(1R,2S,5S)-6,6-ДИМЕТИЛ-3-АЗА-БИЦИКЛ[3.1.0]ГЕКСАН-2-КАРБОНОВОЙ КИСЛОТЫ МЕТИЛОВЫЙ ЭФИР ГИДРОХЛОРИД

Использование

(1S,2S,5R)-Methyl 6,6-diMethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride is an azabicyclohexane derivative used in the preparation of hepatitis C virus (HCV) NS3 serine protease inhibitor.

Общее описание

Boceprevir is a peptidomimetic protease inhibitor with four moieties, P1–P3 and a Cap, where P1 is a racemic β-aminoamide, P2 is a chiral dimethylcyclopropylproline analog, P3 is (S)-tert-leucine, and Cap is a tert-butylcarbamoyl group. The 3-azabicyclo[3.1.0]hexane structure of P2 adopts a constrained conformation, so that the gem-dimethyl group has a fixed angle with respect to the bicyclic ring structure. The incorporation of the 3-azabicyclo[3.1.0]hexane moiety results in a 1000-fold increase in NS3 protease binding over proline in a pentapeptide scaffold. When boceprevir binds to the NS3 protease, the P2 moiety interacts with four amino acid residues at the active site. The starting material for the P2 moiety is the HCl salt of the dimethylcyclopropylproline methyl ester 2. For medicinal chemistry studies, it was prepared by cyclopropanation of a Δ3-pyrroline derivative of pyroglutamic acid.