Synthesis of 2‐Aryl‐12H‐benzothiazolo[2,3‐b]quinazolin‐12‐ones and Their Activity Against Monoamine Oxidases

Abstract

Benzothiazoloquinazolines are known to possess several interesting biological properties. Various arylated benzothiazoloquinazolines were synthesized from readily available 2‐bromo‐12H‐benzothiazolo[2,3‐b]quinazolin‐12‐one by palladium catalysed Suzuki‐Miyaura reactions in 43 – 85% yield. Synthesized derivatives were analysed regarding their in vitro inhibition activity towards monoamine oxidases A and B and showed significant inhibitory values in the micromolar range. Molecular modelling as well as PAINS studies on the binding interaction of most potent inhibitors with both isoforms were studied to verify the experimental results.

Synthesis of 2‐Alkynyl‐ and2‐Amino‐12H‐benzothiazolo[2,3‐b]quinazolin‐12‐ones and Their Inhibitory Potential against Monoamine Oxidase A and B

“…Among all evaluated compounds, 4 h was found as the most potent and selective inhibitor of MAO−A with an IC 50 ± SEM value of 0.42 ± 0.01 μM, followed by 4 g and 4 e showing strong inhibition values of 1.04 ± 0.06 and 4.01 ± 0.22 μM, respectively. Compound 4 h proved to be considerably more active against MAO−A than the best derivative of our recently reported 2‐aryl‐12 H ‐benzothiazolo[2,3‐ b ]quinazolin‐12‐one series (2.82 μM) …”

“…Substitution with 3‐trifluoromethylbenzylamine 4 e is noticed as a potent inhibitor for both isoforms with slightly reduced inhibitory activity towards MAO−A. Analogously, in our previous study on corresponding 2‐aryl‐12 H ‐benzothiazolo[2,3‐ b ]quinazolin‐12‐ones, compounds substituted by fluorinated aryl moieties were identified as the most potent inhibitors among the tested derivatives . Hence, these results indicate a positive impact of aryl fluoride substituents on the inhibitory activity of 12 H ‐benzothiazolo[2,3‐ b ]quinazolin‐12‐ones.…”

“…Recently, we have reported the synthesis of 8‐functionalized‐2‐methyl‐3‐fluoro‐benzo[4,5]thiazolo[3,2‐ a ]pyrimidin‐4‐ones as well as the synthesis of 2‐arylated benzothiazoloquinazolinones and investigated their potential as MAO inhibitors . For the latter compounds we observed good inhibition concentrations for MAO−A and MAO−B which suggested that the benzothiazolo[2,3‐ b ]quinazolin‐12‐one core structure is quite promising as a scaffold for further investigations and SAR studies.…”

Copper-Catalyzed Domino-Double Annulation of o-Aminobenzamides with 2-Iodoisothiocyanates for the Synthesis of 12H-Benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones

“…6 Due to the important academic values and practical applications of 12H-benzo [4,5]thiazolo[2, 3-b]quinazolin-12ones in organic and pharmaceutical chemistry, a series of synthetic strategies have been developed to construct these compounds. 7 For example, Huang and co-workers developed a simple and efficient synthesis of 12H-benzo [4,5]thiazolo[2, 3b]quinazolin-12-ones by copper-catalyzed domino reaction of isatins and 2-bromobenzo[d]thiazoles (Scheme 1a). 8 Phan and co-workers demonstrated that 12H-benzo [4,5]thiazolo[2, 3b]quinazolin-12-ones could be prepared by a copper-catalyzed oxidative C−C bond cleavage pathway (Scheme 1b).…”

Synthesis and Antitumor Activity of 3-Hydrazone Quinazolinone Derivatives

“…喹唑啉酮类衍生 物还对乙酰胆碱酶 [21] 和丁酰胆碱酶 [22] 有抑制活性, 该 类化合物对结核分支杆菌也有抑制活性 [23] . 该类化合 物对单胺氧化酶 A [24] 及单胺氧化酶 B [25] 亦有抑制活性, 有望成为治疗神经退行性疾病帕金森病的先导药物. 由金属催化反应 [26] 、 微波辐射 [27] 和常规加热 [28] 等方 法已成功获得结构多样的喹唑啉酮骨架.…”