ABSTRACT
The synthesis and in vitro binding affinity for a novel series of potent androgen receptor modulators is described. One of the more potent compounds (17, RAD35010) was further characterized in vivo where it restored levator ani weight in castrated male rats to near sham level while having no significant effect on prostate weight.
Subject(s)
Carbazoles/chemistry , Receptors, Androgen/chemistry , Administration, Oral , Animals , Carbazoles/chemical synthesis , Carbazoles/pharmacology , Male , Prostate/drug effects , Rats , Receptors, Androgen/metabolismABSTRACT
In a study aimed at investigating an as yet unknown structure-activity relationship of the nikkomycin family of antifungal peptidyl nucleoside antibiotics, the present research reports the synthesis and antifungal evaluation of a carbohydrate ring-expanded pyranosyl nucleoside analogue of nikkomycin B. Employing a convergent synthetic route, independent synthesis of the N-terminal amino acid side chain and a stereoselective de novo construction of the desired pyranosyl nucleoside amino acid fragment was followed by peptidic coupling of the two components, leading to the first synthesis of a carbohydrate ring-enlarged pyranosyl nikkomycin B analogue. In vitro biological evaluation of the above analogue against a variety of human pathogenic fungi demonstrated significant antifungal activity against several fungal strains of clinical significance.
Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Carbohydrates/chemistry , Dipeptides/chemical synthesis , Dipeptides/pharmacology , Mitosporic Fungi/drug effects , Nucleosides/pharmacology , Aminoglycosides/chemistry , Aminoglycosides/pharmacology , Antifungal Agents/chemistry , Dipeptides/chemistry , Microbial Sensitivity Tests , Molecular Conformation , Nucleosides/chemical synthesis , Nucleosides/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Starting from L-serine, a stereoselective synthesis of pachastrissamine, a structurally novel anhydrosphingosine derivative, is reported in this Letter. [structure: see text]
Subject(s)
Antineoplastic Agents/chemical synthesis , Serine/chemistry , Sphingosine/analogs & derivatives , Animals , Molecular Structure , Porifera/chemistry , Sphingosine/chemical synthesis , StereoisomerismABSTRACT
Employing an amino acid chiral template strategy, the present research describes a general and highly efficient protocol for the rapid construction of enantiopure furanosyl and pyranosyl nucleoside amino acid cores as present in various complex peptidyl nucleoside antibiotics. Starting from easily available d-serine, the strategy and the approach involve rapid and efficient stereoselective synthesis of five- or six-membered lactone amino alcohols, followed by incorporation of the required functionalities of the target molecules on these strategically functionalized chiral templates.
