The AA. describe the synthesis of some 1-substituted 10-phenyl-3,4-dihydropyrazino(1,2-a)indoles and 11-phenyl-4,5-dihydro-3H-1,4-diazepino(1,2-a)indoles. Preliminary pharmacological tests indicate that these products, have lower sedative and antiadrenergic activity than the compounds reported in our previous paper.
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J Org Chem
December 2024
Medicinal Chemistry, Oncology R&D, AstraZeneca, The Discovery Centre, 1 Francis Crick Avenue, Cambridge CB2 0AA, United Kingdom.
The increasing popularity of the dihydrouracil motif in cereblon (CRBN) recruiting proteolysis-targeting chimeras (PROTACs) has necessitated the development of a facile, cost-effective, and high-yielding method for its introduction into molecules. To that end, we disclose herein an N-1 selective Pd-catalyzed cross-coupling of dihydrouracil with aryl electrophiles to provide access to medicinally relevant scaffolds in a single step. This approach exhibits excellent functional group tolerance and broad applicability to an abundance of (hetero)aryl halides and phenol derivatives and utilizes readily available catalyst/ligand systems.
View Article and Find Full Text PDFChemistryOpen
October 2024
CNRS, ICMMO, CP3A Organic Synthesis Group, Université Paris-Saclay, 17 Avenue des Sciences, 91400, Orsay, France.
N-substituted derivatives of anti-(2R,3S)-1,3-diamino-4-phenylbutan-2-ol are important building blocks for the synthesis of therapeutically important molecules. We describe a simple protocol that allows transformation of N,N-dibenzyl-L-phenylalaninal into such compounds in only two steps. The first step is a fully stereoselective three-component MAC (Masked Acyl Cyanide) oxyhomologation reaction implicating different amines to give a panel of ten N,N-dibenzyl-O-tert-butyldimethylsilyl-protected anti-(2S,3S)-allophenylnorstatin amides.
View Article and Find Full Text PDFOrg Lett
November 2024
Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
A two-step procedure, combining a SmI-mediated transannular pinacol coupling reaction with an acid-catalyzed pinacol rearrangement process, was employed to prepare a diverse range of 1-substituted bicyclo[2.1.1]hexan-5-ones from cyclobutanedione derivatives.
View Article and Find Full Text PDFPak J Pharm Sci
May 2024
Department of Pharmacy, Affiliated Hospital of Putian University, Putian, China.
In this study, in order to further search anti-inflammatory drugs with high efficiency and low toxicity, this study took the ring of indoles and imidazole [2,1-b] thiazole as the main skeleton. A total of nine new N-1-substituted derivatives of indole-2-carboxyamide-phenylimidazoles [2,1-b] thiazole (13-20) was synthesized through the processes of cyclization, amino reduction, ester hydrolysis, dehydration condensation and acyl chloride substitution. These derivatives were then tested for their ability to reduce inflammation in RAW 264.
View Article and Find Full Text PDFJ Org Chem
October 2024
Instituto de Química, Universidade Federal da Bahia, Campus de Ondina, Salvador, Bahia 40170-115, Brazil.
A nontoxic bismuth-promoted multicomponent synthesis of 5-aminotetrazoles and bistetrazoles is reported. The reaction of phenyl isothiocyanate, NaN, and amine (primary aliphatic, aromatic, and aliphatic diamine) promoted by Bi(NO)·5HO under microwave heating affords good yields, short reaction times, simple workup, and purification without column chromatography. A set of diagnostic H NMR signals was identified as a guide for quickly elucidating the exclusive (or main) regioisomer formed, with the stronger electron donor group located at heterocyclic nitrogen 1.
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