Synthesis and some novel reactions of 8-chloro-2H-[1,2,4]triazino[3,4-b] [1,3]benzothiazole-3,4-dione and 6-chloro-2-hydrazino-1,3-benzothiazole

Kuberkar, S. V.; Bhosale, Vijay N.; Vartale, Sambhaji P.; Badne, S. G.

doi:10.3184/030823405774663084

Cited by 7 publications

(2 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All starting materials, reagents, and solvents were purchased from common commercial suppliers and were used as such without further purification. Compounds 2 , 60 7 , 61 11 , 53 16 , 53 19 , 62 20 , 54 33 , 63 44 , 64 45 , 65 46 , 66 48 , 64 49 , 67 50 , 68 51 , 69 52 , 70 53 , 69 54 , 71 55 , 72 56 , 72 58 , 71 59 , 71 60 , 73 61 , 74 62 , 70 63 , 71 64 , 75 68 , 75 69 , 75 70 , 75 73 , 75 77–79 , 76 80 , 77 81 , 78 and 82 ( 70 ) were prepared as described in the literature. Organic solutions were dried over anhydrous Na 2 SO 4 and concentrated with a rotary evaporator at low pressure.…”

Section: Methodsmentioning

confidence: 99%

[1,2,4]Triazolo[3,4-b]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes

et al. 2023

View full text Add to dashboard Cite

We report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogues and cocrystal structures with TNKS2, PARP2, PARP14, and PARP15. Based on the substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) and 27 (OUL232) as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15 at nM potencies, with 27 being the most potent PARP10 inhibitor described to date (IC50 of 7.8 nM) and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity toward PARP2. The scaffold does not possess inherent cell toxicity, and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of TBT scaffold for future drug development efforts toward selective inhibitors against specific enzymes.

show abstract

Section: Methodsmentioning

confidence: 99%

[1,2,4]Triazolo[3,4-b]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes

et al. 2023

View full text Add to dashboard Cite

show abstract

“…All starting materials, reagents, and solvents were purchased from common commercial suppliers and were used as such without further purification. Compounds 2 59 , 7 60 , 11 52 , 16 52 , 19 61 , 20 53 , 33 62 , 44 63 , 45 64 , 46 65 , 48 63 , 49 66 , 50 67 , 51 68 , 52 69 , 53 68 , 54 70 , 55 71 , 56 71 , 58 70 , 59 70 , 60 72 , 61 73 , 62 69 , 63 70 , 64 74 , 68 74 , 69 74 , 70 74 , 73 74 , 77-79 75 , 80 76 , 81 77 , and 82 69 were prepared as described in literature. Organic solutions were dried over anhydrous Na 2 SO 4 and concentrated with rotary evaporator at low pressure.…”

Section: Methodsmentioning

confidence: 99%

[1,2,4]Triazolo[3,4-b]benzothiazole scaffold as versatile nicotinamide mimic allowing nanomolar inhibition of different PARP enzymes

Murthy

Nizi

Maksimainen

et al. 2022

Preprint

View full text Add to dashboard Cite

Here we report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogs and their crystal structures with TNKS2, PARP2, PARP14 and PARP15. Based on the substitution pattern, we were able to identify The 3-amino derivatives 21 (OUL243) and 27 (OUL232), as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14 and PARP15 at nM potencies, with compound 27 being the most potent PARP10 inhibitor described to date with an IC50 of 7.8 nM and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity towards PARP2. The scaffold does not possess inherent cell toxicity and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of the TBT scaffold for future drug development efforts towards selective inhibitors against specific enzymes.

show abstract