The 2025 FDA Small-Molecule Portfolio: Clinical Applications, Synthetic Approaches, Challenges, and Solutions

Silva, Felipe L. N. da; Leão, Raquel A. C.; Schaeffer, Edgar; Cavalcante, Samir F. A.; Souza, Rodrigo O. M. A. de

doi:10.21577/0103-5053.20260042

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Review • J. Braz. Chem. Soc. 37 • 2026 • https://doi.org/10.21577/0103-5053.20260042 linkcopy

The 2025 FDA Small-Molecule Portfolio: Clinical Applications, Synthetic Approaches, Challenges, and Solutions

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

In 2025, the U.S. Food and Drug Administration (FDA) approved 46 new drugs comprising 31 small-molecule entities. These approvals represent significant milestones in the evolution of privileged structures and novel mechanisms of action, serving as invaluable leads for the development of next-generation therapeutics with enhanced efficacy. This article reviews the synthetic routes and clinical indications of these newly marketed drugs, highlighting their significance in the current pharmaceutical landscape.

Keywords:
new drugs; chemical synthesis; clinical applications

Authorship

person Felipe L. N. da Silva

Felipe Lopes Nunes da Silva holds a degree in Chemistry from the Federal Institute of Education, Science and Technology of Rio de Janeiro (2017). He earned his MSc in Natural Products Chemistry (2021) and PhD in Chemistry (2025) from the Federal University of Rio de Janeiro, including a sandwich period at Karl-Franzens-Universität Graz, Austria, under the supervision of Prof Dr Christian Oliver Kappe. His current research focuses on the development of continuous-flow synthesis processes for active pharmaceutical ingredients (APIs), as well as the continuous synthesis of cannabinoids. He works as a chemical process development researcher at the startup Novasynth and as a postdoctoral researcher in the Biocatalysis and Organic Synthesis Group (BOSS Group) in Federal University of Rio de Janeiro under the supervision of Prof Dr Rodrigo O. M. A. de Souza. · contributed equally to this manuscript

schoolGrupo de Biocatalálise e Síntese Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, 21941-909 Rio de Janeiro-RJ, BrazilUniversidade Federal do Rio de JaneiroBrazilRio de Janeiro, RJ, BrazilGrupo de Biocatalálise e Síntese Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, 21941-909 Rio de Janeiro-RJ, BrazilschoolNovasynth Tecnologia, Incubadora de Empresas da Coppe, Cidade Universitária, Ilha do Fundão, 21941-914 Rio de Janeiro-RJ, BrazilCidade UniversitáriaBrazilRio de Janeiro, RJ, BrazilNovasynth Tecnologia, Incubadora de Empresas da Coppe, Cidade Universitária, Ilha do Fundão, 21941-914 Rio de Janeiro-RJ, Brazil

0009-0009-9829-9293

person Raquel A. C. Leão

Raquel Ana Capela Leão is a researcher at the Biocatalysis and Organic Synthesis Group (BOSS) at the Institute of Chemistry, UFRJ. She holds a PhD in Organic Chemistry from Fluminense Federal University (UFF) and completed postdoctoral fellowships at the University of Aveiro (Portugal), UFRJ, and the University of Alicante (Spain). Her expertise lies in organic synthesis and biocatalysis, specifically in the application of lipases and the development of innovative synthetic methodologies. Her current work focuses on the implementation of chemoenzymatic processes in continuous flow systems for the efficient and sustainable production of Active Pharmaceutical Ingredients (APIs). · contributed equally to this manuscript

0000-0003-1997-8335

person Edgar Schaeffer

Edgar Schaeffer graduated in Chemistry at Federal Rural University of Rio de Janeiro (2015) and concluded his PhD in Natural Products Chemistry at Federal University of Rio de Janeiro in 2023. Schaeffer has expertise in Chemistry, with emphasis in Organic Chemistry - Organic Synthesis, working primarily on the following topics: Cross-coupling Reactions and structural modifications of flavonoids and quinones. Since 2022, Schaeffer has been contributing to the scientific endeavors of pharmaceutical companies. Currently, Schaeffer is the Founding Partner and Scientific Director of Asymmetra. · contributed equally to this manuscript

schoolInstituto de Pesquissas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro-RJ, BrazilUniversidade Federal do Rio de JaneiroBrazilRio de Janeiro, RJ, BrazilInstituto de Pesquissas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro-RJ, BrazilschoolAsymmetra Científica, Centro, 20080-070 Rio de Janeiro-RJ, BrazilAsymmetra Científica, CentroBrazilRio de Janeiro, RJ, BrazilAsymmetra Científica, Centro, 20080-070 Rio de Janeiro-RJ, Brazil

0000-0002-5262-6983

person Samir F. A. Cavalcante

Samir Cavalcante obtained his PhD (2018) and MSc (2006) in Chemistry of Natural Products from the Walter Mors Institute for Natural Products Research (IPPN) at the Universidade Federal do Rio de Janeiro. As Organisation for the Prohibition of Chemical Weapons Fellow (OPCW), he was visiting researcher at Spiez Laboratory (Switzerland, 2012) and Finnish Institute for Verification of the Chemical Weapons Convention (VERIFIN, Finland, 2016). Currently, Cavalcante is the Organic Chemistry Researcher at Brazilian Army Institute of CBRN (OPCW Designated Laboratory, 2024-2025), United Nations Secretary-General’s Mechanism (UNSGM) Qualified Expert, Patent Advisor at Licks Attorneys and Scientific Consultant at Asymmetra. · contributed equally to this manuscript

schoolAsymmetra Científica, Centro, 20080-070 Rio de Janeiro-RJ, BrazilAsymmetra Científica, CentroBrazilRio de Janeiro, RJ, BrazilAsymmetra Científica, Centro, 20080-070 Rio de Janeiro-RJ, BrazilschoolInstituto de Defesa Química, Biológica, Radiológica e Nuclear, Centro Tecnológico do Exército, Guaratiba, 23020-470 Rio de Janeiro-RJ, BrazilCentro Tecnológico do Exército, GuaratibaBrazilRio de Janeiro, RJ, BrazilInstituto de Defesa Química, Biológica, Radiológica e Nuclear, Centro Tecnológico do Exército, Guaratiba, 23020-470 Rio de Janeiro-RJ, Brazil

0000-0002-3478-2747

person Rodrigo O. M. A. de Souza *

Rodrigo Octavio M. A. de Souza is an Associate Professor at the Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), where he heads the Biocatalysis and Organic Synthesis Group. He holds a PhD in Natural Products Chemistry from UFRJ and has a distinguished international background as a visiting researcher at the University of Graz (Prof Oliver Kappe) and as a Humboldt Research Fellow (Prof Uwe Bornscheuer). A pioneer in establishing continuous-flow chemo-enzymatic processes in Brazil, his research focuses on sustainable and scalable methodologies for the pharmaceutical, cosmetics, and food industries. Beyond academia, he is the co-founder of Novasynth Tecnologia, a startup dedicated to automated continuous synthesis solutions and FlowPrint Innovations focused on automation and 3D printing. Dr. de Souza serves as the South American Editor for the Journal of Flow Chemistry, Associate Editor for RSC Advances (Royal Society of Chemistry) and Organic Chemistry Editor of Quimica Nova. He is a CNPq Productivity Fellow and has published extensively in the fields of flow chemistry, biocatalysis, and organic synthesis. · contributed equally to this manuscript

0000-0002-6422-4025

person*e-mail:
rodrigosouza@iq.ufrj.br

Editor handled this article:

Brenno A. D. Neto (Editor-in-Chief)

SCIMAGO INSTITUTIONS RANKINGS

Grupo de Biocatalálise e Síntese Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, 21941-909 Rio de Janeiro-RJ, BrazilUniversidade Federal do Rio de JaneiroBrazilRio de Janeiro, RJ, BrazilGrupo de Biocatalálise e Síntese Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, 21941-909 Rio de Janeiro-RJ, Brazil

Novasynth Tecnologia, Incubadora de Empresas da Coppe, Cidade Universitária, Ilha do Fundão, 21941-914 Rio de Janeiro-RJ, BrazilCidade UniversitáriaBrazilRio de Janeiro, RJ, BrazilNovasynth Tecnologia, Incubadora de Empresas da Coppe, Cidade Universitária, Ilha do Fundão, 21941-914 Rio de Janeiro-RJ, Brazil

Instituto de Pesquissas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro-RJ, BrazilUniversidade Federal do Rio de JaneiroBrazilRio de Janeiro, RJ, BrazilInstituto de Pesquissas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro-RJ, Brazil

Asymmetra Científica, Centro, 20080-070 Rio de Janeiro-RJ, BrazilAsymmetra Científica, CentroBrazilRio de Janeiro, RJ, BrazilAsymmetra Científica, Centro, 20080-070 Rio de Janeiro-RJ, Brazil

Instituto de Defesa Química, Biológica, Radiológica e Nuclear, Centro Tecnológico do Exército, Guaratiba, 23020-470 Rio de Janeiro-RJ, BrazilCentro Tecnológico do Exército, GuaratibaBrazilRio de Janeiro, RJ, BrazilInstituto de Defesa Química, Biológica, Radiológica e Nuclear, Centro Tecnológico do Exército, Guaratiba, 23020-470 Rio de Janeiro-RJ, Brazil

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