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
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;
The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors.
Sign Up to like & getrecommendations! Published in 2017 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.6b01496
Abstract: Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation… read more here.
Keywords: tricyclic sulfonamides; lead optimization; glycine receptors; optimization ... See more keywords
Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing's Disease.
Sign Up to like & getrecommendations! Published in 2017 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.7b00437
Abstract: Cushing's disease, characterized by elevated plasma cortisol levels, can be controlled by inhibition of 11β-hydroxylase (CYP11B1). The previously identified selective and potent CYP11B1 inhibitor 5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine Ref 7 (IC50= 2 nM) exhibited promutagenic potential as well… read more here.
Keywords: cushing disease; pharmacological profile; lead optimization; optimization generates ... See more keywords
Discovery and Lead Optimization of Atropisomer D1 Agonists with Reduced Desensitization.
Sign Up to like & getrecommendations! Published in 2018 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.8b01622
Abstract: The discovery of D1 subtype-selective agonists with drug-like properties has been an enduring challenge for the greater part of 40 years. All known D1-selective agonists are catecholamines that bring about receptor desensitization and undergo rapid… read more here.
Keywords: atropisomer; lead optimization; discovery; discovery lead ... See more keywords