Cycloalkanoindoles. 2. 1-Alkyl-1,2,3,4-tetrahydrocarbazole-1-ethanamines and related compounds. Potential antidepressants

Abstract

The synthesis is described of a series of cycloalkanoindoles, comprising tetrahydrocarbazoles, a cyclopentindole, and a cycloheptindole, all bearing an ethanamine side chain at position 1. The acute toxicities of these compounds were evaluated, as well as their potential antidepressant properties, using tests based on the prevention of ptosis induced by reserpine and tetrabenazine. 9-Ethyl-N,N1-trimethyl-1,2,3,4-tetrahydrocarbazole-1-ethanamine (AY-24 614) was found to be the most potent analogue, having an ED50 of 0.12 mg/kg ip in preventing reserpine-induced ptosis in mice and an ED50 at 3.3 mg/kg ip in preventing tetrabenazine-induced ptosis in rats.

Strong and Confined Acids Catalyze Asymmetric Intramolecular Hydroarylations of Unactivated Olefins with Indoles

“…Additionally, a C­(sp 3 )–C­(sp 2 ) Suzuki–Miyaura cross-coupling with 2-bromonaphthalene provided compound 2x in 77% yield and, once again, without any erosion of enantiopurity. The subjection of azido-functionalized tetrahydrocarbazole 2u to a sequential N -ethylation, azide reduction, and N , N -dimethylation provided the first enantioselective synthesis of ammonium salt 8 , in 41% overall yield and with retention of enantiopurity, the racemic mixture of which is being investigated as an antidepressant …”

Unexpected [M − H]+ ions in cyclopenta[b]indoles detection by electrospray ionization mass spectrometry

“…Cyclopenta [b]indole skeletons can be found in a number of indole alkaloids, [1] and compounds containing them show various biological activities. Such compounds include antidepressants, [2] anti-implantation agents, [3,4] and effective antagonists of the prostaglandin D 2 receptor. [5] The structure's potential biological applicability has led to organic synthetic studies so as to facilitate its production.…”

Multistep One‐Pot Synthesis of Enantioenriched Polysubstituted Cyclopenta[b]indoles

“…Compounds that contain such a unit exhibit a wide range of biological activities. [3] For example, 2-aminocyclopenta [b]indoles, [4a] cyclopenta [b]indole-substituted acetic acids, [4b] and a series of yuehchukene analogues [5] have been successfully synthesized and used in medicinal chemistry. Although a number of methods have been developed for the synthesis of cyclopenta [b]indoles, [6] only few of them are asymmetric and especially catalytic asymmetric methods.…”

“…The substrate scope of N-Bn-protected indoles and aldehydes were investigated next (Table 4). N-Bn-protected indoles bearing electron-withdrawing or electron-donating groups were all suitable reaction partners and gave the corresponding cyclopenta [b]indoles 9 in good yields, and with excellent enantioselectivities and diastereoselectivities (Table 4, entries [1][2][3][4][5]. Cyclopenta [b]indoles with much greater structural complexities could be obtained by changing the aldehyde component.…”