Indanes—Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors

Abstract

The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system. This bicyclic structure provides a wide range of possibilities to incorporate specific substituents in different directionalities, thus being an attractive scaffold for medicinal chemists. Notably, many indane-based compounds are being used in the clinic to treat various diseases, such as indinavir, an HIV-1 protease inhibitor; indantadol, a potent Monoamine Oxidase (MAO)-inhibitor; the amine uptake inhibitor indatraline; and the ultra-long-acting β-adrenoceptor agonist indacaterol. Given the diversity of targets these drugs act on, one could argue that the indane ring system is a privileged substructure. In the present review, the synthetic and medicinal chemistry of the indane ring system is described. In more detail, it contains a comprehensive overview of compounds bearing the indane substructure with G protein coupled receptor (GPCR) activity, with particular emphasis on their structure-activity relationships (SAR).

Enantioselective Synthesis of Indolines, Benzodihydrothiophenes, and Indanes by C−H Insertion of Donor/Donor Carbenes

“…Indanes are rigid carbocycles that feature prominently in both natural products and in drug discovery. Unlike their heterocyclic counterparts, the electron‐neutral benzene and benzylic carbon are less easily oxidized by enzymes responsible for drug clearance . Enantioselective synthesis of indanes has been achieved primarily by asymmetric reduction of indenes .…”

“…Unlike their heterocyclic counterparts, the electron-neutral benzene and benzylic carbon are less easily oxidized by enzymes responsible for drug clearance. [15] Enantioselective synthesis of indanes has been achieved primarily by asymmetric reduction of indenes. [16] Hashimoto and Lei have reported the enantioselective synthesis of indanes by C–H insertion of donor/acceptor carbenes.…”

Enantioselective Synthesis of Indolines, Benzodihydrothiophenes, and Indanes by C−H Insertion of Donor/Donor Carbenes

“…Indanes are rigid carbocycles that feature prominently in both natural products and in drug discovery.U nlike their heterocyclic counterparts,t he electron-neutral benzene and benzylic carbon are less easily oxidized by enzymes responsible for drug clearance. [15] Enantioselective synthesis of indanes has been achieved primarily by asymmetric reduction of indenes. [16] Hashimoto and Lei have reported the enantioselective synthesis of indanes by C À Hi nsertion of donor/ acceptor carbenes.…”

Enantioselective Stereodivergent Nucleophile‐Dependent Isothiourea‐Catalysed Domino Reactions

“…While the use of a4 -nitrophenol (PNP) ester gave only traces (< 5%)o ft he expected cyclisation product, [13] treating bench-stable 2,4,6-trichlorophenol (TCP) ester 5 with diketone 6 in the presence of the isothiourea HyperBTM 1 (20mol %) using polymer-supported BEMP as ab ase gave isomeric fused indanes 7a and 7b as a7 5:25 mixture in 46 %y ield and excellent 97.5:2.5 e.r.f or 7a ( Table 1, entry 1). [14][15][16][17] The minor isomer 7b was also formed with high enantioselectivity (> 99:1 e.r.). [18] Controlexperiments on isolated samples of each isomer showed that the products do not interconvertu nder the reactionc onditions.…”