Şarm el-Şeyh'teki Gazze zirvesinde ABD, Türkiye, Mısır ve Katar liderleri niyet beyanı imzaladı. Trump imza töreninde övdüğü Erdoğan için "Ne zaman ihtiyaç duysam hep yanımda oldu" dedi.

İsrail, ABD Başkanı Donald Trump'ın Gazze ateşkes planını Hamas ile arabulucular üzerinden müzakere edecek heyetinin Mısır'ın Şarm eş-Şeyh kentine yarın sabah yola çıkması talimatı verdi

The documentary Missing in Paradise, includes new CCTV that has left Sarm Heslop’s mother questioning the behaviour of her daughter’s boyfriend

Daily Herald StaffThe provincial government has announced plans for a new pilot framework that would allow participating communities to use municipal-owned

Krása, šarm, smyslnost i elegance. Do ESPRIT CLUBU, který má letos na Mezinárodním filmovém festivalu v Karlových Varech premiéru, zavítalo i během druhého dne několik osobností ze světa showbyznysu. ...

ABSTRACT Rationale 2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile (LY305) is a transdermal selective androgen receptor modulator (SARM) that has been under development as a potential therapeutic for conditions involving muscle wasting, osteoporosis, or hypogonadism. Due to its proven anabolic effects, its potential (and illicit) use in sport must be taken into consideration, necessitating information on its biotransformation for the implementation of adequate target analytes into routine doping control analytical procedures. In this study, the synthesis of LY305 and in vitro-derived metabolites of the SARM are described. Methods LY305 was synthesized by a Buchwald–Hartwig amination using 2-chloro-4-iodo-3-methylbenzonitrile and (1R,2R)-2-amino-1-methyl-cyclopentanol. The in vitro metabolism experiments were conducted using human liver microsomes (HLM) and the S9 fraction to allow for studying phase-I and phase-II biotransformations. For the detection and separation of LY305 and its metabolites, liquid chromatography–high-resolution tandem mass spectrometry was used. Results Overall, 18 metabolites were detected, nine of which were identified as phase-I metabolites and an additional nine were attributed to phase-II conjugates. Metabolic reactions were as follows: hydroxylation, dehydrogenation, oxidation, oxidation and hydroxylation, O-glucuronidation, hydroxylation with subsequent glucuronidation, and bis-hydroxylation with subsequent glucuronidation. Conclusions The transdermal SARM LY305 was successfully synthesized and subjected to in vitro metabolic studies, yielding chromatographic and mass spectral data that support improving comprehensive anti-doping tests. To the best of our knowledge, no published experimental data exist that report on the in vitro metabolic profile of LY305, a substance that might undergo further (pre)clinical evaluation.