CAS: 187949-02-6; 7-Chloro-3-[(2R,3R)-3-(2,4-Difluorophenyl)-3-Hydroxy-4-(1,2,4-Triazol-1-yl)Butan-2-Yl]Quinazolin-4-One

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CAS号122-51-0 原甲酸三乙酯 | CAS号206350-07-4 2-Amino-4-chlor... | CAS号89-77-0 2-氨基-4-氯苯甲酸

📜2-氨基-4-氯苯甲酸置于盐酸,1-羟基苯并三唑,三乙胺,N,N'-二环己基碳二亚胺体系中,用 1,4-二氧六环,N,N-二甲基甲酰胺 用作溶剂,化学反应 36.0H,反应生成阿巴康唑
参考文献:New Azole Antifungals. 3. Synthesis And Antifungal Activity Of 3-Substituted-4(3H)-Quinazolinones
标题:New Azole Antifungals. 3. Synthesis And Antifungal Activity Of 3-Substituted-4(3H)-Quinazolinones
摘要:A Series Of Azole Antifungal Agents Featuring A Quinazolinone Nucleus Have Been Subjected To Studies Of Structure-Activity Relationships. In General,These Compounds Displayed Higher In Vitro Activities Against Filamentous Fungi And Shorter Half-Lives Than The Structures Described In Our Preceding Paper. The Most Potent Products In Vitro Carried A Halogen (Or An Isostere) At The 7-Position Of The Quinazolinone Ring. Using A Murine Model Of Systemic Candidosis,Oral Activity Was Found To Be Dependent On Hydrophobicity,Which,In Turn,Modulated The Compound'S Half-Life. The 7-Cl Derivative,(1R,2R)-7-Chloro-3-[2-(2,4-Difluorophenyl)-2-Hydroxy-1-Methyl-3-(1H-1,2,4-Triazol-1-yl)Propyl]Quinazolin-4(3H)-One (20,Ur-9825),Was Selected For Further Testing Due To Its High In Vitro Activity,Low Toxicity,Good Pharmacokinetic Profile,And Ease Of Obtention. Compound 20 Is The (1R,2R) Isomer Of Four Possible Stereoisomers. The Other Three Isomers Were Also Prepared And Tested. The Enantiomer (1S,2S) And The (Lr,Bs) Epimer Were Inactive,Whereas The (1S,2R) Epimer Retained Some Activity. In Vitro 20 Was Superior To Fluconazole,Itraconazole,Sch-42427,And Tak-187 And Roughly Similar To Voriconazole And Er-30346. In Vivo,20 Was Only Moderately Active In A Mouse Model Of Systemic Candidosis When Administration Was Limited To The First Day. This Was Attributed To Its Short Half-Life In That Species (T(1/2) = 1 H Po). Protection Levels Comparable To Or Higher Than Those Of Fluconazole,However,Were Observed In Systemic Candidosis Models In Rat And Rabbit,Where The Half-Life Of The Compound Was Found To Be 6 And 9 H,Respectively. Finally,20 Showed Excellent Protection Levels In An Immunocompromised Rat Model Of Disseminated Aspergillosis. The Compound Showed Low Toxicity Signs When Administered To Rats At 250 Mg/kg Qd Or At 100 Mg/kg Bid During 28 Days.
Doi:10.1021/jm9707277

专利信息

专利号:US-2024336559-A1
优先权日:2021-10-06
标 题 :Anti-fungals compounds targeting the synthesis of fungal sphingolipids
发明人：OJIMA IWAO; HARANAHALLI KRUPANANDAN; DEL POETA MAURIZIO; GARG ASHNA
权利人:UNIV NEW YORK STATE RES FOUND
摘要:The present invention provides a compound having the structure: n n n n n n n n n n n n wherein n R 3 , R 4 , R 5 , R 6 , and R 7 are each independently, H, halogen, CN, —CF 3 , —OCF 3 , —NO 2 , alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, —OH, —OAc, —OR 13 , —COR 13 , —CH 2 OR 13 , —SH, —SR 13 , —SO 2 R 13 , —NH 2 , —NHR 13 , —NR 14 R 15 , —NHCOR 12 , or —CONR 14 R 15 ; n R 9 , R 10 , R 11 , and R 12 are each independently, H, CN, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —OAc, —COR 13 , —SH, —SR 13 , —SO 2 R 13 , —NH 2 , —NHR 13 , —NR 14 R 15 , —NHCOR 12 , or —CONR 14 R 15 ;n wherein each occurrence of R 13 is independently alkyl, alkenyl, alkynyl, aryl, or heteroaryl, wherein each occurrence of R 14 is independently —H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, wherein each occurrence of R 15 is independently —H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, n n wherein when R 14 is methyl, R 15 is not methyl; n wherein at least one of R 9 , R 10 , R 11 , and R 12 is not H; n wherein at least one of R 3 , R 4 , R 5 , R 6 , and R 7 is not H.

专利号:US-10443047-B2
优先权日:2014-05-01
标题 :Increasing cellular lipid production by increasing the activity of diacylglycerol acyltransferase and decreasing the activity of triacylglycerol lipase
发明人：TSAKRAKLIDES VASILIKI; BREVNOVA ELENA E
权利人:NOVOGY INC
摘要:Disclosed are methods and compositions for increasing the triacylglycerol content of a cell by up-regulating diacylglycerol acyltransferase and down-regulating triacylglycerol lipase. In some embodiments, a DGA1 protein is expressed and a native TGL3 gene is knocked out, thereby increasing the synthesis of triacylglycerol and decreasing its consumption, respectively.

专利号:US-12325678-B2
优先权日:2017-06-16
标 题 :Anti-fungals compounds targeting the synthesis of fungal sphingolipids
发明人：OJIMA IWAO; DEL POETA MAURIZIO; LAZZARINI CRISTINA; HARANAHALLI KRUPANANDAN; SUN YI
权利人:UNIV NEW YORK STATE RES FOUND
摘要:The present invention provides a compound having the structure: n nand use of the compound for inhibiting the growth of or killing.

专利号:US-2023364251-A1
优先权日:2020-08-06
标 题:Methods for the synthesis of protein-drug conjugates
发明人：BORCHARDT ALLEN; HUGHES ROBERT MICHAEL
权利人:CIDARA THERAPEUTICS INC
摘要:The present invention relates to intermediates and methods for synthesizing protein-drug conjugates that can be used for the treatment of diseases and related conditions.

专利号:US-11858880-B2
优先权日:2017-06-16
标题 :Anti-fungals compounds targeting the synthesis of fungal sphingolipids

专利号:US-11944609-B1
优先权日:2023-06-16
标题:Antifungal ionic liquid and Amphotericin B combination
发明人：RATHER SAMI-ULLAH; WANI MOHMMAD YOUNUS; BAMUFLEH HISHAM S; ALHUMADE HESHAM; SAEED USMAN; TAIMOOR AQEEL AHMAD; ALALAYAH WALID M; RATHER IRFAN AHMAD
权利人:KING ABDULAZIZ UNIVERISTY; UNIV KING ABDULAZIZ
摘要:Provided herein are ionic liquids that can be used as antifungal agents alone or in combination with Amphotericin B. Also disclosed are methods of synthesis of the ionic liquids and inhibiting fungal growth and methods of treating fungal infections using the disclosed compounds. The disclosure provides antifungal agents that potentiate the antifungal activity of Amphotericin B, a commonly used antifungal drug that could be used alone or in combination. This combination will help control and combat the infections caused by drug resistant Candida. auris in immunocompromised patients.