SK118798A3 - Pharmaceutically useful compounds - Google Patents
Pharmaceutically useful compounds Download PDFInfo
- Publication number
- SK118798A3 SK118798A3 SK1187-98A SK118798A SK118798A3 SK 118798 A3 SK118798 A3 SK 118798A3 SK 118798 A SK118798 A SK 118798A SK 118798 A3 SK118798 A3 SK 118798A3
- Authority
- SK
- Slovakia
- Prior art keywords
- pyrazolo
- hydroxy
- formula
- bond
- methyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 285
- 238000000034 method Methods 0.000 claims abstract description 47
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 199
- 150000003839 salts Chemical class 0.000 claims description 177
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- -1 NR 16 R 17 Chemical group 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 23
- UTKNBHYJLFLZRD-UHFFFAOYSA-N isoquinolin-2-ium;hydroxide Chemical compound [OH-].C1=[NH+]C=CC2=CC=CC=C21 UTKNBHYJLFLZRD-UHFFFAOYSA-N 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
- GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- ZDQCLDBVVQUHDH-UHFFFAOYSA-N 6h-isoquinolin-5-one Chemical compound N1=CC=C2C(=O)CC=CC2=C1 ZDQCLDBVVQUHDH-UHFFFAOYSA-N 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 8
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- AWJUIBRHMBBTKR-UHFFFAOYSA-O isoquinolin-2-ium Chemical compound C1=[NH+]C=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-O 0.000 claims description 8
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- DKAKOSUOWJVWSD-UHFFFAOYSA-N COc1ccc(Cn2c3c(O)n(nc3c3ccccc3c2=O)-c2ccc(cc2)C(F)(F)F)cc1 Chemical compound COc1ccc(Cn2c3c(O)n(nc3c3ccccc3c2=O)-c2ccc(cc2)C(F)(F)F)cc1 DKAKOSUOWJVWSD-UHFFFAOYSA-N 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- PVFTVWLLJSNYFC-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(=CC=3)C(F)(F)F)[NH2+]C2=C2C=CC=CC2=C1 PVFTVWLLJSNYFC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- AHFMOFVTPSIFDG-UHFFFAOYSA-N 4-methyl-5-methylsulfanyl-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C(SC)=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C(F)(F)F)C=C1 AHFMOFVTPSIFDG-UHFFFAOYSA-N 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000004001 thioalkyl group Chemical group 0.000 claims description 4
- OOVMRUNJTOSPNP-UHFFFAOYSA-N 2-(4-chlorophenyl)-4-(2-methylsulfanylethyl)-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(CCSC)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(Cl)C=C1 OOVMRUNJTOSPNP-UHFFFAOYSA-N 0.000 claims description 3
- YLICKAKYJGCYNI-UHFFFAOYSA-N 4-(2-methylsulfanylethyl)-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(CCSC)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C(F)(F)F)C=C1 YLICKAKYJGCYNI-UHFFFAOYSA-N 0.000 claims description 3
- ZCQJCHZBLNLFJY-UHFFFAOYSA-N 4-methyl-2-(4-methylthiophen-2-yl)-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC(C)=CS1 ZCQJCHZBLNLFJY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
- KQRHWMBVDDGFJH-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C=1N(C=C1C=CC=CC=21)CC1=CC=C(C=C1)OC)C=1C=NC2=CC=CC=C2C=1 Chemical compound [OH-].OC=1N([NH2+]C=2C=1N(C=C1C=CC=CC=21)CC1=CC=C(C=C1)OC)C=1C=NC2=CC=CC=C2C=1 KQRHWMBVDDGFJH-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- WISWOBVOXDOJLV-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(Cl)C(Cl)=C1 WISWOBVOXDOJLV-UHFFFAOYSA-N 0.000 claims description 2
- WHNDAYMYILZNGT-UHFFFAOYSA-N 2-(4-bromophenyl)-4-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(Br)C=C1 WHNDAYMYILZNGT-UHFFFAOYSA-N 0.000 claims description 2
- IXPCPXXOAVXTCX-UHFFFAOYSA-N 2-(4-chlorophenyl)-3a,4-dimethyl-5h-pyrazolo[4,3-c]isoquinolin-3-one Chemical compound O=C1C2(C)N(C)CC3=CC=CC=C3C2=NN1C1=CC=C(Cl)C=C1 IXPCPXXOAVXTCX-UHFFFAOYSA-N 0.000 claims description 2
- XRYAOHFWRNRGHB-UHFFFAOYSA-N 2-(4-chlorophenyl)-4,5-dimethyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].[NH2+]1C2=C3C=CC=CC3=C(C)N(C)C2=C(O)N1C1=CC=C(Cl)C=C1 XRYAOHFWRNRGHB-UHFFFAOYSA-N 0.000 claims description 2
- ROMNEYAQUBNRLR-UHFFFAOYSA-N 2-(4-hydroxybiphenyl-3-yl)-4-methyl-1h-isoindole-1,3(2h)-dione Chemical compound O=C1C=2C(C)=CC=CC=2C(=O)N1C(C(=CC=1)O)=CC=1C1=CC=CC=C1 ROMNEYAQUBNRLR-UHFFFAOYSA-N 0.000 claims description 2
- RDZKPSLCQMHEMV-UHFFFAOYSA-N 2-(4-iodophenyl)-4-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(I)C=C1 RDZKPSLCQMHEMV-UHFFFAOYSA-N 0.000 claims description 2
- HSKNESSXMAUTOB-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-4-methyl-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C(C)(C)C)C=C1 HSKNESSXMAUTOB-UHFFFAOYSA-N 0.000 claims description 2
- MLAYZCMWRNQKQX-UHFFFAOYSA-N 2-hydroxy-1h-isoquinoline Chemical compound C1=CC=C2C=CN(O)CC2=C1 MLAYZCMWRNQKQX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
- BDCYLEDBRGCNIA-UHFFFAOYSA-N 4-(3-hydroxy-4-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-2-yl)benzoic acid;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C(O)=O)C=C1 BDCYLEDBRGCNIA-UHFFFAOYSA-N 0.000 claims description 2
- JHFCMQCVAAGCCH-UHFFFAOYSA-N 4-methyl-2-(4-methylphenyl)-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C)C=C1 JHFCMQCVAAGCCH-UHFFFAOYSA-N 0.000 claims description 2
- UHMJRIYVFOEEKI-UHFFFAOYSA-N 4-methyl-2-(4-methylsulfinylphenyl)-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(S(C)=O)C=C1 UHMJRIYVFOEEKI-UHFFFAOYSA-N 0.000 claims description 2
- CMSFBHOWFRNPJY-UHFFFAOYSA-N 4-methyl-2-(4-nitrophenyl)-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C([N+]([O-])=O)C=C1 CMSFBHOWFRNPJY-UHFFFAOYSA-N 0.000 claims description 2
- MYDOMCZZXQMLSS-UHFFFAOYSA-N 4-methyl-2-(6-methylpyridin-3-yl)-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C)N=C1 MYDOMCZZXQMLSS-UHFFFAOYSA-N 0.000 claims description 2
- FJJRSCAHJXBCJU-UHFFFAOYSA-N 4-methyl-5-piperazin-1-yl-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].CN1C2=C(O)N(C=3C=CC(=CC=3)C(F)(F)F)[NH2+]C2=C2C=CC=CC2=C1N1CCNCC1 FJJRSCAHJXBCJU-UHFFFAOYSA-N 0.000 claims description 2
- QYJOUBPYPKRTDS-UHFFFAOYSA-N 4-phenyl-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C=3C=CC=CC=3)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C(F)(F)F)C=C1 QYJOUBPYPKRTDS-UHFFFAOYSA-N 0.000 claims description 2
- PQLUVPOJYXZXKA-UHFFFAOYSA-N CC(C)n1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(cc1)C(F)(F)F Chemical compound CC(C)n1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(cc1)C(F)(F)F PQLUVPOJYXZXKA-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- HSXCYGJGXAAURQ-UHFFFAOYSA-N [OH-].C(C)C=1N(C=2C(=C3C=CC=CC13)[NH2+]N(C2O)C2=CC=C(C=C2)C(F)(F)F)C Chemical compound [OH-].C(C)C=1N(C=2C(=C3C=CC=CC13)[NH2+]N(C2O)C2=CC=C(C=C2)C(F)(F)F)C HSXCYGJGXAAURQ-UHFFFAOYSA-N 0.000 claims description 2
- HJQAANGFUHVFRL-UHFFFAOYSA-N [OH-].C(C)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)C(F)(F)F)O Chemical compound [OH-].C(C)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)C(F)(F)F)O HJQAANGFUHVFRL-UHFFFAOYSA-N 0.000 claims description 2
- RSVNVYFYIHNDRN-UHFFFAOYSA-N [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C=2SC=C(C2)C)O Chemical compound [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C=2SC=C(C2)C)O RSVNVYFYIHNDRN-UHFFFAOYSA-N 0.000 claims description 2
- YPDMCSDSADTGGW-UHFFFAOYSA-N [OH-].ClC1=C(C=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)C)=C1O)C(F)(F)F Chemical compound [OH-].ClC1=C(C=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)C)=C1O)C(F)(F)F YPDMCSDSADTGGW-UHFFFAOYSA-N 0.000 claims description 2
- CMWNUFVTYZYHFW-UHFFFAOYSA-N [OH-].ClC1=C(C=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)C2CC2)=C1O)C(F)(F)F Chemical compound [OH-].ClC1=C(C=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)C2CC2)=C1O)C(F)(F)F CMWNUFVTYZYHFW-UHFFFAOYSA-N 0.000 claims description 2
- CYLSDUHKDBQAQL-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CCS(=O)C)=C1O Chemical compound [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CCS(=O)C)=C1O CYLSDUHKDBQAQL-UHFFFAOYSA-N 0.000 claims description 2
- LZPGGCKOJSZMSH-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=N1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CC2=CC=C(C=C2)OC)=C1O Chemical compound [OH-].ClC1=CC=C(C=N1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CC2=CC=C(C=C2)OC)=C1O LZPGGCKOJSZMSH-UHFFFAOYSA-N 0.000 claims description 2
- CRVSEQIRJPWAQK-UHFFFAOYSA-N [OH-].FC(C1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CC(=O)OCC)=C1O)(F)F Chemical compound [OH-].FC(C1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CC(=O)OCC)=C1O)(F)F CRVSEQIRJPWAQK-UHFFFAOYSA-N 0.000 claims description 2
- LQAZGVCPDKIGMG-UHFFFAOYSA-N [OH-].FC=1C2=C3C(N(C(=C2C=CC1)C)CC1=CC=C(C=C1)OC)=C(N([NH2+]3)C3=CC=C(C=C3)C(F)(F)F)O Chemical compound [OH-].FC=1C2=C3C(N(C(=C2C=CC1)C)CC1=CC=C(C=C1)OC)=C(N([NH2+]3)C3=CC=C(C=C3)C(F)(F)F)O LQAZGVCPDKIGMG-UHFFFAOYSA-N 0.000 claims description 2
- FWOYHGSMHOOUCK-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C(=C1C=CC=CC21)N2CCOCC2)C)C2=CC=C(C=C2)C(F)(F)F Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C(=C1C=CC=CC21)N2CCOCC2)C)C2=CC=C(C=C2)C(F)(F)F FWOYHGSMHOOUCK-UHFFFAOYSA-N 0.000 claims description 2
- KVKVNRULGGTDFO-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)C(C)C)C2=CC(=CC=C2)C(F)(F)F Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)C(C)C)C2=CC(=CC=C2)C(F)(F)F KVKVNRULGGTDFO-UHFFFAOYSA-N 0.000 claims description 2
- NZLSLVKJSPNIKJ-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)C(C)C)C2=CC=C(C=C2)C(F)(F)F Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)C(C)C)C2=CC=C(C=C2)C(F)(F)F NZLSLVKJSPNIKJ-UHFFFAOYSA-N 0.000 claims description 2
- FVZUJMMJOPFHHD-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)C)C2=CC=C(C=C2)C(C)C Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)C)C2=CC=C(C=C2)C(C)C FVZUJMMJOPFHHD-UHFFFAOYSA-N 0.000 claims description 2
- PYIJULHKKBJYIL-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)CC2=CC=C(C=C2)OC)C2=CC=CC=C2 Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)CC2=CC=C(C=C2)OC)C2=CC=CC=C2 PYIJULHKKBJYIL-UHFFFAOYSA-N 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000012954 diazonium Substances 0.000 claims description 2
- 150000001989 diazonium salts Chemical class 0.000 claims description 2
- 230000026030 halogenation Effects 0.000 claims description 2
- 238000005658 halogenation reaction Methods 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000012022 methylating agents Substances 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 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 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000007280 thionation reaction Methods 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- HGIQSVCKZQZQHK-UHFFFAOYSA-N 4-methyl-2-(5-methylpyridin-2-yl)-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C)C=N1 HGIQSVCKZQZQHK-UHFFFAOYSA-N 0.000 claims 1
- QUZCXVQFQYDAGV-UHFFFAOYSA-N 4-methyl-2-[3-(trifluoromethyl)phenyl]-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=CC(C(F)(F)F)=C1 QUZCXVQFQYDAGV-UHFFFAOYSA-N 0.000 claims 1
- CGHGYFODLUOFAX-UHFFFAOYSA-N 4-methyl-2-quinolin-3-yl-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].C1=CC=CC2=CC(N3[NH2+]C4=C5C=CC=CC5=CN(C4=C3O)C)=CN=C21 CGHGYFODLUOFAX-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- JEIATIDSGKNVLE-UHFFFAOYSA-N Cn1c2c(O)n(nc2c2ccccc2c1=N)-c1ccc(cc1)C(F)(F)F Chemical compound Cn1c2c(O)n(nc2c2ccccc2c1=N)-c1ccc(cc1)C(F)(F)F JEIATIDSGKNVLE-UHFFFAOYSA-N 0.000 claims 1
- JSVPBGUMJPGDOI-UHFFFAOYSA-N Cn1c2c(O)n(nc2c2ccccc2c1=S)-c1ccc(cc1)C(F)(F)F Chemical compound Cn1c2c(O)n(nc2c2ccccc2c1=S)-c1ccc(cc1)C(F)(F)F JSVPBGUMJPGDOI-UHFFFAOYSA-N 0.000 claims 1
- LBIXUTJTXJGOMF-UHFFFAOYSA-N FC(C1=CC=C(C=C1)N1N=C2C=3C=CC=NC3C=NC2=C1O)(F)F Chemical compound FC(C1=CC=C(C=C1)N1N=C2C=3C=CC=NC3C=NC2=C1O)(F)F LBIXUTJTXJGOMF-UHFFFAOYSA-N 0.000 claims 1
- LMZWHGAOYUMQEN-UHFFFAOYSA-N Oc1n(nc2c1ncc1cc(F)ccc21)-c1ccc(Cl)cc1 Chemical compound Oc1n(nc2c1ncc1cc(F)ccc21)-c1ccc(Cl)cc1 LMZWHGAOYUMQEN-UHFFFAOYSA-N 0.000 claims 1
- AMOXWKQNJBEWNN-UHFFFAOYSA-N Oc1n(nc2c1ncc1ccccc21)-c1ccc(cc1)C(F)(F)C(F)(F)F Chemical compound Oc1n(nc2c1ncc1ccccc21)-c1ccc(cc1)C(F)(F)C(F)(F)F AMOXWKQNJBEWNN-UHFFFAOYSA-N 0.000 claims 1
- NSQSUMSJOITUHV-UHFFFAOYSA-N [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)C(F)(F)F)O Chemical compound [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)C(F)(F)F)O NSQSUMSJOITUHV-UHFFFAOYSA-N 0.000 claims 1
- BIMSDSMRVMTPLI-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(N=C3C=CC=CC23)C)=C1O Chemical compound [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(N=C3C=CC=CC23)C)=C1O BIMSDSMRVMTPLI-UHFFFAOYSA-N 0.000 claims 1
- GMLJRHCWJXOQKE-UHFFFAOYSA-N [OH-].FC(C1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CCO)=C1O)(F)F Chemical compound [OH-].FC(C1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CCO)=C1O)(F)F GMLJRHCWJXOQKE-UHFFFAOYSA-N 0.000 claims 1
- PHMCKYCZNUHJEP-UHFFFAOYSA-N [OH-].FC(OC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)C)=C1O)(F)F Chemical compound [OH-].FC(OC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)C)=C1O)(F)F PHMCKYCZNUHJEP-UHFFFAOYSA-N 0.000 claims 1
- OXICISDWRLMKJH-UHFFFAOYSA-N [OH-].c1[nH]nc2c1[nH+]cc1ccccc21 Chemical compound [OH-].c1[nH]nc2c1[nH+]cc1ccccc21 OXICISDWRLMKJH-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- CXUGAWWYKSOLEL-UHFFFAOYSA-N 2h-cinnolin-3-one Chemical class C1=CC=C2N=NC(O)=CC2=C1 CXUGAWWYKSOLEL-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 238000005481 NMR spectroscopy Methods 0.000 description 78
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 68
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 48
- 239000000203 mixture Substances 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 238000010992 reflux Methods 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 239000007787 solid Substances 0.000 description 31
- 239000012267 brine Substances 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
- 238000004440 column chromatography Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 239000012074 organic phase Substances 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 239000012299 nitrogen atmosphere Substances 0.000 description 18
- 239000000725 suspension Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 206010039083 rhinitis Diseases 0.000 description 14
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 239000008096 xylene Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 208000006673 asthma Diseases 0.000 description 9
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 8
- 239000000443 aerosol Substances 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 241000699670 Mus sp. Species 0.000 description 5
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- WFXUBCDQYAPCPG-UHFFFAOYSA-N 1,2-dihydropyrazolo[4,3-c]isoquinolin-3-one Chemical compound N1=CC2=CC=CC=C2C2=C1C(=O)NN2 WFXUBCDQYAPCPG-UHFFFAOYSA-N 0.000 description 4
- OZMVULSHMIXZBE-UHFFFAOYSA-N Cn1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(cc1)C(F)(F)F Chemical compound Cn1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(cc1)C(F)(F)F OZMVULSHMIXZBE-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 108010058846 Ovalbumin Proteins 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- DBNLGTYGKCMLLR-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]hydrazine Chemical compound NNC1=CC=C(C(F)(F)F)C=C1 DBNLGTYGKCMLLR-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 210000003979 eosinophil Anatomy 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229940095102 methyl benzoate Drugs 0.000 description 4
- 229940092253 ovalbumin Drugs 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000001665 trituration Methods 0.000 description 4
- WELNSIYTQJSNRP-UHFFFAOYSA-N 2-fluoro-6-methylbenzoic acid Chemical compound CC1=CC=CC(F)=C1C(O)=O WELNSIYTQJSNRP-UHFFFAOYSA-N 0.000 description 3
- XXNOGQJZAOXWAQ-UHFFFAOYSA-N 4-chlorophenylhydrazine Chemical compound NNC1=CC=C(Cl)C=C1 XXNOGQJZAOXWAQ-UHFFFAOYSA-N 0.000 description 3
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 3
- RPWHKHJDHYAYKG-UHFFFAOYSA-N methyl 2-(bromomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1CBr RPWHKHJDHYAYKG-UHFFFAOYSA-N 0.000 description 3
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- PNVWNMCAGZBUNK-UHFFFAOYSA-N (5-methylpyridin-2-yl)hydrazine Chemical compound CC1=CC=C(NN)N=C1 PNVWNMCAGZBUNK-UHFFFAOYSA-N 0.000 description 2
- XWKGPVBYRBTGRC-UHFFFAOYSA-N (6-methylpyridin-3-yl)hydrazine Chemical compound CC1=CC=C(NN)C=N1 XWKGPVBYRBTGRC-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PJTVMGSOYRAPIP-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-4,4-dimethyl-5h-1,3-oxazole Chemical compound CC1(C)COC(C=2C(=CC=CC=2F)F)=N1 PJTVMGSOYRAPIP-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- KVYKZBUHIGYCOO-UHFFFAOYSA-N 2-(2-fluoro-6-methylphenyl)-4,4-dimethyl-5h-1,3-oxazole Chemical compound CC1=CC=CC(F)=C1C1=NC(C)(C)CO1 KVYKZBUHIGYCOO-UHFFFAOYSA-N 0.000 description 2
- DQXIGGIUUOIORU-UHFFFAOYSA-N 2-(4-bromophenyl)-4-[(4-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(Br)=CC=3)[NH2+]C2=C2C=CC=CC2=C1 DQXIGGIUUOIORU-UHFFFAOYSA-N 0.000 description 2
- HMLWQFPSKPIFOI-UHFFFAOYSA-N 2-(4-chlorophenyl)-4-[(4-methoxyphenyl)methyl]-5-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C(C)=C2C=CC=CC2=C2[NH2+]N(C=3C=CC(Cl)=CC=3)C(O)=C21 HMLWQFPSKPIFOI-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- CFGASVMZNHUVJV-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]-2-(4-methylphenyl)-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(C)=CC=3)[NH2+]C2=C2C=CC=CC2=C1 CFGASVMZNHUVJV-UHFFFAOYSA-N 0.000 description 2
- GIVKRMJBWLSPAC-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]-2-[3-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=C(C=CC=3)C(F)(F)F)[NH2+]C2=C2C=CC=CC2=C1 GIVKRMJBWLSPAC-UHFFFAOYSA-N 0.000 description 2
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
- KFMMQNJXOUIUCC-UHFFFAOYSA-N 9-fluoro-4-[(4-methoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(=CC=3)C(F)(F)F)[NH2+]C2=C2C(F)=CC=CC2=C1 KFMMQNJXOUIUCC-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- OTYLFVWNWIZYBB-UHFFFAOYSA-N C1=NC=CC=2C(CC=CC1=2)=S Chemical compound C1=NC=CC=2C(CC=CC1=2)=S OTYLFVWNWIZYBB-UHFFFAOYSA-N 0.000 description 2
- CLLHLKCMHYJZIJ-UHFFFAOYSA-N Cc1ccc(nc1)-n1nc-2c(CCc3ccccc-23)c1O Chemical compound Cc1ccc(nc1)-n1nc-2c(CCc3ccccc-23)c1O CLLHLKCMHYJZIJ-UHFFFAOYSA-N 0.000 description 2
- ZWUXBHZHBNBRRJ-UHFFFAOYSA-N Cn1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(Cl)cc1 Chemical compound Cn1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(Cl)cc1 ZWUXBHZHBNBRRJ-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 206010014950 Eosinophilia Diseases 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- ZJAASUXBXXTWJB-UHFFFAOYSA-N Oc1c2CCc3ccccc3-c2nn1-c1ccc(cc1)C(F)(F)F Chemical compound Oc1c2CCc3ccccc3-c2nn1-c1ccc(cc1)C(F)(F)F ZJAASUXBXXTWJB-UHFFFAOYSA-N 0.000 description 2
- UDKJWYFTUASSAT-UHFFFAOYSA-N Oc1n(nc2c1ncc1ccccc21)-c1ccc(OC(F)(F)F)cc1 Chemical compound Oc1n(nc2c1ncc1ccccc21)-c1ccc(OC(F)(F)F)cc1 UDKJWYFTUASSAT-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- DUCFHJLXCBKJMQ-UHFFFAOYSA-N methyl 1-oxo-3,4,4a,5-tetrahydro-2h-naphthalene-2-carboxylate Chemical compound C1C=CC=C2C(=O)C(C(=O)OC)CCC21 DUCFHJLXCBKJMQ-UHFFFAOYSA-N 0.000 description 2
- HADBFGPXVSGIRH-UHFFFAOYSA-N methyl 2,3-dimethyl-4-oxo-1h-isoquinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OC)(C)N(C)CC2=C1 HADBFGPXVSGIRH-UHFFFAOYSA-N 0.000 description 2
- ZUDNSKMFGSEPFB-UHFFFAOYSA-N methyl 2-(bromomethyl)-6-fluorobenzoate Chemical compound COC(=O)C1=C(F)C=CC=C1CBr ZUDNSKMFGSEPFB-UHFFFAOYSA-N 0.000 description 2
- QKASDIPENBEWBU-UHFFFAOYSA-N methyl 2-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC=C1CBr QKASDIPENBEWBU-UHFFFAOYSA-N 0.000 description 2
- CTCSAWGFOPOVEU-UHFFFAOYSA-N methyl 2-fluoro-6-methylbenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1F CTCSAWGFOPOVEU-UHFFFAOYSA-N 0.000 description 2
- WTKFDERRKPYQKV-UHFFFAOYSA-N methyl 5-fluoro-2-[(4-methoxyphenyl)methyl]-4-oxo-1,3-dihydroisoquinoline-3-carboxylate Chemical compound C1C2=CC=CC(F)=C2C(=O)C(C(=O)OC)N1CC1=CC=C(OC)C=C1 WTKFDERRKPYQKV-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 201000009890 sinusitis Diseases 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-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
- NRESDXFFSNBDGP-UHFFFAOYSA-N (4-bromophenyl)hydrazine Chemical compound NNC1=CC=C(Br)C=C1 NRESDXFFSNBDGP-UHFFFAOYSA-N 0.000 description 1
- IQMLCMKMSBMMGR-UHFFFAOYSA-N (4-iodophenyl)hydrazine Chemical compound NNC1=CC=C(I)C=C1 IQMLCMKMSBMMGR-UHFFFAOYSA-N 0.000 description 1
- XAMBIJWZVIZZOG-UHFFFAOYSA-N (4-methylphenyl)hydrazine Chemical compound CC1=CC=C(NN)C=C1 XAMBIJWZVIZZOG-UHFFFAOYSA-N 0.000 description 1
- UQPKIBHPQJMLMI-UHFFFAOYSA-N (4-phenylphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=CC=C1 UQPKIBHPQJMLMI-UHFFFAOYSA-N 0.000 description 1
- XHEJLXPUJJYRBJ-UHFFFAOYSA-N (6-chloropyridin-3-yl)hydrazine Chemical compound NNC1=CC=C(Cl)N=C1 XHEJLXPUJJYRBJ-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- WYLVDQCBKZPULR-UHFFFAOYSA-N 1,7-naphthyridin-3-ol Chemical compound C1=NC=CC2=CC(O)=CN=C21 WYLVDQCBKZPULR-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QWCOVJAVTCLFPO-UHFFFAOYSA-N 2,6-difluoro-n-(1-hydroxy-2-methylpropan-2-yl)benzamide Chemical compound OCC(C)(C)NC(=O)C1=C(F)C=CC=C1F QWCOVJAVTCLFPO-UHFFFAOYSA-N 0.000 description 1
- QRHUZEVERIHEPT-UHFFFAOYSA-N 2,6-difluorobenzoyl chloride Chemical compound FC1=CC=CC(F)=C1C(Cl)=O QRHUZEVERIHEPT-UHFFFAOYSA-N 0.000 description 1
- DOZCZZKHZAGMKO-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-[(4-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=C(Cl)C(Cl)=CC=3)[NH2+]C2=C2C=CC=CC2=C1 DOZCZZKHZAGMKO-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical group OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- AUFHUXSDQUEVRT-UHFFFAOYSA-N 2-(4-chlorophenyl)-1h-pyrazolo[4,3-c]isoquinolin-3-one Chemical compound C1=CC(Cl)=CC=C1N1C(=O)C(N=CC=2C3=CC=CC=2)=C3N1 AUFHUXSDQUEVRT-UHFFFAOYSA-N 0.000 description 1
- YKCAYWYLBMXVDK-UHFFFAOYSA-N 2-(4-chlorophenyl)-4-[(4-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(Cl)=CC=3)[NH2+]C2=C2C=CC=CC2=C1 YKCAYWYLBMXVDK-UHFFFAOYSA-N 0.000 description 1
- ZIRDRYMCICGLCI-UHFFFAOYSA-N 2-(4-chlorophenyl)-4-cyclopropyl-9-fluoro-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C3CC3)C=C3C=CC=C(F)C3=C2[NH2+]N1C1=CC=C(Cl)C=C1 ZIRDRYMCICGLCI-UHFFFAOYSA-N 0.000 description 1
- YJZSNRWSEWJSEE-UHFFFAOYSA-N 2-(4-chlorophenyl)-4-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(Cl)C=C1 YJZSNRWSEWJSEE-UHFFFAOYSA-N 0.000 description 1
- JXTZLGLKTLCHEU-UHFFFAOYSA-N 2-(4-chlorophenyl)-9-fluoro-4-[(4-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(Cl)=CC=3)[NH2+]C2=C2C(F)=CC=CC2=C1 JXTZLGLKTLCHEU-UHFFFAOYSA-N 0.000 description 1
- METLAIYNPSUUOV-UHFFFAOYSA-N 2-(4-methoxy-n-methylanilino)propanoic acid Chemical compound COC1=CC=C(N(C)C(C)C(O)=O)C=C1 METLAIYNPSUUOV-UHFFFAOYSA-N 0.000 description 1
- FRSNRGOQKOQCAT-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-4-[(4-methoxyphenyl)methyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(=CC=3)C(C)(C)C)[NH2+]C2=C2C=CC=CC2=C1 FRSNRGOQKOQCAT-UHFFFAOYSA-N 0.000 description 1
- WRXJZRDDFLTBBX-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-4-methyl-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(Cl)N=C1 WRXJZRDDFLTBBX-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- DHBQQUHYERQIMY-UHFFFAOYSA-N 4-(1,1,2,2,2-pentafluoroethyl)aniline Chemical compound NC1=CC=C(C(F)(F)C(F)(F)F)C=C1 DHBQQUHYERQIMY-UHFFFAOYSA-N 0.000 description 1
- BUKNAXTWYUUEOH-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]-2-(4-phenylphenyl)-1H-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol hydroxide Chemical compound [OH-].C1=CC(OC)=CC=C1CN1C2=C(O)N(C=3C=CC(=CC=3)C=3C=CC=CC=3)[NH2+]C2=C2C=CC=CC2=C1 BUKNAXTWYUUEOH-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- UFWQLPZKOGNICF-UHFFFAOYSA-N 4-cyclopropyl-9-fluoro-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C3CC3)C=C3C=CC=C(F)C3=C2[NH2+]N1C1=CC=C(C(F)(F)F)C=C1 UFWQLPZKOGNICF-UHFFFAOYSA-N 0.000 description 1
- JJQPQPJIDRVWKM-UHFFFAOYSA-N 5-(dimethylamino)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1h-pyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].OC1=C2N(C)C(N(C)C)=C3C=CC=CC3=C2[NH2+]N1C1=CC=C(C(F)(F)F)C=C1 JJQPQPJIDRVWKM-UHFFFAOYSA-N 0.000 description 1
- UENBBJXGCWILBM-UHFFFAOYSA-N 6-methylpyridin-3-amine Chemical compound CC1=CC=C(N)C=N1 UENBBJXGCWILBM-UHFFFAOYSA-N 0.000 description 1
- RLKDMYJHEFDHTJ-UHFFFAOYSA-N 9-fluoro-4-methyl-1-[4-(trifluoromethyl)phenyl]-1,2-dihydropyrazolo[4,3-c]isoquinolin-1-ium-3-ol;hydroxide Chemical compound [OH-].N1C(O)=C2N(C)C=C3C=CC=C(F)C3=C2[NH+]1C1=CC=C(C(F)(F)F)C=C1 RLKDMYJHEFDHTJ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- CQINXWYVIOMBEI-UHFFFAOYSA-N C1=CC(Cl)=CC=C1N1C(=O)C2=CNC3=CC=CC=C3C2=N1 Chemical compound C1=CC(Cl)=CC=C1N1C(=O)C2=CNC3=CC=CC=C3C2=N1 CQINXWYVIOMBEI-UHFFFAOYSA-N 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
- LQPUGPAYBQNAPZ-UHFFFAOYSA-N COC(c1ccccc1)n1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(cc1)C(F)(F)F Chemical compound COC(c1ccccc1)n1c2c(O)n(nc2c2ccccc2c1=O)-c1ccc(cc1)C(F)(F)F LQPUGPAYBQNAPZ-UHFFFAOYSA-N 0.000 description 1
- VFJYUWOESPOUBJ-UHFFFAOYSA-N Cc1ccc(nc1)-n1nc2c(ccc3ccccc23)c1O Chemical compound Cc1ccc(nc1)-n1nc2c(ccc3ccccc23)c1O VFJYUWOESPOUBJ-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- ZLNSKVUNWCLOFY-UHFFFAOYSA-N Cn1c2c(O)n(nc2c2ccccc2c1=O)-c1ncccn1 Chemical compound Cn1c2c(O)n(nc2c2ccccc2c1=O)-c1ncccn1 ZLNSKVUNWCLOFY-UHFFFAOYSA-N 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 1
- 102000044708 Eosinophil peroxidases Human genes 0.000 description 1
- QBBGEMADSMYWTH-UHFFFAOYSA-N FC=1C=2C=3C(N=CC2C=CC1)=C(N(N3)C3=CC=C(C=C3)C(F)(F)F)O Chemical compound FC=1C=2C=3C(N=CC2C=CC1)=C(N(N3)C3=CC=C(C=C3)C(F)(F)F)O QBBGEMADSMYWTH-UHFFFAOYSA-N 0.000 description 1
- 206010016228 Fasciitis Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000009388 Job Syndrome Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010024227 Lepromatous leprosy Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- HYFPIVZNHJILJE-UHFFFAOYSA-N O=C1C=C2C(=O)C=CC=C2C=N1 Chemical compound O=C1C=C2C(=O)C=CC=C2C=N1 HYFPIVZNHJILJE-UHFFFAOYSA-N 0.000 description 1
- YWVGVHXRCWDRJH-UHFFFAOYSA-N OC=1N(N=C2C1N(C(C=1C=CC=CC21)=O)C)C2=CC=C(C=C2)I Chemical compound OC=1N(N=C2C1N(C(C=1C=CC=CC21)=O)C)C2=CC=C(C=C2)I YWVGVHXRCWDRJH-UHFFFAOYSA-N 0.000 description 1
- LMNQMNRQBSQDGE-UHFFFAOYSA-N OC=1N(N=C2C1NC(C=1C=CC=CC21)=O)C2=CC=C(C=C2)C(C)C Chemical compound OC=1N(N=C2C1NC(C=1C=CC=CC21)=O)C2=CC=C(C=C2)C(C)C LMNQMNRQBSQDGE-UHFFFAOYSA-N 0.000 description 1
- SQKGWYUXMCKYQY-UHFFFAOYSA-N Oc1n(nc2c1ccc1ccccc21)-c1ccc(cc1)C(F)(F)F Chemical compound Oc1n(nc2c1ccc1ccccc21)-c1ccc(cc1)C(F)(F)F SQKGWYUXMCKYQY-UHFFFAOYSA-N 0.000 description 1
- FHRKQOISIDRAKM-UHFFFAOYSA-N Oc1n(nc2c1ncc1ccccc21)-c1ccc(Cl)c(Cl)c1 Chemical compound Oc1n(nc2c1ncc1ccccc21)-c1ccc(Cl)c(Cl)c1 FHRKQOISIDRAKM-UHFFFAOYSA-N 0.000 description 1
- KLKKZAVOZSWSRL-UHFFFAOYSA-N Oc1n(nc2c1ncc1ccccc21)-c1ccc(cc1)-c1ccccc1 Chemical compound Oc1n(nc2c1ncc1ccccc21)-c1ccc(cc1)-c1ccccc1 KLKKZAVOZSWSRL-UHFFFAOYSA-N 0.000 description 1
- MODHOZZQEZIXSZ-UHFFFAOYSA-N Oc1n(nc2c1ncc1ccccc21)-c1ccc(cc1)C(F)(F)F Chemical compound Oc1n(nc2c1ncc1ccccc21)-c1ccc(cc1)C(F)(F)F MODHOZZQEZIXSZ-UHFFFAOYSA-N 0.000 description 1
- MENMAINLQQOVDL-UHFFFAOYSA-N Oc1n(nc2c1ncc1ccccc21)-c1cnc2ccccc2c1 Chemical compound Oc1n(nc2c1ncc1ccccc21)-c1cnc2ccccc2c1 MENMAINLQQOVDL-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- RSESUCWJKLHXEZ-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]hydrazine Chemical compound NNC1=CC=CC(C(F)(F)F)=C1 RSESUCWJKLHXEZ-UHFFFAOYSA-N 0.000 description 1
- WALFHMMZZMMWNI-UHFFFAOYSA-N [4-(1,1,2,2,2-pentafluoroethyl)phenyl]hydrazine Chemical compound NNC1=CC=C(C(F)(F)C(F)(F)F)C=C1 WALFHMMZZMMWNI-UHFFFAOYSA-N 0.000 description 1
- GWFWCTYACJWQKP-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]hydrazine Chemical compound NNC1=CC=C(OC(F)(F)F)C=C1 GWFWCTYACJWQKP-UHFFFAOYSA-N 0.000 description 1
- GCLPFEPNXNLONH-UHFFFAOYSA-N [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)OC(F)(F)F)O Chemical compound [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)OC(F)(F)F)O GCLPFEPNXNLONH-UHFFFAOYSA-N 0.000 description 1
- RCWLNJAUPJKVTJ-UHFFFAOYSA-N [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C=2C=NC(=CC2)C)O Chemical compound [OH-].C1(CC1)N1C=C2C=CC=CC2=C2C1=C(N([NH2+]2)C=2C=NC(=CC2)C)O RCWLNJAUPJKVTJ-UHFFFAOYSA-N 0.000 description 1
- XPHWFJVCFFNOAD-UHFFFAOYSA-N [OH-].CN1C(=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)C(F)(F)F)O)C(C)C Chemical compound [OH-].CN1C(=C2C=CC=CC2=C2C1=C(N([NH2+]2)C2=CC=C(C=C2)C(F)(F)F)O)C(C)C XPHWFJVCFFNOAD-UHFFFAOYSA-N 0.000 description 1
- HHKQRWLAAKASSQ-UHFFFAOYSA-N [OH-].C[N+]=1NC=C2N=CC=3C=CC=CC3C21 Chemical compound [OH-].C[N+]=1NC=C2N=CC=3C=CC=CC3C21 HHKQRWLAAKASSQ-UHFFFAOYSA-N 0.000 description 1
- CTVUBWRPCHVMBJ-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C(=C3C=CC=C(C23)F)C)CC2=CC=C(C=C2)OC)=C1O Chemical compound [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C(=C3C=CC=C(C23)F)C)CC2=CC=C(C=C2)OC)=C1O CTVUBWRPCHVMBJ-UHFFFAOYSA-N 0.000 description 1
- SVFZETKCHCJZFX-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=C(C=CC23)F)C)=C1O Chemical compound [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=C(C=CC23)F)C)=C1O SVFZETKCHCJZFX-UHFFFAOYSA-N 0.000 description 1
- BPGSMEUCVCIKMQ-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=C(C23)F)C)=C1O Chemical compound [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=C(C23)F)C)=C1O BPGSMEUCVCIKMQ-UHFFFAOYSA-N 0.000 description 1
- AXRKVXAXVRPXNX-UHFFFAOYSA-N [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CCN(C)C)=C1O Chemical compound [OH-].ClC1=CC=C(C=C1)N1[NH2+]C=2C(N(C=C3C=CC=CC23)CCN(C)C)=C1O AXRKVXAXVRPXNX-UHFFFAOYSA-N 0.000 description 1
- LNARHFZHSCYKQV-UHFFFAOYSA-N [OH-].FC=1C=CC2=C3C(N(C=C2C1)C)=C(N([NH2+]3)C3=CC=C(C=C3)C(F)(F)F)O Chemical compound [OH-].FC=1C=CC2=C3C(N(C=C2C1)C)=C(N([NH2+]3)C3=CC=C(C=C3)C(F)(F)F)O LNARHFZHSCYKQV-UHFFFAOYSA-N 0.000 description 1
- JOJOOYOZWVNPBY-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C(=C1C=CC=CC21)C)C(C)C)C2=CC=C(C=C2)C(F)(F)F Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C(=C1C=CC=CC21)C)C(C)C)C2=CC=C(C=C2)C(F)(F)F JOJOOYOZWVNPBY-UHFFFAOYSA-N 0.000 description 1
- CWOUJXKTQGKELJ-UHFFFAOYSA-N [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)CCS(=O)C)C2=CC=C(C=C2)C(F)(F)F Chemical compound [OH-].OC=1N([NH2+]C=2C1N(C=C1C=CC=CC21)CCS(=O)C)C2=CC=C(C=C2)C(F)(F)F CWOUJXKTQGKELJ-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000036428 airway hyperreactivity Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- HKVFISRIUUGTIB-UHFFFAOYSA-O azanium;cerium;nitrate Chemical compound [NH4+].[Ce].[O-][N+]([O-])=O HKVFISRIUUGTIB-UHFFFAOYSA-O 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 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
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000017760 chronic graft versus host disease Diseases 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 208000024711 extrinsic asthma Diseases 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 201000010659 intrinsic asthma Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- PQIUHUKRJAOTLS-BYPYZUCNSA-N methyl (2s)-2-(methylamino)propanoate Chemical class CN[C@@H](C)C(=O)OC PQIUHUKRJAOTLS-BYPYZUCNSA-N 0.000 description 1
- GBUDQKPPRXTNNL-UHFFFAOYSA-N methyl 2-methyl-4-oxo-1,3-dihydroisoquinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OC)N(C)CC2=C1 GBUDQKPPRXTNNL-UHFFFAOYSA-N 0.000 description 1
- KLHWBYHFWALOIJ-UHFFFAOYSA-N methyl 2-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1C KLHWBYHFWALOIJ-UHFFFAOYSA-N 0.000 description 1
- XWTFDPRPTPQOOQ-UHFFFAOYSA-N methyl 4-hydroxy-2-methyl-1-oxoisoquinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)N(C)C(C(=O)OC)=C(O)C2=C1 XWTFDPRPTPQOOQ-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- FIJVLOLRDDEZQZ-UHFFFAOYSA-N pyrazolo[4,3-c]isoquinolin-3-one Chemical class N1=CC2=CC=CC=C2C2=C1C(=O)N=N2 FIJVLOLRDDEZQZ-UHFFFAOYSA-N 0.000 description 1
- QDGHXQFTWKRQTG-UHFFFAOYSA-N pyrimidin-2-ylhydrazine Chemical compound NNC1=NC=CC=N1 QDGHXQFTWKRQTG-UHFFFAOYSA-N 0.000 description 1
- IISWOHCLTBUICM-UHFFFAOYSA-N quinolin-3-ylhydrazine Chemical compound C1=CC=CC2=CC(NN)=CN=C21 IISWOHCLTBUICM-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 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
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 208000029761 vertebral disease Diseases 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
- A61K31/435—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9605803.7A GB9605803D0 (en) | 1996-03-20 | 1996-03-20 | Pharmaceutically-active compound |
| GBGB9610474.0A GB9610474D0 (en) | 1996-05-18 | 1996-05-18 | Pharmaceutically active compounds |
| GBGB9610894.9A GB9610894D0 (en) | 1996-05-24 | 1996-05-24 | Pharmaceutically useful compounds |
| GBGB9700862.7A GB9700862D0 (en) | 1997-01-16 | 1997-01-16 | Pharmaceutically useful compounds |
| PCT/SE1997/000471 WO1997034893A1 (en) | 1996-03-20 | 1997-03-20 | Pharmaceutically useful compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK118798A3 true SK118798A3 (en) | 1999-03-12 |
Family
ID=27451427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1187-98A SK118798A3 (en) | 1996-03-20 | 1997-03-20 | Pharmaceutically useful compounds |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0888347A1 (is) |
| JP (1) | JP2000506884A (is) |
| KR (1) | KR20000064716A (is) |
| CN (1) | CN1218472A (is) |
| AR (1) | AR006520A1 (is) |
| AU (1) | AU712141B2 (is) |
| BR (1) | BR9708103A (is) |
| CA (1) | CA2247814A1 (is) |
| CZ (1) | CZ297798A3 (is) |
| EE (1) | EE9800298A (is) |
| ID (1) | ID16283A (is) |
| IL (1) | IL126271A0 (is) |
| IS (1) | IS4848A (is) |
| NO (1) | NO984290L (is) |
| NZ (1) | NZ331614A (is) |
| PL (1) | PL328921A1 (is) |
| SK (1) | SK118798A3 (is) |
| TR (1) | TR199801861T2 (is) |
| WO (1) | WO1997034893A1 (is) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10110749A1 (de) * | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| JP2003002863A (ja) * | 2001-06-25 | 2003-01-08 | Nippon Soda Co Ltd | 安息香酸類の製造方法および新規化合物 |
| SE0102404D0 (sv) * | 2001-07-04 | 2001-07-04 | Active Biotech Ab | Novel immunomodulating compounds |
| US6642249B2 (en) | 2001-07-04 | 2003-11-04 | Active Biotech Ab | Immunomodulating compounds |
| DE10229762A1 (de) * | 2002-07-03 | 2004-01-22 | Aventis Pharma Deutschland Gmbh | Pyrazoloisoquinolinenderivaten zur Inhibierung von NFkappaB-induzierende Kinase |
| NZ540081A (en) | 2002-11-22 | 2008-03-28 | Active Biotech Ab | Pyrazoloquinolines with immunomodulating activity |
| ATE425164T1 (de) | 2002-12-16 | 2009-03-15 | Active Biotech Ab | Tetrazyklische immunmodulierende verbindungen |
| KR101133959B1 (ko) * | 2003-03-14 | 2012-04-09 | 메디진 아게 | 면역조절 헤테로고리 화합물 |
| GB0325644D0 (en) | 2003-11-04 | 2003-12-10 | Avidex Ltd | Immuno ihibitory pyrazolone compounds |
| KR20070001922A (ko) | 2003-12-12 | 2007-01-04 | 와이어쓰 | 심장혈관질환 치료에 유용한 퀴놀린 |
| FR2870239B1 (fr) * | 2004-05-11 | 2006-06-16 | Sanofi Synthelabo | Derives de carbamate de 2h- ou 3h-benzo[e]indazol-1-yle, leur preparation et leur application en therapeutique. |
| GB0411770D0 (en) * | 2004-05-26 | 2004-06-30 | Avidex Ltd | Immuno inhibitory heterocyclic compouds |
| ATE411318T1 (de) | 2004-08-09 | 2008-10-15 | Medigene Ltd | Immunmodulierende oxopyrazolocinnoline als cd80- inhibitoren |
| CA2667966C (en) | 2006-10-31 | 2011-08-02 | Pfizer Products Inc. | Pyrazoline compounds as mineralocorticoid receptor antagonists |
| CN102372710A (zh) * | 2010-08-18 | 2012-03-14 | 山东轩竹医药科技有限公司 | 作为盐皮质激素受体拮抗剂的并环类化合物 |
| BR112013020282A2 (pt) | 2011-02-09 | 2017-07-18 | Nissan Chemical Ind Ltd | derivado pirazol e agente de controle |
| EP3846904B1 (en) * | 2018-09-07 | 2023-05-31 | Merck Patent GmbH | 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives |
| WO2021257863A1 (en) | 2020-06-19 | 2021-12-23 | Incyte Corporation | Pyrrolotriazine compounds as jak2 v617f inhibitors |
| US11691971B2 (en) | 2020-06-19 | 2023-07-04 | Incyte Corporation | Naphthyridinone compounds as JAK2 V617F inhibitors |
| WO2022006457A1 (en) | 2020-07-02 | 2022-01-06 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| WO2022006456A1 (en) | 2020-07-02 | 2022-01-06 | Incyte Corporation | Tricyclic pyridone compounds as jak2 v617f inhibitors |
| WO2022046989A1 (en) | 2020-08-27 | 2022-03-03 | Incyte Corporation | Tricyclic urea compounds as jak2 v617f inhibitors |
| US11919908B2 (en) | 2020-12-21 | 2024-03-05 | Incyte Corporation | Substituted pyrrolo[2,3-d]pyrimidine compounds as JAK2 V617F inhibitors |
| US11958861B2 (en) | 2021-02-25 | 2024-04-16 | Incyte Corporation | Spirocyclic lactams as JAK2 V617F inhibitors |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4524146A (en) * | 1982-12-08 | 1985-06-18 | Ciba-Geigy Corporation | Certain -2-heterocycle substituted pyrazoloquinolines |
| JPS61112075A (ja) * | 1984-11-05 | 1986-05-30 | Shionogi & Co Ltd | チエニルピラゾロキノリン誘導体 |
| SE8903564D0 (sv) * | 1989-10-26 | 1989-10-26 | Pharmacia Ab | New use condensed quinoline compound |
| JPH05194515A (ja) * | 1991-07-31 | 1993-08-03 | Kyowa Hakko Kogyo Co Ltd | 縮合ナフチリジン誘導体 |
-
1997
- 1997-03-19 AR ARP970101094A patent/AR006520A1/es unknown
- 1997-03-19 ID IDP970892A patent/ID16283A/id unknown
- 1997-03-20 NZ NZ331614A patent/NZ331614A/xx unknown
- 1997-03-20 IL IL12627197A patent/IL126271A0/xx unknown
- 1997-03-20 WO PCT/SE1997/000471 patent/WO1997034893A1/en not_active Application Discontinuation
- 1997-03-20 PL PL97328921A patent/PL328921A1/xx unknown
- 1997-03-20 CA CA002247814A patent/CA2247814A1/en not_active Abandoned
- 1997-03-20 JP JP9533412A patent/JP2000506884A/ja active Pending
- 1997-03-20 EP EP97914729A patent/EP0888347A1/en not_active Withdrawn
- 1997-03-20 CN CN97194665A patent/CN1218472A/zh active Pending
- 1997-03-20 TR TR1998/01861T patent/TR199801861T2/xx unknown
- 1997-03-20 BR BR9708103A patent/BR9708103A/pt unknown
- 1997-03-20 CZ CZ982977A patent/CZ297798A3/cs unknown
- 1997-03-20 SK SK1187-98A patent/SK118798A3/sk unknown
- 1997-03-20 AU AU21867/97A patent/AU712141B2/en not_active Ceased
- 1997-03-20 EE EE9800298A patent/EE9800298A/xx unknown
- 1997-03-20 KR KR1019980707441A patent/KR20000064716A/ko not_active Application Discontinuation
-
1998
- 1998-09-16 NO NO984290A patent/NO984290L/no unknown
- 1998-09-16 IS IS4848A patent/IS4848A/is unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IS4848A (is) | 1998-09-16 |
| KR20000064716A (ko) | 2000-11-06 |
| CN1218472A (zh) | 1999-06-02 |
| BR9708103A (pt) | 1999-07-27 |
| CA2247814A1 (en) | 1997-09-25 |
| AR006520A1 (es) | 1999-09-08 |
| PL328921A1 (en) | 1999-03-01 |
| AU712141B2 (en) | 1999-10-28 |
| JP2000506884A (ja) | 2000-06-06 |
| AU2186797A (en) | 1997-10-10 |
| NO984290D0 (no) | 1998-09-16 |
| NZ331614A (en) | 2000-07-28 |
| CZ297798A3 (cs) | 1999-03-17 |
| ID16283A (id) | 1997-09-18 |
| IL126271A0 (en) | 1999-05-09 |
| NO984290L (no) | 1998-10-27 |
| TR199801861T2 (xx) | 1998-12-21 |
| EP0888347A1 (en) | 1999-01-07 |
| EE9800298A (et) | 1999-02-15 |
| WO1997034893A1 (en) | 1997-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK118798A3 (en) | Pharmaceutically useful compounds | |
| ES2743208T3 (es) | Derivados de tetrahidroimidazopiridina como moduladores de la actividad TNF | |
| RU2124015C1 (ru) | Производные пирроло [2,3-d] пиримидинов, фармацевтическая композиция, пирроло [2,3-d] пиримидины, производные пиррола | |
| ES2817051T3 (es) | Derivados de imidazopirimidina como moduladores de la actividad de TNF | |
| ES2809535T3 (es) | Derivados de imidazopiridina como moduladores de la actividad de TNF | |
| US9783552B2 (en) | Soluble guanylate cyclase activators | |
| ES2809530T3 (es) | Derivados de imidazotriazina como moduladores de la actividad de TNF | |
| ES2775535T3 (es) | Derivados de benzotriazol como moduladores de la actividad del TNF | |
| US7495015B2 (en) | Indazole derivatives and methods for using the same | |
| BG107166A (bg) | Имидазопиримидинови производни и триазолопиримидинови производни | |
| KR101081446B1 (ko) | 2-치환페닐-5,7-디알킬-3,7-디하이드로피롤[2,3-ｄ]피리미딘-4-온유도체, 그의 제법 및 약학적 용도 | |
| EP1732541A2 (en) | Cyclic compounds | |
| JPH0256484A (ja) | 縮合ピリミジン誘導体およびその製造方法 | |
| AU708809B2 (en) | 6-aryl pyrazolo{3,4-d}pyrimidin-4-ones and compositions and methods of use thereof | |
| SK168499A3 (en) | 3-substituted 3,4 dihydro-thieno[2,3-d]pyrimidine derivatives and production and use of the same | |
| BR112016011844B1 (pt) | Derivados de triazolpiridina como moduladores de atividade de tnf | |
| EP1325009B1 (en) | Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same | |
| WO2022175745A1 (en) | Tyk2 inhibitors and uses thereof | |
| AU2002211827A1 (en) | Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same | |
| CZ170693A3 (en) | NOVEL 4,5-DIHYDRO-4-OXOPYRROLO(1,2-a)QUINOXALINES AND CORRESPONDING AZA-ANALOGS, AND PROCESS FOR PREPARING THEREOF | |
| US20060229307A1 (en) | Substituted-1-phthalazinamines as vr-1 antagonists | |
| HUT77349A (hu) | Eljárás csontritkulás kezelésére alkalmas kondenzált triazepinszármazékokat tartalmazó gyógyszerkészítmények előállítására, valamint új kondenzált triazepinszármazékok és intermedierjeik | |
| SK1052000A3 (en) | 3-substituted 3,4,5,7-tetrahydro-pyrrolo[3',4':4,5]thieno[2,3-d] pyrimidine derivatives, their preparation and use as 5ht antagonists | |
| EP3277687B1 (en) | 7-(morpholin-4-yl)pyrazole[1,5-a]pyrimidine derivatives which are useful for the treatment of immune or inflammatory diseases or cancer | |
| IE55096B1 (en) | 3-amino-6-aryl-1,2,4-triazolo(4,3-b)pyridazines,their preparation and their use |