ES2238341T3 - Derivados de carbamoiloxialquilazoles sustituidos por n. - Google Patents
Derivados de carbamoiloxialquilazoles sustituidos por n.Info
- Publication number
- ES2238341T3 ES2238341T3 ES00992946T ES00992946T ES2238341T3 ES 2238341 T3 ES2238341 T3 ES 2238341T3 ES 00992946 T ES00992946 T ES 00992946T ES 00992946 T ES00992946 T ES 00992946T ES 2238341 T3 ES2238341 T3 ES 2238341T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- difluorophenyl
- triazol
- butyl
- hydroxy
- 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.)
- Expired - Lifetime
Links
- -1 acoxycarbonyl Chemical group 0.000 claims abstract description 154
- 150000001875 compounds Chemical class 0.000 claims abstract description 109
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 17
- 150000004677 hydrates Chemical class 0.000 claims abstract description 16
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 239000012453 solvate Substances 0.000 claims abstract description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 12
- 125000002252 acyl group Chemical group 0.000 claims abstract description 10
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
- 239000000460 chlorine Substances 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 5
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims abstract description 4
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims abstract description 4
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 claims abstract description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
- 239000011737 fluorine Substances 0.000 claims abstract description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 3
- 150000001450 anions Chemical class 0.000 claims abstract description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract 2
- 229930195733 hydrocarbon Natural products 0.000 claims abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 75
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 45
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 17
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 12
- 229940121375 antifungal agent Drugs 0.000 claims description 11
- 206010017533 Fungal infection Diseases 0.000 claims description 7
- 230000000843 anti-fungal effect Effects 0.000 claims description 7
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 208000031888 Mycoses Diseases 0.000 claims description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- JTSRPXNPVLMJLB-UHFFFAOYSA-N 2H-pyridin-2-ide Chemical compound N1=[C-]C=CC=C1 JTSRPXNPVLMJLB-UHFFFAOYSA-N 0.000 claims 3
- 125000005354 acylalkyl group Chemical group 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 87
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 150000002148 esters Chemical class 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000005160 1H NMR spectroscopy Methods 0.000 description 43
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 40
- 239000000203 mixture Substances 0.000 description 40
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 34
- 230000014759 maintenance of location Effects 0.000 description 29
- 239000012230 colorless oil Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 26
- 238000004128 high performance liquid chromatography Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 11
- AJKLKFPOECCSOO-UHFFFAOYSA-N hydrochloride;hydroiodide Chemical compound Cl.I AJKLKFPOECCSOO-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 239000012267 brine Substances 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 230000009885 systemic effect Effects 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 201000002909 Aspergillosis Diseases 0.000 description 5
- 208000036641 Aspergillus infections Diseases 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VYPMWCUNCNMNOM-UHFFFAOYSA-N [2-(methylamino)pyridin-3-yl]methanol Chemical compound CNC1=NC=CC=C1CO VYPMWCUNCNMNOM-UHFFFAOYSA-N 0.000 description 5
- 230000002538 fungal effect Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PHENPABYBHPABM-UHFFFAOYSA-N acetic acid;octane Chemical compound CC(O)=O.CCCCCCCC PHENPABYBHPABM-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 208000024386 fungal infectious disease Diseases 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 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
- 239000000463 material Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010006473 Bronchopulmonary aspergillosis Diseases 0.000 description 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 208000004430 Pulmonary Aspergillosis Diseases 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010042938 Systemic candida Diseases 0.000 description 3
- 150000003851 azoles Chemical class 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 201000003984 candidiasis Diseases 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000005956 quaternization reaction Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 206010052366 systemic mycosis Diseases 0.000 description 3
- ANFZGSBFEPFDNR-NFJWQWPMSA-N (2r)-1-morpholin-4-yl-2-(oxan-2-yloxy)propan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C1CCCCO1 ANFZGSBFEPFDNR-NFJWQWPMSA-N 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- 241000335423 Blastomyces Species 0.000 description 2
- 241000223682 Exophiala Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910010084 LiAlH4 Inorganic materials 0.000 description 2
- 241001480037 Microsporum Species 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- XEKAUTDWPYQNFU-UHFFFAOYSA-N chlorane Chemical compound Cl.Cl.Cl XEKAUTDWPYQNFU-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical compound OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000003898 horticulture Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000005905 mesyloxy group Chemical group 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- YKXZSPYFYXXSMK-UHFFFAOYSA-N methyl 1-formamido-2h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN(NC=O)C1 YKXZSPYFYXXSMK-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- VFFNHRMFPPAZHT-UHFFFAOYSA-N n-[(2-nitrophenyl)methyl]propan-2-amine Chemical compound CC(C)NCC1=CC=CC=C1[N+]([O-])=O VFFNHRMFPPAZHT-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- PYYRNLDFMZVKCV-UHFFFAOYSA-N (2-nitrophenyl)methanamine Chemical compound NCC1=CC=CC=C1[N+]([O-])=O PYYRNLDFMZVKCV-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
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- FPFVVQKLBOAJKZ-UHFFFAOYSA-N 1-(2,5-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound FC1=C(C=C(C=C1)F)C(C(CC)O)N1N=CN=C1 FPFVVQKLBOAJKZ-UHFFFAOYSA-N 0.000 description 1
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- OPAHEYNNJWPQPX-RCDICMHDSA-N ravuconazole Chemical compound C=1SC([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=1C1=CC=C(C#N)C=C1 OPAHEYNNJWPQPX-RCDICMHDSA-N 0.000 description 1
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- REFMEZARFCPESH-UHFFFAOYSA-M sodium;heptane-1-sulfonate Chemical compound [Na+].CCCCCCCS([O-])(=O)=O REFMEZARFCPESH-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cephalosporin Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99121694 | 1999-11-02 | ||
| EP99121694 | 1999-11-02 | ||
| PCT/EP2000/010524 WO2001032652A2 (en) | 1999-11-02 | 2000-10-25 | N-substituted carbamoyloxyalkyl-azolium derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2238341T3 true ES2238341T3 (es) | 2005-09-01 |
| ES2238341T9 ES2238341T9 (es) | 2016-03-02 |
Family
ID=8239312
Family Applications (1)
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| MY148805A (en) | 2002-10-16 | 2013-05-31 | Takeda Pharmaceutical | Controlled release preparation |
| PL2192893T3 (pl) | 2007-08-21 | 2015-12-31 | Basilea Pharmaceutica Ag | Kompozycja przeciwgrzybicza |
| US9907812B2 (en) | 2011-06-22 | 2018-03-06 | Vyome Biosciences Pvt. Ltd. | Conjugate-based antifungal and antibacterial prodrugs |
| MX2015016675A (es) | 2013-06-04 | 2016-07-15 | Vyome Biosciences Pvt Ltd | Particulas recubiertas y composiciones que comprenden las mismas. |
| CN104230894B (zh) * | 2013-06-06 | 2016-08-24 | 南京华威医药科技开发有限公司 | 三唑类化合物 |
| CN107207414B (zh) | 2014-12-30 | 2021-03-30 | 美国陶氏益农公司 | 具有杀真菌活性的吡啶酰胺化合物 |
| CN106032356B (zh) * | 2015-03-13 | 2018-09-14 | 江苏正大丰海制药有限公司 | 一种[n-甲基-吡啶-2-基]氨基甲酸-1-氯乙酯的制备方法 |
| CN104974143A (zh) * | 2015-05-12 | 2015-10-14 | 深圳致君制药有限公司 | 一种季铵盐类化合物、其制备方法以及用途 |
| CN106467519B (zh) * | 2015-08-17 | 2019-08-13 | 南京华威医药科技集团有限公司 | 一种水溶性三唑化合物 |
| CN106467534B (zh) * | 2015-08-17 | 2019-10-11 | 江苏奥赛康药业有限公司 | 一种硫酸艾沙康唑鎓化合物及其药物组合物 |
| CN106565699B (zh) * | 2015-10-10 | 2019-07-26 | 江苏正大丰海制药有限公司 | 一种艾沙康唑硫酸盐晶体及其制备方法 |
| US10683387B2 (en) | 2016-10-04 | 2020-06-16 | Massachusetts Institute Of Technology | Bottlebrush copolymers and uses thereof |
| US11040958B2 (en) | 2017-02-17 | 2021-06-22 | Wuhan Ll Science And Technology Development Co., Ltd. | Triazole antimicrobial derivative, pharmaceutical composition and use thereof |
| CN106916152B (zh) * | 2017-04-27 | 2019-09-17 | 扬子江药业集团有限公司 | 氧化还原反应制备艾沙康唑鎓单硫酸盐的方法 |
| US10716858B2 (en) | 2017-06-30 | 2020-07-21 | Massachusetts Institute Of Technology | Branched multi-functional macromonomers and uses thereof |
| US11752221B2 (en) | 2017-06-30 | 2023-09-12 | Massachusetts Institute Of Technology | Brush-arm star polymer imaging agents and uses thereof |
| US10368502B2 (en) | 2017-09-25 | 2019-08-06 | Multiple Energy Technologies Llc | Bioceramic and carbon-based hydroponic systems, methods and devices |
| CN110317165A (zh) * | 2018-03-28 | 2019-10-11 | 上海医药工业研究院 | 一种药物中间体2-甲胺基-3-吡啶甲醇的制备方法 |
| CN110551064B (zh) * | 2018-06-01 | 2021-01-01 | 重庆世森医药科技有限公司 | 艾沙康唑硫酸酯及其中间体的制备方法 |
| JP7433288B2 (ja) | 2018-08-01 | 2024-02-19 | バジリア・ファルマスーチカ・インターナショナル・アーゲー，アルシュヴィル | イサブコナゾニウム硫酸塩を精製するための方法 |
| EP3837266A1 (en) | 2018-08-17 | 2021-06-23 | Massachusetts Institute of Technology | Degradable polymers of a cyclic silyl ether and uses thereof |
| CN110128420A (zh) * | 2019-05-08 | 2019-08-16 | 阴启明 | 硫酸氢根/硫酸根型阴离子交换技术制备艾沙康唑鎓单硫酸盐的方法 |
| WO2021037597A1 (en) | 2019-08-26 | 2021-03-04 | Synthon B.V. | Isavuconazonium salts and process for preparing thereof |
| AU2020368453A1 (en) * | 2019-10-16 | 2022-04-21 | Massachusetts Institute Of Technology | Brush prodrugs and uses thereof |
| US12042513B2 (en) | 2020-01-10 | 2024-07-23 | Massachusetts Institute Of Technology | Proteolysis targeting chimeric molecules (PROTACs) with functional handles and uses thereof |
| JP7454905B2 (ja) * | 2021-09-28 | 2024-03-25 | 旭化成ファーマ株式会社 | 有効成分であるイサブコナゾール又はそのプロドラッグを含有する真菌症治療及び／又は予防剤 |
| JP7570382B2 (ja) | 2021-09-28 | 2024-10-21 | 旭化成ファーマ株式会社 | エアベント付き輸液フィルタを備える点滴静脈投与用輸液セット |
| US12084415B2 (en) | 2021-12-20 | 2024-09-10 | Massachusetts Institute Of Technology | Biomolecule-polymer-pharmaceutical agent conjugates for delivering the pharmaceutical agent |
| EP4289840A1 (en) | 2022-06-07 | 2023-12-13 | Zaklady Farmaceutyczne Polpharma S.A. | A process for preparing isavuconazonium sulfate |
| WO2024094329A1 (en) | 2022-11-01 | 2024-05-10 | Basilea Pharmaceutica International Ag, Allschwil | Blister-packaged capsule preparation containing isavuconazonium sulfate |
| WO2024189550A1 (en) * | 2023-03-13 | 2024-09-19 | Apitoria Pharma Private Limited | Process for the preparation of isavuconazonium sulfate and its crystalline forms |
| WO2025114603A1 (en) | 2023-11-30 | 2025-06-05 | Basilea Pharmaceutica International Ag, Allschwil | Pharmaceutical combinations for use in the treatment of fungal infections |
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| JP3108997B2 (ja) * | 1997-03-31 | 2000-11-13 | 武田薬品工業株式会社 | アゾール化合物、その製造法および用途 |
| KR20010005792A (ko) * | 1997-03-31 | 2001-01-15 | 다케다 야쿠힌 고교 가부시키가이샤 | 아졸 화합물, 이의 제조 방법 및 용도 |
| WO1999045008A1 (en) * | 1998-03-06 | 1999-09-10 | F. Hoffmann-La Roche Ag | 3-[4-(4-cyanophenyl)thiazol-2-y)]-1-(1h-1,2,4-triazol-1-yl)-butan-2-ol derivatives having antifungal activity |
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- 2000-10-25 KR KR10-2002-7005574A patent/KR100449797B1/ko not_active Expired - Lifetime
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