title: Big Data from Pharmaceutical Patents: A Computational Analysis of Medicinal Chemists' Bread and Butter.
abstract: Multiple recent studies have focused on unraveling the content of the medicinal chemist's toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reaction schemes, including reaction roles and yields, from pharmaceutical patents. The reactions were assigned to well-known reaction types such as Wittig olefination or Buchwald-Hartwig amination using an expert system. Analyzing the evolution of reaction types over time, we observe the previously reported bias toward reaction classes like amide bond formations or Suzuki couplings. Our study also shows a steady increase in the number of different reaction types used in pharmaceutical patents but a trend toward lower median yield for some of the reaction classes. Finally, we found that today's typical product molecule is larger, more hydrophobic, and more rigid than 40 years ago.
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4002 Basel, Switzerland.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schneider
authors.affiliation: NextMove Software Ltd. , Innovation Centre, Unit 23, Science Park, Milton Road, Cambridge CB4 0EY, U.K.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Lowe
authors.affiliation: NextMove Software Ltd. , Innovation Centre, Unit 23, Science Park, Milton Road, Cambridge CB4 0EY, U.K.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Sayle
authors.affiliation: Novartis Institutes for BioMedical Research , 186 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tarselli
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4002 Basel, Switzerland.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Landrum
mesh_terms: D002626:Chemistry, Pharmaceutical; D004345:Drug Industry; D049673:History, 20th Century; D049674:History, 21st Century; D010330:Patents as Topic; D000078329:Workforce