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 89 publications

(36 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

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 89 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

Contact Info

Product

Resources

About