Effects of novel hybrids of caffeic acid phenethyl ester and NSAIDs on experimental ocular inflammation.

In this study, we report the design and synthesis of novel hybrids of caffeic acid phenetyl ester (CAPE) and non-steroidal anti-inflammatory drugs (NSAIDs). We assessed their effects on an experimental ocular inflammation in New Zealand rabbits. The formulations of CAPE-aspirin and CAPE-indomethacin hybrids were topical instilled in the rabbit׳s eye.

Synthesis and endothelin receptor binding affinity of a novel class of 2-substituted-4-aryl-3-quinolinecarboxylic acid derivatives.

The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the endothelin peptide family, which includes ET-2, and ET-3. These peptides display a variety of physiological activities including vasoconstriction and the stimulation of cell proliferation in tissues both within and outside of the cardiovascular system. They exert their actions via activation of two distinct receptor subtypes, ET(A) and ET(B), belonging to the G protein-coupled receptor (GPCR) superfamily.

5-HT7 receptor ligands: recent developments and potential therapeutic applications.

The 5-HT(7) receptors (5-HT(7)Rs) are the most recent classified members of the serotonin family. Characterized in 1993, they belong to the G protein-coupled receptor family. Since their discovery, they have been the subject of intense research due to their widespread distribution in the brain, suggestive of multiple central roles.

New pyrimido[5,4-b]indoles and [1]benzothieno[3,2-d]pyrimidines: high affinity ligands for the alpha(1)-adrenoceptor subtypes.

A number of new pyrimido[5,4-b]indole and [1]benzothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their binding and functional properties at alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes. They behaved as potent alpha(1)-AR antagonists. In binding experiments, some of them (RC24 and RC23) showed very high affinity for the alpha(1D)-AR subtype.

3-Arylpiperazinylethyl-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione derivatives as novel, high-affinity and selective alpha(1)-adrenoceptor ligands.

The discovery of a new series of selective and high-affinity alpha(1)-adrenoceptor (alpha(1)-AR) ligands, characterized by a 1H-pyrrolo[2,3-d]-pyrimidine-2,4(3H,7H)-dione system, is described in this paper. Some synthesized compounds, including 20, 22, and 30, displayed affinity in the nanomolar range for alpha(1)-ARs and substantial selectivity with respect to 5-HT(1A) and dopaminergic D(1) and D(2) receptors. Functional assays, performed on selected derivatives, showed antagonistic properties.

Novel (E)-alpha-[(1H-indol-3-yl)methylene]benzeneacetic acids as endothelin receptor ligands.

Endothelin-1 (ET-1), a peptide of 21 amino acid residues, is the most potent vasoconstrictor substance known and now it is understood to be one of a family of three mammalian vasoactive peptides that also includes ET-2 and ET-3. The endothelins (ETs) affect multiple organ systems and seem to be involved in the pathogenesis of many diseases such as hypertension, pulmonary hypertension, atherosclerosis, apoptosis inhibition and angiogenesis. The ETs exert their effects via activation of two distinct G-protein coupled receptor subtypes termed ET(A) and ET(B).

Synthesis of 3-arylpiperazinylalkylpyrrolo[3,2-d]pyrimidine-2,4-dione derivatives as novel, potent, and selective alpha1-adrenoceptor ligands.

Novel compounds characterized by a pyrrolo[3,2-d]pyrimidine-2,4-dione (PPm) system connected through an alkyl chain to a phenylpiperazine (PPz) residue were designed as structural analogues of the alpha(1)-adrenoceptor (alpha(1)-AR) ligand RN5 (1). In this new series of derivatives an arylpyrrolo moiety has replaced the indole nucleus of RN5. Several structural modifications were performed on the PPm and PPz moieties and the connecting alkyl chain.