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    • 8. 发明授权
    • Seryl-lysyl-based peptide and peptidomimetic inhibitors of N-myristoyl transferase as anti-infective agents
    • 作为抗感染剂的N-肉豆蔻酰基转移酶的丝氨酰赖氨酰基肽和肽模拟抑制剂
    • US06632921B1
    • 2003-10-14
    • US09277573
    • 1999-03-26
    • James A. SikorskiDevadas BalekudruDaniel P. GetmanDavid L. BrownSrinivasan NagarajanMark E. ZupecJeffrey I. Gordon
    • James A. SikorskiDevadas BalekudruDaniel P. GetmanDavid L. BrownSrinivasan NagarajanMark E. ZupecJeffrey I. Gordon
    • C07K508
    • C07K5/06191A61K38/00C07K5/0606C07K5/081
    • Seryl-lysyl-based peptide and peptidomimetic compounds are described as inhibitors of the enzyme N-myristoyl transferase to provide selective control of the fungal organism Candida albicans. Peptidomimetic compounds of particular interest are those of the formula: wherein R1 is selected form aminoalkyl, p-aminoalkylphenylalkyl, imidazolylalkylphenylalkyl, 2-alkylimidazolylalkylphenylalkyl, benzimidazolylalkylphenylalkyl and 2-alkylbenzimidazolylalkylphenylalkyl; wherein R2 is selected from hydrido, alkyl, cycloalkyl, akenyl, alkynyl, haloalkyl, benzyl, alkylphenylalkyl, alkoxyphenylalkyl, halophenylalkyl, phenethyl, cycloalkylalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, alkoxycycloalkylalkyl and naphthylalkyl; wherein Y is selected from carboxylic acid, hydroxamic acid, phosphonic acid and tetrazolyl; or a pharmaceutically-acceptable salt, amide or ester thereof. Compounds of the formula are species-specific inhibitors of C. albicans with little effect on human NMT enzyme and thus would.be useful in treating C. albicans fungal infections in humans.
    • 描述了基于丝氨酰赖氨酰的肽和拟肽化合物作为N-肉豆蔻酰转移酶酶的抑制剂,以提供对真菌生物体 的真菌生物的选择性控制。 特别感兴趣的拟肽化合物是下式的化合物:其中R 1选自氨基烷基,对氨基烷基苯基烷基,咪唑基烷基苯基烷基,2-烷基咪唑基烷基苯基烷基,苯并咪唑基烷基苯基烷基和2-烷基苯并咪唑基烷基苯基烷基; 其中R 1选自氢,烷基,环烷基,亚烯基,炔基,卤代烷基,苄基,烷基苯基烷基,烷氧基苯基烷基,卤代苯基烷基,苯乙基,环烷基烷基,卤代环烷基烷基,烷基环烷基烷基, 其中Y选自羧酸,异羟肟酸,膦酸和四唑基; 或其药学上可接受的盐,酰胺或酯。 式的化合物是 C的物种特异性抑制剂。 白色念珠菌 对人NMT酶几乎没有影响,因此可用于治疗 C。 白色念珠菌 人类真菌感染。