DE60112330T2 - Pyrazolopyridinderivate - Google Patents

Info

Publication number

DE60112330T2

DE60112330T2 DE60112330T DE60112330T DE60112330T2 DE 60112330 T2 DE60112330 T2 DE 60112330T2 DE 60112330 T DE60112330 T DE 60112330T DE 60112330 T DE60112330 T DE 60112330T DE 60112330 T2 DE60112330 T2 DE 60112330T2

Authority

DE

Germany

Prior art keywords

fluorophenyl

pyridin

pyrazolo

amine

pyrimidinyl

Prior art date

2000-12-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• DPMA
• Discuss

• 150000005229 pyrazolopyridines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 366
• 238000000034 method Methods 0.000 claims abstract description 97
• 230000008569 process Effects 0.000 claims abstract description 39
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 96
• -1 2 - {[3- (1H-imidazol-1-yl) propyl] amino} -4-pyrimidinyl Chemical group 0.000 claims description 63
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 62
• 150000001412 amines Chemical class 0.000 claims description 54
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 125000003342 alkenyl group Chemical group 0.000 claims description 45
• 229910052736 halogen Inorganic materials 0.000 claims description 42
• 238000011282 treatment Methods 0.000 claims description 41
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 40
• 150000002367 halogens Chemical class 0.000 claims description 39
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 38
• 150000003973 alkyl amines Chemical class 0.000 claims description 36
• 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 36
• 238000002360 preparation method Methods 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 35
• 150000005215 alkyl ethers Chemical class 0.000 claims description 34
• 238000011321 prophylaxis Methods 0.000 claims description 31
• 239000012453 solvate Substances 0.000 claims description 28
• 241001465754 Metazoa Species 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
• 201000010099 disease Diseases 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 150000004820 halides Chemical class 0.000 claims description 22
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 21
• 125000001072 heteroaryl group Chemical group 0.000 claims description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
• MBDYVBQWQPYENL-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-(2-methylsulfinylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(N=CC=2)S(C)=O)C=1C1=CC=C(F)C=C1 MBDYVBQWQPYENL-UHFFFAOYSA-N 0.000 claims description 15
• 125000005157 alkyl carboxy group Chemical group 0.000 claims description 14
• SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 14
• DFHONGUGPWFSRD-UHFFFAOYSA-N 7-chloro-2-(4-fluorophenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC=NC=C1 DFHONGUGPWFSRD-UHFFFAOYSA-N 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• ASGXYPABAFMGKT-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-6-methylpyrimidin-2-amine Chemical compound N=1C(C)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 ASGXYPABAFMGKT-UHFFFAOYSA-N 0.000 claims description 9
• 208000029433 Herpesviridae infectious disease Diseases 0.000 claims description 9
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 9
• 125000006309 butyl amino group Chemical group 0.000 claims description 9
• HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 claims description 8
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 8
• 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• BZRMUMBJGGACCU-UHFFFAOYSA-N 2-(4-bromophenyl)-n-butyl-3-[2-(butylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NCCCC)N3N=C2C=2C=CC(Br)=CC=2)=N1 BZRMUMBJGGACCU-UHFFFAOYSA-N 0.000 claims description 7
• CCEYYRWZLBJDHK-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentylpyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 CCEYYRWZLBJDHK-UHFFFAOYSA-N 0.000 claims description 7
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
• 229960004150 aciclovir Drugs 0.000 claims description 7
• 230000001590 oxidative effect Effects 0.000 claims description 7
• 229940093257 valacyclovir Drugs 0.000 claims description 7
• QELOEPYXLVHTIO-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(Cl)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 QELOEPYXLVHTIO-UHFFFAOYSA-N 0.000 claims description 6
• PYLRHIDDAWYMMF-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-5-methylpyrimidin-2-amine Chemical compound N1=C(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)C(C)=CN=C1NC1CCCC1 PYLRHIDDAWYMMF-UHFFFAOYSA-N 0.000 claims description 6
• QVRZLKHJUGMNMS-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-6-[(dimethylamino)methyl]pyrimidin-2-amine Chemical compound N=1C(CN(C)C)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 QVRZLKHJUGMNMS-UHFFFAOYSA-N 0.000 claims description 6
• UMBKZMBLMSTZKH-UHFFFAOYSA-N 6-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-(cyclopentylamino)pyrimidine-4-carboxylic acid Chemical compound N=1C(C(=O)O)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 UMBKZMBLMSTZKH-UHFFFAOYSA-N 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
• GYPRSMQRMSLJFX-UHFFFAOYSA-N [6-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-(cyclopentylamino)pyrimidin-4-yl]methanol Chemical compound N=1C(CO)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 GYPRSMQRMSLJFX-UHFFFAOYSA-N 0.000 claims description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
• 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• YHJZUXLASHHBBN-UHFFFAOYSA-N n-butyl-3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NCCCC)N3N=C2C=2C=CC(F)=CC=2)=N1 YHJZUXLASHHBBN-UHFFFAOYSA-N 0.000 claims description 6
• DRYPZCHURHDLRN-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)-6-(oxan-2-yloxymethyl)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC(COC2OCCCC2)=NC(NC2CCCC2)=N1 DRYPZCHURHDLRN-UHFFFAOYSA-N 0.000 claims description 6
• ZPODCQWVJFCDKN-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 ZPODCQWVJFCDKN-UHFFFAOYSA-N 0.000 claims description 6
• QDZOJLCCONWJLX-UHFFFAOYSA-N 2-(4-fluorophenyl)-7-iodo-3-pyridin-4-ylpyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(I)=CC=C2)C2=C1C1=CC=NC=C1 QDZOJLCCONWJLX-UHFFFAOYSA-N 0.000 claims description 5
• PPLLZTCPKKKXMG-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[2-(1-methylpyrrolidin-2-yl)ethyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound CN1CCCC1CCNC1=CC=CC2=C(C=3C=CN=CC=3)C(C=3C=CC(F)=CC=3)=NN12 PPLLZTCPKKKXMG-UHFFFAOYSA-N 0.000 claims description 5
• 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 5
• DQLJJCYPTKDOOT-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n,n-dimethylpyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(N3N=C2C=2C=CC(F)=CC=2)N(C)C)=N1 DQLJJCYPTKDOOT-UHFFFAOYSA-N 0.000 claims description 5
• GMUUSVOJOHJMLL-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-(2-methoxyethyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NCCOC)N3N=C2C=2C=CC(F)=CC=2)=N1 GMUUSVOJOHJMLL-UHFFFAOYSA-N 0.000 claims description 5
• MFNRTZFIEGKCLO-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-prop-2-enylpyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NCC=C)N3N=C2C=2C=CC(F)=CC=2)=N1 MFNRTZFIEGKCLO-UHFFFAOYSA-N 0.000 claims description 5
• DJQUIJVLWKXCPL-UHFFFAOYSA-N 3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(N)=CC=CC2=C(C=2N=C(NC3CCCC3)N=CC=2)C=1C1=CC=C(F)C=C1 DJQUIJVLWKXCPL-UHFFFAOYSA-N 0.000 claims description 5
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
• 239000003443 antiviral agent Substances 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 229910052740 iodine Inorganic materials 0.000 claims description 5
• 239000011630 iodine Substances 0.000 claims description 5
• CEJCMEFOUUNONM-UHFFFAOYSA-N n,n-diethyl-2-(4-fluorophenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(N(CC)CC)=CC=CC2=C(C=2C=CN=CC=2)C=1C1=CC=C(F)C=C1 CEJCMEFOUUNONM-UHFFFAOYSA-N 0.000 claims description 5
• MWWGXXSVLAIUPG-UHFFFAOYSA-N n-butyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NC3CCCC3)N=CC=2)C=1C1=CC=C(F)C=C1 MWWGXXSVLAIUPG-UHFFFAOYSA-N 0.000 claims description 5
• MPLQLGYBGSLDNE-UHFFFAOYSA-N n-cyclopentyl-2-(4-fluorophenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC=C1 MPLQLGYBGSLDNE-UHFFFAOYSA-N 0.000 claims description 5
• ZGQFMRKGMPUTDW-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyridin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(NC2CCCC2)=C1 ZGQFMRKGMPUTDW-UHFFFAOYSA-N 0.000 claims description 5
• AXPWWMOKPKUOBH-UHFFFAOYSA-N 2-(4-bromophenyl)-n-butyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NC3CCCC3)N=CC=2)C=1C1=CC=C(Br)C=C1 AXPWWMOKPKUOBH-UHFFFAOYSA-N 0.000 claims description 4
• CORKTNDUUHUEOV-UHFFFAOYSA-N 2-(4-fluorophenyl)-7-imidazol-1-yl-3-pyridin-4-ylpyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(=CC=C2)N3C=NC=C3)C2=C1C1=CC=NC=C1 CORKTNDUUHUEOV-UHFFFAOYSA-N 0.000 claims description 4
• KJUKBZFXBJVVKE-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-3-pyridin-4-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NC)=CC=CC2=C(C=2C=CN=CC=2)C=1C1=CC=C(F)C=C1 KJUKBZFXBJVVKE-UHFFFAOYSA-N 0.000 claims description 4
• MTUPINQDZNXFAG-UHFFFAOYSA-N 2-[[3-[2-(cyclopentylamino)-6-methylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-yl]amino]acetic acid Chemical compound N=1C(C)=CC(C2=C3C=CC=C(NCC(O)=O)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 MTUPINQDZNXFAG-UHFFFAOYSA-N 0.000 claims description 4
• DHQDJKDJLHMFJJ-UHFFFAOYSA-N 3-(2-aminopyrimidin-4-yl)-n-cyclopentyl-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound NC1=NC=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=N1 DHQDJKDJLHMFJJ-UHFFFAOYSA-N 0.000 claims description 4
• PVPVPEUVKPDJFD-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-methylpyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NC)N3N=C2C=2C=CC(F)=CC=2)=N1 PVPVPEUVKPDJFD-UHFFFAOYSA-N 0.000 claims description 4
• HEXZUPKPEJRFJV-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-n-cyclopropyl-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NC4CC4)N3N=C2C=2C=CC(F)=CC=2)=N1 HEXZUPKPEJRFJV-UHFFFAOYSA-N 0.000 claims description 4
• BMZKFFLGTXCJOT-UHFFFAOYSA-N 3-[2-(cyclopentylamino)-6-methylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1C(C)=CC(C2=C3C=CC=C(N)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 BMZKFFLGTXCJOT-UHFFFAOYSA-N 0.000 claims description 4
• FGQGOAHAWIMCAX-UHFFFAOYSA-N 3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(OC)=CC=C1NC1=CC=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3C=CC(F)=CC=3)=NN12 FGQGOAHAWIMCAX-UHFFFAOYSA-N 0.000 claims description 4
• AGHBQALSJZKTMH-UHFFFAOYSA-N 3-[[4-[7-(butylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl]amino]propan-1-ol Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NCCCO)N=CC=2)C=1C1=CC=C(F)C=C1 AGHBQALSJZKTMH-UHFFFAOYSA-N 0.000 claims description 4
• VKZZXFMSDDDGAV-UHFFFAOYSA-N 7-chloro-2-(4-fluorophenyl)-3-(2-phenylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC=NC(C=2C=CC=CC=2)=N1 VKZZXFMSDDDGAV-UHFFFAOYSA-N 0.000 claims description 4
• NUWOQZYQRBYBRO-UHFFFAOYSA-N 7-chloro-2-(4-fluorophenyl)-3-(2-propan-2-ylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine Chemical compound CC(C)C1=NC=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=N1 NUWOQZYQRBYBRO-UHFFFAOYSA-N 0.000 claims description 4
• NMGBNZIPZPBKAJ-UHFFFAOYSA-N [2-(cyclopentylamino)-6-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-4-yl]methanol Chemical compound N=1C(CO)=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 NMGBNZIPZPBKAJ-UHFFFAOYSA-N 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• PVUFXIOCHVKIMH-UHFFFAOYSA-N methyl 2-[[3-[2-(cyclopentylamino)-6-methylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-yl]amino]acetate Chemical compound N=1N2C(NCC(=O)OC)=CC=CC2=C(C=2N=C(NC3CCCC3)N=C(C)C=2)C=1C1=CC=C(F)C=C1 PVUFXIOCHVKIMH-UHFFFAOYSA-N 0.000 claims description 4
• CRPGNJUEUBZRCD-UHFFFAOYSA-N n'-[4-[3-[2-(3-aminopropylamino)pyridin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-yl]pyridin-2-yl]propane-1,3-diamine Chemical compound C1=NC(NCCCN)=CC(C2=C3C=CC=C(N3N=C2C=2C=CC(F)=CC=2)C=2C=C(NCCCN)N=CC=2)=C1 CRPGNJUEUBZRCD-UHFFFAOYSA-N 0.000 claims description 4
• BNIPJZUJUWWJMR-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2C=CN=CC=2)C=1C1=CC=C(F)C=C1 BNIPJZUJUWWJMR-UHFFFAOYSA-N 0.000 claims description 4
• GXHNSOFFXNOAST-UHFFFAOYSA-N n-butyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NC3CC3)N=CC=2)C=1C1=CC=C(F)C=C1 GXHNSOFFXNOAST-UHFFFAOYSA-N 0.000 claims description 4
• TZRRNEDYZWOVNI-UHFFFAOYSA-N n-butyl-4-[2-(4-fluorophenyl)-7-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(N3N=C2C=2C=CC(F)=CC=2)N2CCN(C)CC2)=N1 TZRRNEDYZWOVNI-UHFFFAOYSA-N 0.000 claims description 4
• XXUMHEXVTRQQTL-UHFFFAOYSA-N n-butyl-4-[2-(4-fluorophenyl)-7-(furan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(N3N=C2C=2C=CC(F)=CC=2)C=2OC=CC=2)=N1 XXUMHEXVTRQQTL-UHFFFAOYSA-N 0.000 claims description 4
• GOPRMCBDOSYWOP-UHFFFAOYSA-N n-butyl-4-[2-(4-fluorophenyl)-7-morpholin-4-ylpyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(N3N=C2C=2C=CC(F)=CC=2)N2CCOCC2)=N1 GOPRMCBDOSYWOP-UHFFFAOYSA-N 0.000 claims description 4
• OKMIJQUBSOQGJL-UHFFFAOYSA-N n-cyclopentyl-2-(cyclopentylamino)-6-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidine-4-carboxamide Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC(C(=O)NC2CCCC2)=NC(NC2CCCC2)=N1 OKMIJQUBSOQGJL-UHFFFAOYSA-N 0.000 claims description 4
• ZZMXDTJHYHXNBR-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)-6-[(dimethylamino)methyl]pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1C(CN(C)C)=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 ZZMXDTJHYHXNBR-UHFFFAOYSA-N 0.000 claims description 4
• RKZLHCSYPKUCAC-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)-6-methylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1C(C)=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 RKZLHCSYPKUCAC-UHFFFAOYSA-N 0.000 claims description 4
• ZLSXFULLFJBYCB-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)-6-phenylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC(C=2C=CC=CC=2)=NC(NC2CCCC2)=N1 ZLSXFULLFJBYCB-UHFFFAOYSA-N 0.000 claims description 4
• UDNOMPRVOYSIRF-UHFFFAOYSA-N n-cyclopentyl-3-[2-(dimethylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CN(C)C1=NC=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=N1 UDNOMPRVOYSIRF-UHFFFAOYSA-N 0.000 claims description 4
• OYAODPKCRFZVSL-UHFFFAOYSA-N n-cyclopentyl-4-[2-(4-fluorophenyl)-7-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl]-6-methylpyrimidin-2-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=C(C=3N=C(NC4CCCC4)N=C(C)C=3)C(C=3C=CC(F)=CC=3)=NN12 OYAODPKCRFZVSL-UHFFFAOYSA-N 0.000 claims description 4
• GUDXKTGWOFKDLD-UHFFFAOYSA-N n-cyclopentyl-4-[2-(4-fluorophenyl)-7-hydrazinylpyrazolo[1,5-a]pyridin-3-yl]-6-methylpyrimidin-2-amine Chemical compound N=1C(C)=CC(C2=C3C=CC=C(NN)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 GUDXKTGWOFKDLD-UHFFFAOYSA-N 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• XVAFXYJCEWERCO-UHFFFAOYSA-N 2-(4-bromophenyl)-n-butyl-3-(2-pyrrolidin-1-ylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(N=CC=2)N2CCCC2)C=1C1=CC=C(Br)C=C1 XVAFXYJCEWERCO-UHFFFAOYSA-N 0.000 claims description 3
• BBCVQUQRQXCLCZ-UHFFFAOYSA-N 2-(4-fluorophenyl)-7-pyrrolidin-1-yl-3-(2-pyrrolidin-1-ylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(=CC=C2)N3CCCC3)C2=C1C1=CC=NC(N2CCCC2)=N1 BBCVQUQRQXCLCZ-UHFFFAOYSA-N 0.000 claims description 3
• SBVLXTAGVHUBTM-UHFFFAOYSA-N 2-[4-[4-[7-(butylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl]piperazin-1-yl]ethanol Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(N=CC=2)N2CCN(CCO)CC2)C=1C1=CC=C(F)C=C1 SBVLXTAGVHUBTM-UHFFFAOYSA-N 0.000 claims description 3
• VVUNVHXOSPRUEP-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-(2-morpholin-4-ylethyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NCCN4CCOCC4)N3N=C2C=2C=CC(F)=CC=2)=N1 VVUNVHXOSPRUEP-UHFFFAOYSA-N 0.000 claims description 3
• HWWATJDGLHIOIC-UHFFFAOYSA-N 3-[2-(butylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)-n-propylpyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(NCCC)N3N=C2C=2C=CC(F)=CC=2)=N1 HWWATJDGLHIOIC-UHFFFAOYSA-N 0.000 claims description 3
• OYVQYHGDOBNBLY-UHFFFAOYSA-N 4-[2-(4-fluorophenyl)-7-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-yl]-n,n-dimethylpyrimidin-2-amine Chemical compound CN(C)C1=NC=CC(C2=C3C=CC=C(N3N=C2C=2C=CC(F)=CC=2)N2CCCC2)=N1 OYVQYHGDOBNBLY-UHFFFAOYSA-N 0.000 claims description 3
• KSJXRAKGFZZVQM-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-propylpyridin-2-amine Chemical compound C1=NC(NCCC)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=C1 KSJXRAKGFZZVQM-UHFFFAOYSA-N 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• LDWJJTHIKWQNPM-UHFFFAOYSA-N N=1N2C(C(N)CN)=CC=CC2=C(C=2N=C(NC3CCCC3)N=C(C=2)C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 Chemical compound N=1N2C(C(N)CN)=CC=CC2=C(C=2N=C(NC3CCCC3)N=C(C=2)C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 LDWJJTHIKWQNPM-UHFFFAOYSA-N 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• QFJYFNSUAFKMKT-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-(2-morpholin-4-ylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(N=CC=2)N2CCOCC2)C=1C1=CC=C(F)C=C1 QFJYFNSUAFKMKT-UHFFFAOYSA-N 0.000 claims description 3
• ZSNDOSHJGAPYCQ-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-(2-pyrrolidin-1-ylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(N=CC=2)N2CCCC2)C=1C1=CC=C(F)C=C1 ZSNDOSHJGAPYCQ-UHFFFAOYSA-N 0.000 claims description 3
• KGIKCYUNEWFWPG-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(OCC(F)(F)F)N=CC=2)C=1C1=CC=C(F)C=C1 KGIKCYUNEWFWPG-UHFFFAOYSA-N 0.000 claims description 3
• BAORXFJEZZVNBT-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-[2-(2-morpholin-4-ylethoxy)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(OCCN3CCOCC3)N=CC=2)C=1C1=CC=C(F)C=C1 BAORXFJEZZVNBT-UHFFFAOYSA-N 0.000 claims description 3
• RYNVQBIIRPBVGV-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-[2-(2-morpholin-4-ylethylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NCCN3CCOCC3)N=CC=2)C=1C1=CC=C(F)C=C1 RYNVQBIIRPBVGV-UHFFFAOYSA-N 0.000 claims description 3
• HWWJRISFZBFHPZ-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-[2-(pyridin-2-ylmethylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NCC=3N=CC=CC=3)N=CC=2)C=1C1=CC=C(F)C=C1 HWWJRISFZBFHPZ-UHFFFAOYSA-N 0.000 claims description 3
• IFFWMEDYOGFZLQ-UHFFFAOYSA-N n-butyl-4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyridin-2-amine Chemical compound C1=NC(NCCCC)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=C1 IFFWMEDYOGFZLQ-UHFFFAOYSA-N 0.000 claims description 3
• CDFZKTOECHOGJW-UHFFFAOYSA-N n-cyclopentyl-2-(4-fluorophenyl)-3-(2-hydrazinylpyridin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=NC(NN)=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=C1 CDFZKTOECHOGJW-UHFFFAOYSA-N 0.000 claims description 3
• IYJUEDGXLGOONJ-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)-5-methylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N1=C(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)C(C)=CN=C1NC1CCCC1 IYJUEDGXLGOONJ-UHFFFAOYSA-N 0.000 claims description 3
• KUXIDIXKISAOGO-UHFFFAOYSA-N n-cyclopentyl-3-[2-(dimethylamino)-6-methylpyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound CN(C)C1=NC(C)=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CC(F)=CC=2)=N1 KUXIDIXKISAOGO-UHFFFAOYSA-N 0.000 claims description 3
• IOCBVAIMEJTMSG-UHFFFAOYSA-N n-cyclopentyl-3-[6-(cyclopentylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC(NC2CCCC2)=NC=N1 IOCBVAIMEJTMSG-UHFFFAOYSA-N 0.000 claims description 3
• FAGDUAPMWFGDMN-UHFFFAOYSA-N n-cyclopentyl-4-[2-(4-fluorophenyl)-7-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridin-3-yl]-6-phenylpyrimidin-2-amine;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC=CC2=C(C=3N=C(NC4CCCC4)N=C(C=3)C=3C=CC=CC=3)C(C=3C=CC(F)=CC=3)=NN12 FAGDUAPMWFGDMN-UHFFFAOYSA-N 0.000 claims description 3
• KLRJIYIAXBHQAR-UHFFFAOYSA-N n-cyclopentyl-6-[2-(4-fluorophenyl)-7-methylsulfanylpyrazolo[1,5-a]pyridin-3-yl]pyrimidin-4-amine Chemical compound N=1N2C(SC)=CC=CC2=C(C=2N=CN=C(NC3CCCC3)C=2)C=1C1=CC=C(F)C=C1 KLRJIYIAXBHQAR-UHFFFAOYSA-N 0.000 claims description 3
• CTLCJJPQDYDSQF-UHFFFAOYSA-N pyrazolo[1,5-a]pyridin-7-amine Chemical compound NC1=CC=CC2=CC=NN12 CTLCJJPQDYDSQF-UHFFFAOYSA-N 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• UOYBJJNQHHCQBI-UHFFFAOYSA-N n-cyclohexyl-3-[2-(cyclohexylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCCC2)=CC=C2)C2=C1C1=CC=NC(NC2CCCCC2)=N1 UOYBJJNQHHCQBI-UHFFFAOYSA-N 0.000 claims description 2
• OQUNIDPVPXXPKP-UHFFFAOYSA-N n-cyclopentyl-2-(4-fluorophenyl)-3-[2-(3-morpholin-4-ylpropylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(NCCCN2CCOCC2)=N1 OQUNIDPVPXXPKP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• JPIRERSKZZYEMK-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-[2-[4-(2-methoxyethyl)piperazin-1-yl]pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(N=CC=2)N2CCN(CCOC)CC2)C=1C1=CC=C(F)C=C1 JPIRERSKZZYEMK-UHFFFAOYSA-N 0.000 claims 1
• 239000008177 pharmaceutical agent Substances 0.000 abstract 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 310
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 153
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
• 238000005160 1H NMR spectroscopy Methods 0.000 description 135
• 239000007787 solid Substances 0.000 description 104
• 239000000243 solution Substances 0.000 description 97
• 239000000203 mixture Substances 0.000 description 94
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 61
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
• 238000005481 NMR spectroscopy Methods 0.000 description 56
• 239000002585 base Substances 0.000 description 45
• 238000006243 chemical reaction Methods 0.000 description 45
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
• 238000001914 filtration Methods 0.000 description 34
• 239000011541 reaction mixture Substances 0.000 description 34
• 235000019441 ethanol Nutrition 0.000 description 33
• 239000002904 solvent Substances 0.000 description 33
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
• 239000012267 brine Substances 0.000 description 28
• 238000003818 flash chromatography Methods 0.000 description 27
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 27
• 235000019341 magnesium sulphate Nutrition 0.000 description 27
• 239000012044 organic layer Substances 0.000 description 26
• 230000003612 virological effect Effects 0.000 description 26
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
• 239000003921 oil Substances 0.000 description 23
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 22
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• 238000009472 formulation Methods 0.000 description 21
• 235000019198 oils Nutrition 0.000 description 21
• 239000003795 chemical substances by application Substances 0.000 description 19
• 239000010410 layer Substances 0.000 description 19
• 206010019973 Herpes virus infection Diseases 0.000 description 18
• 229910000027 potassium carbonate Inorganic materials 0.000 description 18
• 239000006260 foam Substances 0.000 description 17
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
• 239000012442 inert solvent Substances 0.000 description 16
• 208000015181 infectious disease Diseases 0.000 description 16
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 15
• 208000036142 Viral infection Diseases 0.000 description 15
• 230000009385 viral infection Effects 0.000 description 15
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
• 239000000543 intermediate Substances 0.000 description 14
• 239000000463 material Substances 0.000 description 14
• 0 *c(cc1)ccc1C(Cc1cccc(*)n1)=N Chemical compound *c(cc1)ccc1C(Cc1cccc(*)n1)=N 0.000 description 13
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 13
• 238000010438 heat treatment Methods 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 125000000623 heterocyclic group Chemical group 0.000 description 12
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• 241000282414 Homo sapiens Species 0.000 description 10
• 241000124008 Mammalia Species 0.000 description 10
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 10
• RDKYLZULJQZSGO-UHFFFAOYSA-N n-butyl-4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound CCCCNC1=NC=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=N1 RDKYLZULJQZSGO-UHFFFAOYSA-N 0.000 description 10
• 239000011701 zinc Substances 0.000 description 10
• IOOJBDSYMIVHQI-UHFFFAOYSA-N 2-cyclopentylguanidine;hydrochloride Chemical compound Cl.NC(N)=NC1CCCC1 IOOJBDSYMIVHQI-UHFFFAOYSA-N 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 9
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
• 241000700605 Viruses Species 0.000 description 9
• 239000004480 active ingredient Substances 0.000 description 9
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 9
• NGCGXWSHHRXJPS-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]prop-2-yn-1-one Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C(=O)C#C NGCGXWSHHRXJPS-UHFFFAOYSA-N 0.000 description 8
• 241000700588 Human alphaherpesvirus 1 Species 0.000 description 8
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• 239000011777 magnesium Substances 0.000 description 8
• 208000037803 restenosis Diseases 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• WGWRAABKDQDZMQ-CCEZHUSRSA-N (e)-1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)prop-2-en-1-one Chemical compound C=1C=CC2=C(C(=O)/C=C/N(C)C)C(C=3C=CC(F)=CC=3)=NN2C=1NC1CCCC1 WGWRAABKDQDZMQ-CCEZHUSRSA-N 0.000 description 7
• LFGGATHPICJAAT-UHFFFAOYSA-N 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C=O LFGGATHPICJAAT-UHFFFAOYSA-N 0.000 description 7
• 241000701074 Human alphaherpesvirus 2 Species 0.000 description 7
• 241000701027 Human herpesvirus 6 Species 0.000 description 7
• 125000004093 cyano group Chemical group *C#N 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• 150000002736 metal compounds Chemical class 0.000 description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
• 239000007800 oxidant agent Substances 0.000 description 7
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• UGEDLFYKZYZGHF-FYWRMAATSA-N (e)-1-[7-(butylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)prop-2-en-1-one Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C(=O)\C=C\N(C)C)C=1C1=CC=C(F)C=C1 UGEDLFYKZYZGHF-FYWRMAATSA-N 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• MPACVOLQDZSTSW-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound N=1N2C(Cl)=CC=CC2=C(C(=O)C)C=1C1=CC=C(F)C=C1 MPACVOLQDZSTSW-UHFFFAOYSA-N 0.000 description 6
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
• GXZDYRYYNXYPMQ-UHFFFAOYSA-N 2-chloro-6-methylpyridine Chemical compound CC1=CC=CC(Cl)=N1 GXZDYRYYNXYPMQ-UHFFFAOYSA-N 0.000 description 6
• 241000701022 Cytomegalovirus Species 0.000 description 6
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
• 241000701085 Human alphaherpesvirus 3 Species 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
• 229910052749 magnesium Inorganic materials 0.000 description 6
• 238000002156 mixing Methods 0.000 description 6
• 201000006417 multiple sclerosis Diseases 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• ATENWFZPEVYXTK-UHFFFAOYSA-N 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN2C(Cl)=CC=CC2=C1 ATENWFZPEVYXTK-UHFFFAOYSA-N 0.000 description 5
• 241000700721 Hepatitis B virus Species 0.000 description 5
• 208000007514 Herpes zoster Diseases 0.000 description 5
• 241000701041 Human betaherpesvirus 7 Species 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 229910052744 lithium Inorganic materials 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
• 238000012746 preparative thin layer chromatography Methods 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• 241001529453 unidentified herpesvirus Species 0.000 description 5
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
• TVCYMPSMNBWCSN-FYWRMAATSA-N (e)-1-[2-(4-bromophenyl)-7-(butylamino)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)prop-2-en-1-one Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C(=O)\C=C\N(C)C)C=1C1=CC=C(Br)C=C1 TVCYMPSMNBWCSN-FYWRMAATSA-N 0.000 description 4
• CAVUKHNKANLRIS-NTCAYCPXSA-N (e)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-7-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-yl]prop-2-en-1-one Chemical compound C=1C=CC2=C(C(=O)/C=C/N(C)C)C(C=3C=CC(F)=CC=3)=NN2C=1N1CCCC1 CAVUKHNKANLRIS-NTCAYCPXSA-N 0.000 description 4
• TVWMHJOLEDVFFP-UHFFFAOYSA-N 2-(4-fluorophenyl)-3,7-bis(2-fluoropyridin-4-yl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(=CC=C2)C=3C=C(F)N=CC=3)C2=C1C1=CC=NC(F)=C1 TVWMHJOLEDVFFP-UHFFFAOYSA-N 0.000 description 4
• BUAIGJRXIAKFCN-UHFFFAOYSA-N 2-(4-fluorophenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C=CC=C2)C2=C1C1=CC=NC=C1 BUAIGJRXIAKFCN-UHFFFAOYSA-N 0.000 description 4
• QHYGFUYNHIWHLC-UHFFFAOYSA-N 2-butylguanidine;sulfuric acid Chemical compound OS(O)(=O)=O.CCCCN=C(N)N QHYGFUYNHIWHLC-UHFFFAOYSA-N 0.000 description 4
• JVDQDOUMMGFLNG-UHFFFAOYSA-N 3-bromo-7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1Br JVDQDOUMMGFLNG-UHFFFAOYSA-N 0.000 description 4
• JPCHUGJACCMNKC-UHFFFAOYSA-N 3-bromo-n-cyclopentyl-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1Br JPCHUGJACCMNKC-UHFFFAOYSA-N 0.000 description 4
• GLPJDQIQSSJMOR-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-6-phenylpyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC(C=2C=CC=CC=2)=NC(NC2CCCC2)=N1 GLPJDQIQSSJMOR-UHFFFAOYSA-N 0.000 description 4
• 244000215068 Acacia senegal Species 0.000 description 4
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
• 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 4
• 229920000084 Gum arabic Polymers 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 241000725303 Human immunodeficiency virus Species 0.000 description 4
• 241000701806 Human papillomavirus Species 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical group Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
• 206010028980 Neoplasm Diseases 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 235000010489 acacia gum Nutrition 0.000 description 4
• 239000000205 acacia gum Substances 0.000 description 4
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
• 150000000475 acetylene derivatives Chemical class 0.000 description 4
• 150000001298 alcohols Chemical class 0.000 description 4
• 125000003545 alkoxy group Chemical group 0.000 description 4
• 150000001409 amidines Chemical class 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 238000002399 angioplasty Methods 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 239000012091 fetal bovine serum Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 229910052751 metal Inorganic materials 0.000 description 4
• 239000002184 metal Substances 0.000 description 4
• 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 4
• WZNLDODEGLUOEA-UHFFFAOYSA-N n-cyclopentyl-2-(4-fluorophenyl)-3-(2-fluoropyridin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(F)=C1 WZNLDODEGLUOEA-UHFFFAOYSA-N 0.000 description 4
• IWHNNBJRAOIAPH-UHFFFAOYSA-N n-cyclopentyl-4-[2-(4-fluorophenyl)-7-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(=CC=C2)N3CCCC3)C2=C1C1=CC=NC(NC2CCCC2)=N1 IWHNNBJRAOIAPH-UHFFFAOYSA-N 0.000 description 4
• 239000012038 nucleophile Substances 0.000 description 4
• 230000003647 oxidation Effects 0.000 description 4
• 238000007254 oxidation reaction Methods 0.000 description 4
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 4
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 230000035755 proliferation Effects 0.000 description 4
• 238000001953 recrystallisation Methods 0.000 description 4
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 4
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
• WXGBZJJAGLSBPR-UHFFFAOYSA-N (2-fluoropyridin-4-yl)boronic acid Chemical compound OB(O)C1=CC=NC(F)=C1 WXGBZJJAGLSBPR-UHFFFAOYSA-N 0.000 description 3
• JBRLWUNBLVMLAD-OUKQBFOZSA-N (e)-1-[2-(3-bromo-4-chlorophenyl)-7-(cyclopentylamino)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)prop-2-en-1-one Chemical compound C=1C=CC2=C(C(=O)/C=C/N(C)C)C(C=3C=C(Br)C(Cl)=CC=3)=NN2C=1NC1CCCC1 JBRLWUNBLVMLAD-OUKQBFOZSA-N 0.000 description 3
• ONKPEJWLROTMIA-ZHACJKMWSA-N (e)-1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)prop-2-en-1-one Chemical compound N=1N2C(Cl)=CC=CC2=C(C(=O)/C=C/N(C)C)C=1C1=CC=C(F)C=C1 ONKPEJWLROTMIA-ZHACJKMWSA-N 0.000 description 3
• PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
• JNLDACWSVVKSDW-UHFFFAOYSA-N 1-(3-bromo-4-chlorophenyl)-2-(6-chloropyridin-2-yl)ethanone Chemical compound ClC1=CC=CC(CC(=O)C=2C=C(Br)C(Cl)=CC=2)=N1 JNLDACWSVVKSDW-UHFFFAOYSA-N 0.000 description 3
• JTNKPESREHKERS-UHFFFAOYSA-N 1-(4-bromophenyl)-2-(6-chloropyridin-2-yl)ethanone Chemical compound ClC1=CC=CC(CC(=O)C=2C=CC(Br)=CC=2)=N1 JTNKPESREHKERS-UHFFFAOYSA-N 0.000 description 3
• LXTQLOCPYFAHLT-UHFFFAOYSA-N 1-[2-(3-bromo-4-chlorophenyl)-7-(cyclopentylamino)pyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound C=1C=CC2=C(C(=O)C)C(C=3C=C(Br)C(Cl)=CC=3)=NN2C=1NC1CCCC1 LXTQLOCPYFAHLT-UHFFFAOYSA-N 0.000 description 3
• LWRVHVLQOOWUCC-UHFFFAOYSA-N 1-[2-(3-bromo-4-chlorophenyl)-7-chloropyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound N=1N2C(Cl)=CC=CC2=C(C(=O)C)C=1C1=CC=C(Cl)C(Br)=C1 LWRVHVLQOOWUCC-UHFFFAOYSA-N 0.000 description 3
• RUSALXMMPPJKNB-UHFFFAOYSA-N 1-[2-(4-bromophenyl)-7-(butylamino)pyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C(C)=O)C=1C1=CC=C(Br)C=C1 RUSALXMMPPJKNB-UHFFFAOYSA-N 0.000 description 3
• QJFIVRAGJKNLSN-UHFFFAOYSA-N 1-[2-(4-bromophenyl)-7-chloropyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound N=1N2C(Cl)=CC=CC2=C(C(=O)C)C=1C1=CC=C(Br)C=C1 QJFIVRAGJKNLSN-UHFFFAOYSA-N 0.000 description 3
• XHDCJIUUJPCCEL-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-7-pyrrolidin-1-ylpyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound C=1C=CC2=C(C(=O)C)C(C=3C=CC(F)=CC=3)=NN2C=1N1CCCC1 XHDCJIUUJPCCEL-UHFFFAOYSA-N 0.000 description 3
• XESCXGMECQHKPX-UHFFFAOYSA-N 1-[7-(butylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C(C)=O)C=1C1=CC=C(F)C=C1 XESCXGMECQHKPX-UHFFFAOYSA-N 0.000 description 3
• BTGJRHAIEUPLAI-UHFFFAOYSA-N 1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone Chemical compound C=1C=CC2=C(C(=O)C)C(C=3C=CC(F)=CC=3)=NN2C=1NC1CCCC1 BTGJRHAIEUPLAI-UHFFFAOYSA-N 0.000 description 3
• KLCWHDKKCLHSTO-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-methylprop-2-en-1-one Chemical compound N=1N2C(Cl)=CC=CC2=C(C(=O)C(=C)C)C=1C1=CC=C(F)C=C1 KLCWHDKKCLHSTO-UHFFFAOYSA-N 0.000 description 3
• CAKBGGBOEVDEIX-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-3-phenylprop-2-yn-1-one Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C(=O)C#CC1=CC=CC=C1 CAKBGGBOEVDEIX-UHFFFAOYSA-N 0.000 description 3
• TZUROHOKXLJCHS-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]but-2-yn-1-ol Chemical compound N=1N2C(Cl)=CC=CC2=C(C(O)C#CC)C=1C1=CC=C(F)C=C1 TZUROHOKXLJCHS-UHFFFAOYSA-N 0.000 description 3
• LDTSPOSKOLOQQZ-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]prop-2-yn-1-ol Chemical compound N=1N2C(Cl)=CC=CC2=C(C(C#C)O)C=1C1=CC=C(F)C=C1 LDTSPOSKOLOQQZ-UHFFFAOYSA-N 0.000 description 3
• AZQWIDZJMCVVCL-UHFFFAOYSA-N 2-(3-bromo-4-chlorophenyl)-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=C(Br)C(Cl)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 AZQWIDZJMCVVCL-UHFFFAOYSA-N 0.000 description 3
• FPCJNWCMEYGIPD-UHFFFAOYSA-N 2-(4-bromophenyl)-7-chloropyrazolo[1,5-a]pyridine Chemical compound N=1N2C(Cl)=CC=CC2=CC=1C1=CC=C(Br)C=C1 FPCJNWCMEYGIPD-UHFFFAOYSA-N 0.000 description 3
• ZMPCHEOJUQKYBJ-UHFFFAOYSA-N 2-(6-chloropyridin-2-yl)-1-(4-fluorophenyl)ethanone Chemical compound C1=CC(F)=CC=C1C(=O)CC1=CC=CC(Cl)=N1 ZMPCHEOJUQKYBJ-UHFFFAOYSA-N 0.000 description 3
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• NSOXJFUTZQOYNS-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-6-(iodomethyl)pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC(CI)=NC(NC2CCCC2)=N1 NSOXJFUTZQOYNS-UHFFFAOYSA-N 0.000 description 3
• LRSNFQBSTKTYKI-UHFFFAOYSA-N 6-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-2-(cyclopentylamino)pyrimidine-4-carboxamide Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC(C(=O)NC2CCCC2)=NC(NC2CCCC2)=N1 LRSNFQBSTKTYKI-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 208000024172 Cardiovascular disease Diseases 0.000 description 3
• AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 3
• SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 3
• 206010015108 Epstein-Barr virus infection Diseases 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 241000711557 Hepacivirus Species 0.000 description 3
• 208000009889 Herpes Simplex Diseases 0.000 description 3
• 206010061598 Immunodeficiency Diseases 0.000 description 3
• 229930194542 Keto Natural products 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 206010037660 Pyrexia Diseases 0.000 description 3
• 150000001241 acetals Chemical class 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 150000001450 anions Chemical class 0.000 description 3
• 230000000840 anti-viral effect Effects 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
• 210000004204 blood vessel Anatomy 0.000 description 3
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 210000004027 cell Anatomy 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000006352 cycloaddition reaction Methods 0.000 description 3
• SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 3
• RGWHQCVHVJXOKC-SHYZEUOFSA-N dCTP Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-N 0.000 description 3
• HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
• QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 3
• SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 230000002140 halogenating effect Effects 0.000 description 3
• 208000002672 hepatitis B Diseases 0.000 description 3
• 238000009396 hybridization Methods 0.000 description 3
• 150000003840 hydrochlorides Chemical class 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 238000011065 in-situ storage Methods 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 125000000468 ketone group Chemical group 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000011968 lewis acid catalyst Substances 0.000 description 3
• YCMJPDKXPDSIGE-UHFFFAOYSA-N methyl 6-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-(cyclopentylamino)pyrimidine-4-carboxylate Chemical compound N=1C(C(=O)OC)=CC(C2=C3C=CC=C(Cl)N3N=C2C=2C=CC(F)=CC=2)=NC=1NC1CCCC1 YCMJPDKXPDSIGE-UHFFFAOYSA-N 0.000 description 3
• 239000007758 minimum essential medium Substances 0.000 description 3
• HOACKJDYHSOYCC-UHFFFAOYSA-N n-[1-(3-bromo-4-chlorophenyl)-2-(6-chloropyridin-2-yl)ethylidene]hydroxylamine Chemical compound C=1C=C(Cl)C(Br)=CC=1C(=NO)CC1=CC=CC(Cl)=N1 HOACKJDYHSOYCC-UHFFFAOYSA-N 0.000 description 3
• JUPZDNHBBCUQGU-UHFFFAOYSA-N n-[1-(4-bromophenyl)-2-(6-chloropyridin-2-yl)ethylidene]hydroxylamine Chemical compound C=1C=C(Br)C=CC=1C(=NO)CC1=CC=CC(Cl)=N1 JUPZDNHBBCUQGU-UHFFFAOYSA-N 0.000 description 3
• IXPKAIUODGJXTC-UHFFFAOYSA-N n-[2-(6-chloropyridin-2-yl)-1-(4-fluorophenyl)ethylidene]hydroxylamine Chemical compound C=1C=C(F)C=CC=1C(=NO)CC1=CC=CC(Cl)=N1 IXPKAIUODGJXTC-UHFFFAOYSA-N 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 230000008707 rearrangement Effects 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 235000010356 sorbitol Nutrition 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 238000003756 stirring Methods 0.000 description 3
• 229940124530 sulfonamide Drugs 0.000 description 3
• 150000003456 sulfonamides Chemical class 0.000 description 3
• 230000001629 suppression Effects 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 2
• HSIRMHBLQDRNFR-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-3-phenylprop-2-yn-1-ol Chemical compound C=1C=C(F)C=CC=1C1=NN2C(Cl)=CC=CC2=C1C(O)C#CC1=CC=CC=C1 HSIRMHBLQDRNFR-UHFFFAOYSA-N 0.000 description 2
• VZXUHJMNPSOJAQ-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-4-(oxan-2-yloxy)but-2-yn-1-ol Chemical compound C=1C=C(F)C=CC=1C1=NN2C(Cl)=CC=CC2=C1C(O)C#CCOC1CCCCO1 VZXUHJMNPSOJAQ-UHFFFAOYSA-N 0.000 description 2
• JCNRYJPNSJSNTA-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-4-(oxan-2-yloxy)but-2-yn-1-one Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C(=O)C#CCOC1OCCCC1 JCNRYJPNSJSNTA-UHFFFAOYSA-N 0.000 description 2
• XVBGRFOOYHSQGW-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]but-2-yn-1-one Chemical compound N=1N2C(Cl)=CC=CC2=C(C(=O)C#CC)C=1C1=CC=C(F)C=C1 XVBGRFOOYHSQGW-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• ZHKJHQBOAJQXQR-UHFFFAOYSA-N 1H-azirine Chemical compound N1C=C1 ZHKJHQBOAJQXQR-UHFFFAOYSA-N 0.000 description 2
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 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
• SYPHWRQINWALNC-UHFFFAOYSA-N 2-(3-bromo-4-chlorophenyl)-7-chloropyrazolo[1,5-a]pyridine Chemical compound C1=C(Br)C(Cl)=CC=C1C1=NN2C(Cl)=CC=CC2=C1 SYPHWRQINWALNC-UHFFFAOYSA-N 0.000 description 2
• ZRXYWQKYSSVZNJ-UHFFFAOYSA-N 2-(4-fluorophenyl)ethynyl-trimethylsilane Chemical group C[Si](C)(C)C#CC1=CC=C(F)C=C1 ZRXYWQKYSSVZNJ-UHFFFAOYSA-N 0.000 description 2
• DYHFSYYPUBIUHN-UHFFFAOYSA-N 2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carboxylic acid Chemical compound N=1N2C=CC=CC2=C(C(=O)O)C=1C1=CC=C(F)C=C1 DYHFSYYPUBIUHN-UHFFFAOYSA-N 0.000 description 2
• SSHWJSLWQRXJGM-UHFFFAOYSA-N 2-cyclopropylguanidine;sulfuric acid Chemical compound OS(O)(=O)=O.NC(=N)NC1CC1 SSHWJSLWQRXJGM-UHFFFAOYSA-N 0.000 description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
• NCVIAWGVEVTBIO-UHFFFAOYSA-N 3-bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C=CC=C2)C2=C1Br NCVIAWGVEVTBIO-UHFFFAOYSA-N 0.000 description 2
• ZDMZAUOREPFGIC-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentyl-6-(oxan-2-yloxymethyl)pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC(COC2OCCCC2)=NC(NC2CCCC2)=N1 ZDMZAUOREPFGIC-UHFFFAOYSA-N 0.000 description 2
• UPZNIWHYDALZKC-UHFFFAOYSA-N 4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopropylpyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC=NC(NC2CC2)=N1 UPZNIWHYDALZKC-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical group CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• MKMQOVQANWMIIT-UHFFFAOYSA-N 7-bromo-2-(4-fluorophenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Br)=CC=C2)C2=C1C1=CC=NC=C1 MKMQOVQANWMIIT-UHFFFAOYSA-N 0.000 description 2
• BGGHDYVFINORAH-UHFFFAOYSA-N 7-chloro-3-(2-cyclopropylpyrimidin-4-yl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine Chemical compound C1=CC(F)=CC=C1C1=NN(C(Cl)=CC=C2)C2=C1C1=CC=NC(C2CC2)=N1 BGGHDYVFINORAH-UHFFFAOYSA-N 0.000 description 2
• 239000004254 Ammonium phosphate Substances 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 229910052684 Cerium Inorganic materials 0.000 description 2
• 201000006082 Chickenpox Diseases 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• 206010011831 Cytomegalovirus infection Diseases 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
• 208000001860 Eye Infections Diseases 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 208000001688 Herpes Genitalis Diseases 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
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 229910021577 Iron(II) chloride Inorganic materials 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• 208000030289 Lymphoproliferative disease Diseases 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 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
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 206010037898 Rash vesicular Diseases 0.000 description 2
• 206010038910 Retinitis Diseases 0.000 description 2
• 241000700584 Simplexvirus Species 0.000 description 2
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 206010046980 Varicella Diseases 0.000 description 2
• 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 2
• 229910000148 ammonium phosphate Inorganic materials 0.000 description 2
• 235000019289 ammonium phosphates Nutrition 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 238000005899 aromatization reaction Methods 0.000 description 2
• 150000001543 aryl boronic acids Chemical class 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 150000001542 azirines Chemical class 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000013592 cell lysate Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 230000007012 clinical effect Effects 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
• KFGVRWGDTLZAAO-UHFFFAOYSA-N cyclopenta-1,3-diene dicyclohexyl(cyclopenta-1,3-dien-1-yl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.C1CCC(CC1)P(C1CCCCC1)c1ccc[cH-]1 KFGVRWGDTLZAAO-UHFFFAOYSA-N 0.000 description 2
• SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 238000012631 diagnostic technique Methods 0.000 description 2
• MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 2
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• 230000008034 disappearance Effects 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
• 238000007876 drug discovery Methods 0.000 description 2
• 239000012039 electrophile Substances 0.000 description 2
• 238000000132 electrospray ionisation Methods 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 150000002085 enols Chemical class 0.000 description 2
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 2
• 210000002744 extracellular matrix Anatomy 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 208000011323 eye infectious disease Diseases 0.000 description 2
• 230000022244 formylation Effects 0.000 description 2
• 238000006170 formylation reaction Methods 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 201000004946 genital herpes Diseases 0.000 description 2
• 238000005658 halogenation reaction Methods 0.000 description 2
• 235000015220 hamburgers Nutrition 0.000 description 2
• 229940094991 herring sperm dna Drugs 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 201000006747 infectious mononucleosis Diseases 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 2
• RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical group [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 239000007937 lozenge Substances 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
• 239000011159 matrix material Substances 0.000 description 2
• OSFSZNMZOPCBLS-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carboxylate Chemical compound N=1N2C=CC=CC2=C(C(=O)OC)C=1C1=CC=C(F)C=C1 OSFSZNMZOPCBLS-UHFFFAOYSA-N 0.000 description 2
• RXGVUTFSIPIPDU-UHFFFAOYSA-N methyl 3-(4-fluorophenyl)prop-2-ynoate Chemical compound COC(=O)C#CC1=CC=C(F)C=C1 RXGVUTFSIPIPDU-UHFFFAOYSA-N 0.000 description 2
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 238000000465 moulding Methods 0.000 description 2
• JNQXRJALXAMYCK-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(SC)N=CC=2)C=1C1=CC=C(F)C=C1 JNQXRJALXAMYCK-UHFFFAOYSA-N 0.000 description 2
• MFRRZLPOMUHMLV-UHFFFAOYSA-N n-butyl-2-(4-fluorophenyl)-3-[2-(3-imidazol-1-ylpropylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound N=1N2C(NCCCC)=CC=CC2=C(C=2N=C(NCCCN3C=NC=C3)N=CC=2)C=1C1=CC=C(F)C=C1 MFRRZLPOMUHMLV-UHFFFAOYSA-N 0.000 description 2
• 230000000269 nucleophilic effect Effects 0.000 description 2
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 230000000306 recurrent effect Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• VWXLCWNPSOUPPE-UHFFFAOYSA-N (1-amino-2-methylpropylidene)azanium;chloride Chemical compound Cl.CC(C)C(N)=N VWXLCWNPSOUPPE-UHFFFAOYSA-N 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 description 1
• VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• AFTVHUKPIJKGQH-UHFFFAOYSA-N 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-methylprop-2-en-1-ol Chemical compound N=1N2C(Cl)=CC=CC2=C(C(O)C(=C)C)C=1C1=CC=C(F)C=C1 AFTVHUKPIJKGQH-UHFFFAOYSA-N 0.000 description 1
• VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 1
• KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 1
• VZOPVKZLLGMDDG-UHFFFAOYSA-N 1-oxido-4-phenylpyridin-1-ium Chemical compound C1=C[N+]([O-])=CC=C1C1=CC=CC=C1 VZOPVKZLLGMDDG-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• PNHGJPJOMCXSKN-UHFFFAOYSA-N 2-(1-methylpyrrolidin-2-yl)ethanamine Chemical compound CN1CCCC1CCN PNHGJPJOMCXSKN-UHFFFAOYSA-N 0.000 description 1
• KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
• KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
• VLEIUWBSEKKKFX-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O VLEIUWBSEKKKFX-UHFFFAOYSA-N 0.000 description 1
• ADPRIAVYIGHFSO-UHFFFAOYSA-N 2-fluoro-4-iodopyridine Chemical compound FC1=CC(I)=CC=N1 ADPRIAVYIGHFSO-UHFFFAOYSA-N 0.000 description 1
• 150000005749 2-halopyridines Chemical class 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
• HQAXHIGPGBPPFU-UHFFFAOYSA-N 2-prop-2-ynoxyoxane Chemical compound C#CCOC1CCCCO1 HQAXHIGPGBPPFU-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• GKECDORWWXXNRY-UHFFFAOYSA-N 2h-pyridin-3-one Chemical compound O=C1CN=CC=C1 GKECDORWWXXNRY-UHFFFAOYSA-N 0.000 description 1
• KHOLMDPKJYSCCG-UHFFFAOYSA-N 3-[[2-(4-fluorophenyl)-3-[2-(3-hydroxypropylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-yl]amino]propan-1-ol Chemical compound OCCCNC1=NC=CC(C2=C3C=CC=C(NCCCO)N3N=C2C=2C=CC(F)=CC=2)=N1 KHOLMDPKJYSCCG-UHFFFAOYSA-N 0.000 description 1
• KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-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
• WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-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
• JYCQQPHGFMYQCF-UHFFFAOYSA-N 4-tert-Octylphenol monoethoxylate Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCO)C=C1 JYCQQPHGFMYQCF-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 208000030507 AIDS Diseases 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 244000144730 Amygdalus persica Species 0.000 description 1
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
• 241000972773 Aulopiformes Species 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• QMMQWHNDJNKTIV-UHFFFAOYSA-N CCCCNC(N=CC1)=NC1c1c(cccc2NCCC)[n]2nc1-c(cc1)ccc1F Chemical compound CCCCNC(N=CC1)=NC1c1c(cccc2NCCC)[n]2nc1-c(cc1)ccc1F QMMQWHNDJNKTIV-UHFFFAOYSA-N 0.000 description 1
• LXIBUTKNIUMFOB-UHFFFAOYSA-N CCCCNc([n]1nc2-c(cc3)ccc3[Br]=C)cccc1c2-c1ccnc(N2CCCC2)n1 Chemical compound CCCCNc([n]1nc2-c(cc3)ccc3[Br]=C)cccc1c2-c1ccnc(N2CCCC2)n1 LXIBUTKNIUMFOB-UHFFFAOYSA-N 0.000 description 1
• PDVDPCMXAVXTHR-UHFFFAOYSA-N CCCCNc1nccc(C2=C(C=CC=C3NC)N3N(C)C2c(cc2)ccc2F)n1 Chemical compound CCCCNc1nccc(C2=C(C=CC=C3NC)N3N(C)C2c(cc2)ccc2F)n1 PDVDPCMXAVXTHR-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• 206010010071 Coma Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 206010062343 Congenital infection Diseases 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 201000000054 Coronary Restenosis Diseases 0.000 description 1
• 206010056489 Coronary artery restenosis Diseases 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 241000450599 DNA viruses Species 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 241001295925 Gegenes Species 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
• 208000005794 Hairy Leukoplakia Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000004898 Herpes Labialis Diseases 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000817629 Homo sapiens Dymeclin Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 241001502974 Human gammaherpesvirus 8 Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000029523 Interstitial Lung disease Diseases 0.000 description 1
• QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
• 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
• VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
• 206010023126 Jaundice Diseases 0.000 description 1
• 239000005909 Kieselgur Substances 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 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
• 208000032420 Latent Infection Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000036626 Mental retardation Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• YRTBMIIEKFIGHK-UHFFFAOYSA-N N=Cc(cc1)ccc1C#CO Chemical compound N=Cc(cc1)ccc1C#CO YRTBMIIEKFIGHK-UHFFFAOYSA-N 0.000 description 1
• 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 206010067152 Oral herpes Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• 206010033799 Paralysis Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 206010035742 Pneumonitis Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
• 235000006040 Prunus persica var persica Nutrition 0.000 description 1
• 108700026039 Simplexvirus UL13 Proteins 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 101150048584 TRM3 gene Proteins 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 239000007984 Tris EDTA buffer Substances 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 208000033779 X-linked lymphoproliferative disease Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
• 229960004748 abacavir Drugs 0.000 description 1
• GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000004647 alkyl sulfenyl group Chemical group 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 235000010210 aluminium Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 229960001830 amprenavir Drugs 0.000 description 1
• YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 1
• 208000022531 anorexia Diseases 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 229910052791 calcium Inorganic materials 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
• 201000011510 cancer Diseases 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 229920001429 chelating resin Polymers 0.000 description 1
• 238000000451 chemical ionisation Methods 0.000 description 1
• 239000007910 chewable tablet Substances 0.000 description 1
• WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000012875 competitive assay Methods 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 230000036461 convulsion Effects 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 229960003624 creatine Drugs 0.000 description 1
• 239000006046 creatine Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical compound Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 230000005595 deprotonation Effects 0.000 description 1
• 238000010537 deprotonation reaction Methods 0.000 description 1
• ACPFLXJEPKOPGF-UHFFFAOYSA-N diaminomethylidene(dimethyl)azanium;hydrogen sulfate Chemical compound [O-]S([O-])(=O)=O.C[NH+](C)C([NH3+])=N ACPFLXJEPKOPGF-UHFFFAOYSA-N 0.000 description 1
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 1
• 231100000676 disease causative agent Toxicity 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 229960000735 docosanol Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• KSEVRYZEZZJQSN-UHFFFAOYSA-N ethyl 3-bromo-4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(Br)=C1 KSEVRYZEZZJQSN-UHFFFAOYSA-N 0.000 description 1
• XZIAFENWXIQIKR-UHFFFAOYSA-N ethyl 4-bromobenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C=C1 XZIAFENWXIQIKR-UHFFFAOYSA-N 0.000 description 1
• UMPRJGKLMUDRHL-UHFFFAOYSA-N ethyl 4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C=C1 UMPRJGKLMUDRHL-UHFFFAOYSA-N 0.000 description 1
• AZLPEJUVWWGLHA-UHFFFAOYSA-N ethyl acetate;hexane;methanol Chemical compound OC.CCCCCC.CCOC(C)=O AZLPEJUVWWGLHA-UHFFFAOYSA-N 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 229960004396 famciclovir Drugs 0.000 description 1
• GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
• IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
• 229960002963 ganciclovir Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 150000002307 glutamic acids Chemical class 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 230000009548 growth disturbance Effects 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 229940116364 hard fat Drugs 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 206010019847 hepatosplenomegaly Diseases 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• WVKIFIROCHIWAY-UHFFFAOYSA-N hydron;2-(methylamino)acetic acid;chloride Chemical compound Cl.CNCC(O)=O WVKIFIROCHIWAY-UHFFFAOYSA-N 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000007813 immunodeficiency Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000012678 infectious agent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 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
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 206010023332 keratitis Diseases 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960001627 lamivudine Drugs 0.000 description 1
• JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 description 1
• QBNOPZJAURRQCE-UHFFFAOYSA-M magnesium;prop-1-yne;bromide Chemical compound [Mg+2].[Br-].CC#[C-] QBNOPZJAURRQCE-UHFFFAOYSA-M 0.000 description 1
• 206010025482 malaise Diseases 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000010907 mechanical stirring Methods 0.000 description 1
• 238000013160 medical therapy Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 210000002418 meninge Anatomy 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 208000004141 microcephaly Diseases 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-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
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• SJECIYLGISUNRO-UHFFFAOYSA-N o-diphenylphosphorylhydroxylamine Chemical compound C=1C=CC=CC=1P(=O)(ON)C1=CC=CC=C1 SJECIYLGISUNRO-UHFFFAOYSA-N 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• 230000000414 obstructive effect Effects 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
• 206010030979 oral hairy leukoplakia Diseases 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 150000004965 peroxy acids Chemical group 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 235000020004 porter Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• 239000011698 potassium fluoride Substances 0.000 description 1
• 235000003270 potassium fluoride Nutrition 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 238000003825 pressing Methods 0.000 description 1
• 208000037920 primary disease Diseases 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• NDRLPYIMWROJBG-UHFFFAOYSA-M pyridin-1-ium-1-amine;iodide Chemical compound [I-].N[N+]1=CC=CC=C1 NDRLPYIMWROJBG-UHFFFAOYSA-M 0.000 description 1
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• YFQLHYLNOMNMMW-UHFFFAOYSA-N pyrrolidine-1-carboximidamide;sulfuric acid Chemical compound OS(O)(=O)=O.NC(=N)N1CCCC1 YFQLHYLNOMNMMW-UHFFFAOYSA-N 0.000 description 1
• 230000007420 reactivation Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 235000019515 salmon Nutrition 0.000 description 1
• 102000012498 secondary active transmembrane transporter activity proteins Human genes 0.000 description 1
• 108040003878 secondary active transmembrane transporter activity proteins Proteins 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 235000020374 simple syrup Nutrition 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229940080313 sodium starch Drugs 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 229940032147 starch Drugs 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005017 substituted alkenyl group Chemical group 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
• 208000008732 thymoma Diseases 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 125000005208 trialkylammonium group Chemical group 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
• LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 1
• UNEPXPMBVGDXGH-UHFFFAOYSA-N tributyl(pyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=NC=C1 UNEPXPMBVGDXGH-UHFFFAOYSA-N 0.000 description 1
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 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
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 125000004953 trihalomethyl group Chemical group 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 229940108442 valtrex Drugs 0.000 description 1
• 230000008016 vaporization Effects 0.000 description 1
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 244000052613 viral pathogen Species 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 239000007762 w/o emulsion Substances 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229960002555 zidovudine Drugs 0.000 description 1
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 229940107931 zovirax Drugs 0.000 description 1