators |
EP3112363A1 (en) | 2011-12-27 | 2017-01-04 | Ironwood Pharmaceuticals, Inc. | 2-[1-[(2-fluorophenyl)methyl]-5-(3-isoxazolyl)-1h-pyrazol-3-yl]-pyrimidine derivatives and related compounds as soluble guanylate cyclase (sgc) stimulators for the treatment of pulmonary hypertension |
US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
WO2014047111A1 (en) | 2012-09-18 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2014047325A1 (en) | 2012-09-19 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
EP3998260A1 (en) | 2013-03-15 | 2022-05-18 | Cyclerion Therapeutics, Inc. | Sgc stimulators |
WO2014144100A2 (en) | 2013-03-15 | 2014-09-18 | Takashi Nakai | Sgc stimulators |
EP3660013A1 (en) | 2013-03-15 | 2020-06-03 | Cyclerion Therapeutics, Inc. | Sgc stimulators |
WO2015089182A1 (en) | 2013-12-11 | 2015-06-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
US9828359B2 (en) | 2013-12-17 | 2017-11-28 | Atopix Therapeutics Limited | Process for the preparation of 3-substituted (indol-1-yl)-acetic acid esters |
WO2015106268A1 (en) | 2014-01-13 | 2015-07-16 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
WO2016044445A2 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
WO2016044447A1 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | Pyrazole derivatives as sgc stimulators |
WO2016044446A2 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2018009609A1 (en) | 2016-07-07 | 2018-01-11 | Ironwood Pharmaceuticals, Inc. | Solid forms of an sgc stimulator |
WO2018009596A1 (en) | 2016-07-07 | 2018-01-11 | Ironwood Pharmaceuticals, Inc. | Phosphorus prodrugs of sgc stimulators |
US10973809B2 (en) | 2016-11-23 | 2021-04-13 | Chemocentryx, Inc. | Method of treating focal segmental glomerulosclerosis |
US11324736B2 (en) | 2016-11-23 | 2022-05-10 | Chemocentryx, Inc. | Method of Treating Focal Segmental Glomerulosclerosis |
US10758540B2 (en) | 2017-10-11 | 2020-09-01 | Chemocentryx, Inc. | Treatment of focal segmental glomerulosclerosis with CCR2 antagonists |
US11382915B2 (en) | 2017-10-11 | 2022-07-12 | Chemocentryx, Inc. | Treatment of focal segmental glomerulosclerosis with CCR2 antagonists |
US11191747B2 (en) | 2019-04-03 | 2021-12-07 | Aligos Therapeutics, Inc. | Pyrrole compounds |
US11771680B2 (en) | 2019-04-03 | 2023-10-03 | Aligos Therapeutics, Inc. | Pyrrole compounds |
Also Published As
Publication number | Publication date |
---|---|
AU2003297398B2 (en) | 2009-09-24 |
WO2004058164A3 (en) | 2004-08-26 |
PL377314A1 (en) | 2006-01-23 |
AU2003297398A1 (en) | 2004-07-22 |
US20080085891A1 (en) | 2008-04-10 |
CA2511214A1 (en) | 2004-07-15 |
KR20050111314A (en) | 2005-11-24 |
NO20053114D0 (en) | 2005-06-24 |
EA200501017A1 (en) | 2006-02-24 |
EP1585511A4 (en) | 2007-08-29 |
ZA200505523B (en) | 2006-09-27 |
JP2006516143A (en) | 2006-06-22 |
EP1585511B1 (en) | 2013-01-23 |
NO20053114L (en) | 2005-09-19 |
MXPA05006701A (en) | 2006-03-30 |
ES2401079T3 (en) | 2013-04-16 |
CA2511214C (en) | 2012-12-18 |
EA011087B1 (en) | 2008-12-30 |
IS7907A (en) | 2005-06-22 |
EP1585511A2 (en) | 2005-10-19 |
US20040220237A1 (en) | 2004-11-04 |
US7321001B2 (en) | 2008-01-22 |
BR0317591A (en) | 2005-11-22 |
US7541383B2 (en) | 2009-06-02 |
CN1767823A (en) | 2006-05-03 |
JP4457017B2 (en) | 2010-04-28 |
CN100406007C (en) | 2008-07-30 |
NZ541234A (en) | 2008-06-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1585511B1 (en) | Asthma and allergic inflammation modulators | |
CA2685215C (en) | Compounds and methods useful for treating asthma and allergic inflammation | |
JP4253126B2 (en) | PPAR-gamma modulator | |
JP2005508318A (en) | Linked biaryl compounds | |
US20050038070A1 (en) | Asthma and allergic inflammation modulators | |
JP2009539880A (en) | Substituted phenylacetic acid as a DP-2 antagonist | |
US8183293B2 (en) | Phenyl acetic acid derivatives | |
NO973001L (en) | Pyrimidine derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2004563827 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2005/006701 Country of ref document: MX Ref document number: 169299 Country of ref document: IL Ref document number: 377314 Country of ref document: PL Ref document number: 2511214 Country of ref document: CA Ref document number: 1-2005-501185 Country of ref document: PH Ref document number: 1020057011677 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005/05523 Country of ref document: ZA Ref document number: 200505523 Country of ref document: ZA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 541234 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003297398 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003814219 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200501017 Country of ref document: EA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 20038A97235 Country of ref document: CN |
|
WWP | Wipo information: published in national office |
Ref document number: 2003814219 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: PI0317591 Country of ref document: BR |
|
WWP | Wipo information: published in national office |
Ref document number: 1020057011677 Country of ref document: KR |