Showing papers by "Enza Lacivita published in 2008"
TL;DR: The present review will focus on those 5 HT(1A) receptor agents that entered preclinical trials starting from 2000.
Abstract: The serotonin receptor subtype 5-HT1A was one of the first serotonin receptor subtypes pharmacologically characterized. Over the last twenty years the 5-HT1A receptor has been the object of intense research efforts as witnessed by the 5-HT1A acting drugs marketed as anxiolytics. In recent years, several new chemical entities targeting the 5-HT1A receptor (alone or in combination with other molecular targets) have been proposed for novel therapeutic indications (neuroprotection, cognitive impairment, Parkinson Disease and related disorders, pain treatment). The present review will focus on those 5-HT1A receptor agents that entered preclinical trials starting from 2000.
79 citations
TL;DR: N-(4-cyanophenylmethylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT 7 receptor affinity, high selectivity over 5- HT 1A and D 2 receptors, and agonist properties (maximal effect = 82%, EC 50 = 0.60 microM), indicating that 25 rapidly and freely distributes across the blood-brain barrier.
Abstract: Starting from the previously reported 5-HT7 receptor agents 4−7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8−31 were designed with the primary aim to obtain new compounds endowed with suitable physicochemical properties for rapid and extensive penetration into the brain. The affinities for 5-HT7, 5-HT1A, and D2 receptors of compounds 8−31 were assessed, and several compounds displayed 5-HT7 receptor affinities in the nanomolar range. Among these, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT7 receptor affinity (Ki = 0.58 nM), high selectivity over 5-HT1A and D2 receptors (324- and 245-fold, respectively), and agonist properties (maximal effect = 82%, EC50 = 0.60 μM). After intraperitoneal injection in mice, 25 rapidly reached the systemic circulation and entered the brain. Its brain concentration−time profile para...
70 citations
TL;DR: The design, synthesis, binding affinities, and fluorescent properties of a series of serotonin 5-HT 1A receptor ligands, with N-[omega-[4-(2-methoxyphenyl)-1-piperazinyl]alkyl]-2-quinolinamine structure are reported on.
Abstract: We here report on the design, synthesis, binding affinities, and fluorescent properties of a series of serotonin 5-HT1A receptor ligands, with N-[ω-[4-(2-methoxyphenyl)-1-piperazinyl]alkyl]-2-quinolinamine structure. Several of the new ligands displayed nanomolar affinity at 5-HT1A receptor and good fluorescent properties. In particular, derivative 24 showed a favorable combination of 5-HT1A receptor affinity (Ki = 0.4 nM), Stokes shift (excitation wavelength = 381 nm, emission wavelength = 455 nm), and quantum yield in ethanol (Φ = 0.45).
10 citations