Pamicogrel

A compound's synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction databases and the availability of starting materials. We developed a new method of predicting SA using commercially available compound databases and molecular descriptors. SA was estimated from the probability of existence of substructures consisting of the compound in question, the number of symmetry atoms, the graph complexity, and the number of chiral centers of the compound. The probabilities of the existence of given substructures were estimated based on a compound library. The predicted SA results reproduced the expert manual assessments with a Pearson correlation coefficient of 0.56. Since our method required a compound database and not a reaction database, it should be easy to customize the prediction for compound vendors. The correlation between the sales price of approved drugs and the SA values was also examined and found to be weak. The price most likely depends on the total cost of development and other factors.

Background: KBT-3022 is a new antiplatelet agent whose main mechanism of action is cyclooxygenase inhibition.Objective: This study was conducted to investigate the clin. efficacy and safety of KBT-3022, as well as its antithrombocytic action and pharmacokinetics in elderly (≥65 yr of age) and nonelderly patients.Methods: Patients with chronic arterial occlusive disease (arteriosclerosis obliterans or thromboangiitis obliterans) were divided into 2 groups: elderly (≥65 yr of age) and nonelderly.KBT-3022 5 mg once daily was administered orally for 6 wk.Blood sampling was performed before administration, at weeks 2 and 6, and 7 days after completion of administration.Platelet aggregation was measured with 3 aggregation inducers using the platelet-rich plasma transmission method: 3 concentrations of ADP (ADP) (2, 5, and 10 μM); collagen 2 μg/mL; and arachidonic acid 2 mM.Plasma concentrations of the drug were measured at the same time points.Changes in platelet aggregation before and after administration of the study drug were compared using the paired t test.Results: A total of 21 patients were enrolled in this study (11 in the elderly [≥65 yr of age] group and 10 in the nonelderly group).Nine patients in the elderly group and 10 in the nonelderly group were included in the anal. of inhibition of platelet aggregation.Drug plasma concentrations were analyzed in 8 patients in the elderly group and 9 in the nonelderly group.In both groups, KBT-3022 significantly (P < 0.05) inhibited arachidonic acid-induced platelet aggregation at week 2 compared with pretreatment.In the elderly group, KBT-3022 significantly inhibited ADP 5 μM- and 10 μM-induced platelet aggregation at week 2 (P < 0.01 and P < 0.05, resp.) compared with pretreatment.In the nonelderly group, KBT-3022 significantly inhibited all 3 levels of ADP-induced platelet aggregation at week 2 (2 and 5 μM, P < 0.01; 10 μM, P < 0.05) compared with pretreatment.The study drug also significantly (P < 0.01) inhibited collagen-induced platelet aggregation at week 6 compared with pretreatment.There was no significant difference between groups in degree of aggregation induced by the 3 agents.No difference in plasma clearance rate was observed between the 2 groups.Recovery to 80% of preadministration values was observed 7 days after completion of administration in >80% of patients.No patient withdrew because of exacerbation of disease or adverse events.Conclusion: In the present study, KBT-3022 5 mg administered orally once daily inhibited platelet aggregation.Platelet aggregation returned to normal in most patients 7 days after completion of administration, indicating that the effects of KBT-3022 are reversible.There was no difference in inhibition of platelet aggregation between elderly and nonelderly patients, and the previously determined optimal dose of 5 mg once daily can thus be prescribed without regard to patient age.