ABSTRACT
A family of 15 N-substituted phenothiazines was designed, synthesized and their acaricidal activity against Rhipicephalus microplus was determined in vitro. The synthetic methodology is simple and can be employed in multigram scale. The rationale for the structure-based design of these compounds is the potential for azines and phenothiazine to engage in π-π interactions; these fragments, joined together by a short, flexible alkoxide linker, structurally resemble phenothiazine-based cholinesterase inhibitors, while their weak basicity implies a neutral active form, rather than a cationic one, thus facilitating penetration of the cuticle of ticks. One compound displayed excellent acaricidal activity (LD50=0.58 µg/mL). Preliminary SAR analysis suggests that the activity is influenced by the presence of a weakly basic nitrogen atom, as well as the substitution pattern within the heterocycles.
Subject(s)
Drug Design , Phenothiazines/pharmacology , Rhipicephalus/drug effects , Tick Control , Animals , Dose-Response Relationship, Drug , Molecular Structure , Phenothiazines/chemical synthesis , Phenothiazines/chemistry , Structure-Activity RelationshipABSTRACT
Se reporta una vía alternativa para la síntesis del 3-etilencetal-androsta-3, 17-diona, el cual es un intermedio importante para la obtención de corticoides por construcción de la cadena lateral de 17-ceto esteroides. En nuestro caso, partiendo de la androsta-4-ene-3, 17-diona, se obtuvo el producto deseado en 3 pasos de síntesis con buenos rendimientos
Subject(s)
Androsterone/antagonists & inhibitors , Androsterone/chemical synthesis , Cholesterol Side-Chain Cleavage Enzyme , Complement Pathway, AlternativeABSTRACT
Se reporta una vía alternativa para la síntesis del 3-etilencetal-androsta-3, 17-diona, el cual es un intermedio importante para la obtención de corticoides por construcción de la cadena lateral de 17-ceto esteroides. En nuestro caso, partiendo de la androsta-4-ene-3, 17-diona, se obtuvo el producto deseado en 3 pasos de síntesis con buenos rendimientos(AU)
