4-Oxo-1,2,3,4-tetrahydroquinazolines. I. Syntheses and pharmacological properties of 2-methyl-3-aryl-4-oxo-1,2,3,4-tetrahydroquinazolines and their 1-acyl derivatives

Okumura, Kentaro; Oine, Toyonari; Yamada, Yoshihisa; Hayashi, Gosuke; Nakama, Mototaka

doi:10.1021/jm00308a036

Cited by 88 publications

(36 citation statements)

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“…Substituted 2,3-dihydroquinazolin-4(1 H )-ones have been well studied for various biological properties81617181920212223. Racemization of the aminal stereo center in the substituted 2,3-dihydroquinazolin-4(1 H )-ones has been reported8.…”

Section: Discussionmentioning

confidence: 99%

Common Pharmacophore of Structurally Distinct Small-Molecule Inhibitors of Intracellular Retrograde Trafficking of Ribosome Inactivating Proteins

Shen

Park

Kahn

et al. 2013

Sci Rep

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We reported previously (±)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one [(±)-Retro-2cycl] as the chemical structure of Retro-2 that showed mouse protection against ricin, a notorious ribosome inactivating protein (RIP). Herein we report our chemical resolution of (±)-Retro-2cycl, analog synthesis, and cell-based evaluation showing that the two optically pure enantiomers and their achiral analog have nearly the same degree of cell protection against ricin as (±)-Retro-2cycl. We also report our computational studies explaining the lack of stereo preference and revealing a common pharmacophore of structurally distinct inhibitors of intracellular retrograde trafficking of RIPs. This pharmacophore comprises a central aromatic ring o-substituted by an aromatic ring and a moiety bearing an O or S atom attached to sp2 C atom(s). These results offer new insights into lead identification and optimization for RIP antidote development to minimize the global health threat caused by ribosome-inactivating proteins.

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Section: Discussionmentioning

confidence: 99%

Common Pharmacophore of Structurally Distinct Small-Molecule Inhibitors of Intracellular Retrograde Trafficking of Ribosome Inactivating Proteins

Shen

Park

Kahn

et al. 2013

Sci Rep

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“…2,3-Dihydroquinazolin-4(1H)-one derivatives are an important class of fused Ncontaining heterocycles with various biological, medicinal, and pharmacological activities such as antitumor [3] , antibiotic [4] , antifungal [5] , analgesic [6] , diuretic [7] , antifertility [8] , antidepressant [9] , antihistaminic [10] , vasodilating [11] , and antifibrillatory agent [12] . In addition, these compounds can act as potent tubulin inhibitors with promising anti-proliferative activity against several human cancer cell lines [13] .…”

Section: Introductionmentioning

confidence: 99%

Convenient and Scalable Synthesis of 2,3-Dihydroquinazolin-4(1H)-one Derivatives and Their Anticancer Activities

Lingayya

Penumati

Nagaiah

et al. 2015

Synthetic Communications

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An efficient and mild InBr 3 -catalyzed approach to synthesize 2,3-dihydroquinazolin-4(1H)-one derivatives (3a-3aa) has been developed. Notably, all the products were isolated by recrystallization and the reaction is accessible on a gram scale. Moreover, the reactions only require 10-60 min. All the synthesized compounds were evaluated for their in vitro anticancer activity against four human cancer cell lines.

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“…The quinazolinone moiety contained in natural products (Luotonin, Rutaecarpine, Tryptanthrin, Chloroqualone, Alloqualone, etc) represents medicinally and pharmaceutically important class of compounds [23,24] because of their diverse range of biological activities such as anti-cancer, diuretic, anti-inflammatory, anticonvulsant and anti-hypertensive [25,26]. In recent years, quinazolinone embedded numerous natural products have been identified [27].…”

Section: Introductionmentioning

confidence: 99%

Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells

Venkatesh

Ramaiah

Gaikwad

et al. 2015

European Journal of Medicinal Chemistry

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4-Oxo-1,2,3,4-tetrahydroquinazolines. I. Syntheses and pharmacological properties of 2-methyl-3-aryl-4-oxo-1,2,3,4-tetrahydroquinazolines and their 1-acyl derivatives

Cited by 88 publications

References 0 publications

Common Pharmacophore of Structurally Distinct Small-Molecule Inhibitors of Intracellular Retrograde Trafficking of Ribosome Inactivating Proteins

Common Pharmacophore of Structurally Distinct Small-Molecule Inhibitors of Intracellular Retrograde Trafficking of Ribosome Inactivating Proteins

Convenient and Scalable Synthesis of 2,3-Dihydroquinazolin-4(1H)-one Derivatives and Their Anticancer Activities

Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells

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