title: Synthesis and molecular modeling of (4'R)- and (4'S)- 4'-substituted 2'-{[(E)-androst-5-en-17-ylidene]-methyl}oxazolines.
abstract: Synthesis of four novel (4'R)- and (4'S)- 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]-methyl} oxazolines, comprising 4'-hydroxymethyl (1 and 2) and 4'-methoxycarbonyl (3 and 4) substituents is presented. Reaction of 17α-bromo-21-iodo-3β-acetoxypregn-5-en-20-one with either (L)-serine methyl ester, or (D)-serine methyl ester resulted in methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(L)-serinate and methyl N-[3β-acetoxy-21-oxopregna-5,17(20)-dien-21-yl]-(D)-serinate (as mixtures of related [17(20)E]- and [17(20)Z]-isomers). Cyclization of obtained amides led to methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'S)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate and methyl 2'-{[(E)-3β-acetoxyandrost-5-en-17-ylidene]methyl}-(4'R)-4',5'-dihydro-1',3'-oxazole-4'-carboxylate which were transformed to titled compounds 1-4. The molecular docking of compounds 1-4 to ligand binding site of nuclear receptor LXRβ revealed significant differences due to stereochemical configuration of 4' atom and structure of 4'-substituent.
authors.affiliation: Orekhovich Institute of Biomedical Chemistry RAMS, Moscow, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Stulov
authors.forename: Olga V
authors.initials: OV
authors.lastname: Mankevich
authors.forename: Roman A
authors.initials: RA
authors.lastname: Novikov
authors.forename: Yaroslav V
authors.initials: YV
authors.lastname: Tkachev
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Timofeev
authors.forename: Nikita O
authors.initials: NO
authors.lastname: Dugin
authors.forename: Vladimir F
authors.initials: VF
authors.lastname: Pozdnev
authors.forename: Irina V
authors.initials: IV
authors.lastname: Fedyushkina
authors.forename: Dmitri S
authors.initials: DS
authors.lastname: Scherbinin
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Veselovsky
authors.forename: Alexander Yu
authors.initials: AY
authors.lastname: Misharin
mesh_terms: D060326:Chemistry Techniques, Synthetic; D056945:Hep G2 Cells; D006801:Humans; D000071518:Liver X Receptors; D062105:Molecular Docking Simulation; D057093:Orphan Nuclear Receptors / Q000737:chemistry / Q000378:metabolism; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010080:Oxazoles