3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3

Havran, Lisa M.; Chong, Dan C.; Childers, Wayne E.; Dollings, Paul; Dietrich, Arlene; Harrison, Boyd L.; Marathias, Vasilios M.; Tawa, Gregory J.; Aulabaugh, Ann; Cowling, Rebecca; Kapoor, Bhupesh; Xu, Weixin; Mosyak, Lidia; Moy, Fred; Hum, Wah-Tung; Wood, Andrew; Robichaud, Albert J.

doi:10.1016/j.bmc.2009.09.036

Cited by 21 publications

(18 citation statements)

References 25 publications

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“…Compounds 12 [50], 13 [51], 14 [52], 20 [53], 21 [54], 22 , 23 , 25 [55], and 24 [56] in Scheme 4 provided spectral data matching those reported in the literature. Compounds 26 , 27 [57], and 28 [58] in Scheme 5 were prepared following reported procedures.…”

Section: Methodssupporting

confidence: 55%

Chiral Aminophosphines as Catalysts for Enantioselective Double-Michael Indoline Syntheses

Khong

Kwon

2012

Molecules

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The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient acetylenes is an efficient process for the synthesis of many nitrogen-containing heterocycles. Because the resulting heterocycles contain at least one stereogenic center, this double-Michael reaction would be even more useful if an asymmetric variant of the reaction were to be developed. Aminophosphines can also facilitate the double-Michael reaction and chiral amines are more readily available in Nature and synthetically; therefore, in this study we prepared several new chiral aminophosphines. When employed in the asymmetric double-Michael reaction between ortho-tosylamidophenyl malonate and 3-butyn-2-one, the chiral aminophosphines produced indolines in excellent yields with moderate asymmetric induction.

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Section: Methodssupporting

confidence: 55%

Chiral Aminophosphines as Catalysts for Enantioselective Double-Michael Indoline Syntheses

Khong

Kwon

2012

Molecules

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“…Havran et al screened a library of compounds against caspase-3 and detected one lead structure 408, which was further optimized. 345 Several structurally different ligands were attached to 3,4-dihydropyrimido(1,2-α)indol-10(2H)-on scaffold, leading to the discovery of a set of potent caspase inhibitors. Compound 409 displayed the highest potency from the series but only moderate chemical stability.…”

Section: Caspase Inhibitorsmentioning

confidence: 99%

Small Molecule Active Site Directed Tools for Studying Human Caspases

et al. 2015

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Caspases are proteases of clan CD and were described for the first time more than two decades ago. They play critical roles in the control of regulated cell death pathways including apoptosis and inflammation. Due to their involvement in the development of various diseases like cancer, neurodegenerative diseases or autoimmune disorders, caspases have been intensively investigated as potential drug targets, both in academic and industrial laboratories. This review presents a thorough, deep, and systematic assessment of all technologies developed over the years for the investigation of caspase activity and specificity using substrates and inhibitors, as well as activity based probes, which in recent years have attracted considerable interest due to their usefulness in the investigation of biological functions of this family of enzymes.

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“…To better understand the binding model of synthesized inhibitors with caspase-3 and guide further design and research, compounds 11, 24, and co-crystallized inhibitor 24 were selected and docked into the active site for docking simulation studies (Fig. 3).…”

Section: Docking Studiesmentioning

confidence: 99%

Synthesis and evaluation of N-acyl-substituted 1,2-benzisothiazol-3-one derivatives as caspase-3 inhibitors

Pan

Zhong

et al. 2014

Bioorganic & Medicinal Chemistry

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3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3

Cited by 21 publications

References 25 publications

Chiral Aminophosphines as Catalysts for Enantioselective Double-Michael Indoline Syntheses

Chiral Aminophosphines as Catalysts for Enantioselective Double-Michael Indoline Syntheses

Small Molecule Active Site Directed Tools for Studying Human Caspases

Synthesis and evaluation of N-acyl-substituted 1,2-benzisothiazol-3-one derivatives as caspase-3 inhibitors

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