PH26314A - Benzopyrano [4,3-c] pyrazoles derivatives - Google Patents
Benzopyrano [4,3-c] pyrazoles derivatives Download PDFInfo
- Publication number
- PH26314A PH26314A PH38993A PH38993A PH26314A PH 26314 A PH26314 A PH 26314A PH 38993 A PH38993 A PH 38993A PH 38993 A PH38993 A PH 38993A PH 26314 A PH26314 A PH 26314A
- Authority
- PH
- Philippines
- Prior art keywords
- group
- represents hydrogen
- hydrogen
- formula
- fluoro
- Prior art date
Links
- ZHEAXGGEDWGTDP-UHFFFAOYSA-N chromeno[4,3-c]pyrazole Chemical class C1=CC=C2C3=NN=CC3=COC2=C1 ZHEAXGGEDWGTDP-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 190
- 229910052739 hydrogen Inorganic materials 0.000 claims description 138
- 239000001257 hydrogen Substances 0.000 claims description 137
- 239000000203 mixture Substances 0.000 claims description 108
- 150000002431 hydrogen Chemical class 0.000 claims description 74
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 58
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 54
- -1 chloro, bromo, acetyl Chemical group 0.000 claims description 47
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
- 125000001153 fluoro group Chemical group F* 0.000 claims description 33
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 23
- 125000004414 alkyl thio group Chemical group 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000004423 acyloxy group Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- XBYRMPXUBGMOJC-UHFFFAOYSA-N 1,2-dihydropyrazol-3-one Chemical compound OC=1C=CNN=1 XBYRMPXUBGMOJC-UHFFFAOYSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 230000002519 immonomodulatory effect Effects 0.000 claims description 4
- 230000001900 immune effect Effects 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 241001620634 Roger Species 0.000 claims 1
- 235000013405 beer Nutrition 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 239000007787 solid Substances 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000001914 filtration Methods 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000010992 reflux Methods 0.000 description 27
- 238000012360 testing method Methods 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000012258 stirred mixture Substances 0.000 description 15
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 14
- 235000011167 hydrochloric acid Nutrition 0.000 description 14
- 229960000443 hydrochloric acid Drugs 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 239000008096 xylene Substances 0.000 description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 238000001953 recrystallisation Methods 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 10
- 239000012265 solid product Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000011928 denatured alcohol Substances 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- XXNOGQJZAOXWAQ-UHFFFAOYSA-N 4-chlorophenylhydrazine Chemical compound NNC1=CC=C(Cl)C=C1 XXNOGQJZAOXWAQ-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- ZRHUHDUEXWHZMA-UHFFFAOYSA-N 1,4-dihydropyrazol-5-one Chemical compound O=C1CC=NN1 ZRHUHDUEXWHZMA-UHFFFAOYSA-N 0.000 description 6
- VXIXUWQIVKSKSA-UHFFFAOYSA-N 4-hydroxycoumarin Chemical compound C1=CC=CC2=C1OC(=O)C=C2O VXIXUWQIVKSKSA-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- DCSQXFAJSPSNQL-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC=C1)O DCSQXFAJSPSNQL-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 5
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- DZEVUMSAIVIXGZ-UHFFFAOYSA-N 2h-chromeno[4,3-c]pyrazol-3-one Chemical compound C1=CC=C2C3=NNC(=O)C3=COC2=C1 DZEVUMSAIVIXGZ-UHFFFAOYSA-N 0.000 description 4
- XYFXTIBDEAZMAH-UHFFFAOYSA-N 5-methoxychromen-2-one Chemical compound O1C(=O)C=CC2=C1C=CC=C2OC XYFXTIBDEAZMAH-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 3
- DLNFNWJHKVHKDD-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-methylchromeno[4,3-c]pyrazol-3-one Chemical compound ClC=1C=C(C=CC1Cl)N1N=C2C(C1=O)=C(OC1=C2C=CC=C1)C DLNFNWJHKVHKDD-UHFFFAOYSA-N 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 238000011725 BALB/c mouse Methods 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000002027 dichloromethane extract Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 235000019271 petrolatum Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- HGTBAIVLETUVCG-UHFFFAOYSA-M (methylthio)acetate Chemical compound CSCC([O-])=O HGTBAIVLETUVCG-UHFFFAOYSA-M 0.000 description 2
- DEXCPLHFZPWIJU-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-5-(2-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC=1C=C(C=CC1Cl)N1N=C(CC1=O)C1=C(C=CC=C1)O DEXCPLHFZPWIJU-UHFFFAOYSA-N 0.000 description 2
- KQXWARNSGFTTHT-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2,5-dihydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC(=C1)O)O KQXWARNSGFTTHT-UHFFFAOYSA-N 0.000 description 2
- BGCFMMGBLBWXIH-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2-hydroxy-6-methoxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC=C1OC)O BGCFMMGBLBWXIH-UHFFFAOYSA-N 0.000 description 2
- IEEHKTFVUIVORU-UHFFFAOYSA-N 2-methylpropanedioyl dichloride Chemical compound ClC(=O)C(C)C(Cl)=O IEEHKTFVUIVORU-UHFFFAOYSA-N 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- MHZZDYJKWIQMFN-UHFFFAOYSA-N 4-hydroxy-7-methylchromen-2-one Chemical compound OC1=CC(=O)OC2=CC(C)=CC=C21 MHZZDYJKWIQMFN-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- UEDAWBSXQAEIBZ-UHFFFAOYSA-N 5-ethoxy-4-hydroxychromen-2-one Chemical compound O1C(=O)C=C(O)C2=C1C=CC=C2OCC UEDAWBSXQAEIBZ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 102100023053 Band 4.1-like protein 5 Human genes 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- 206010012434 Dermatitis allergic Diseases 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 101001049973 Homo sapiens Band 4.1-like protein 5 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 208000010247 contact dermatitis Diseases 0.000 description 2
- 229960000956 coumarin Drugs 0.000 description 2
- 235000001671 coumarin Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- PUNIIEHHUHGISF-UHFFFAOYSA-N (2-fluorophenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1F PUNIIEHHUHGISF-UHFFFAOYSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- YMJSQPNVQRHZDW-UHFFFAOYSA-N (3,4-dichlorophenyl)hydrazine Chemical compound NNC1=CC=C(Cl)C(Cl)=C1 YMJSQPNVQRHZDW-UHFFFAOYSA-N 0.000 description 1
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PSNPXFMLAVLPPP-UHFFFAOYSA-N 1-(2-fluoro-6-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=C(O)C=CC=C1F PSNPXFMLAVLPPP-UHFFFAOYSA-N 0.000 description 1
- WXTHZWWWCICGAN-UHFFFAOYSA-N 1-(3-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1O WXTHZWWWCICGAN-UHFFFAOYSA-N 0.000 description 1
- KOFFXZYMDLWRHX-UHFFFAOYSA-N 1-(5-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1O KOFFXZYMDLWRHX-UHFFFAOYSA-N 0.000 description 1
- HKHWEILYYFMRDF-UHFFFAOYSA-N 2-(3-chloro-4-methylphenyl)-5-(2-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC=1C=C(C=CC1C)N1N=C(CC1=O)C1=C(C=CC=C1)O HKHWEILYYFMRDF-UHFFFAOYSA-N 0.000 description 1
- RQOLCRHOTDFTPY-UHFFFAOYSA-N 2-(3-chlorophenyl)-5-(2-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC=1C=C(C=CC1)N1N=C(CC1=O)C1=C(C=CC=C1)O RQOLCRHOTDFTPY-UHFFFAOYSA-N 0.000 description 1
- SSEKRNWNSQNZBW-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2,6-dihydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC=C1O)O SSEKRNWNSQNZBW-UHFFFAOYSA-N 0.000 description 1
- PDUYYNKPMJUKCE-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2-ethoxy-6-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC=C1OCC)O PDUYYNKPMJUKCE-UHFFFAOYSA-N 0.000 description 1
- IIPZZGXHODOVTR-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2-hydroxy-3-methoxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C(=CC=C1)OC)O IIPZZGXHODOVTR-UHFFFAOYSA-N 0.000 description 1
- RJPYFADSMJAAGK-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(2-hydroxy-5-methylphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC(=C1)C)O RJPYFADSMJAAGK-UHFFFAOYSA-N 0.000 description 1
- MRQCCQGEEFNWJC-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(3-fluoro-2-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C(=CC=C1)F)O MRQCCQGEEFNWJC-UHFFFAOYSA-N 0.000 description 1
- ROVSBUBPVYVGOT-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(5-ethyl-2-hydroxyphenyl)-4H-pyrazol-3-one Chemical compound ClC1=CC=C(C=C1)N1N=C(CC1=O)C1=C(C=CC(=C1)CC)O ROVSBUBPVYVGOT-UHFFFAOYSA-N 0.000 description 1
- KOZGHFQQEHVFQB-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-methylchromeno[4,3-c]pyrazol-3-one Chemical compound O=C1C2=C(C)OC3=CC=CC=C3C2=NN1C1=CC=C(F)C=C1 KOZGHFQQEHVFQB-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- YPMSIWYNTPSPMV-UHFFFAOYSA-N 2-fluoro-6-methoxybenzonitrile Chemical compound COC1=CC=CC(F)=C1C#N YPMSIWYNTPSPMV-UHFFFAOYSA-N 0.000 description 1
- NCDSEQNSIBPEKG-UHFFFAOYSA-N 2-methyl-2,3-dihydrochromen-4-one Chemical compound C1=CC=C2OC(C)CC(=O)C2=C1 NCDSEQNSIBPEKG-UHFFFAOYSA-N 0.000 description 1
- ZLJNSNMVVJZROT-UHFFFAOYSA-N 2h-pyrano[4,3-c]pyrazol-3-one Chemical compound C1=COC=C2C(O)=NN=C21 ZLJNSNMVVJZROT-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- PKRMXFQTESAARM-UHFFFAOYSA-N 3-(2-hydroxyphenyl)-1,4-dihydropyrazol-5-one Chemical compound OC1=C(C=CC=C1)C1=NNC(C1)=O PKRMXFQTESAARM-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- PQQIIAHYPFFGDK-UHFFFAOYSA-N 4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one;3h-1,3-oxazol-2-one Chemical compound O=C1NC=CO1.O1C(=O)C(=COCC)N=C1C1=CC=CC=C1 PQQIIAHYPFFGDK-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- LFFCJEOKCYTBDD-UHFFFAOYSA-N 4-hydroxy-5-methoxychromen-2-one Chemical compound O1C(=O)C=C(O)C2=C1C=CC=C2OC LFFCJEOKCYTBDD-UHFFFAOYSA-N 0.000 description 1
- ABCLPXHJIKFYLL-UHFFFAOYSA-N 4-hydroxy-8-methoxychromen-2-one Chemical compound OC1=CC(=O)OC2=C1C=CC=C2OC ABCLPXHJIKFYLL-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- KQZKICNKRDOKTD-UHFFFAOYSA-N 5-(2-hydroxyphenyl)-2-(4-methylphenyl)-4H-pyrazol-3-one Chemical compound OC1=C(C=CC=C1)C1=NN(C(C1)=O)C1=CC=C(C=C1)C KQZKICNKRDOKTD-UHFFFAOYSA-N 0.000 description 1
- TVPSUYBGLNBOAN-UHFFFAOYSA-N 5-(2-hydroxyphenyl)-2-phenyl-4H-pyrazol-3-one Chemical compound OC1=C(C=CC=C1)C1=NN(C(C1)=O)C1=CC=CC=C1 TVPSUYBGLNBOAN-UHFFFAOYSA-N 0.000 description 1
- CKFCTIYBSRVPPN-UHFFFAOYSA-N 5-(3-chloro-2-hydroxyphenyl)-2-phenyl-4H-pyrazol-3-one Chemical compound ClC=1C(=C(C=CC1)C1=NN(C(C1)=O)C1=CC=CC=C1)O CKFCTIYBSRVPPN-UHFFFAOYSA-N 0.000 description 1
- GVRPUSZJKXVREF-UHFFFAOYSA-N 6,8-difluoro-4-hydroxychromen-2-one Chemical compound FC1=CC(F)=CC2=C1OC(=O)C=C2O GVRPUSZJKXVREF-UHFFFAOYSA-N 0.000 description 1
- JYULRNGSVREOJU-UHFFFAOYSA-N 6-ethyl-4-hydroxychromen-2-one Chemical compound O1C(=O)C=C(O)C2=CC(CC)=CC=C21 JYULRNGSVREOJU-UHFFFAOYSA-N 0.000 description 1
- RPAIBTVEPAACRP-UHFFFAOYSA-N 6-fluoro-2-methyl-2,3-dihydrochromen-4-one Chemical compound FC1=CC=C2OC(C)CC(=O)C2=C1 RPAIBTVEPAACRP-UHFFFAOYSA-N 0.000 description 1
- ZHJUAZUEYFSEGF-UHFFFAOYSA-N 6-fluoro-2-methyl-4-oxo-2,3-dihydrochromene-3-carboxamide Chemical compound C1=C(F)C=C2C(=O)C(C(N)=O)C(C)OC2=C1 ZHJUAZUEYFSEGF-UHFFFAOYSA-N 0.000 description 1
- LDVPZYAULOHROF-UHFFFAOYSA-N 6-fluoro-3-(hydroxymethylidene)-2-methylchromen-4-one Chemical compound C1=C(F)C=C2C(=O)C(=CO)C(C)OC2=C1 LDVPZYAULOHROF-UHFFFAOYSA-N 0.000 description 1
- JCOYNGQUPPGRNB-UHFFFAOYSA-N 6-fluoro-4-hydroxychromen-2-one Chemical compound C1=CC(F)=CC2=C1OC(=O)C=C2O JCOYNGQUPPGRNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000428352 Amma Species 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 206010014025 Ear swelling Diseases 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- MUPNGJKWWFAGFQ-UHFFFAOYSA-N [2-(4-chlorophenyl)-5-(2-hydroxyphenyl)pyrazol-3-yl] acetate Chemical compound C(C)(=O)OC1=CC(=NN1C1=CC=C(C=C1)Cl)C1=C(C=CC=C1)O MUPNGJKWWFAGFQ-UHFFFAOYSA-N 0.000 description 1
- VLBWKRHHLQMLGA-UHFFFAOYSA-N [2-(4-chlorophenyl)-5-(2-hydroxyphenyl)pyrazol-3-yl] butanoate Chemical compound C(CCC)(=O)OC1=CC(=NN1C1=CC=C(C=C1)Cl)C1=C(C=CC=C1)O VLBWKRHHLQMLGA-UHFFFAOYSA-N 0.000 description 1
- ISXFGPZHGWSNLC-UHFFFAOYSA-N [3-acetyloxy-2-[5-acetyloxy-1-(4-chlorophenyl)pyrazol-3-yl]phenyl] acetate Chemical compound CC(=O)OC1=CC(C=2C(=CC=CC=2OC(C)=O)OC(C)=O)=NN1C1=CC=C(Cl)C=C1 ISXFGPZHGWSNLC-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- VBWVNOAJTGIORL-UHFFFAOYSA-N carbamoyl acetate Chemical compound CC(=O)OC(N)=O VBWVNOAJTGIORL-UHFFFAOYSA-N 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- PMHQVHHXPFUNSP-UHFFFAOYSA-M copper(1+);methylsulfanylmethane;bromide Chemical compound Br[Cu].CSC PMHQVHHXPFUNSP-UHFFFAOYSA-M 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-M ethanimidate Chemical compound CC([O-])=N DLFVBJFMPXGRIB-UHFFFAOYSA-M 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- CBTJGVADJJWJBK-UHFFFAOYSA-N ethoxycarbonyl propanoate Chemical compound CCOC(=O)OC(=O)CC CBTJGVADJJWJBK-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000012750 in vivo screening Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000019809 paraffin wax Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000000063 preceeding effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- YTLRPLVCLPUBBQ-UHFFFAOYSA-N propan-2-yloxycarbonyl acetate Chemical compound CC(C)OC(=O)OC(C)=O YTLRPLVCLPUBBQ-UHFFFAOYSA-N 0.000 description 1
- BPCRWPUOAHMDGM-UHFFFAOYSA-N propoxycarbonyl acetate Chemical compound CCCOC(=O)OC(C)=O BPCRWPUOAHMDGM-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB888818894A GB8818894D0 (en) | 1988-08-09 | 1988-08-09 | Therapeutic agents |
| CN91105263A CN1069271A (zh) | 1988-08-09 | 1991-08-02 | 制备[1]苯并吡喃并[4，3-c]吡唑类化合物的方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PH26314A true PH26314A (en) | 1994-04-29 |
Family
ID=25742706
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PH38993A PH26314A (en) | 1988-08-09 | 1989-07-25 | Benzopyrano [4,3-c] pyrazoles derivatives |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0354693A1 (zh) |
| JP (1) | JPH03500418A (zh) |
| CN (1) | CN1069271A (zh) |
| AU (1) | AU4060289A (zh) |
| DD (1) | DD284019A5 (zh) |
| DK (1) | DK88790A (zh) |
| FI (1) | FI901753A0 (zh) |
| HU (1) | HU208977B (zh) |
| MX (1) | MX17041A (zh) |
| NZ (1) | NZ230231A (zh) |
| PH (1) | PH26314A (zh) |
| PT (1) | PT91408A (zh) |
| WO (1) | WO1990001481A1 (zh) |
| YU (1) | YU155189A (zh) |
| ZA (1) | ZA895646B (zh) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8907799D0 (en) * | 1989-04-06 | 1989-05-17 | Erba Carlo Spa | Heteroaryl-3-oxo-propanenitrile derivatives useful in the treatment of rheumatoid arthritis and other autoimmune diseases |
| US5260328A (en) * | 1989-04-06 | 1993-11-09 | Farmitalia Carlo Erba Srl | Phenyl-indenopurazol 3-oxo-propanamide derivatives useful in the treatment of rheumatoid arthritis |
| GB9002423D0 (en) * | 1990-02-06 | 1990-04-04 | Boots Co Plc | Therapeutic agents |
| GB9116241D0 (en) * | 1991-07-27 | 1991-09-11 | Boots Co Plc | Therapeutic agents |
| US6642249B2 (en) | 2001-07-04 | 2003-11-04 | Active Biotech Ab | Immunomodulating compounds |
| SE0102404D0 (sv) * | 2001-07-04 | 2001-07-04 | Active Biotech Ab | Novel immunomodulating compounds |
| DE60326639D1 (de) * | 2002-12-16 | 2009-04-23 | Active Biotech Ab | Tetrazyklische immunmodulierende verbindungen |
| CN102391272B (zh) * | 2011-09-30 | 2014-07-02 | 浙江工业大学 | 1,4-二取代基-1,4-二氢苯并吡喃[4,3-c]吡唑类化合物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4268516A (en) * | 1978-10-11 | 1981-05-19 | Pfizer Inc. | [1]Benzothiopyrano[4,3-c]pyrazoles as immunoregulatory agents |
-
1989
- 1989-07-25 PH PH38993A patent/PH26314A/en unknown
- 1989-07-25 ZA ZA895646A patent/ZA895646B/xx unknown
- 1989-07-28 HU HU894659A patent/HU208977B/hu not_active IP Right Cessation
- 1989-07-28 AU AU40602/89A patent/AU4060289A/en not_active Abandoned
- 1989-07-28 JP JP1508715A patent/JPH03500418A/ja active Pending
- 1989-07-28 EP EP89307724A patent/EP0354693A1/en not_active Withdrawn
- 1989-07-28 WO PCT/GB1989/000859 patent/WO1990001481A1/en active Application Filing
- 1989-08-02 MX MX1704189A patent/MX17041A/es unknown
- 1989-08-07 DD DD89331553A patent/DD284019A5/de not_active IP Right Cessation
- 1989-08-07 YU YU01551/89A patent/YU155189A/xx unknown
- 1989-08-07 NZ NZ230231A patent/NZ230231A/en unknown
- 1989-08-09 PT PT91408A patent/PT91408A/pt unknown
-
1990
- 1990-04-06 FI FI901753A patent/FI901753A0/fi not_active IP Right Cessation
- 1990-04-09 DK DK088790A patent/DK88790A/da not_active Application Discontinuation
-
1991
- 1991-08-02 CN CN91105263A patent/CN1069271A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MX17041A (es) | 1994-02-28 |
| JPH03500418A (ja) | 1991-01-31 |
| CN1069271A (zh) | 1993-02-24 |
| AU4060289A (en) | 1990-03-05 |
| DD284019A5 (de) | 1990-10-31 |
| EP0354693A1 (en) | 1990-02-14 |
| WO1990001481A1 (en) | 1990-02-22 |
| HU208977B (en) | 1994-02-28 |
| FI901753A0 (fi) | 1990-04-06 |
| HU894659D0 (en) | 1990-07-28 |
| DK88790D0 (da) | 1990-04-09 |
| PT91408A (pt) | 1990-03-08 |
| NZ230231A (en) | 1992-03-26 |
| ZA895646B (en) | 1990-04-25 |
| YU155189A (en) | 1991-02-28 |
| HUT58337A (en) | 1992-02-28 |
| DK88790A (da) | 1990-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH069606A (ja) | ヘテロビサイクリック化合物 | |
| WO2004092181A1 (en) | Heterocyclic mchr1 antagonists | |
| EP0264586A1 (en) | Hydantoin derivatives for treating complications of diabetes | |
| PH26314A (en) | Benzopyrano [4,3-c] pyrazoles derivatives | |
| WO2020241853A1 (ja) | ベンゾトリアゾール誘導体 | |
| IL94302A (en) | History of N-Arleic Acid (Il-Oxo) Theoxo (Pyrido] -D-3,2 [Pyridazinate | |
| SU568366A3 (ru) | Способ получени производных бензодиазепина или их 5-окисей или солей | |
| CS195325B2 (en) | Method of producing 4-aminoalkoxy-2/2h/pyranones 3-substituted and 5,6-condensed | |
| HU182712B (en) | Process for producing substituted thieno-aenzodiazepines | |
| US3560525A (en) | 5-phenyl-2-furanacetic acids,5-phenyl-2-thiopheneacetic acids,and their derivatives | |
| KURASAWA et al. | Synthesis and Reactions of 3-(1, 3, 4-Oxadiazol-2-yl) methylene-2-oxo-1, 2, 3, 4-tetrahydroquinoxalines | |
| US5075317A (en) | Spirofurane derivatives | |
| LU82419A1 (fr) | Pyrido(1,2-a)pyrimidines substituees | |
| HU207313B (en) | Process for thianaphtene derivatives and pharmaceutical compositions containing them | |
| EP0339358B1 (en) | Pyrazolopyridine type mevalonolactones | |
| US4968708A (en) | Imidazo[2,1-B]benzothiazole compounds and antiulcer compositions containing the same | |
| EP0014079B1 (en) | Spiro-quinolylhydantoins, process for their preparation and pharmaceutical compositions thereof | |
| AU625915B2 (en) | Synthesis of (1)-benzothiopyrano (4,3-c)-pyrazoles | |
| US4128549A (en) | Precursors of 4-(1-alkyl-4-piperidylidene-4H-benzo[4,5]cyclohepta-[1,2-b]thiophen-10(9H)-ones | |
| GB2209336A (en) | Germinally substituted cyclic ether carboxylic acids | |
| EP0030038B1 (en) | 1,2,4-triazine derivatives, process for their production and pharmaceutical composition | |
| CS214806B2 (en) | Method of making the derivatives of the auron | |
| JPH0480027B2 (zh) | ||
| Siddiqui et al. | Novel pyrazolopyrones from enol lactones | |
| CA1221976A (en) | Process for the manufacture of novel dioxaheterocyclic compounds |