Design, synthesis, in vitro evaluation of a new pyrrolo[1,2‐a]thiazolo[5,4‐d]pyrimidinone derivatives as cholinesterase inhibitors against Alzheimer's disease

Abstract

A novel of 40 pyrrolo[1,2‐a]thiazolo[5,4‐d]pyrimidinone derivatives were designed and synthesized as cholinesterase inhibitor agents. The in vitro enzyme assays proved that most of the compounds effectively inhibited cholinesterases in the micromolar range with little cytotoxicity. Compound G15 exhibited the best inhibitory activity against acetylcholinesterase with an IC50 of 2.69 ± 0.17 μM. Kinetic analysis and molecular modeling testified the competitive inhibition manner of G15 was more likely to bind to the active center of acetylcholinesterase. Thus, compound G15 can be considered as promising lead compounds or candidates for the development of novel drugs against Alzheimer's disease.

Xinazolin Alkaloidlarining Tiofenli Analoglari: 2-N(alkil, Aril)-Tieno[2,3-D]pirimidinonlarning Sintezi Va Modifikasiyasi

“…In recent years, much information has been published about pyrimidine derivatives condensed with various heterocycles [12], such as: purines, pteridines, quinazolines, pyridopyrimidines, pyrimidoazepines, furo-and pyrrolopyrimidines, thienopyrimidines, their synthesis and chemical transformations. also confirm the importance of these class combinations [13][14][15][16]3,[17][18][19][20][21][22].…”

“…Kondensirlangan pirimidinlarning kimyosi va amaliy ahamiyati, jumladan keng ko'lamli biologik faolligi turli davlatlarning olimlari e'tiborini tortib kelmoqda [11]. So'nggi yillarda pirimidin xalqasining turli geteroxalqalar bilan kondensirlangan hosilalari [12], masalan: purinlar, pteridinlar, xinazolinlar, piridopirimidinlar, pirimidoazepinlar, furo-va pirrolopirimidinlar, tiyenopirimidinlar, ularning sintezi va kimyoviy o'zgarishlari haqida keng ko'lamda chop etilayotgan ma'lumotlar ham bu sinf birikmalarining muhimligini tasdiqlaydi [13][14][15][16]3,[17][18][19][20][21][22].…”

“…В последние годы опубликовано большое количество информации о производных пиримидина, конденсированных с различными гетероциклами [12], таких как: пурины, птеридины, хиназолины, пиридопиримидины, пиримидоазепины, фуро-и пирролопиримидины, тиенопиримидины, их синтезе и химических превращениях. также подтверждают важность этих комбинаций классов [13][14][15][16]3,[17][18][19][20][21][22].…”

Furo[2,3‐d]pyrimidines as Mackinazolinone/Isaindigotone Analogs: Synthesis, Modification, Antitumor Activity, and Molecular Docking Study

“…[31] Our research group performed a large scientific investigation targeting the synthesis [35][36][37] and biological potentials [38,39] of the synthetic analogs of deoxyvasicinone and mackinazolinone, which are natural alkaloids isolated from the plants Adhatoda vasica and Mackilaya subulata Philipson, respectively. These include tricyclic quinazolines, [40] thieno[2,3-d]pyrimidines, [41] pyrrolo [2,3-d]pyrimidines, [42,43] furo [2,3d]pyrimidines, [42,43] oxazolo [5,4-d]pyrimidines, [44,45] thiazolo [5,4-d]pyrimidines, [46] purines, [47] and their sources monocyclic five-membered esters, which found as antiproliferative agents against human cancer cell lines. In addition, another natural compound isaindigotone, isolated from the root of the traditional Chinese herb Isatis indigotica [47,48] also bears a quinazoline skeleton in its own structure and contains deoxyvasicinone and mackinazolinone family.…”

Parallel synthesis of condensed pyrimidine-thiones and their antitumor activities

“…Naturally-occurring alkaloids deoxyvasicinone [21,22] and mackinazolinone [23] are isolated from the plants Adhatoda vasica and Mackilaya subulata Philipson, respectively. These pyrimidine-based derivatives have demonstrated potential biological properties [24][25][26].…”