JP2009511559A - 炎症の治療に有用なベンゾオキサゾール類 - Google Patents
炎症の治療に有用なベンゾオキサゾール類 Download PDFInfo
- Publication number
- JP2009511559A JP2009511559A JP2008535097A JP2008535097A JP2009511559A JP 2009511559 A JP2009511559 A JP 2009511559A JP 2008535097 A JP2008535097 A JP 2008535097A JP 2008535097 A JP2008535097 A JP 2008535097A JP 2009511559 A JP2009511559 A JP 2009511559A
- Authority
- JP
- Japan
- Prior art keywords
- represent
- chloro
- compound
- formula
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 33
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 33
- 238000011282 treatment Methods 0.000 title claims abstract description 30
- 150000000183 1,3-benzoxazoles Chemical class 0.000 title description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 230000000694 effects Effects 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 102000042256 MAPEG family Human genes 0.000 claims abstract description 18
- 108091077604 MAPEG family Proteins 0.000 claims abstract description 18
- 229910052721 tungsten Inorganic materials 0.000 claims abstract description 11
- 230000005764 inhibitory process Effects 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 230
- -1 —R 3a Chemical group 0.000 claims description 120
- 125000001424 substituent group Chemical group 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000000203 mixture Substances 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 102100033076 Prostaglandin E synthase Human genes 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 29
- 101710096361 Prostaglandin E synthase Proteins 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- 239000002671 adjuvant Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 239000003085 diluting agent Substances 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 208000024891 symptom Diseases 0.000 claims description 11
- 208000006673 asthma Diseases 0.000 claims description 10
- 125000001246 bromo group Chemical group Br* 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 230000002757 inflammatory effect Effects 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 201000004624 Dermatitis Diseases 0.000 claims description 5
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 102000004023 5-Lipoxygenase-Activating Proteins Human genes 0.000 claims description 4
- 108090000411 5-Lipoxygenase-Activating Proteins Proteins 0.000 claims description 4
- 206010065390 Inflammatory pain Diseases 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 206010010741 Conjunctivitis Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 3
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 206010039083 rhinitis Diseases 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 231100000397 ulcer Toxicity 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000008035 Back Pain Diseases 0.000 claims description 2
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 206010006811 Bursitis Diseases 0.000 claims description 2
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 2
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 2
- 208000001640 Fibromyalgia Diseases 0.000 claims description 2
- 206010017533 Fungal infection Diseases 0.000 claims description 2
- 201000005569 Gout Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 2
- 208000008930 Low Back Pain Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000031888 Mycoses Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 206010039705 Scleritis Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 208000029078 coronary artery disease Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 201000004614 iritis Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 201000008383 nephritis Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 208000028169 periodontal disease Diseases 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 201000003068 rheumatic fever Diseases 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 230000029663 wound healing Effects 0.000 claims description 2
- 239000013066 combination product Substances 0.000 claims 1
- 229940127555 combination product Drugs 0.000 claims 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims 1
- 210000003195 fascia Anatomy 0.000 claims 1
- 201000000306 sarcoidosis Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 50
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 108090000748 Prostaglandin-E Synthases Proteins 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- OGLKKYALUKXVPQ-UHFFFAOYSA-N 2-chloro-5-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C(Cl)=O)=C1 OGLKKYALUKXVPQ-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- MXIUWSYTQJLIKE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC=C1C(Cl)=O MXIUWSYTQJLIKE-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 8
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 230000000144 pharmacologic effect Effects 0.000 description 8
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- ZMXYNJXDULEQCK-UHFFFAOYSA-N 2-amino-p-cresol Chemical compound CC1=CC=C(O)C(N)=C1 ZMXYNJXDULEQCK-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102100022278 Arachidonate 5-lipoxygenase-activating protein Human genes 0.000 description 6
- 101710187011 Arachidonate 5-lipoxygenase-activating protein Proteins 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- GGHLXLVPNZMBQR-UHFFFAOYSA-N 3,5-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CC(Cl)=C1 GGHLXLVPNZMBQR-UHFFFAOYSA-N 0.000 description 5
- NXTNASSYJUXJDV-UHFFFAOYSA-N 3-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(C(Cl)=O)=C1 NXTNASSYJUXJDV-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- FHYVXFHFFQYGEQ-UHFFFAOYSA-N 2-(2-chloro-5-nitrophenyl)-5-methyl-1,3-benzoxazole Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC([N+]([O-])=O)=CC=C1Cl FHYVXFHFFQYGEQ-UHFFFAOYSA-N 0.000 description 4
- QBAYIBZITZBSFO-UHFFFAOYSA-N 2-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=CC=C1C(F)(F)F QBAYIBZITZBSFO-UHFFFAOYSA-N 0.000 description 4
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 108010024636 Glutathione Proteins 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 229910021293 PO 4 Inorganic materials 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229960003180 glutathione Drugs 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 229940065725 leukotriene receptor antagonists for obstructive airway diseases Drugs 0.000 description 4
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 4
- 150000002617 leukotrienes Chemical class 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 4
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 3
- SWFNPENEBHAHEB-UHFFFAOYSA-N 2-amino-4-chlorophenol Chemical compound NC1=CC(Cl)=CC=C1O SWFNPENEBHAHEB-UHFFFAOYSA-N 0.000 description 3
- RXTRRIFWCJEMEL-UHFFFAOYSA-N 2-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1Cl RXTRRIFWCJEMEL-UHFFFAOYSA-N 0.000 description 3
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 3
- GVDLZDRAQAXRJO-UHFFFAOYSA-N 4-bromo-2-(5-methyl-1,3-benzoxazol-2-yl)phenol Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC(Br)=CC=C1O GVDLZDRAQAXRJO-UHFFFAOYSA-N 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 3
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000007885 bronchoconstriction Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229940111134 coxibs Drugs 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- JBSIZAZIRIQSHM-UHFFFAOYSA-N 2-(5-bromo-2-propan-2-yloxyphenyl)-5-methyl-1,3-benzoxazole Chemical compound CC(C)OC1=CC=C(Br)C=C1C1=NC2=CC(C)=CC=C2O1 JBSIZAZIRIQSHM-UHFFFAOYSA-N 0.000 description 2
- XXTXDVUAHROLBN-UHFFFAOYSA-N 2-(trifluoromethoxy)benzamide Chemical compound NC(=O)C1=CC=CC=C1OC(F)(F)F XXTXDVUAHROLBN-UHFFFAOYSA-N 0.000 description 2
- JSHJJLQJRLNBBA-UHFFFAOYSA-N 2-amino-3-chlorophenol Chemical compound NC1=C(O)C=CC=C1Cl JSHJJLQJRLNBBA-UHFFFAOYSA-N 0.000 description 2
- RPJUVNYXHUCRMG-UHFFFAOYSA-N 2-amino-4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C(N)=C1 RPJUVNYXHUCRMG-UHFFFAOYSA-N 0.000 description 2
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 2
- OOIHXTWGXLBRKO-UHFFFAOYSA-N 2-chloro-5-methylsulfonylbenzoyl chloride Chemical compound CS(=O)(=O)C1=CC=C(Cl)C(C(Cl)=O)=C1 OOIHXTWGXLBRKO-UHFFFAOYSA-N 0.000 description 2
- QFMTZDVPNFJPLG-UHFFFAOYSA-N 2-chloro-n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-5-methylsulfonylbenzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C=1)=CC=CC=1NC(=O)C1=CC(S(C)(=O)=O)=CC=C1Cl QFMTZDVPNFJPLG-UHFFFAOYSA-N 0.000 description 2
- SLQZREZBAGAION-UHFFFAOYSA-N 2-chloro-n-[4-chloro-3-(5-chloro-1,3-benzoxazol-2-yl)phenyl]-5-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C(=O)NC=2C=C(C(Cl)=CC=2)C=2OC3=CC=C(Cl)C=C3N=2)=C1 SLQZREZBAGAION-UHFFFAOYSA-N 0.000 description 2
- NIIKYUQKAUTNJP-UHFFFAOYSA-N 2-chloro-n-[4-methyl-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]pyridine-3-carboxamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)C)=CC=1NC(=O)C1=CC=CN=C1Cl NIIKYUQKAUTNJP-UHFFFAOYSA-N 0.000 description 2
- QMOIDPQJCJYGTN-UHFFFAOYSA-N 4-amino-n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C=1)=CC=CC=1NC(=O)C1=CC=C(N)C=C1 QMOIDPQJCJYGTN-UHFFFAOYSA-N 0.000 description 2
- FIGIRGARTKWPOJ-UHFFFAOYSA-N 4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)aniline Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC(N)=CC=C1Cl FIGIRGARTKWPOJ-UHFFFAOYSA-N 0.000 description 2
- FKMUFBITBYUAKN-UHFFFAOYSA-N 4-n,4-n-dimethyl-2-(5-methyl-1,3-benzoxazol-2-yl)benzene-1,4-diamine;hydrochloride Chemical compound Cl.CN(C)C1=CC=C(N)C(C=2OC3=CC=C(C)C=C3N=2)=C1 FKMUFBITBYUAKN-UHFFFAOYSA-N 0.000 description 2
- DLJXHPMGVJBBMU-UHFFFAOYSA-N 5-bromo-2-(2-chloro-5-nitrophenyl)-1,3-benzoxazole Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=2OC3=CC=C(Br)C=C3N=2)=C1 DLJXHPMGVJBBMU-UHFFFAOYSA-N 0.000 description 2
- BZRKTCTVXNLZPL-UHFFFAOYSA-N 5-chloro-2-(3-nitrophenyl)-1,3-benzoxazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2OC3=CC=C(Cl)C=C3N=2)=C1 BZRKTCTVXNLZPL-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 2
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 101000628796 Homo sapiens Microsomal glutathione S-transferase 2 Proteins 0.000 description 2
- 101000628785 Homo sapiens Microsomal glutathione S-transferase 3 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 102100026741 Microsomal glutathione S-transferase 1 Human genes 0.000 description 2
- 102100026723 Microsomal glutathione S-transferase 2 Human genes 0.000 description 2
- 102100026722 Microsomal glutathione S-transferase 3 Human genes 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- WTPPIRSWFQERCU-UHFFFAOYSA-N N-[4-hydroxy-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)O)=CC=1NC(=O)C1=CC=CC=C1C(F)(F)F WTPPIRSWFQERCU-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108010074917 microsomal glutathione S-transferase-I Proteins 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- DEAXWXKYKLQHPE-UHFFFAOYSA-N n-(2-methoxyphenyl)-2,2-dimethylpropanamide Chemical compound COC1=CC=CC=C1NC(=O)C(C)(C)C DEAXWXKYKLQHPE-UHFFFAOYSA-N 0.000 description 2
- KJKIURIMRIGOBF-UHFFFAOYSA-N n-[3-(5-methyl-1,3-benzoxazol-2-yl)-4-propan-2-yloxyphenyl]-2-(trifluoromethoxy)benzamide Chemical compound C1=C(C=2OC3=CC=C(C)C=C3N=2)C(OC(C)C)=CC=C1NC(=O)C1=CC=CC=C1OC(F)(F)F KJKIURIMRIGOBF-UHFFFAOYSA-N 0.000 description 2
- WLIQQSSOVHZBED-UHFFFAOYSA-N n-[3-(5-methyl-1,3-benzoxazol-2-yl)-4-pyrrolidin-1-ylphenyl]-2-(trifluoromethyl)benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)N2CCCC2)=CC=1NC(=O)C1=CC=CC=C1C(F)(F)F WLIQQSSOVHZBED-UHFFFAOYSA-N 0.000 description 2
- BRXGHSPQUWULQE-UHFFFAOYSA-N n-[3-(5-tert-butyl-1,3-benzoxazol-2-yl)-4-chlorophenyl]-2-(trifluoromethyl)benzamide Chemical compound N=1C2=CC(C(C)(C)C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CC=C1C(F)(F)F BRXGHSPQUWULQE-UHFFFAOYSA-N 0.000 description 2
- ORPVWYINBBJUNB-UHFFFAOYSA-N n-[4-(dimethylamino)-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound C1=C(C=2OC3=CC=C(C)C=C3N=2)C(N(C)C)=CC=C1NC(=O)C1=CC=CC=C1C(F)(F)F ORPVWYINBBJUNB-UHFFFAOYSA-N 0.000 description 2
- CGCJGSPKNQBWLP-UHFFFAOYSA-N n-[4-chloro-3-(4-methyl-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound N=1C=2C(C)=CC=CC=2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CC=C1C(F)(F)F CGCJGSPKNQBWLP-UHFFFAOYSA-N 0.000 description 2
- NWBYRLDFSXKWSX-UHFFFAOYSA-N n-[4-chloro-3-(5-chloro-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC=C1C(=O)NC1=CC=C(Cl)C(C=2OC3=CC=C(Cl)C=C3N=2)=C1 NWBYRLDFSXKWSX-UHFFFAOYSA-N 0.000 description 2
- OFBUVXGWAHBXKZ-UHFFFAOYSA-N n-[4-cyclopentyloxy-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)OC2CCCC2)=CC=1NC(=O)C1=CC=CC=C1C(F)(F)F OFBUVXGWAHBXKZ-UHFFFAOYSA-N 0.000 description 2
- YZHDLFQGLNVLIX-UHFFFAOYSA-N n-[4-fluoro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethoxy)benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)F)=CC=1NC(=O)C1=CC=CC=C1OC(F)(F)F YZHDLFQGLNVLIX-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 102000004277 11-beta-hydroxysteroid dehydrogenases Human genes 0.000 description 1
- 108090000874 11-beta-hydroxysteroid dehydrogenases Proteins 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- BXCOSWRSIISQSL-UHFFFAOYSA-N 2,5-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(Cl)C(S(Cl)(=O)=O)=C1 BXCOSWRSIISQSL-UHFFFAOYSA-N 0.000 description 1
- RSINFFVFOTUDEC-UHFFFAOYSA-N 2,5-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CC=C1Cl RSINFFVFOTUDEC-UHFFFAOYSA-N 0.000 description 1
- VNFPMFGQNUVWET-UHFFFAOYSA-N 2-(2-chloro-5-nitrophenyl)-4-methyl-1,3-benzoxazole Chemical compound N=1C=2C(C)=CC=CC=2OC=1C1=CC([N+]([O-])=O)=CC=C1Cl VNFPMFGQNUVWET-UHFFFAOYSA-N 0.000 description 1
- MZFREZYSFXTNDD-UHFFFAOYSA-N 2-(3-bromophenyl)-5-methyl-1,3-benzoxazole Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC=CC(Br)=C1 MZFREZYSFXTNDD-UHFFFAOYSA-N 0.000 description 1
- YDAUPNVKXUYPQC-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-5-methyl-1,3-benzoxazole Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC(Br)=CC=C1F YDAUPNVKXUYPQC-UHFFFAOYSA-N 0.000 description 1
- ONZXPNFLFJYPFD-UHFFFAOYSA-N 2-(5-iodo-2-propan-2-yloxyphenyl)-5-methyl-1,3-benzoxazole Chemical compound CC(C)OC1=CC=C(I)C=C1C1=NC2=CC(C)=CC=C2O1 ONZXPNFLFJYPFD-UHFFFAOYSA-N 0.000 description 1
- KSHPWYXAJJCUMJ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzoyl chloride Chemical compound FC(F)(F)OC1=CC=CC=C1C(Cl)=O KSHPWYXAJJCUMJ-UHFFFAOYSA-N 0.000 description 1
- FEDLEBCVFZMHBP-UHFFFAOYSA-N 2-amino-3-methylphenol Chemical compound CC1=CC=CC(O)=C1N FEDLEBCVFZMHBP-UHFFFAOYSA-N 0.000 description 1
- JHRIPENGTGSNPJ-UHFFFAOYSA-N 2-amino-4-bromophenol Chemical compound NC1=CC(Br)=CC=C1O JHRIPENGTGSNPJ-UHFFFAOYSA-N 0.000 description 1
- UPJVUFCLBYQKFH-UHFFFAOYSA-N 2-amino-4-ethylsulfonylphenol Chemical compound CCS(=O)(=O)C1=CC=C(O)C(N)=C1 UPJVUFCLBYQKFH-UHFFFAOYSA-N 0.000 description 1
- WZNVLFGQZNIOMW-UHFFFAOYSA-N 2-amino-5-(2-methylbutan-2-yl)phenol Chemical compound CCC(C)(C)C1=CC=C(N)C(O)=C1 WZNVLFGQZNIOMW-UHFFFAOYSA-N 0.000 description 1
- MLTFVKFUUNLURL-UHFFFAOYSA-N 2-amino-5-chloro-n-[4-methoxy-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]benzamide Chemical compound C1=C(C=2OC3=CC=C(C)C=C3N=2)C(OC)=CC=C1NC(=O)C1=CC(Cl)=CC=C1N MLTFVKFUUNLURL-UHFFFAOYSA-N 0.000 description 1
- DNRVZOZGQHHDAT-UHFFFAOYSA-N 2-amino-5-chlorobenzamide Chemical compound NC(=O)C1=CC(Cl)=CC=C1N DNRVZOZGQHHDAT-UHFFFAOYSA-N 0.000 description 1
- FZCQMIRJCGWWCL-UHFFFAOYSA-N 2-amino-5-chlorophenol Chemical compound NC1=CC=C(Cl)C=C1O FZCQMIRJCGWWCL-UHFFFAOYSA-N 0.000 description 1
- SKWDIXBVQATQSG-UHFFFAOYSA-N 2-chloro-5-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=C(Cl)C(C(O)=O)=C1 SKWDIXBVQATQSG-UHFFFAOYSA-N 0.000 description 1
- SEZKSJHQUIRBCN-UHFFFAOYSA-N 2-chloro-6-methoxyaniline Chemical compound COC1=CC=CC(Cl)=C1N SEZKSJHQUIRBCN-UHFFFAOYSA-N 0.000 description 1
- SQFVEOAHQRSSAA-UHFFFAOYSA-N 2-chloro-n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]pyridine-3-carboxamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C=1)=CC=CC=1NC(=O)C1=CC=CN=C1Cl SQFVEOAHQRSSAA-UHFFFAOYSA-N 0.000 description 1
- XTTKOXIPOWDBKT-UHFFFAOYSA-N 2-chloro-n-[4-chloro-3-(5-chloro-1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzamide Chemical compound ClC1=CC([N+](=O)[O-])=CC=C1C(=O)NC1=CC=C(Cl)C(C=2OC3=CC=C(Cl)C=C3N=2)=C1 XTTKOXIPOWDBKT-UHFFFAOYSA-N 0.000 description 1
- HRGUMSJPVPZBDI-UHFFFAOYSA-N 2-chloro-n-[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CC=C1Cl HRGUMSJPVPZBDI-UHFFFAOYSA-N 0.000 description 1
- HFJDJVAGKLEWKF-UHFFFAOYSA-N 2-chloro-n-[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]pyridine-3-carboxamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CN=C1Cl HFJDJVAGKLEWKF-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- RAAGZOYMEQDCTD-UHFFFAOYSA-N 2-fluorobenzoyl chloride Chemical compound FC1=CC=CC=C1C(Cl)=O RAAGZOYMEQDCTD-UHFFFAOYSA-N 0.000 description 1
- 125000003816 2-hydroxybenzoyl group Chemical group OC1=C(C(=O)*)C=CC=C1 0.000 description 1
- RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 1
- IZBCECJKBKJUIM-UHFFFAOYSA-N 2-methyl-5-nitrobenzoyl chloride Chemical compound CC1=CC=C([N+]([O-])=O)C=C1C(Cl)=O IZBCECJKBKJUIM-UHFFFAOYSA-N 0.000 description 1
- DQSHFKPKFISSNM-UHFFFAOYSA-N 2-methylbenzoxazole Chemical compound C1=CC=C2OC(C)=NC2=C1 DQSHFKPKFISSNM-UHFFFAOYSA-N 0.000 description 1
- GPZXFICWCMCQPF-UHFFFAOYSA-N 2-methylbenzoyl chloride Chemical compound CC1=CC=CC=C1C(Cl)=O GPZXFICWCMCQPF-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VTXNOVCTHUBABW-UHFFFAOYSA-N 3,4-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C(Cl)=C1 VTXNOVCTHUBABW-UHFFFAOYSA-N 0.000 description 1
- HACZYTKGJWWYLZ-UHFFFAOYSA-N 3,4-dimethoxy-n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]benzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC1=CC=CC(C=2OC3=CC=C(C)C=C3N=2)=C1 HACZYTKGJWWYLZ-UHFFFAOYSA-N 0.000 description 1
- VIOBGCWEHLRBEP-UHFFFAOYSA-N 3,4-dimethoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1OC VIOBGCWEHLRBEP-UHFFFAOYSA-N 0.000 description 1
- RJSQINMKOSOUGT-UHFFFAOYSA-N 3,5-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC(Cl)=CC(S(Cl)(=O)=O)=C1 RJSQINMKOSOUGT-UHFFFAOYSA-N 0.000 description 1
- BNWGICWTIRDFLH-UHFFFAOYSA-N 3-(5-bromo-1,3-benzoxazol-2-yl)-4-chloroaniline Chemical compound NC1=CC=C(Cl)C(C=2OC3=CC=C(Br)C=C3N=2)=C1 BNWGICWTIRDFLH-UHFFFAOYSA-N 0.000 description 1
- QZWFTMFERGNVLX-UHFFFAOYSA-N 3-(5-chloro-1,3-benzoxazol-2-yl)aniline Chemical compound NC1=CC=CC(C=2OC3=CC=C(Cl)C=C3N=2)=C1 QZWFTMFERGNVLX-UHFFFAOYSA-N 0.000 description 1
- RHXMIEIETYZDGD-UHFFFAOYSA-N 3-(5-methyl-1,3-benzoxazol-2-yl)-4-pyrrolidin-1-ylaniline;hydrochloride Chemical compound Cl.N=1C2=CC(C)=CC=C2OC=1C1=CC(N)=CC=C1N1CCCC1 RHXMIEIETYZDGD-UHFFFAOYSA-N 0.000 description 1
- YGMVUJGLTNKWJJ-UHFFFAOYSA-N 3-(5-methyl-1,3-benzoxazol-2-yl)aniline Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC=CC(N)=C1 YGMVUJGLTNKWJJ-UHFFFAOYSA-N 0.000 description 1
- QEINFLYJHJVTFD-UHFFFAOYSA-N 3-amino-4-methyl-n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C=1)=CC=CC=1NC(=O)C1=CC=C(C)C(N)=C1 QEINFLYJHJVTFD-UHFFFAOYSA-N 0.000 description 1
- VYBKAZXQKUFAHG-UHFFFAOYSA-N 3-amino-4-methylbenzamide Chemical compound CC1=CC=C(C(N)=O)C=C1N VYBKAZXQKUFAHG-UHFFFAOYSA-N 0.000 description 1
- PBOOZQFGWNZNQE-UHFFFAOYSA-N 3-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Br)=C1 PBOOZQFGWNZNQE-UHFFFAOYSA-N 0.000 description 1
- ZSIYKAQPQRTBPF-UHFFFAOYSA-N 3-chloro-2-methylbenzenesulfonyl chloride Chemical compound CC1=C(Cl)C=CC=C1S(Cl)(=O)=O ZSIYKAQPQRTBPF-UHFFFAOYSA-N 0.000 description 1
- OWVNHDVCKAQWMM-UHFFFAOYSA-N 3-chloro-n-[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-2-methylbenzenesulfonamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NS(=O)(=O)C1=CC=CC(Cl)=C1C OWVNHDVCKAQWMM-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- RDQJFTOPACYEKO-UHFFFAOYSA-N 4-chloro-2-(2-chloro-5-nitrophenyl)-1,3-benzoxazole Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=2OC3=CC=CC(Cl)=C3N=2)=C1 RDQJFTOPACYEKO-UHFFFAOYSA-N 0.000 description 1
- ZVELTGQXALDYDU-UHFFFAOYSA-N 4-chloro-3-(5-chloro-1,3-benzoxazol-2-yl)aniline Chemical compound NC1=CC=C(Cl)C(C=2OC3=CC=C(Cl)C=C3N=2)=C1 ZVELTGQXALDYDU-UHFFFAOYSA-N 0.000 description 1
- WURQDOFCUHIBOB-UHFFFAOYSA-N 4-chloro-n-[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]benzamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=C(Cl)C=C1 WURQDOFCUHIBOB-UHFFFAOYSA-N 0.000 description 1
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
- HJHWKQXWHMMSIN-UHFFFAOYSA-N 4-methyl-2-(3-nitrophenyl)-1,3-benzoxazole Chemical compound N=1C=2C(C)=CC=CC=2OC=1C1=CC=CC([N+]([O-])=O)=C1 HJHWKQXWHMMSIN-UHFFFAOYSA-N 0.000 description 1
- XZZVKDBMBORHEX-UHFFFAOYSA-N 4-methyl-3-(5-methyl-1,3-benzoxazol-2-yl)aniline Chemical compound N=1C2=CC(C)=CC=C2OC=1C1=CC(N)=CC=C1C XZZVKDBMBORHEX-UHFFFAOYSA-N 0.000 description 1
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
- IPEIDGXNXFPGBG-UHFFFAOYSA-N 4-methylsulfonylbenzoyl chloride Chemical compound CS(=O)(=O)C1=CC=C(C(Cl)=O)C=C1 IPEIDGXNXFPGBG-UHFFFAOYSA-N 0.000 description 1
- USRKDQLKRQMYKX-UHFFFAOYSA-N 4-propan-2-yloxybenzoyl chloride Chemical compound CC(C)OC1=CC=C(C(Cl)=O)C=C1 USRKDQLKRQMYKX-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004606 5,6,7,8-tetrahydroisoquinolinyl group Chemical group C1(=NC=CC=2CCCCC12)* 0.000 description 1
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
- LEGBISULKASFCD-UHFFFAOYSA-N 5-bromo-2-fluorobenzoyl chloride Chemical compound FC1=CC=C(Br)C=C1C(Cl)=O LEGBISULKASFCD-UHFFFAOYSA-N 0.000 description 1
- AQZSCSNIVCYLMB-UHFFFAOYSA-N 5-chloro-2-(2-chloro-5-nitrophenyl)-1,3-benzoxazole Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=2OC3=CC=C(Cl)C=C3N=2)=C1 AQZSCSNIVCYLMB-UHFFFAOYSA-N 0.000 description 1
- KFXGXVIUFMJHLW-UHFFFAOYSA-N 5-ethylsulfonyl-2-(3-nitrophenyl)-1,3-benzoxazole Chemical compound N=1C2=CC(S(=O)(=O)CC)=CC=C2OC=1C1=CC=CC([N+]([O-])=O)=C1 KFXGXVIUFMJHLW-UHFFFAOYSA-N 0.000 description 1
- BDCGLOWVUVCDJZ-UHFFFAOYSA-N 5-tert-butyl-2-(2-chloro-5-nitrophenyl)-1,3-benzoxazole Chemical compound N=1C2=CC(C(C)(C)C)=CC=C2OC=1C1=CC([N+]([O-])=O)=CC=C1Cl BDCGLOWVUVCDJZ-UHFFFAOYSA-N 0.000 description 1
- XBPALIOZPJVRKB-UHFFFAOYSA-N 5-tert-butyl-2-(3-nitrophenyl)-1,3-benzoxazole Chemical compound N=1C2=CC(C(C)(C)C)=CC=C2OC=1C1=CC=CC([N+]([O-])=O)=C1 XBPALIOZPJVRKB-UHFFFAOYSA-N 0.000 description 1
- CKYHVXPWFXFWAK-UHFFFAOYSA-N 6-(2-methylbutan-2-yl)-2-(3-nitrophenyl)-1,3-benzoxazole Chemical compound O1C2=CC(C(C)(C)CC)=CC=C2N=C1C1=CC=CC([N+]([O-])=O)=C1 CKYHVXPWFXFWAK-UHFFFAOYSA-N 0.000 description 1
- GJFHBNPILAOMAN-UHFFFAOYSA-N 6-chloro-2-(2-chloro-5-nitrophenyl)-1,3-benzoxazole Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=2OC3=CC(Cl)=CC=C3N=2)=C1 GJFHBNPILAOMAN-UHFFFAOYSA-N 0.000 description 1
- FMEBIWNKYZUWFV-UHFFFAOYSA-N 6-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)N=C1 FMEBIWNKYZUWFV-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- COBXBOZLMIYBRJ-UHFFFAOYSA-N BrC1=CC(=C(C=C1)O)C=1OC2=C(N1)C=C(C=C2)C.C(C2=CC=CC=C2)OC2=C(C=C(C=C2)Br)C=2OC1=C(N2)C=C(C=C1)C Chemical compound BrC1=CC(=C(C=C1)O)C=1OC2=C(N1)C=C(C=C2)C.C(C2=CC=CC=C2)OC2=C(C=C(C=C2)Br)C=2OC1=C(N2)C=C(C=C1)C COBXBOZLMIYBRJ-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KHDREFACJWGBGS-UHFFFAOYSA-N ClC1=C(C(=O)O)C=C(C=C1)SC.ClC1=C(C(=O)O)C=C(C=C1)S(=O)(=O)C Chemical compound ClC1=C(C(=O)O)C=C(C=C1)SC.ClC1=C(C(=O)O)C=C(C=C1)S(=O)(=O)C KHDREFACJWGBGS-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 102000010918 Cysteinyl leukotriene receptors Human genes 0.000 description 1
- 108050001116 Cysteinyl leukotriene receptors Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 102100024025 Heparanase Human genes 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- LDQLYYLVRZNFHS-UHFFFAOYSA-N OS(=O)(=O)I(Cl)Br Chemical group OS(=O)(=O)I(Cl)Br LDQLYYLVRZNFHS-UHFFFAOYSA-N 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102100030484 Prostaglandin E synthase 2 Human genes 0.000 description 1
- 108050003514 Prostaglandin E synthase 2 Proteins 0.000 description 1
- 102000004226 Prostaglandin-E Synthases Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical class C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 208000037769 antenatal Bartter syndrome Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000008430 aromatic amides Chemical group 0.000 description 1
- 125000005604 azodicarboxylate group Chemical group 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 206010007604 cardiac sarcoidosis Diseases 0.000 description 1
- 230000005800 cardiovascular problem Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- KFGVRWGDTLZAAO-UHFFFAOYSA-N cyclopenta-1,3-diene dicyclohexyl(cyclopenta-1,3-dien-1-yl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.C1CCC(CC1)P(C1CCCCC1)c1ccc[cH-]1 KFGVRWGDTLZAAO-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- LMAJREOZDVKQCZ-UHFFFAOYSA-N ditert-butyl-[2-(2-ditert-butylphosphanylphenyl)phenyl]phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C LMAJREOZDVKQCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 108010037536 heparanase Proteins 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-M leukotriene B4(1-) Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC([O-])=O VNYSSYRCGWBHLG-AMOLWHMGSA-M 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- DKZGDFQURLWNNO-UHFFFAOYSA-N n,n-dimethyl-2-(5-methyl-1,3-benzoxazol-2-yl)-4-nitroaniline Chemical compound CN(C)C1=CC=C([N+]([O-])=O)C=C1C1=NC2=CC(C)=CC=C2O1 DKZGDFQURLWNNO-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- VRQCQOASVHGGSY-UHFFFAOYSA-N n-(2-chloro-6-methoxyphenyl)-2,2-dimethylpropanamide Chemical compound COC1=CC=CC(Cl)=C1NC(=O)C(C)(C)C VRQCQOASVHGGSY-UHFFFAOYSA-N 0.000 description 1
- HUPBIIPQIRGJCS-UHFFFAOYSA-N n-[3-(5-bromo-1,3-benzoxazol-2-yl)-4-chlorophenyl]-2,5-dichlorobenzamide Chemical compound ClC1=CC=C(Cl)C(C(=O)NC=2C=C(C(Cl)=CC=2)C=2OC3=CC=C(Br)C=C3N=2)=C1 HUPBIIPQIRGJCS-UHFFFAOYSA-N 0.000 description 1
- AVATUWFZYXACJC-UHFFFAOYSA-N n-[3-(5-methyl-1,3-benzoxazol-2-yl)-4-propan-2-yloxyphenyl]-2-(trifluoromethyl)benzamide Chemical compound C1=C(C=2OC3=CC=C(C)C=C3N=2)C(OC(C)C)=CC=C1NC(=O)C1=CC=CC=C1C(F)(F)F AVATUWFZYXACJC-UHFFFAOYSA-N 0.000 description 1
- VQXJWNOEBYJNKK-UHFFFAOYSA-N n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-3-propan-2-yloxybenzamide Chemical compound CC(C)OC1=CC=CC(C(=O)NC=2C=C(C=CC=2)C=2OC3=CC=C(C)C=C3N=2)=C1 VQXJWNOEBYJNKK-UHFFFAOYSA-N 0.000 description 1
- YPBLDQCUCQLPCV-UHFFFAOYSA-N n-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]-4-propan-2-yloxybenzamide Chemical compound C1=CC(OC(C)C)=CC=C1C(=O)NC1=CC=CC(C=2OC3=CC=C(C)C=C3N=2)=C1 YPBLDQCUCQLPCV-UHFFFAOYSA-N 0.000 description 1
- SUAWTBQNRQOMRK-UHFFFAOYSA-N n-[3-(5-tert-butyl-1,3-benzoxazol-2-yl)phenyl]-3,5-dichlorobenzamide Chemical compound N=1C2=CC(C(C)(C)C)=CC=C2OC=1C(C=1)=CC=CC=1NC(=O)C1=CC(Cl)=CC(Cl)=C1 SUAWTBQNRQOMRK-UHFFFAOYSA-N 0.000 description 1
- UXCZEFTVNZTUKZ-UHFFFAOYSA-N n-[4-chloro-3-(4-chloro-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC=C1C(=O)NC1=CC=C(Cl)C(C=2OC3=CC=CC(Cl)=C3N=2)=C1 UXCZEFTVNZTUKZ-UHFFFAOYSA-N 0.000 description 1
- UEXSIUFIYBHQEN-UHFFFAOYSA-N n-[4-chloro-3-(5-chloro-1,3-benzoxazol-2-yl)phenyl]-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=CC=C1C(=O)NC1=CC=C(Cl)C(C=2OC3=CC=C(Cl)C=C3N=2)=C1 UEXSIUFIYBHQEN-UHFFFAOYSA-N 0.000 description 1
- FUIOOOPLVCWYEH-UHFFFAOYSA-N n-[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]pyrazine-2-carboxamide Chemical compound N=1C2=CC(C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CN=CC=N1 FUIOOOPLVCWYEH-UHFFFAOYSA-N 0.000 description 1
- ZDNYQWMBJRWRBF-UHFFFAOYSA-N n-[4-chloro-3-(5-propan-2-yl-1,3-benzoxazol-2-yl)phenyl]-2-nitrobenzamide Chemical compound N=1C2=CC(C(C)C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CC=C1[N+]([O-])=O ZDNYQWMBJRWRBF-UHFFFAOYSA-N 0.000 description 1
- AQRNYUQDLPHKDM-UHFFFAOYSA-N n-[4-chloro-3-(5-propan-2-yl-1,3-benzoxazol-2-yl)phenyl]-4-methoxy-3-nitrobenzamide Chemical compound C1=C([N+]([O-])=O)C(OC)=CC=C1C(=O)NC1=CC=C(Cl)C(C=2OC3=CC=C(C=C3N=2)C(C)C)=C1 AQRNYUQDLPHKDM-UHFFFAOYSA-N 0.000 description 1
- TVAZEDFZMIYYRX-UHFFFAOYSA-N n-[4-chloro-3-(5-propan-2-yl-1,3-benzoxazol-2-yl)phenyl]pyridine-3-carboxamide Chemical compound N=1C2=CC(C(C)C)=CC=C2OC=1C(C(=CC=1)Cl)=CC=1NC(=O)C1=CC=CN=C1 TVAZEDFZMIYYRX-UHFFFAOYSA-N 0.000 description 1
- AFWIWFZJVXXPEG-UHFFFAOYSA-N n-[4-chloro-3-(6-chloro-1,3-benzoxazol-2-yl)phenyl]-2-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=CC=C1C(=O)NC1=CC=C(Cl)C(C=2OC3=CC(Cl)=CC=C3N=2)=C1 AFWIWFZJVXXPEG-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- TXJKATOSKLUITR-UHFFFAOYSA-N pyrazine-2-carbonyl chloride Chemical compound ClC(=O)C1=CN=CC=N1 TXJKATOSKLUITR-UHFFFAOYSA-N 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- ZNICOTLOPCODTO-UHFFFAOYSA-N tert-butyl 3-butylpiperazine-1-carboxylate Chemical compound CCCCC1CN(C(=O)OC(C)(C)C)CCN1 ZNICOTLOPCODTO-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 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 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Communicable Diseases (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Otolaryngology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72530105P | 2005-10-12 | 2005-10-12 | |
| PCT/GB2006/003792 WO2007042816A1 (en) | 2005-10-12 | 2006-10-12 | Benzoxazoles useful in the treatment of inflammation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009511559A true JP2009511559A (ja) | 2009-03-19 |
| JP2009511559A5 JP2009511559A5 (enExample) | 2009-12-03 |
Family
ID=36129701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008535097A Withdrawn JP2009511559A (ja) | 2005-10-12 | 2006-10-12 | 炎症の治療に有用なベンゾオキサゾール類 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20090258917A1 (enExample) |
| EP (1) | EP1933834A1 (enExample) |
| JP (1) | JP2009511559A (enExample) |
| CA (1) | CA2620899A1 (enExample) |
| WO (1) | WO2007042816A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080081913A1 (en) * | 2006-09-29 | 2008-04-03 | General Electric Company | Benzoxazole and benzothiazole compounds and methods therefor |
| US20080081210A1 (en) | 2006-09-29 | 2008-04-03 | General Electric Company | Authenticatable articles and methods therefor |
| JP2010513253A (ja) * | 2006-12-14 | 2010-04-30 | ベーリンガー インゲルハイム インテルナショナール ゲーエムベーハー | 炎症の治療に有用なベンゾオキサゾール類 |
| TW200916458A (en) * | 2007-09-05 | 2009-04-16 | Astrazeneca Ab | Heterocyclic compounds and methods of use thereof |
| WO2009080788A2 (en) * | 2007-12-21 | 2009-07-02 | Universite Catholique De Louvain | Antibacterial agents |
| EP2078711A1 (en) * | 2007-12-28 | 2009-07-15 | AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A. | (Aza)indole derivative substituted in position 5, pharmaceutical composition comprising it, intermediate compounds and preparation process therefor |
| GB201006846D0 (en) | 2010-04-23 | 2010-06-09 | Glaxo Group Ltd | Novel compounds |
| EP2495244A1 (en) | 2011-03-02 | 2012-09-05 | NovaSaid AB | Piperidinyl benzoimidazole derivatives as mPGEs-1 inhibitors |
| CA2953747A1 (en) | 2013-06-28 | 2014-12-31 | Auckland Uniservices Limited | Amino acid and peptide conjugates and conjugation process |
| LT3066089T (lt) | 2013-11-08 | 2020-02-25 | Promentis Pharmaceuticals, Inc. | Pakeistieji n-acetil-l-cisteino dariniai ir giminingi junginiai |
| JP2018505152A (ja) | 2014-12-23 | 2018-02-22 | アン ブリンブル マーガレット | アミノ酸複合体及びペプチド複合体ならびにそれらの使用 |
| CN104788398B (zh) * | 2015-03-24 | 2017-09-08 | 上海交通大学 | 苯并恶唑类化合物及其制备方法和用途 |
| WO2017145097A2 (en) | 2016-02-26 | 2017-08-31 | Auckland Uniservices Limited | Amino acid and peptide conjugates and conjugation process |
| US12036286B2 (en) | 2021-03-18 | 2024-07-16 | Seagen Inc. | Selective drug release from internalized conjugates of biologically active compounds |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5298189A (en) * | 1992-04-24 | 1994-03-29 | Nanoptics Incorporated | Proton transfer bis-benzazole fluors and their use in scintillator detectors |
| AU2003283597A1 (en) * | 2002-11-16 | 2004-06-15 | Oxford Glycosciences (Uk) Ltd | Benzoxazole, benzthiazole and benzimidazole acid derivatives and their use as heparanase inhibitors |
| EP1603897A1 (en) * | 2003-03-14 | 2005-12-14 | Biolipox AB | Pyrazole compounds useful in the treatment of inflammation |
| CA2528626A1 (en) * | 2003-07-09 | 2005-01-20 | Biolipox Ab | Indoles useful in the treatment of inflammation |
| WO2005030705A1 (en) * | 2003-09-24 | 2005-04-07 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US20060052425A1 (en) * | 2004-03-23 | 2006-03-09 | Wisconsin Alumni Research Foundation | Method for modulating microbial quorum sensing |
| CA2587489C (en) * | 2004-11-03 | 2013-12-31 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
-
2006
- 2006-10-12 CA CA002620899A patent/CA2620899A1/en not_active Abandoned
- 2006-10-12 US US12/083,384 patent/US20090258917A1/en not_active Abandoned
- 2006-10-12 WO PCT/GB2006/003792 patent/WO2007042816A1/en not_active Ceased
- 2006-10-12 JP JP2008535097A patent/JP2009511559A/ja not_active Withdrawn
- 2006-10-12 EP EP06794740A patent/EP1933834A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP1933834A1 (en) | 2008-06-25 |
| US20090258917A1 (en) | 2009-10-15 |
| CA2620899A1 (en) | 2007-04-19 |
| WO2007042816A1 (en) | 2007-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100004301A1 (en) | Benzoxazoles Useful in the Treatment of Inflammation | |
| CA2701053C (en) | Oxadiazole- and oxazole-substituted benzimidazole- and indole-derivatives as dgat1 inhibitors | |
| US20100234377A1 (en) | Piperazine compounds for the inhibition of haematopoietic prostaglandin d synthase | |
| US20090076004A1 (en) | Indoles Useful in the Treatment of Inflammation | |
| AU2007230911A1 (en) | Benzimidazolyl-pyridine compounds for inflammation and immune-related uses | |
| AU2005286701A1 (en) | Compounds for inflammation and immune-related uses | |
| JP2009511559A (ja) | 炎症の治療に有用なベンゾオキサゾール類 | |
| JP2011502148A (ja) | 疼痛の治療用としてのｐ２ｘ３受容体アンタゴニスト | |
| WO2004020393A1 (ja) | ジベンジルアミン化合物及びその医薬用途 | |
| US7705023B2 (en) | Indoles useful in the treatment of inflammation | |
| JP2008527028A (ja) | 炎症の治療に有用なインドール類 | |
| JP2008527030A (ja) | 炎症の治療に有用なインドール類 | |
| JP6927042B2 (ja) | グアニジン誘導体及びその医薬用途 | |
| WO1998046594A1 (en) | Pyrazole derivatives and cox inhibitors containing them | |
| JPWO2012014910A1 (ja) | Ｐ２ｘ４受容体拮抗剤 | |
| JP2006520373A (ja) | 炎症の治療に有用なピラゾール化合物 | |
| JP2008502670A (ja) | 炎症の治療に有用なインドール類 | |
| JPWO2005026127A1 (ja) | プラスミノゲンアクチベータインヒビター−１阻害剤 | |
| JP2007516203A (ja) | 炎症の治療に有用なインドール類 | |
| AU2007298540B2 (en) | 3 -amino- pyridine derivatives for the treatment of metabolic disorders | |
| US20130035358A1 (en) | Bis Aromatic Compounds for Use as LTC4 Synthase Inhibitors | |
| TW200400026A (en) | Use of substituted 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones for producing medicaments with an inhibitory effect on pancreatic lipase | |
| US20060160879A1 (en) | Indoles useful in the treatment of inflammation | |
| JP2009511560A (ja) | 炎症の治療に有用なナフタレン−ジスルホンアミド類 | |
| JPWO2018159650A1 (ja) | グアニジン誘導体及びその医薬用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091013 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20091013 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20101201 |