Novel 7-methoxy-6-oxazol-5-yl-2,3-dihydro-1H-quinazolin-4-ones as IMPDH inhibitors

Birch, Helen; Buckley, George M.; Davies, Natasha; Dyke, Hazel J.; Frost, Elizabeth J.; Gilbert, Philip J.; Hannah, Duncan R.; Haughan, Alan F.; Madigan, Michael J.; Morgan, Trevor; Pitt, William R.; Ratcliffe, Andrew J.; Ray, Nicholas C.; Richard, Marianna D.; Sharpe, Andrew; Taylor, Alicia J.; Whitworth, Justine M.; Williams, Sophie C.

doi:10.1016/j.bmcl.2005.06.108

Cited by 53 publications

(21 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3. The crystal is of monoclinic, space group P21 with 34, the thiophene ring is disordered, and the oxazole ring and benzene ring are almost coplanar [dihedral angle ¼ 5.6 (0) ]. The dihedral angle between thiophene ring and benzene ring is 85.6 (0) .…”

Section: Chemistrymentioning

confidence: 99%

“…The (5-oxazolyl) phenyl compounds containing amide (e.g., 8 and 9) [26] and diamide (e.g., 10) [27] linkers have been synthesized as inhibitors of IMPDH, and compound 9 is a dual inhibitor of IMPDH and histone deacetylases (HDACs) [28,29]. The analogues of oxazolyl-indole [30], oxazolyl-quinolone [31,32], oxazolyl-quinazolinone and quinazolinethione [33,34] based linkers, compounds 11, 12, 13 and 14 yield good IMPDH inhibitors.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines

Zhong

Zhang

Peng

et al. 2013

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines

Zhong

Zhang

Peng

et al. 2013

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

“…VX-497 recently entered clinical studies as a potential anti-hepatitis C drug and as an immunosuppressant. In the past several years other major pharmaceutical companies such as Bristol-Myers Squibb (BMS), [63,64] Roche, [65] Gilead, [66] and UCB [67,68] have published numerous reports on similar inhibitors of IMPDH that bind at the cofactor site.…”

Section: Heterocyclic Inhibitors Bound At the N Sub-sitementioning

confidence: 99%

Rehab of NAD(P)-Dependent Enzymes with NAD(P)-Based Inhibitors

Felczak

Pankiewicz

2011

CMC

View full text Add to dashboard Cite

A large number of enzymes that use nicotinamide adenine dinucleotide NAD or its phosphorylated form NADP as a cofactor or substrate were found to play an important role in the growth and reproduction of living organisms. NAD(P)-dependent and NAD(P)-utilizing enzymes [NAD(P)-addicted?] have been extensively investigated and implicated in a wide variety of diseases. NAD, generally considered a key component involved in redox reactions, has been found to participate in a broad spectrum of cellular processes, including signal transduction, DNA repair, and post-translational protein modifications. The reduced form of NADP, i.e. NADPH, guards the cell against oxidative stress and it has been suggested that suppression of NADPH oxidase activity could result in anti-angiogenesis and anticancer effects. Consequently, small molecule NAD(P)-based inhibitors that selectively bind at the NAD(P)-binding domain of the targeted enzyme have been designed for novel treatment of medical disorders. The NAD(P)-binding domain is modular in nature; it can be divided into three sub-sites, the nicotinamide monophosphate (NMN) binding sub-site (N sub-site), the adenosine monophosphate (AMP) binding sub-site (A sub-site), and the pyrophosphate binding sub-site (P sub-site or P-groove). Each sub-site plays an important role in securing proper and tight binding; however, each has its own requirements. In this review we discuss a number of conformational and structural factors that might affect (improve) the affinity of various inhibitors to these sub-sites, as well as to the whole binding domain. We have focused on potential selectivity of NAD(P)-like molecules toward targeted enzymes and their potential application in biology and medicine.

show abstract

“…Apart from this, dihydroquinazolinones exhibited different biological activities like antibacterial, [7] anticonvaluscent, [8] antiemetic and gastrointestinal motility enhancing agents, [9] IMPDH inhibitors, [10] antifibrillatory activity, [11] antihistaminic action, [12] antiinflammatory, [13,14] antitubercular activities, [15] potential inhibitors of SIRT1, [16] Antileishmanial agents [17] and antitumor agents [18].…”

Section: Introductionmentioning

confidence: 99%

Dihydroquinazolinones as Potential Antiproliferative and Tumor Inhibiting agents

Rangappa¹

2016

OMCIJ

View full text Add to dashboard Cite

Novel 7-methoxy-6-oxazol-5-yl-2,3-dihydro-1H-quinazolin-4-ones as IMPDH inhibitors

Cited by 53 publications

References 14 publications

Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines

Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines

Rehab of NAD(P)-Dependent Enzymes with NAD(P)-Based Inhibitors

Dihydroquinazolinones as Potential Antiproliferative and Tumor Inhibiting agents

Contact Info

Product

Resources

About