Synthesis, NMR conformational analysis and pharmacological evaluation of 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a′]diindole analogues as melatonin receptor ligands

Attia, Mohamed I.; Güclü, Deniz; Hertlein, Barbara; Julius, Justin; Witt‐Enderby, Paula A.; Zlotos, Darius P.

doi:10.1039/b705550a

Cited by 26 publications

(17 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Almost all the scaffolds shown in Figure 2 were bearing at least one of these features, with rare exceptions. The ethylamide moiety was either included in a cycle, 33,43,87,94,106,118,122 or bearing a double bond 87,94 or various substituents, such as CF 3 , 45,109,110,120 CHF 2 , 45,132 CH 2 Cl, 34,117 a cyclopropyl moiety 29,102,114,116,133 or a cyclobutyl moiety 42,66 to name only a few.…”

Section: The Alkoxy and N‐acylamino Decorationsmentioning

confidence: 99%

Melatonin receptor ligands: A pharmaco‐chemical perspective

Boutin

Witt‐Enderby

Sotriffer

et al. 2020

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

Melatonin MT1 and MT2 receptor ligands have been vigorously explored for the last 4 decades. Inspection of approximately 80 publications in the field revealed that most melatonergic ligands were structural analogues of melatonin combining three essential features of the parent compound: an aromatic ring bearing a methoxy group and an amide side chain in a relative arrangement similar to that present in melatonin. While several series of MT2‐selective agents—agonists, antagonists, or partial agonists—were reported, the field was lacking MT1‐selective agents. Herein, we describe various approaches toward the development of melatonergic ligands, keeping in mind that most of the molecules/pharmacophores obtained were essentially melatonin copies, even though diverse tri‐ or tetra‐cyclic compounds were explored. In addition to lack of structural diversity, only few studies examined the activity of the reported melatonergic ligands in vivo. Moreover, an extensive pharmacological characterization including biopharmaceutical stability, pharmacokinetic properties, specificity toward other major receptors to name a few remained scarce. For example, many of the antagonists described were not stable in vivo, were not selective for the melatonin receptor subtype of interest, and were not fully characterized from a pharmacological standpoint. Indeed, virtual screening of large compound libraries has led to the recent discovery of potent and selective melatonin receptor agonists and partial agonists of new chemotypes. Having said this, the melatonergic field is still lacking subtype‐selective melatonin receptor antagonists “active” in vivo, which are critical to our understanding of melatonin and melatonin receptors’ role in basic physiology and disease.

show abstract

Section: The Alkoxy and N‐acylamino Decorationsmentioning

confidence: 99%

Melatonin receptor ligands: A pharmaco‐chemical perspective

Boutin

Witt‐Enderby

Sotriffer

et al. 2020

Journal of Pineal Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…More recently, several benzimidazole containing indole and tetrahydronaphthalene indole derivatives were reported as strong inhibitors of lipid peroxidation and superoxide anion formation 16,17 . Several antioxidant pyrimidodiindole and pyridoindole derivatives were studied as melatonin receptor antagonists 18,19 . Recent data from our laboratory showed important antioxidant effects of N-substituted amide [20][21][22][23][24] and ester 25 derivatives of indole.…”

Section: Research Articlementioning

confidence: 99%

Synthesis of new indole-2-carboxamide and 3-acetamide derivatives and evaluation their antioxidant properties

Ölgen¹,

Bakar

Aydin³

et al. 2011

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

“…Furthermore, Moody et al reported that reductive cyclisation of the ethyl 4-(2-nitropheny)-acetoacetate using titanium(III) chloride in aqueous acetone gave 2-(1H-indol-2-yl) acetate with a 75% yield [22]. Despite producing good yields, these methods suffer from indispensable multi-step pre-transformations of commercially available starting materials, and are therefore of limited synthetic scope [23]. Wilkens et al described a one-pot reaction of N-phenylhydroxylamine, benzaldehyde and ethyl 2,3-butadienoate followed by hydrolysismediated production of 2-(1H-indol-2-yl)acetate [24].…”

Section: Introductionmentioning

confidence: 99%