4-Alkyl- and 3,4-dialkyl-1,2,3,4,-tetrahydro-8-pyridono[5,6-g]quinolines: Potent, nonsteroidal androgen receptor agonists
Nonsteroidal androgen receptor (AR) agonists based on 4- and 3,4-substituted-1,2,3,4-tetrahydro-8-pyridono-[5,6-g]quinolines were synthesized and evaluated in hAR cotransfection and receptor binding assays. Several potent (2–10 nM) and efficacious (80–110%) AR agonists were discovered.
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Cited by (54)
Construction of diverse polycyclic N-heterocycles via cascade allylic amination/Diels-Alder reaction
2022, Chemical CommunicationsOverview of the development of selective androgen receptor modulators (SARMs) as pharmacological treatment for osteoporosis (1998–2021)
2022, European Journal of Medicinal ChemistryCitation Excerpt :Replacement of the indole core with the quinolone core exhibited total loss of AR agonist activity. 2-quinolinones and variations were developed from different hAR antagonists [113–117]. Through structural modification of antagonists, companies and scholars have prepared many compounds with AR agonist activity.
Molecular mechanisms of apoptosis induced by a novel synthetic quinolinone derivative in HL-60 human leukemia cells
2020, Chemico-Biological InteractionsCitation Excerpt :Even though quinolinones are known mainly as very effective antibiotics [2–4], some of them possess anti-tumor activity [5–8] and have already reached clinical trials in cancer patients [9–12]. An important subgroup of quinolinones are the quinolin-4(1H)-ones (Fig. 1) which have been used as intermediates in the synthesis of several biologically important compounds, including nonsteroidal androgen receptor agonists [13], antibacterial martinellines [14], antifungal quinolone alkaloids [15] and diuretic agents [16]. Quinolin-4(1H)-ones showing anti-cancer properties have also been synthesized [17–19].
Development of selective androgen receptor modulators (SARMs)
2018, Molecular and Cellular EndocrinologyCitation Excerpt :Enobosarm has been or is being evaluated in several phase II and phase III clinical trials for multiple indications such as cancer cachexia, sarcopenia, breast cancer, and stress urinary incontinence (Crawford et al., 2016; Dobs et al., 2013; Dalton et al., 2011). Ligand Pharmaceuticals developed tricyclic quinolinones that coincided with the discovery of arylpropionamide SARMs (Edwards et al., 1998; Higuchi et al., 1999). Similar to the arylpropionamide SARMs, these quinolinones also bind to and activate the AR in low nanomolar concentrations while eliciting tissue-selective activation of the AR in muscle.
Synthesis, spectral characterization and density functional theory exploration of 1-(quinolin-3-yl)piperidin-2-ol
2015, Spectrochimica Acta - Part A: Molecular and Biomolecular SpectroscopyCitation Excerpt :Quinoline and its derivatives have also been used as novel inhibitors, i.e., topoisomerase inhibitors [8], kinase inhibitor [9] and lipoxygenase inhibitor. The quinoline derivatives are also vastly utilized as receptor agonists [10–14]. Panda et al., have been reported in their “acid base behavior of 3-aminoquinoline in its ground and excited state” that is to derive quinoline is a potential fluorescent sensors.
- 1
Present Address: The R. W. Johnson Pharmaceutical Research Institute, 3535 General Atomics Court, San Diego, CA 92121.
- 2
Present Address: University of California-Berkeley, Department of Chemistry, Berkeley, CA.
- 3
Present Address: Ontogen Corporation, 2325 Camino Vida Roble, Carlsbad, CA 92009.
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Present Address: Vertex Pharmaceuticals, Medicinal Chemistry, Cambridge, MA 02139.