γ-Carboline AC190 analogues via palladium catalysed allene insertion stereo and regioselective 3- and 5-component cascades

Abstract

ABSTRACT-Carbolines were prepared from pyrido[4,3-b]-5H-indoles via Pd(0)-catalysed, stereo and regioselective allene/uridine allene insertion 3-and 5-component cascades. This versatile reaction sequence gives a range of structurally diverse carboline derivatives and tolerates a broad range of substrates. The power of this approach has been harnessed to produce -carboline based HDAC inhibitors.

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…In these examples, almost equimolar amounts of the desired 2,5-dialkylation product and unexpected 3,4-dihydropyrimido­[3,4- a ]­indole heterocycle were formed. Some of the freshly prepared compounds showed inhibition of HDAC3 and HDAC2, being potential candidates for antitumor drugs …”

“…Some of the freshly prepared compounds showed inhibition of HDAC3 and HDAC2, being potential candidates for anti-tumor drugs. 90 Scheme 58. Synthesis of structurally diverse γ-carboline analogues.…”

“…Some of the freshly prepared compounds showed inhibition of HDAC3 and HDAC2, being potential candidates for antitumor drugs. 90 Employing the same relay system concept, a simple synthesis of substituted functionalized isoquinolinones and isoquinolines-type compounds was reported by same group. From readily available 2-iodobenzoates, benzaldehydes, or acetophenones and substituted allenes, the three-component cascade process was mediated via Pd catalysis.…”

New derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors: Synthesis, biological testing and solubility in pharmaceutically relevant solvents

“…A number of the most important drug structures have been identified by analyzing the results of experimental bioscreening of a large set of substances, their medical applications and structural data (Rekker and Mannhold, 1992). Among them are pyrido[4,3-b]indole derivatives with a wide range of biological activity: antihistamine, central depressant, anti-inflammatory, neuroleptic and other types (Ivachtchenko et al, 2010, Stefek et al, 2011, Dondas et al, 2016). The structural analogues of this series, and the antihistamine drug Dimebon (Latrepirdine) in particular, were found to slow down the neurodegenerative process (Ikonomidou and Turski, 2002, Doody et al, 2008).…”