Synthesis of new piperidyl indanone derivatives as anticonvulsant agents

Abstract

A series of 5,6-dimethoxy-2-{1-[arylamino/ alkylamino(thioxo)methyl]-4-piperidyl-methyl}-1-indanones (4a-l) were designed and synthesized by the reaction of 5,6-dimethoxy-2-(piperidin-4-yl-methyl)-indan-1-one with aryl/ alkyl isothiocyanates. The anticonvulsant activity was evaluated in animal models by maximal electroshock seizure and subcutaneous pentylenetetrazole tests. The neurotoxic effects were assessed by rotorod and ethanol potentiation tests. Gamma amino butyric acid (GABA) estimation of the selected compounds was performed in rat brain utilizing UV absorbance data. Compounds 4d, 4g, and 4j displayed encouraging anticonvulsant profile against both seizure models with remarkably lower neurotoxicity. These compounds were found to increase the GABA level in rat brain significantly.

Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

“…Compounds with aminothiazole scaffold display a wide range of biological activities, 9 including antiparasitic-, 10 antifungal-, 11 antibacterial-, 12 antitubucular-, 13 antiviral-, 14 anticancer-, 15, 16 and antiprion 17 action. The study described here was carried out to establish the basic anti- Histoplasma and anti- Cryptococcus specific aminothiazole Structure-Activity Relationships (SARs) .…”

Thiazoyl phosphines. Design, reactivity, and complexation

“…Yield 0.335 g (90%). 1 H NMR (DMF d8 , 400 MHz) δ: 7.82-7.13 (m, 23H, OAr, Ar, NH 2 , CH-thiazoyl). 13 C{ 1 H} NMR (DMF d8 , 400 MHz) δ: 176.9 (d, 3 J C-P = 10.9 Hz, 2-thiazoyl), 152.7 (d, 1 J C-P = 7.6 Hz, 5-thiazoyl), 152.1 (d, 3 J C-P = 11.8 Hz, 4-thiazoyl), 152.1 (d, 3 J C-P = 4.8 Hz, ipso-Ar), 132.9 (d, 3 J C-P = 2.9 Hz, m-Ar), 132.0 (d, 2 J C-P = 11.5 Hz, o-Ar), 130.5 (d, 1 J C-P = 113.8 Hz, ipso-OAr, d, 3 J C-P = 4.8 Hz, ipso-Ar), 129.4 (s, p-Ar), 128.9 (d, 4 J C-P = 13.2 Hz, m-OAr), 123.8 (s, p-OAr), 120.5 (d, 3 J C-P = 5.0 Hz, o-OAr), 109.5 (d, 2 J C-P = 113.8 Hz, ipso-OAr, d, 4 J C-P = 3.1 Hz, ipso-Ar).…”

“…Yield 0.305 g (80%). 1 H NMR (DMF d8 , 400 MHz) δ: 8.30-7.30 (m, 23H, O-Ar, Ar, NH 2 , CH-thiazoyl). 13 C{ 1 H} NMR (DMF d8 , 100 MHz) δ: 177.4 (d, 3 J C-P = 11.2 Hz, 2-thiazoyl, minor isomer), 177.2 (d, 3 J C-P = 10.9 Hz, 2-thiazoyl, major isomer), 152.9 (d, 2 J C-P = 12.0 Hz, 4-thiazoyl, minor isomer), 152.6 (d, J C-P = 9.1 Hz, 5-thiazoyl, major isomer), 152.4 (d, 2 J C-P = 9.1 Hz, 4-thiazoyl, major isomer), 151.9 (d, 1 J C-P = 9.9 Hz, 5-thiazoyl, minor isomer), 130.6 (d, 1 J C-P = 116.1 Hz, and d, 3 J C-P = 4.7 Hz, ipso-Ar, major isomer), 129.6-129.0 (m-Ar, m-OAr, o-Ar, o-OAr, major and minor isomers), 122.1 (s, p-OAr, minor isomer), 121.8 (s, p-OAr, major isomer), 125.1 (s, p-Ar, minor isomer), 124.4 (s, p-Ar, major isomer).…”

“…Indeed numerous drugs containing these heterocyclic moieties are intensively studied in medicinal chemistry for their anticancer, antibacterial, antiviral, antifungal, anticonvulsant, and anti-inflammatory properties. [1][2][3][4] Recently the role of thiazoles and more specifically thiazolines in catalysis was emphasized. 5 The versatile chemistry of these compounds is mainly due to the presence of two nucleophilic centres localized on nitrogen and sulphur atoms and due to the electrophilic carbon centre on the intracyclic imine function.…”

Synthesis and structure-activity-relationships of indan acid derivatives as analgesic and anti-inflammatory agents

“…Indan (also known as indane or benzocyclopentane) ring system ( Figure 1) is regarded as an ideal chemical feature associated with various biological activities [1][2][3]. Over the years, several indan derivatives have been synthesized with the expectation of generating pharmacologically active compounds as new drug candidates.…”