BucketListPapers 71/100: Thinking through the chemistry paves the way to success.

A triumph of the decade (2010 – 2019) is the suite of Hepatitis C small molecule drugs treatments. These took a previously fatal disease...

BucketListPapers 72/100: Improving pharmacokinetics and reactive metabolites.

Lead optimisation frequently includes involves work to improve bio-availability, lower clearance and improve solubility. In addition, early safety studies take place, and usually this...

BucketListPapers 73/100: Amide isosteres and fluorines in the right place.

The discovery of Sitagliptin is a story of finding an amide isostere that worked, then optimisation of pharmacokinetics via some fluorines in the right...

BucketListPapers 74/100: Unusual chemical groups can make it into drugs.

Carbapenem-resistant Enterobacteriaceae (CRE), due to the Klebsiella pneumoniae carbapenemase (KPC) and other β-lactamases, now threatens the usefulness of all β-lactam antibiotics. Boronic acids offered...

BucketListPapers 75/100: Starting from the natural substrate as a drug hunting lead : a modern example.

Before the days of high through screening, starting from the natural substrate was the method of generating chemical leads for drug discovery. Beginning with...

BucketListPapers 76/100: Macrocyclisation as the route to success?

The story of Lorlatinib started with an existing inihibitor and used macrocyclization to improve properties. Macrocyclisation has been a recent approach to improving small...

BucketListPapers 77/100: The first tyrosine kinase inhibitor…

Perhaps this paper is showing its age, but at the time BMCL papers were basic, with just a table of two of measurements and...

BucketListPapers 78/100: Improving on existing drugs, covalent binders and the late LO medicinal chemistry

A successful drug in the clinic is the final proof that modulation of a protein target yields benefits. The drug in question may have...

BucketListPapers 79/100: Designing CNS penetrant drugs….maybe the hardest thing?

Perhaps the hardest medicinal chemistry challenge is taking a series of compounds, and modifying them, so they pass through the blood brain barrier. Such...

BucketListPapers 80/100: Polar exploration complements non-polar exploration

By investigating the correlation of a variety of group descriptors, Craig established that there are a group of non-polar descriptors such as π, molecular...