Solid-Phase Synthesis of Lidocaine and Procainamide Analogues Using Backbone Amide Linker (BAL) Anchoring (original) (raw)
Related papers
Bioorganic & Medicinal Chemistry Letters, 2008
The present structure-activity relationship (SAR) study focused on chemical modifications of the structure of the local anesthetic lidocaine, and indicated analogues having reduced anesthetic potency, but with superior potency relative to the prototype in preventing anaphylactic or histamine-evoked ileum contraction. From the SAR analysis, 2-(diethylamino)-N-(trifluoromethylphenyl) and 2-(diethylamino)-N-(dimethyl-phenyl) acetamides were selected as the most promising compounds. New insights into the applicability of non-anesthetic lidocaine derivatives as templates in drug discovery for allergic syndromes are provided.
X-ray structures and pharmacological activities of lidocaine derivatives
Structural Chemistry, 2008
The molecular and crystal structures of the lidocaine analogs 2-(pyrazol-1-yl)-2′-methylacetanilide (1), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2′-methylacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-3′-methylacetanilide (3), and 2-(pyrazol-1-yl)-4′-methylacetanilide (4), are reported, with a summary of their pharmacological activities. In this series, the moiety comprising the heterocyclic ring and the amide alkyl linker displays a common conformation. Molecules of 1–4 form identical hydrogen bonded motifs in their crystals, namely linear chains via intermolecular N–H···O=C hydrogen bonding. Moderate anesthetic and anti-arrhythmic potencies recorded for 1–4 relative to lidocaine are countered by their significantly lower toxicities.
ChemInform, 2010
In this account dedicated to' 100 years Roche' in CHIMIA, we present some of our strategies towards the synthesis of interesting novel amino-acid-derived building blocks; multi generation synthesis of thiazole libraries in solution; a novel solid-phase approach towards highly substituted pyrimidines using a novel safety-catch linker principle and a multidirectional cleavage procedure; a versatile solid-phase synthesis of quinazolones taking advantage of the Staudinger phosphorylimine chemistry combined with a novel cyclization and cleavage strategy, and finally a novel solid-phase diketopiperazine synthesis combining the Ugi four-component reaction with a final ring-forming cleavage step.
A novel approach for the synthesis of lophocladines A, B and C1 analogues
Tetrahedron Letters, 2011
A novel approach for the syntheses of lophocladines A and B has been developed. These compounds were prepared in 4-6 steps with moderate to excellent overall yields. The key step involved the nucleophilic substitution of 4-chloronicotinic acid with the carbanion generated from phenylacetonitrile. Subsequent reduction of the cyano group, lactamization and oxidation furnished lophocladine A in 50% yield over 4 steps. Further amination with various amines led to lophocladine B and its C1 analogues in good yields. In addition, the synthesized compounds were evaluated for their cytotoxicity against leukaemia cells.
Solidphase synthesis of diketopiperazines, useful scaffolds for combinatorial chemistry
Tetrahedron Letters, 1998
Diketopiperazines, which are cyclic dipeptides, are often formed by a side reaction of solid-phase peptide synthesis. Using the new “Backbone Amide Linker,” this chemistry can be conveniently harnessed for the intentional preparation of diketopiperazines. These products will be useful scaffolds for combinatorial chemistry, since they incorporate three different points of diversity: both amino acid side-chains and one (of the two)