In vitro Controlled Release from Solid Pharmaceutical Formulations of two new Adamantane Aminoethers with Antitubercular Activity (I).

Abstract

The aim of the present investigation was to develop matrix tablet formulations for the in vitro controlled release of 2 new tuberculocidal adamantane aminoethers (compounds and), congeneric to the adamantane derivative , which is in final clinical trials, using carefully selected excipients, such as polyvinylpyrrolidone, sodium alginate and lactose. The tablets were prepared using the direct compression method and dissolution experiments were conducted using the US Pharmacopoeia type II apparatus (paddle method) in gastric and intestinal fluids. The results confirm that both analogues, albeit more lipophilic than, showed satisfactory in vitro release characteristics from solid pharmaceutical formulations. In conclusion, these formulations merit further assessment by conducting in the future bioavailability in vivo studies.

In vitro Controlled Release of two new Tuberculocidal Adamantane Aminoethers from Solid Pharmaceutical Formulations (II)

“…molecules are congeneric to the previously reported analogues (I) and (II) (▶ Fig. 1) [12,13]. Albeit the fact that the lipophilicities of compounds (IΙΙ) (QPlogP 0 / w = 6.964) and (IV) (QPlogP 0 / w = 7.264) are higher than that of SQ109 (clogP = 6.205), and of compounds (I) (QPlogP 0 / w = 4.773) and (II) (QPlogP 0 / w = 5.382), they are, however, within the allowed limits for oral administration [14] (▶ Table 1).…”

“…In the context of our ongoing search on new orally administered adamantane based analogues with an antitubecular profile [12], the in vitro controlled release of two new compounds (ΙΙΙ and IV) with noticeable antitubercular action is presented herein. molecules are congeneric to the previously reported analogues (I) and (II) (▶ Fig.…”

Synthesis of diphenoxyadamantane alkylamines with pharmacological interest

“…The 1,2-diamine congeners, such as the adamantane derivative SQ-109 18,19 and the camphane aminoalcohols 20 exhibit very low toxicity and improved pharmacokinetic properties. Our lab has also reported antimycobacterial adamantane derivatives [21][22][23] bearing a diarylmethane scaffold. 24 The synthesis of the new adamantane piperazines Ia-c is depicted in Scheme 1.…”

Synthesis of New Indole and Adamantane Amido Derivatives with Pharmacological Interest

“…Based on the fact that 2‐indole carboxamides are targeting MmpL3 transporter functions of M. tuberculosis, we replaced the indole scaffold with the adamantane core in amides 2 c , d , g , h . Our laboratory has previously published various antimycobacterial adamantane adducts with diverse structures …”