The size and/or configuration of the cycloalkane D′ ring in pentacyclic progesterone derivatives are crucial for their high-affinity binding to a protein in addition to progesterone receptor in rat uterine cytosol☆

Synthesis of 19-substituted steroids of the 16α,17α-cyclohexanopregnane series and study of their interactions with rat uterine cytosol and blood serum proteins

“…However, the elongation of 19 aldimine substituent together with the ester group at the end of the chain in compound 15 brings about a sharp decrease in binding. A high affinity to the SP (6.5 times as high as that of 6α methyl 16α,17α cyclohexanopro gesterone (16)) and a very low affinity to the UP were found for 19 O methyloxime 14. The other 19 substitu ents in the pentarane molecule exerted a rather weak in fluence on the affinity to the SP.…”

“…The equilibrium dissociation con stants (K D ) were determined by selecting the parameters K D and B max , which ensured the least deviation of the experimental data from the "one protein-two ligands" kinetic model. 16 The di mensionless RBA values were calculated from the ratio of the K d values of progesterone (for the PR) or 6α methyl 16α,17α cyclohexanoprogesterone (for the UP and SP) to those of the ligand under comparison determined in separate experiments; the calculated RBA values were then averaged. To unify the analysis of the effect of substituents at the C(10) atom of the pentarane molecule on the affinity to three proteins, the RBA values found for the synthesized compounds were considered as relative values with respect to the affinity of the basic com pound, 16α,17α cyclohexanoprogesterone 17, to the same proteins.…”

Pregna-D′-pentaranes, Progestins and Antiprogestins: II. Pathways and Realization Mechanisms of Separate Biological Functions of Steroid Hormones

“…A comprehensive study of the kinetics of direct and competitive interaction of labeled progesterone and pentaranes with the cytosol receptors of uterus clearly showed that PR is the only center of specific binding that is common for all of them [11]. In addition to the receptors, some representatives of the pregna-D'-pentarane series exhibited affinity to other two proteins, which we named pentaranofilins [11,13,14].…”

“…In addition to the receptors, some representatives of the pregna-D'-pentarane series exhibited affinity to other two proteins, which we named pentaranofilins [11,13,14]. One of them was found in rat uterus, and another, in rat blood.…”

Molecular docking and 3D-QSAR on 16a,17a-cycloalkanoprogesterone analogues as progesterone receptor ligands

“…Âñåãî â êà÷åñòâå îáó÷àþùåé âûáîðêè â ðàáîòå èñïîëüçîâàíû äàííûå î ñòðóêòóðå 42 ðàçëè÷íûõ 16α,17α-öèêëîàëêàíîïðîãåñòåðîíîâ è äàííûå ïî îòíîñèòåëüíîé êîíêóðåíòíîé àêòèâíîñòè (ÎÊÀ). Ñèíòåç è áèîëîãè÷åñêîå òåñòèðîâàíèå ýòèõ ïåíòàðàíîâ áûëè âûïîëíåíû ðàíåå [9][10][11][12].  òàáëèöå 1 ïðåäñòàâëåíû èõ ñòðóêòóðíûå õàðàêòåðèñòèêè è âåëè÷èíû ÎÊÀ.…”