Eco‐friendly Synthesis and Molecular Modelling of 2‐Phenylimidazo[1,2‐b]pyridazine Derivatives: In Vitro and In Vivo Studies for Lead Optimization
Sign Up to like & getrecommendations! Published in 2024 at "ChemMedChem"
DOI: 10.1002/cmdc.202400721
Abstract: 7‐methyl‐2‐phenylimidazo[1,2‐b]pyridazin‐3‐carboxylic acid (DM1) and 6‐methoxy‐2‐phenylimidazo[1,2‐b]pyridazin‐3‐carboxylic acid (DM2) have been shown to act as human (h) Cav3.1 voltage‐gated calcium channel blockers with promising in vivo anti‐absence activity, positioning them as potential antiepileptic drugs. The primary aim of… read more here.
Keywords: pyridazine derivatives; phenylimidazo; phenylimidazo pyridazine; lead optimization ... See more keywords
Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents.
Sign Up to like & getrecommendations! Published in 2020 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2020.112349
Abstract: In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity… read more here.
Keywords: high efficiency; gastric cancer; lead optimization; discover high ... See more keywords
Role of basic aminoalkyl chains in the lead optimization of Indoloquinoline alkaloids.
Sign Up to like & getrecommendations! Published in 2021 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2021.113938
Abstract: Indoloquinoline (IQ) is an important class of naturally occurring antimalarial alkaloids, mainly represented by cryptolepine, isocryptolepine, and neocryptolepine. The IQ structural framework consists of four isomeric ring systems differing via the linkage of indole with… read more here.
Keywords: basic aminoalkyl; aminoalkyl chains; role; lead optimization ... See more keywords
AutoDesigner, a De Novo Design Algorithm for Rapidly Exploring Large Chemical Space for Lead Optimization: Application to the Design and Synthesis of d-Amino Acid Oxidase Inhibitors
Sign Up to like & getrecommendations! Published in 2022 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.2c00072
Abstract: The lead optimization stage of a drug discovery program generally involves the design, synthesis, and assaying of hundreds to thousands of compounds. The design phase is usually carried out via traditional medicinal chemistry approaches and/or… read more here.
Keywords: lead optimization; design; chemical space; autodesigner ... See more keywords
DGMM: A Deep Learning-Genetic Algorithm Framework for Efficient Lead Optimization in Drug Discovery
Sign Up to like & getrecommendations! Published in 2025 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.5c01017
Abstract: Lead optimization in drug discovery faces the dual challenge of maintaining structural diversity while preserving core molecular features and optimizing the balance between biological activity and drug-like properties. To address these challenges, we introduce the… read more here.
Keywords: drug; optimization drug; dgmm; lead optimization ... See more keywords
Successful and Unsuccessful Prediction of Human Hepatic Clearance for Lead Optimization.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c01930
Abstract: Development of new chemical entities is costly, time-consuming, and has a low success rate. Accurate prediction of pharmacokinetic properties is critical to progress compounds with favorable drug-like characteristics in lead optimization. Of particular importance is… read more here.
Keywords: successful unsuccessful; lead optimization; clearance; hepatic clearance ... See more keywords
Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug Design.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01215
Abstract: The benzene moiety is the most prevalent ring system in marketed drugs, underscoring its historic popularity in drug design either as a pharmacophore or as a scaffold that projects pharmacophoric elements. However, introspective analyses of… read more here.
Keywords: phenyl ring; lead optimization; chemistry; drug design ... See more keywords
Lead Optimization to Advance Protease-Activated Receptor-1 Antagonists in Early Discovery.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c02048
Abstract: Vorapaxar is an approved drug for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Subsequent to the discovery of Vorapaxar, medicinal chemistry efforts were… read more here.
Keywords: optimization advance; lead optimization; chemistry; advance protease ... See more keywords
Novel Efficient Multistage Lead Optimization Pipeline Experimentally Validated for DYRK1B Selective Inhibitors
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.2c00988
Abstract: In addition to general challenges in drug discovery such as the identification of lead compounds in time- and cost-effective ways, specific challenges also exist. Particularly, it is necessary to develop pharmacological inhibitors that effectively discriminate… read more here.
Keywords: efficient multistage; lead optimization; novel efficient; optimization pipeline ... See more keywords
Lead Optimization of Androgen Receptor-HSP27 Disrupting Agents in Glioblastoma.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c02022
Abstract: Glioblastoma (GBM) is the most common malignant brain tumor with poor prognosis under the current standard treatment. It is critical to develop new approaches to selectively battle the disease. GBM sex differences suggest that an… read more here.
Keywords: androgen receptor; hsp27; lead optimization;
Lead Optimization of Positive Allosteric KV7.2/3 Channel Modulators toward Improved Balance of Lipophilicity and Aqueous Solubility.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c03112
Abstract: The voltage-gated potassium channel KV7.2/3 is gaining attention for its association with several medical indications. While recently reported, potent compounds aimed to fill the therapeutic gap left by market-withdrawn activators, key physicochemical parameters did not… read more here.
Keywords: lead optimization; aqueous solubility; channel; lipophilicity ... See more keywords