SYNTHESIS OF NOVEL γ-CARBOLINE DERIVATIVES AND THEIR IN SILICO STUDIES ON 5HT1, H1 AND CCR2 ANTAGONIST RECEPTORS
Keywords:
Fisher indole synthesis, Nil, T P catalyst through Fischer indole synthesis was developed 3P, In silico docking studyAbstract
Objective: Synthesis of novel γ-carboline precursor 4 by using mild, inexpensive and eco friendly T3
Methods: The reaction was carried out by taking mixture of 1 equiv. of phenyl hydrazine hydrochloride, 1 equiv. of N-Boc piperidone and 0.25 equiv. of TP as catalyst and synthesis of γ-carbolinesulfonamides, amides and tertiary amines 5a-l from compound 4 as a key intermediate. In silico docking studies against 5HT1, H1 and
CCR2 antagonist receptors of all 5a-l compounds.
Results: An excellent yield of γ-carboline precursor 4 was obtained by using mild, inexpensive and eco friendly TP(50% in EtOAc) in toulene at 90 °C. After 6hr the product γ-carboline 4 was obtained by water workup followed boc deprotection by HCl in dioxane treatment. Further, the sulfonation, amidation and reductive amination were carried out to γ-carboline 4 to get derivatives of γ- carboline 5a-l. The synthesized compounds were docked against 5HT1, H1 and CCR2 antagonist receptors using AutoDock v 4.2.3
Conclusion: An eco friendly procedure to prepare γ-carboline 4 using mild and inexpensive T
P catalyst. Among the synthesized compounds, the 5b and 5c were shown three hydrogen bonding interaction having-10.1082 and-13.9105 kcal/mol of interaction energy with H1protein at the active site amino acids ARG175, TYR185 and SER128 respectively. The inhibitory constants were found to be 88.7015 and 56.2123
µM respectively.3
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