New analogues (2a-p) of the previously reported CB(2) ligands 6-methyl- and 6-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) have been synthesized and evaluated for cannabinoid receptor affinity. One example, 1-(2',4'-dichlorophenyl)-6-methyl-N-cyclohexyilamine-1,4-dihydroindeno[1,2-c] pyrazole-3-carboxamide (2a) was shown to have single digit nanomolar affinity for cannabinoid CB(2) receptors. Furthermore, compounds 2a and 2b, as well as lead structures 1a,b, were also shown to be agonist in an in vitro model based on human promyelocytic leukemia HL-60 cells.

e CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. e presence of polymorphisms in the CYP2D6 gene may modulate the enzyme level and activity affecting individual responses, to pharmacological treatment in drug level, response and adverse reactions. Aims. is study aimed to analyze the determination of allele frequencies in Sardinians and the comparison to frequencies found in the Caucasian Population. Methods and Materials. We used a Long PCR strategy coupled to direct genomic DNA sequencing analysis. An ampli�cation allele-speci�c was carried out to infer the correct allelic phase. e TaqMan Gene Copy Number Assay (Applied Biosystems) was used to verify the presence of gene deletions/multiplications. Results and Conclusions. Our results indicated that CYP2D6 allele frequencies in Sardinians differed from those previously detected in the Caucasian Population. Moreover, three new SNPs and four novel haplotypes were identi�ed.

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The multiple CYP450 gene testing achieved with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes.

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