Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F13%3A00392261" target="_blank" >RIV/61388963:_____/13:00392261 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023752:_____/13:43914448

Výsledek na webu

<a href="http://dx.doi.org/10.1021/jm3016365" target="_blank" >http://dx.doi.org/10.1021/jm3016365</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jm3016365" target="_blank" >10.1021/jm3016365</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity

Popis výsledku v původním jazyce

25R-3 beta-Hydroxy-5 alpha-spirostan-12-one (hecogenin) and 11 alpha-hydroxypregn-4-ene-3,20-dione (11 alpha-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5 xi-pregnanolone (3alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one), the principal neurosteroid acting via gamma-aminobutyric acid (GABA). These analogues were designed to study the structural requirements of the corresponding GABA(A) receptor. Their biological activity was measured by in vitro test with [H-3]flunitrazepam as radio-ligand in which allopregnanolone and its active analogues stimulated the binding to the GABA(A) receptor. Analysis of the SAR data suggests dependence of the flunitrazepam binding activity on the hydrophobic-hydrophilic balance of the groups at the C-ring edge rather than on specific interactions between them and the receptor.

Název v anglickém jazyce

Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity

Popis výsledku anglicky

25R-3 beta-Hydroxy-5 alpha-spirostan-12-one (hecogenin) and 11 alpha-hydroxypregn-4-ene-3,20-dione (11 alpha-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5 xi-pregnanolone (3alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one), the principal neurosteroid acting via gamma-aminobutyric acid (GABA). These analogues were designed to study the structural requirements of the corresponding GABA(A) receptor. Their biological activity was measured by in vitro test with [H-3]flunitrazepam as radio-ligand in which allopregnanolone and its active analogues stimulated the binding to the GABA(A) receptor. Analysis of the SAR data suggests dependence of the flunitrazepam binding activity on the hydrophobic-hydrophilic balance of the groups at the C-ring edge rather than on specific interactions between them and the receptor.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/GAP303%2F12%2F1464" target="_blank" >GAP303/12/1464: Studium modulačního vlivu neurosteroidů na NMDA receptory</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

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Svazek periodika

56

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

2323-2336

Kód UT WoS článku

000317032200013

EID výsledku v databázi Scopus

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