AU2014278172B2 - Metalloenzyme inhibitor compounds - Google Patents
Metalloenzyme inhibitor compounds Download PDFInfo
- Publication number
- AU2014278172B2 AU2014278172B2 AU2014278172A AU2014278172A AU2014278172B2 AU 2014278172 B2 AU2014278172 B2 AU 2014278172B2 AU 2014278172 A AU2014278172 A AU 2014278172A AU 2014278172 A AU2014278172 A AU 2014278172A AU 2014278172 B2 AU2014278172 B2 AU 2014278172B2
- Authority
- AU
- Australia
- Prior art keywords
- optionally substituted
- difluoro
- ethynyl
- tetrazol
- pyridin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 285
- 229940125956 metalloenzyme inhibitor Drugs 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 123
- 238000000034 method Methods 0.000 claims abstract description 85
- 201000010099 disease Diseases 0.000 claims abstract description 67
- 208000035475 disorder Diseases 0.000 claims abstract description 55
- 230000000694 effects Effects 0.000 claims abstract description 30
- 125000001188 haloalkyl group Chemical group 0.000 claims description 180
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 164
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 156
- -1 -CH2CF2CF3 Chemical group 0.000 claims description 152
- 125000000217 alkyl group Chemical group 0.000 claims description 146
- 125000005843 halogen group Chemical group 0.000 claims description 111
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 107
- 125000001072 heteroaryl group Chemical group 0.000 claims description 96
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 82
- 125000003545 alkoxy group Chemical group 0.000 claims description 78
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 72
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 71
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 70
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 66
- 125000003107 substituted aryl group Chemical group 0.000 claims description 61
- 125000000623 heterocyclic group Chemical group 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 37
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 36
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 35
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 33
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- 125000001153 fluoro group Chemical group F* 0.000 claims description 29
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 29
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 22
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 22
- KWZYOTGGTDCHLM-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[2-[4-[[5-(trifluoromethyl)thiophen-2-yl]methoxy]phenyl]ethynyl]pyridin-2-yl]propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2SC(=CC=2)C(F)(F)F)=CC=1)(O)CN1C=NN=N1 KWZYOTGGTDCHLM-UHFFFAOYSA-N 0.000 claims description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 14
- 210000003169 central nervous system Anatomy 0.000 claims description 14
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 12
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 9
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 8
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 8
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 8
- MWJTXCAJFGPQPZ-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[(5-fluorothiophen-2-yl)methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2SC(F)=CC=2)=CC=1)(O)CN1C=NN=N1 MWJTXCAJFGPQPZ-UHFFFAOYSA-N 0.000 claims description 7
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 7
- 208000012931 Urologic disease Diseases 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 7
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 7
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 7
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
- 125000003368 amide group Chemical group 0.000 claims description 7
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 7
- 125000001769 aryl amino group Chemical group 0.000 claims description 7
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 7
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 125000005518 carboxamido group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 7
- 125000004986 diarylamino group Chemical group 0.000 claims description 7
- 208000010643 digestive system disease Diseases 0.000 claims description 7
- 208000016097 disease of metabolism Diseases 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 7
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 7
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
- 208000030159 metabolic disease Diseases 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 125000000858 thiocyanato group Chemical group *SC#N 0.000 claims description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 7
- 208000014001 urinary system disease Diseases 0.000 claims description 7
- HOOPTQYPCOZSOB-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(pyrazol-1-ylmethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3N=CC=C3)=CC=2)=CC=1)(O)CN1C=NN=N1 HOOPTQYPCOZSOB-UHFFFAOYSA-N 0.000 claims description 6
- 125000005094 alkyl carbonyl amino alkyl group Chemical group 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- ARADWGQKFCFEJC-UHFFFAOYSA-N 4-[2-[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]-2-oxoethyl]benzonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(=CC=1)C(=O)CC=1C=CC(=CC=1)C#N)(O)CN1C=NN=N1 ARADWGQKFCFEJC-UHFFFAOYSA-N 0.000 claims description 5
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- JDLIGMDIPUEOPH-UHFFFAOYSA-N n-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]acetamide Chemical compound C1=CC(CNC(=O)C)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 JDLIGMDIPUEOPH-UHFFFAOYSA-N 0.000 claims description 5
- LBSOYTIILZKBBF-UHFFFAOYSA-N 1-[5-[2-[4-[(4-chlorophenyl)-hydroxymethyl]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=CC=1C(O)C1=CC=C(Cl)C=C1 LBSOYTIILZKBBF-UHFFFAOYSA-N 0.000 claims description 4
- HZTPLXQVUPNTOW-UHFFFAOYSA-N 1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]pyrazole-4-carbonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3N=CC(=C3)C#N)=CC=2)=CC=1)(O)CN1C=NN=N1 HZTPLXQVUPNTOW-UHFFFAOYSA-N 0.000 claims description 4
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 claims description 4
- DOAOCQOFMHKDBN-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[1-hydroxy-2-(2,2,2-trifluoroethoxy)ethyl]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(C(COCC(F)(F)F)O)=CC=C1C#CC1=CC=C(C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)N=C1 DOAOCQOFMHKDBN-UHFFFAOYSA-N 0.000 claims description 4
- AITXUEMRKLKEAL-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(1-hydroxyethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(C(O)C)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 AITXUEMRKLKEAL-UHFFFAOYSA-N 0.000 claims description 4
- XHRXWJSVLIERAL-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(hydroxymethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(CO)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 XHRXWJSVLIERAL-UHFFFAOYSA-N 0.000 claims description 4
- WYOMUWIPXVJIQO-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3CCOCC3)=CC=2)=CC=1)(O)CN1C=NN=N1 WYOMUWIPXVJIQO-UHFFFAOYSA-N 0.000 claims description 4
- NLIRDJQZVTYAAB-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(pyrrolidin-1-ylmethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3CCCC3)=CC=2)=CC=1)(O)CN1C=NN=N1 NLIRDJQZVTYAAB-UHFFFAOYSA-N 0.000 claims description 4
- JUJDSXNXSGENHH-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[(1,3-oxazol-2-ylamino)methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CNC=3OC=CN=3)=CC=2)=CC=1)(O)CN1C=NN=N1 JUJDSXNXSGENHH-UHFFFAOYSA-N 0.000 claims description 4
- IAKDRXVYNVLKES-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[(4-fluoropyrazol-1-yl)methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3N=CC(F)=C3)=CC=2)=CC=1)(O)CN1C=NN=N1 IAKDRXVYNVLKES-UHFFFAOYSA-N 0.000 claims description 4
- WRAJGSYVOCAYCT-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[[4-(2-hydroxypropan-2-yl)pyrazol-1-yl]methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=C(C(C)(O)C)C=NN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 WRAJGSYVOCAYCT-UHFFFAOYSA-N 0.000 claims description 4
- VBRIDLUYWZVABY-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[[4-(2-methoxyethyl)pyrazol-1-yl]methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=C(CCOC)C=NN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 VBRIDLUYWZVABY-UHFFFAOYSA-N 0.000 claims description 4
- NWHWQSRZKIFCTF-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[2-[4-[[4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]propan-2-ol Chemical compound C1=CC(C(O)C(F)(F)F)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 NWHWQSRZKIFCTF-UHFFFAOYSA-N 0.000 claims description 4
- JSLLQSWHQWTAQR-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[2-[4-[[4-(2,2,2-trifluoroethoxymethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(COCC(F)(F)F)=CC=2)=CC=1)(O)CN1C=NN=N1 JSLLQSWHQWTAQR-UHFFFAOYSA-N 0.000 claims description 4
- FCKZXSSBYARFPX-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[2-[4-[[4-[(2,2,2-trifluoroethylamino)methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CNCC(F)(F)F)=CC=2)=CC=1)(O)CN1C=NN=N1 FCKZXSSBYARFPX-UHFFFAOYSA-N 0.000 claims description 4
- NKYSEDLJBNZIFT-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound OC(Cn1cnnn1)(C(F)F)c1ccc(F)cc1F NKYSEDLJBNZIFT-UHFFFAOYSA-N 0.000 claims description 4
- LUOXUHROCRVTTE-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1-[5-[2-[4-[[3-[1-(dimethylamino)-2-hydroxyethyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound CN(C)C(CO)C1=CC=CC(COC=2C=CC(=CC=2)C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)=C1 LUOXUHROCRVTTE-UHFFFAOYSA-N 0.000 claims description 4
- QXRBUKMCPDVWEJ-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1-[5-[2-[4-[[4-[(dimethylamino)methyl]-3-fluorophenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=C(F)C(CN(C)C)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 QXRBUKMCPDVWEJ-UHFFFAOYSA-N 0.000 claims description 4
- CHWQBIXLDCSMPI-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1-[5-[2-[4-[[4-[1-(dimethylamino)-2-hydroxyethyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(C(CO)N(C)C)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 CHWQBIXLDCSMPI-UHFFFAOYSA-N 0.000 claims description 4
- SJSHIOIEIZPUGH-UHFFFAOYSA-N 2-[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 SJSHIOIEIZPUGH-UHFFFAOYSA-N 0.000 claims description 4
- RVUBTWDXFKGEDI-UHFFFAOYSA-N 2-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methoxy]acetonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(COCC#N)=CC=2)=CC=1)(O)CN1C=NN=N1 RVUBTWDXFKGEDI-UHFFFAOYSA-N 0.000 claims description 4
- ZIRBHNQVPBFJGX-UHFFFAOYSA-N 2-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl-methylamino]acetonitrile Chemical compound C1=CC(CN(CC#N)C)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 ZIRBHNQVPBFJGX-UHFFFAOYSA-N 0.000 claims description 4
- MVZCVVSHSKSALL-UHFFFAOYSA-N 2-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methylamino]acetonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CNCC#N)=CC=2)=CC=1)(O)CN1C=NN=N1 MVZCVVSHSKSALL-UHFFFAOYSA-N 0.000 claims description 4
- XRQUQRDHBTZOTA-UHFFFAOYSA-N 4-[2-[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]-2-oxoethyl]-2-fluorobenzonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(=CC=1)C(=O)CC=1C=C(F)C(C#N)=CC=1)(O)CN1C=NN=N1 XRQUQRDHBTZOTA-UHFFFAOYSA-N 0.000 claims description 4
- WCFRYQVKVKWSBK-ZTPFDXHGSA-N 4-[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]-2-[(3s)-2-methylpentan-3-yl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C(C)C)CC)N=CN1C(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 WCFRYQVKVKWSBK-ZTPFDXHGSA-N 0.000 claims description 4
- VLGODEJAXGCYGP-UHFFFAOYSA-N 4-[[4-[2-[6-[1,1-difluoro-2-hydroxy-3,3-dimethyl-2-(tetrazol-1-ylmethyl)butyl]pyridin-3-yl]ethynyl]phenoxy]methyl]benzonitrile Chemical compound C=1C=C(C#CC=2C=CC(OCC=3C=CC(=CC=3)C#N)=CC=2)C=NC=1C(F)(F)C(O)(C(C)(C)C)CN1C=NN=N1 VLGODEJAXGCYGP-UHFFFAOYSA-N 0.000 claims description 4
- SQNBTVHAPBTFQH-UHFFFAOYSA-N 4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]methylamino]benzonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(CNC=2C=CC(=CC=2)C#N)=CC=1)(O)CN1C=NN=N1 SQNBTVHAPBTFQH-UHFFFAOYSA-N 0.000 claims description 4
- OGUQOXDWJWGPNU-UHFFFAOYSA-N 4-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]piperazine-1-carbaldehyde Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3CCN(CC3)C=O)=CC=2)=CC=1)(O)CN1C=NN=N1 OGUQOXDWJWGPNU-UHFFFAOYSA-N 0.000 claims description 4
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
- 230000001028 anti-proliverative effect Effects 0.000 claims description 4
- 239000003429 antifungal agent Substances 0.000 claims description 4
- 229940121375 antifungal agent Drugs 0.000 claims description 4
- 239000002327 cardiovascular agent Substances 0.000 claims description 4
- 229940125692 cardiovascular agent Drugs 0.000 claims description 4
- 239000002254 cytotoxic agent Substances 0.000 claims description 4
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- SMMCQBIZVOEZER-UHFFFAOYSA-N 1-[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]-2-[4-[(dimethylamino)methyl]phenyl]ethanone Chemical compound C1=CC(CN(C)C)=CC=C1CC(=O)C1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 SMMCQBIZVOEZER-UHFFFAOYSA-N 0.000 claims 2
- KZYVQWCFDFYFPI-UHFFFAOYSA-N 1-[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]-3,3,4,4,4-pentafluorobutan-1-ol Chemical compound C1=CC(C(CC(F)(F)C(F)(F)F)O)=CC=C1C#CC1=CC=C(C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)N=C1 KZYVQWCFDFYFPI-UHFFFAOYSA-N 0.000 claims 2
- YVEPNCOUVHVTRI-UHFFFAOYSA-N 1-[5-[2-[4-(1-amino-2,2,3,3,3-pentafluoropropyl)phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(C(N)C(F)(F)C(F)(F)F)=CC=C1C#CC1=CC=C(C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)N=C1 YVEPNCOUVHVTRI-UHFFFAOYSA-N 0.000 claims 2
- ZPQOYWREYJYVGJ-UHFFFAOYSA-N 1-[5-[2-[4-[[4-(2,2-difluoroethoxymethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(COCC(F)F)=CC=2)=CC=1)(O)CN1C=NN=N1 ZPQOYWREYJYVGJ-UHFFFAOYSA-N 0.000 claims 2
- XTVWQCSKCZRFRG-UHFFFAOYSA-N 1-[5-[2-[4-[[4-[(4-chloropyrazol-1-yl)methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3N=CC(Cl)=C3)=CC=2)=CC=1)(O)CN1C=NN=N1 XTVWQCSKCZRFRG-UHFFFAOYSA-N 0.000 claims 2
- BOUTUNMDQCCCRD-UHFFFAOYSA-N 1-[5-[2-[4-[[4-[[(2,2-difluoro-2-hydroxyethyl)-methylamino]methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(CN(C)CC(O)(F)F)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 BOUTUNMDQCCCRD-UHFFFAOYSA-N 0.000 claims 2
- FZRQVQHHWAVKSV-UHFFFAOYSA-N 1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]imidazole-4-carbonitrile Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3C=C(N=C3)C#N)=CC=2)=CC=1)(O)CN1C=NN=N1 FZRQVQHHWAVKSV-UHFFFAOYSA-N 0.000 claims 2
- OCZZKEGNBSNPHG-UHFFFAOYSA-N 1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]imidazolidin-2-one Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3C(NCC3)=O)=CC=2)=CC=1)(O)CN1C=NN=N1 OCZZKEGNBSNPHG-UHFFFAOYSA-N 0.000 claims 2
- GLYQAYBJYAWJRP-UHFFFAOYSA-N 1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]imidazolidine-2,4-dione Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CN3C(NC(=O)C3)=O)=CC=2)=CC=1)(O)CN1C=NN=N1 GLYQAYBJYAWJRP-UHFFFAOYSA-N 0.000 claims 2
- LBUIJCLOWMDZHP-UHFFFAOYSA-N 1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 LBUIJCLOWMDZHP-UHFFFAOYSA-N 0.000 claims 2
- RLEFSFNZLWQOTH-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[(4-fluoroanilino)methyl]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(CNC=2C=CC(F)=CC=2)=CC=1)(O)CN1C=NN=N1 RLEFSFNZLWQOTH-UHFFFAOYSA-N 0.000 claims 2
- ZYUITBYGDUFXKH-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[3-fluoro-4-(pyrazol-1-ylmethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=C(F)C(CN3N=CC=C3)=CC=2)=CC=1)(O)CN1C=NN=N1 ZYUITBYGDUFXKH-UHFFFAOYSA-N 0.000 claims 2
- NQQMNLGFIBGSLS-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(1-pyrazol-1-ylethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC=NN1C(C)C(C=C1)=CC=C1COC(C=C1)=CC=C1C#CC(C=N1)=CC=C1C(F)(F)C(O)(C=1C(=CC(F)=CC=1)F)CN1C=NN=N1 NQQMNLGFIBGSLS-UHFFFAOYSA-N 0.000 claims 2
- LZGNMBWRNHSPDA-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[(4-methylpiperazin-1-yl)methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1CN(C)CCN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 LZGNMBWRNHSPDA-UHFFFAOYSA-N 0.000 claims 2
- CKTUOEAWMAINCF-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[[4-(1-hydroxyethyl)pyrazol-1-yl]methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=C(C(O)C)C=NN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 CKTUOEAWMAINCF-UHFFFAOYSA-N 0.000 claims 2
- SCUQVDYZPFVKML-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[5-(pyrazol-1-ylmethyl)thiophen-2-yl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2SC(CN3N=CC=C3)=CC=2)=CC=1)(O)CN1C=NN=N1 SCUQVDYZPFVKML-UHFFFAOYSA-N 0.000 claims 2
- YBYCSFLMHWCJJG-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[2-[4-[(2,2,2-trifluoroethylamino)methyl]phenyl]ethynyl]pyridin-2-yl]propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(CNCC(F)(F)F)=CC=1)(O)CN1C=NN=N1 YBYCSFLMHWCJJG-UHFFFAOYSA-N 0.000 claims 2
- QRVHDITUOJTQBQ-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1-[5-[2-[4-[3-(dimethylamino)-2,2-difluoro-1-hydroxypropyl]phenyl]ethynyl]pyridin-2-yl]-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(C(O)C(F)(F)CN(C)C)=CC=C1C#CC1=CC=C(C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)N=C1 QRVHDITUOJTQBQ-UHFFFAOYSA-N 0.000 claims 2
- OVXLGWLWBGSWHC-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1-[5-[2-[4-[[5-[(dimethylamino)methyl]thiophen-2-yl]methoxy]phenyl]ethynyl]pyridin-2-yl]-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound S1C(CN(C)C)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 OVXLGWLWBGSWHC-UHFFFAOYSA-N 0.000 claims 2
- GBNPFBHERKIOIZ-UHFFFAOYSA-N 2-(4-chloro-3-fluorophenyl)-1-[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]ethanone Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(=CC=1)C(=O)CC=1C=C(F)C(Cl)=CC=1)(O)CN1C=NN=N1 GBNPFBHERKIOIZ-UHFFFAOYSA-N 0.000 claims 2
- HWIKDRHCOWNVKK-UHFFFAOYSA-N 2-[[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methylamino]methyl]imidazole-1-carbaldehyde Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=CC(CNCC=3N(C=CN=3)C=O)=CC=2)=CC=1)(O)CN1C=NN=N1 HWIKDRHCOWNVKK-UHFFFAOYSA-N 0.000 claims 2
- NFXRVNNWRDKZDL-UHFFFAOYSA-N n-[[1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]pyrazol-3-yl]methyl]acetamide Chemical compound N1=C(CNC(=O)C)C=CN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 NFXRVNNWRDKZDL-UHFFFAOYSA-N 0.000 claims 2
- YYFWRLMSEPEZEN-UHFFFAOYSA-N 1-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl]-n-methylimidazole-2-carboxamide Chemical compound CNC(=O)C1=NC=CN1CC(C=C1)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 YYFWRLMSEPEZEN-UHFFFAOYSA-N 0.000 claims 1
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 abstract description 19
- 208000024891 symptom Diseases 0.000 abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 239000012071 phase Substances 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- 239000000651 prodrug Substances 0.000 description 34
- 229940002612 prodrug Drugs 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 238000011282 treatment Methods 0.000 description 27
- 239000008194 pharmaceutical composition Substances 0.000 description 20
- 241000196324 Embryophyta Species 0.000 description 19
- 239000012453 solvate Substances 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- 230000003993 interaction Effects 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000000463 material Substances 0.000 description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 229910052751 metal Inorganic materials 0.000 description 12
- 239000002184 metal Substances 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 11
- 239000000839 emulsion Substances 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- 241000222122 Candida albicans Species 0.000 description 10
- 230000008901 benefit Effects 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 230000007423 decrease Effects 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 125000006809 haloalkylaminocarbonyl group Chemical group 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 0 CC1=CC=C**1 Chemical compound CC1=CC=C**1 0.000 description 7
- 208000031888 Mycoses Diseases 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 description 7
- 235000012054 meals Nutrition 0.000 description 7
- 230000000069 prophylactic effect Effects 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 206010017533 Fungal infection Diseases 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 125000004995 haloalkylthio group Chemical group 0.000 description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- 230000003405 preventing effect Effects 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 125000001544 thienyl group Chemical group 0.000 description 6
- LOWZLAYIYJVTAA-UHFFFAOYSA-N 1-[5-[2-[4-[[4-(aminomethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(CN)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 LOWZLAYIYJVTAA-UHFFFAOYSA-N 0.000 description 5
- 241001225321 Aspergillus fumigatus Species 0.000 description 5
- 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 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000005907 alkyl ester group Chemical group 0.000 description 5
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 5
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 235000013311 vegetables Nutrition 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 239000000080 wetting agent Substances 0.000 description 5
- GSKAYKHMBWJMNV-UHFFFAOYSA-N 1-[5-[2-[4-[(4-chloroanilino)methyl]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(CNC=2C=CC(Cl)=CC=2)=CC=1)(O)CN1C=NN=N1 GSKAYKHMBWJMNV-UHFFFAOYSA-N 0.000 description 4
- TZRGXDCDWCSASW-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[3-(pyrazol-1-ylmethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2C=C(CN3N=CC=C3)C=CC=2)=CC=1)(O)CN1C=NN=N1 TZRGXDCDWCSASW-UHFFFAOYSA-N 0.000 description 4
- LHFUJMHGAGAHJA-UHFFFAOYSA-N 2-[6-[[2-(2,4-difluorophenyl)oxiran-2-yl]-difluoromethyl]pyridin-3-yl]ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#Cc1ccc(nc1)C(F)(F)C1(CO1)c1ccc(F)cc1F LHFUJMHGAGAHJA-UHFFFAOYSA-N 0.000 description 4
- KXMKOCYJUSCCCZ-UHFFFAOYSA-N 2-[[2-(2,4-difluorophenyl)oxiran-2-yl]-difluoromethyl]-5-ethynylpyridine Chemical compound FC1=CC(F)=CC=C1C1(C(F)(F)C=2N=CC(=CC=2)C#C)OC1 KXMKOCYJUSCCCZ-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 241001522757 Coccidioides posadasii Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 125000002541 furyl group Chemical group 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003094 microcapsule Substances 0.000 description 4
- 125000002971 oxazolyl group Chemical group 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 4
- PMUXIMRQLVTGNV-UHFFFAOYSA-N 2-[[2-(2,4-difluorophenyl)oxiran-2-yl]-difluoromethyl]-5-[2-[4-[[4-(pyrazol-1-ylmethyl)phenyl]methoxy]phenyl]ethynyl]pyridine Chemical compound Fc1ccc(c(F)c1)C1(CO1)C(F)(F)c1ccc(cn1)C#Cc1ccc(OCc2ccc(Cn3cccn3)cc2)cc1 PMUXIMRQLVTGNV-UHFFFAOYSA-N 0.000 description 3
- FAUXJAGOYAFCKE-UHFFFAOYSA-N 5-bromo-2-[[2-(2,4-difluorophenyl)oxiran-2-yl]-difluoromethyl]pyridine Chemical compound FC1=CC(F)=CC=C1C1(C(F)(F)C=2N=CC(Br)=CC=2)OC1 FAUXJAGOYAFCKE-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000017667 Chronic Disease Diseases 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 241000221204 Cryptococcus neoformans Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 244000286779 Hansenula anomala Species 0.000 description 3
- 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 3
- 241001465754 Metazoa Species 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 3
- 108010074633 Mixed Function Oxygenases Proteins 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
- 229920002472 Starch Polymers 0.000 description 3
- KGVHHYKBXOWVKG-UHFFFAOYSA-N [4-[(4-bromophenoxy)methyl]phenyl]methanol Chemical compound OCc1ccc(COc2ccc(Br)cc2)cc1 KGVHHYKBXOWVKG-UHFFFAOYSA-N 0.000 description 3
- WQXAJDIWFKJHRB-UHFFFAOYSA-N [4-[(4-bromophenoxy)methyl]phenyl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCc1ccc(COc2ccc(Br)cc2)cc1 WQXAJDIWFKJHRB-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000011162 core material Substances 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 3
- 229960004884 fluconazole Drugs 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- 239000007789 gas Substances 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
- 239000008103 glucose Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000099 in vitro assay Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229960001375 lactose Drugs 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 125000006574 non-aromatic ring group Chemical group 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 125000003831 tetrazolyl group Chemical group 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 3
- 229960004740 voriconazole Drugs 0.000 description 3
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 2
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 2
- CVGUUIPPPGQTET-UHFFFAOYSA-N 1-[5-[2-[4-[(5-chlorothiophen-2-yl)methoxy]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(OCC=2SC(Cl)=CC=2)=CC=1)(O)CN1C=NN=N1 CVGUUIPPPGQTET-UHFFFAOYSA-N 0.000 description 2
- HOBLEQIKYHAQKE-UHFFFAOYSA-N 1-[5-[2-[4-[2-(4-chlorophenyl)-1-hydroxyethyl]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=CC=1C(O)CC1=CC=C(Cl)C=C1 HOBLEQIKYHAQKE-UHFFFAOYSA-N 0.000 description 2
- VETPSPBJHXUMIP-UHFFFAOYSA-N 1-[5-[2-[4-[[4-(difluoromethyl)anilino]methyl]phenyl]ethynyl]pyridin-2-yl]-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)propan-2-ol Chemical compound C=1C=C(F)C=C(F)C=1C(C(F)(F)C=1N=CC(=CC=1)C#CC=1C=CC(CNC=2C=CC(=CC=2)C(F)F)=CC=1)(O)CN1C=NN=N1 VETPSPBJHXUMIP-UHFFFAOYSA-N 0.000 description 2
- IKGMFUZVFADVCZ-UHFFFAOYSA-N 1-[[4-[(4-bromophenoxy)methyl]phenyl]methyl]pyrazole Chemical compound Brc1ccc(OCc2ccc(Cn3cccn3)cc2)cc1 IKGMFUZVFADVCZ-UHFFFAOYSA-N 0.000 description 2
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 2
- VWATUZNZBJTPFM-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[3-(2-hydroxy-1-pyrazol-1-ylethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC=NN1C(CO)C(C=1)=CC=CC=1COC(C=C1)=CC=C1C#CC(C=N1)=CC=C1C(F)(F)C(O)(C=1C(=CC(F)=CC=1)F)CN1C=NN=N1 VWATUZNZBJTPFM-UHFFFAOYSA-N 0.000 description 2
- YLXSANZVOQOJLH-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[3-(hydroxymethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound OCC1=CC=CC(COC=2C=CC(=CC=2)C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)=C1 YLXSANZVOQOJLH-UHFFFAOYSA-N 0.000 description 2
- VWAFBNSPCIVRMV-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(2-hydroxy-1-pyrazol-1-ylethyl)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC=NN1C(CO)C(C=C1)=CC=C1COC(C=C1)=CC=C1C#CC(C=N1)=CC=C1C(F)(F)C(O)(C=1C(=CC(F)=CC=1)F)CN1C=NN=N1 VWAFBNSPCIVRMV-UHFFFAOYSA-N 0.000 description 2
- NNAUSMHNTWRFRS-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-(2-hydroxyethoxy)phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound C1=CC(OCCO)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 NNAUSMHNTWRFRS-UHFFFAOYSA-N 0.000 description 2
- ZLOQRYFBROYSOO-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-1,1-difluoro-1-[5-[2-[4-[[4-[[methyl(1,3-oxazol-2-yl)amino]methyl]phenyl]methoxy]phenyl]ethynyl]pyridin-2-yl]-3-(tetrazol-1-yl)propan-2-ol Chemical compound N=1C=COC=1N(C)CC(C=C1)=CC=C1COC(C=C1)=CC=C1C#CC(C=N1)=CC=C1C(F)(F)C(O)(C=1C(=CC(F)=CC=1)F)CN1C=NN=N1 ZLOQRYFBROYSOO-UHFFFAOYSA-N 0.000 description 2
- CCHVWLHUMXFPQA-UHFFFAOYSA-N 2-[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methylamino]acetic acid Chemical compound C1=CC(CNCC(=O)O)=CC=C1COC1=CC=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=C1 CCHVWLHUMXFPQA-UHFFFAOYSA-N 0.000 description 2
- ICKOFPONQMXURI-UHFFFAOYSA-N 2-[[[4-[[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenoxy]methyl]phenyl]methyl-methylamino]methyl]imidazole-1-carbaldehyde Chemical compound C=1C=C(COC=2C=CC(=CC=2)C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=CC=1CN(C)CC1=NC=CN1C=O ICKOFPONQMXURI-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 2
- PVOMSYLWVYURPF-UHFFFAOYSA-N 4-[(4-bromophenoxy)methyl]benzaldehyde Chemical compound Brc1ccc(OCc2ccc(C=O)cc2)cc1 PVOMSYLWVYURPF-UHFFFAOYSA-N 0.000 description 2
- SIXSXFAFKVJVJE-UHFFFAOYSA-N 4-[2-[4-[2-[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(tetrazol-1-yl)propyl]pyridin-3-yl]ethynyl]phenyl]-2-hydroxyethyl]benzonitrile Chemical compound C=1C=C(C#CC=2C=NC(=CC=2)C(F)(F)C(O)(CN2N=NN=C2)C=2C(=CC(F)=CC=2)F)C=CC=1C(O)CC1=CC=C(C#N)C=C1 SIXSXFAFKVJVJE-UHFFFAOYSA-N 0.000 description 2
- 108091007505 ADAM17 Proteins 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 102100029361 Aromatase Human genes 0.000 description 2
- 108010078554 Aromatase Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010005098 Blastomycosis Diseases 0.000 description 2
- 240000002791 Brassica napus Species 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- PAPNRQCYSFBWDI-UHFFFAOYSA-N Cc1ccc(C)[nH]1 Chemical compound Cc1ccc(C)[nH]1 PAPNRQCYSFBWDI-UHFFFAOYSA-N 0.000 description 2
- 241000223205 Coccidioides immitis Species 0.000 description 2
- 201000007336 Cryptococcosis Diseases 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 108010009911 Cytochrome P-450 CYP11B2 Proteins 0.000 description 2
- 102100024329 Cytochrome P450 11B2, mitochondrial Human genes 0.000 description 2
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 2
- 235000014683 Hansenula anomala Nutrition 0.000 description 2
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 2
- 206010020751 Hypersensitivity 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
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 2
- 102100021695 Lanosterol 14-alpha demethylase Human genes 0.000 description 2
- 101710146773 Lanosterol 14-alpha demethylase Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100027159 Membrane primary amine oxidase Human genes 0.000 description 2
- 101710132836 Membrane primary amine oxidase Proteins 0.000 description 2
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 2
- 241000235048 Meyerozyma guilliermondii Species 0.000 description 2
- 241000893980 Microsporum canis Species 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 241000893974 Nannizzia fulva Species 0.000 description 2
- 241000893976 Nannizzia gypsea Species 0.000 description 2
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 2
- 208000010195 Onychomycosis Diseases 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 241000235645 Pichia kudriavzevii Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000497386 Silveira Species 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 244000062793 Sorghum vulgare Species 0.000 description 2
- 108010015330 Steroid 17-alpha-Hydroxylase Proteins 0.000 description 2
- 102000001854 Steroid 17-alpha-Hydroxylase Human genes 0.000 description 2
- 208000002474 Tinea Diseases 0.000 description 2
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 2
- 241000223104 Trypanosoma Species 0.000 description 2
- XNPNERJNCVQGTH-UHFFFAOYSA-N [SnH3]C#[C-] Chemical compound [SnH3]C#[C-] XNPNERJNCVQGTH-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229940095731 candida albicans Drugs 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000004927 clay Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- VDQVEACBQKUUSU-UHFFFAOYSA-M disodium;sulfanide Chemical compound [Na+].[Na+].[SH-] VDQVEACBQKUUSU-UHFFFAOYSA-M 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010410 dusting Methods 0.000 description 2
- 150000002118 epoxides Chemical class 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 238000000185 intracerebroventricular administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229940058690 lanosterol Drugs 0.000 description 2
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 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 2
- 239000002245 particle Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 229910052979 sodium sulfide Inorganic materials 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 201000005882 tinea unguium Diseases 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- YINHBOOQLSMMSR-UHFFFAOYSA-N tributyl-[2-[6-[[2-(2,4-difluorophenyl)oxiran-2-yl]-difluoromethyl]pyridin-3-yl]ethynyl]stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#Cc1ccc(nc1)C(F)(F)C1(CO1)c1ccc(F)cc1F YINHBOOQLSMMSR-UHFFFAOYSA-N 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- SYYSBZOSEAUMEY-UHFFFAOYSA-N 1,1,1-trifluoro-2-$l^{1}-sulfanylethane Chemical group FC(F)(F)C[S] SYYSBZOSEAUMEY-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- 102100027518 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Human genes 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- RKWWASUTWAFKHA-UHFFFAOYSA-N 1-bromo-2,3-difluorobenzene Chemical compound FC1=CC=CC(Br)=C1F RKWWASUTWAFKHA-UHFFFAOYSA-N 0.000 description 1
- MGHBDQZXPCTTIH-UHFFFAOYSA-N 1-bromo-2,4-difluorobenzene Chemical compound FC1=CC=C(Br)C(F)=C1 MGHBDQZXPCTTIH-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 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
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- PZJFUNZDCRKXPZ-UHFFFAOYSA-N 2,5-dihydro-1h-tetrazole Chemical class C1NNN=N1 PZJFUNZDCRKXPZ-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- BEGLXWWZKKYVHR-UHFFFAOYSA-N 2-(5-bromopyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoroethanone Chemical compound FC1=CC(F)=CC=C1C(=O)C(F)(F)C1=CC=C(Br)C=N1 BEGLXWWZKKYVHR-UHFFFAOYSA-N 0.000 description 1
- QZDDFQLIQRYMBV-UHFFFAOYSA-N 2-[3-nitro-2-(2-nitrophenyl)-4-oxochromen-8-yl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(C=2[N+]([O-])=O)=O)=C1OC=2C1=CC=CC=C1[N+]([O-])=O QZDDFQLIQRYMBV-UHFFFAOYSA-N 0.000 description 1
- XYPVBKDHERGKJG-UHFFFAOYSA-N 4-(bromomethyl)benzaldehyde Chemical compound BrCC1=CC=C(C=O)C=C1 XYPVBKDHERGKJG-UHFFFAOYSA-N 0.000 description 1
- 108010060511 4-Aminobutyrate Transaminase Proteins 0.000 description 1
- 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- 102100028626 4-hydroxyphenylpyruvate dioxygenase Human genes 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 241000191412 Alternaria infectoria Species 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 102100022749 Aminopeptidase N Human genes 0.000 description 1
- 102000001921 Aminopeptidase P Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 241000702021 Aridarum minimum Species 0.000 description 1
- 241000893451 Arthroderma Species 0.000 description 1
- 201000002909 Aspergillosis Diseases 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000228197 Aspergillus flavus Species 0.000 description 1
- 208000036641 Aspergillus infections Diseases 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 241000209763 Avena sativa Species 0.000 description 1
- 235000007558 Avena sp Nutrition 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000228405 Blastomyces dermatitidis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000011293 Brassica napus Nutrition 0.000 description 1
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000079253 Byssochlamys spectabilis Species 0.000 description 1
- UQHCUZNDSRDFAQ-UHFFFAOYSA-N CC#Cc1ccc(C(C2(c(ccc(F)c3)c3F)OC2)(F)F)nc1 Chemical compound CC#Cc1ccc(C(C2(c(ccc(F)c3)c3F)OC2)(F)F)nc1 UQHCUZNDSRDFAQ-UHFFFAOYSA-N 0.000 description 1
- 108010049990 CD13 Antigens Proteins 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 241000222173 Candida parapsilosis Species 0.000 description 1
- 241000222178 Candida tropicalis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000003846 Carbonic anhydrases Human genes 0.000 description 1
- 108090000209 Carbonic anhydrases Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 1
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 1
- 208000024699 Chagas disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008803 Chromoblastomycosis Diseases 0.000 description 1
- 208000015116 Chromomycosis Diseases 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 241001668502 Cladophialophora carrionii Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 240000009226 Corylus americana Species 0.000 description 1
- 235000001543 Corylus americana Nutrition 0.000 description 1
- 235000007466 Corylus avellana Nutrition 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 244000168525 Croton tiglium Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 241000667819 Cunninghamella sp. Species 0.000 description 1
- 241000223233 Cutaneotrichosporon cutaneum Species 0.000 description 1
- 241001634927 Cutaneotrichosporon mucoides Species 0.000 description 1
- 235000005853 Cyperus esculentus Nutrition 0.000 description 1
- 244000285774 Cyperus esculentus Species 0.000 description 1
- 102100039282 Cytochrome P450 26A1 Human genes 0.000 description 1
- 102100036194 Cytochrome P450 2A6 Human genes 0.000 description 1
- 101710101909 Cytochrome P450 2A6 Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020003338 D-alanine-D-alanine ligase Proteins 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 description 1
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 description 1
- 244000133098 Echinacea angustifolia Species 0.000 description 1
- 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 1
- 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241001480036 Epidermophyton floccosum Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241000248325 Exophiala dermatitidis Species 0.000 description 1
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 1
- 240000008620 Fagopyrum esculentum Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000122864 Fonsecaea pedrosoi Species 0.000 description 1
- 208000014260 Fungal keratitis Diseases 0.000 description 1
- 241000427940 Fusarium solani Species 0.000 description 1
- 244000168141 Geotrichum candidum Species 0.000 description 1
- 235000017388 Geotrichum candidum Nutrition 0.000 description 1
- 108090000369 Glutamate Carboxypeptidase II Proteins 0.000 description 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 229930189936 Glyoxalase Natural products 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 108010002459 HIV Integrase Proteins 0.000 description 1
- 108050006318 Haem oxygenases Proteins 0.000 description 1
- 102000016761 Haem oxygenases Human genes 0.000 description 1
- 244000020551 Helianthus annuus Species 0.000 description 1
- 235000003222 Helianthus annuus Nutrition 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 241000228402 Histoplasma Species 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000861278 Homo sapiens 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Proteins 0.000 description 1
- 101000745891 Homo sapiens Cytochrome P450 26A1 Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 241000308509 Hortaea Species 0.000 description 1
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 108010036012 Iodide peroxidase Proteins 0.000 description 1
- 102000029793 Isoleucine-tRNA ligase Human genes 0.000 description 1
- 108700040464 Isoleucine-tRNA ligases Proteins 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- 206010062353 Keratitis fungal Diseases 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 description 1
- 241000144128 Lichtheimia corymbifera Species 0.000 description 1
- 235000019738 Limestone Nutrition 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 241001444195 Madurella Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241000555688 Malassezia furfur Species 0.000 description 1
- 241001291474 Malassezia globosa Species 0.000 description 1
- 241001291472 Malassezia obtusa Species 0.000 description 1
- 241001299738 Malassezia pachydermatis Species 0.000 description 1
- 241001291477 Malassezia restricta Species 0.000 description 1
- 241001291475 Malassezia slooffiae Species 0.000 description 1
- 241001291478 Malassezia sympodialis Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 240000004658 Medicago sativa Species 0.000 description 1
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 101000859568 Methanobrevibacter smithii (strain ATCC 35061 / DSM 861 / OCM 144 / PS) Carbamoyl-phosphate synthase Proteins 0.000 description 1
- 101710181812 Methionine aminopeptidase Proteins 0.000 description 1
- 102100023174 Methionine aminopeptidase 2 Human genes 0.000 description 1
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 241000306281 Mucor ambiguus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000526686 Paracoccidioides brasiliensis Species 0.000 description 1
- 206010033767 Paracoccidioides infections Diseases 0.000 description 1
- 201000000301 Paracoccidioidomycosis Diseases 0.000 description 1
- 235000010678 Paulownia tomentosa Nutrition 0.000 description 1
- 240000002834 Paulownia tomentosa Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010026809 Peptide deformylase Proteins 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 208000031956 Phaehyphomycosis Diseases 0.000 description 1
- 201000011404 Phaeohyphomycosis Diseases 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002396 Polyurea Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108010031852 Pyruvate Synthase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000004364 Rhinosporidiosis Diseases 0.000 description 1
- 240000005384 Rhizopus oryzae Species 0.000 description 1
- 235000013752 Rhizopus oryzae Nutrition 0.000 description 1
- 241000223254 Rhodotorula mucilaginosa Species 0.000 description 1
- 102000028649 Ribonucleoside-diphosphate reductase Human genes 0.000 description 1
- 108010038105 Ribonucleoside-diphosphate reductase Proteins 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 241000132889 Scedosporium Species 0.000 description 1
- 241000223598 Scedosporium boydii Species 0.000 description 1
- 241000222481 Schizophyllum commune Species 0.000 description 1
- 241000209056 Secale Species 0.000 description 1
- 235000007238 Secale cereale Nutrition 0.000 description 1
- 240000003705 Senecio vulgaris Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 244000040738 Sesamum orientale Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
- 235000019764 Soybean Meal Nutrition 0.000 description 1
- 241001149963 Sporothrix schenckii Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241001523006 Talaromyces marneffei Species 0.000 description 1
- 240000006474 Theobroma bicolor Species 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 102000014267 Thyroid peroxidases Human genes 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 241000130764 Tinea Species 0.000 description 1
- 206010056131 Tinea versicolour Diseases 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
- 241000893969 Trichophyton benhamiae Species 0.000 description 1
- 241000223229 Trichophyton rubrum Species 0.000 description 1
- 241000893966 Trichophyton verrucosum Species 0.000 description 1
- 241001480050 Trichophyton violaceum Species 0.000 description 1
- 241001634961 Trichosporon asahii Species 0.000 description 1
- 241001634942 Trichosporon inkin Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 241000223109 Trypanosoma cruzi Species 0.000 description 1
- 102000010861 Type 3 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037543 Type 3 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 235000019752 Wheat Middilings Nutrition 0.000 description 1
- 108010038900 X-Pro aminopeptidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 206010061418 Zygomycosis Diseases 0.000 description 1
- 241000222126 [Candida] glabrata Species 0.000 description 1
- 241001231403 [Nectria] haematococca Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 1
- 125000005015 aryl alkynyl group Chemical group 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 229940091771 aspergillus fumigatus Drugs 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 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
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 208000032343 candida glabrata infection Diseases 0.000 description 1
- 229940055022 candida parapsilosis Drugs 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 239000000828 canola oil Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000004464 cereal grain Substances 0.000 description 1
- 238000009614 chemical analysis method Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229910052570 clay Inorganic materials 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 201000003486 coccidioidomycosis Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229940097362 cyclodextrins Drugs 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
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 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
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000010459 dolomite Substances 0.000 description 1
- 229910000514 dolomite Inorganic materials 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000014134 echinacea Nutrition 0.000 description 1
- 238000004924 electrostatic deposition Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- IRSJDVYTJUCXRV-UHFFFAOYSA-N ethyl 2-bromo-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Br IRSJDVYTJUCXRV-UHFFFAOYSA-N 0.000 description 1
- ASMQVZDBWOTSAV-UHFFFAOYSA-N ethynyl-dimethyl-(trimethylsilylmethyl)silane Chemical compound C[Si](C)(C)C[Si](C)(C)C#[C-] ASMQVZDBWOTSAV-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000004426 flaxseed Nutrition 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 102000003642 glutaminyl-peptide cyclotransferase Human genes 0.000 description 1
- 108010081484 glutaminyl-peptide cyclotransferase Proteins 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940087559 grape seed Drugs 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000005191 hydroxyalkylamino group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 1
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007130 inorganic reaction Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 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
- 230000001788 irregular Effects 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 108010072713 leukotriene A4 hydrolase Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 239000006028 limestone Substances 0.000 description 1
- 201000006506 lobomycosis Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000005226 mechanical processes and functions Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 235000019713 millet Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000007524 mucormycosis Diseases 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 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
- 239000002088 nanocapsule Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000010451 perlite Substances 0.000 description 1
- 235000019362 perlite Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000013772 propylene glycol 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
- 235000019833 protease Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 229910052903 pyrophyllite Inorganic materials 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- VEMKTZHHVJILDY-UHFFFAOYSA-N resmethrin Chemical compound CC1(C)C(C=C(C)C)C1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001395 thiirenyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 229940055035 trichophyton verrucosum Drugs 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000006250 trifluoro ethyl amino group Chemical group [H]N(*)C([H])([H])C(F)(F)F 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 239000004562 water dispersible granule Substances 0.000 description 1
- 235000015099 wheat brans Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/713—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with four or more nitrogen atoms as the only ring hetero atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Agronomy & Crop Science (AREA)
- Environmental Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Plant Pathology (AREA)
- Pest Control & Pesticides (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361834324P | 2013-06-12 | 2013-06-12 | |
| US61/834,324 | 2013-06-12 | ||
| PCT/US2014/041984 WO2014201161A1 (en) | 2013-06-12 | 2014-06-11 | Metalloenzyme inhibitor compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2014278172A1 AU2014278172A1 (en) | 2016-01-28 |
| AU2014278172B2 true AU2014278172B2 (en) | 2018-08-09 |
Family
ID=52022749
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2014278172A Ceased AU2014278172B2 (en) | 2013-06-12 | 2014-06-11 | Metalloenzyme inhibitor compounds |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9688671B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3008051A4 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6386035B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR20160018811A (cg-RX-API-DMAC7.html) |
| CN (1) | CN105431418B (cg-RX-API-DMAC7.html) |
| AU (1) | AU2014278172B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2915054A1 (cg-RX-API-DMAC7.html) |
| EA (1) | EA201690007A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2014201161A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102070345B1 (ko) | 2011-12-11 | 2020-01-28 | 마이코비아 파마슈티컬즈, 인코포레이티드 | 금속효소 억제제 화합물 |
| CN104136427B (zh) * | 2012-01-20 | 2017-03-01 | 威尔金制药有限公司 | 金属酶抑制剂化合物 |
| US10017494B2 (en) | 2014-03-19 | 2018-07-10 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| AU2015231275B2 (en) | 2014-03-19 | 2019-03-07 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| JP2017507991A (ja) | 2014-03-19 | 2017-03-23 | ヴィアメット ファーマスーティカルズ，インコーポレイテッド | 抗真菌化合物の調製方法 |
| EA201691648A1 (ru) | 2014-03-19 | 2017-01-30 | Ваймет Фармасьютикалс, Инк. | Способ получения противогрибковых соединений |
| AU2015231216B2 (en) | 2014-03-19 | 2019-04-04 | Mycovia Pharmaceuticals, Inc. | Antifungal compound process |
| EP3119756B9 (en) | 2014-03-19 | 2021-08-25 | Dow AgroSciences LLC | 2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-substituted-pyridin-2-yl)-3-(1h-tetrazol-1-yl)propan-2-ols and processes for their preparation |
| BR112016021257B1 (pt) | 2014-03-19 | 2021-03-02 | Viamet Pharmaceuticals (NC), Inc. | 2-(2,4- difluorofenil-1,1-diflúor-1-(5-substituído-piridin-2-il)-3- (1h-tetrazol-1-il)propan-2-óis e processos para preparação e uso dos mesmos |
| CA2942972A1 (en) | 2014-03-19 | 2015-09-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antifungal compound process |
| KR102151082B1 (ko) | 2014-03-19 | 2020-09-03 | 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 시크리터리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비시스 | 항진균 화합물 제조방법 |
| JP6639497B2 (ja) | 2014-11-10 | 2020-02-05 | ジェネンテック， インコーポレイテッド | ブロモドメインインヒビターおよびその使用 |
| MA40940A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| MA40943A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| CN107531692B (zh) * | 2015-01-29 | 2020-12-25 | 基因泰克公司 | 治疗化合物及其用途 |
| KR102798709B1 (ko) * | 2015-09-18 | 2025-04-23 | 마이코비아 파마슈티컬즈, 인코포레이티드 | 항진균 화합물 제조 방법 |
| EP3397629B1 (en) * | 2015-12-30 | 2023-04-19 | NQP 1598, Ltd. | Metalloenzyme inhibitor compounds |
| SG11202008113RA (en) | 2018-03-05 | 2020-09-29 | Arcus Biosciences Inc | Arginase inhibitors |
| JP7503561B2 (ja) * | 2018-10-29 | 2024-06-20 | ファーハイ ユーエス インコーポレイテッド | 新規ジペプチド化合物及びその使用方法 |
| TWI828800B (zh) | 2018-11-16 | 2024-01-11 | 美商阿克思生物科學有限公司 | Arg1及/或arg2之抑制劑 |
| ES3034708T3 (en) * | 2019-06-27 | 2025-08-21 | Univ Nanyang Tech | 1,1'-[1,3-(5-methoxy)phenylenebis(methylene)]bis[4,5-diphenyl-1h-imidazole] and similar compounds for the treatment of malaria |
| CN110885323A (zh) * | 2019-12-02 | 2020-03-17 | 中国人民解放军第二军医大学 | 一种三氮唑醇类衍生物、其制备方法及应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080062876A (ko) | 2006-12-29 | 2008-07-03 | 주식회사 대웅제약 | 신규한 항진균성 트리아졸 유도체 |
| JP5266430B2 (ja) * | 2010-04-24 | 2013-08-21 | ヴィアメット ファーマスーティカルズ，インコーポレイテッド | 金属酵素阻害化合物 |
| EA201490038A1 (ru) | 2011-06-19 | 2014-04-30 | Вайамет Фармасьютикалс, Инк. | Соединения, ингибирующие металлоферменты |
| AU2012273103B2 (en) | 2011-06-19 | 2017-04-20 | Viamet Pharmaceuticals (NC), Inc. | Metalloenzyme inhibitor compounds |
| AU2012273004B2 (en) * | 2011-06-23 | 2017-04-13 | Mycovia Pharmaceuticals, Inc. | Metalloenzyme inhibitor compounds |
| KR102070345B1 (ko) | 2011-12-11 | 2020-01-28 | 마이코비아 파마슈티컬즈, 인코포레이티드 | 금속효소 억제제 화합물 |
-
2014
- 2014-06-11 CA CA2915054A patent/CA2915054A1/en not_active Abandoned
- 2014-06-11 WO PCT/US2014/041984 patent/WO2014201161A1/en not_active Ceased
- 2014-06-11 CN CN201480038709.9A patent/CN105431418B/zh not_active Expired - Fee Related
- 2014-06-11 EP EP14811695.7A patent/EP3008051A4/en not_active Withdrawn
- 2014-06-11 US US14/897,331 patent/US9688671B2/en active Active
- 2014-06-11 KR KR1020167000819A patent/KR20160018811A/ko not_active Ceased
- 2014-06-11 EA EA201690007A patent/EA201690007A1/ru unknown
- 2014-06-11 AU AU2014278172A patent/AU2014278172B2/en not_active Ceased
- 2014-06-11 JP JP2016519625A patent/JP6386035B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN105431418A (zh) | 2016-03-23 |
| EP3008051A4 (en) | 2017-03-01 |
| CN105431418B (zh) | 2019-02-05 |
| EA201690007A1 (ru) | 2016-04-29 |
| JP6386035B2 (ja) | 2018-09-05 |
| US9688671B2 (en) | 2017-06-27 |
| WO2014201161A1 (en) | 2014-12-18 |
| EP3008051A1 (en) | 2016-04-20 |
| US20160130263A1 (en) | 2016-05-12 |
| AU2014278172A1 (en) | 2016-01-28 |
| KR20160018811A (ko) | 2016-02-17 |
| CA2915054A1 (en) | 2014-12-18 |
| JP2016526535A (ja) | 2016-09-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2014278172B2 (en) | Metalloenzyme inhibitor compounds | |
| US10919874B2 (en) | Metalloenzyme inhibitor compounds | |
| US8236962B2 (en) | Metalloenzyme inhibitor compounds | |
| HK1202872B (en) | Metalloenzyme inhibitor compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HB | Alteration of name in register |
Owner name: VIAMET PHARMACEUTICALS (NC), INC. Free format text: FORMER NAME(S): VIAMET PHARMACEUTICALS, INC. |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| HB | Alteration of name in register |
Owner name: MYCOVIA PHARMACEUTICALS, INC. Free format text: FORMER NAME(S): VIAMET PHARMACEUTICALS (NC), INC. |
|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |