A Practical Synthetic Route to Cinnolines: Application to the Design and Synthesis of RSV NNI Inhibitor JNJ-8003 Analogues.

The manuscript describes the development of an efficient synthetic route to cinnolines, facilitating faster access to JNJ-8003 related Respiratory Syncytial Virus (RSV) non-nucleoside (NNI) inhibitors. Starting from correctly functionalized aryl halides, a Sonogashira reaction followed by SNAr reaction with hydrazine 1,2-dicabroxylate reagents provided dihydrocinnolines directly via in situ 6-endo-dig cyclization. The dihydrocinnolines were conveniently transformed to corresponding cinnolines in one step.

What Does Pharmaceutical 3D Printing Cost? A Framework and Case Study with Hydrocortisone for Adrenal Insufficiency.

Background: Pharmaceutical three-dimensional printing (3DP) technology offers an automated platform that can be utilized to manufacture personalized medicine, improving pharmacotherapy. Although 3D-printed products have entered clinical trials, no costing studies have been performed yet. Cost insights can aid researchers and industry in making informed decisions about the feasibility and scalability of 3DP.

A Systematic Review of Challenges and Opportunities in the Implementation of Managed Entry Agreements for Advanced Therapy Medicinal Products.

Purpose: Managed Entry Agreements (MEAs) are agreements between firms and competent authorities for pricing and reimbursement, designed to enable coverage of new medicines while managing uncertainties around their financial impact or performance. Although these agreements can facilitate patient access, their complexity and costs seem to dampen enthusiasm for implementation. Nevertheless, MEAs remain a potential route, particularly for high-cost drugs with uncertain value claims.