512776-95-3Relevant academic research and scientific papers
PYRAZOLYLPROPANAMIDE COMPOUNDS AND USES THEREOF FOR TREATMENT OF PROSTATE CANCER
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, (2021/10/11)
This invention relates to pyrazolylpropanamide compounds and uses thereof for treatment of prostate cancer, advanced prostate cancer, refractory prostate cancer, AR overexpressing prostate cancer, castration-resistant prostate cancer, castration-sensitive
Exploration and Biological Evaluation of Basic Heteromonocyclic Propanamide Derivatives as SARDs for the Treatment of Enzalutamide-Resistant Prostate Cancer
He, Yali,Hwang, Dong-Jin,Ponnusamy, Suriyan,Thiyagarajan, Thirumagal,Mohler, Michael L.,Narayanan, Ramesh,Miller, Duane D.
, p. 11045 - 11062 (2021/08/03)
A series of propanamide derivatives were designed, synthesized, and pharmacologically characterized as selective androgen receptor degraders (SARDs) and pan-antagonists that exert a broad-scope androgen receptor (AR) antagonism. Incorporating different ba
Pyrazol-1-yl-propanamides as SARD and Pan-Antagonists for the Treatment of Enzalutamide-Resistant Prostate Cancer
He, Yali,Hwang, Dong-Jin,Ponnusamy, Suriyan,Thiyagarajan, Thirumagal,Mohler, Michael L.,Narayanan, Ramesh,Miller, Duane D.
, p. 12642 - 12665 (2020/11/13)
We report herein the design, synthesis, and pharmacological characterization of a library of novel aryl pyrazol-1-yl-propanamides as selective androgen receptor degraders (SARDs) and pan-Antagonists that exert broad-scope AR antagonism. Pharmacological ev
New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity
Hwang, Dong-Jin,He, Yali,Ponnusamy, Suriyan,Mohler, Michael L.,Thiyagarajan, Thirumagal,McEwan, Iain J.,Narayanan, Ramesh,Miller, Duane D.
, p. 491 - 511 (2019/01/11)
In our effort to find small-molecule treatments of advanced prostate cancers (PCs), a novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with novel SARD activity but poor metabolic stability. Cyclization to II and III produced submicromolar AR antagonism and protein degradation selective to AR and AR splice variant (AR SV). II and III maintained potency against enzalutamide-resistant (Enz-R) mutant ARs and PC cells and were efficacious in Enz-R xenografts, suggesting their potential to treat advanced PCs. Design, synthesis, and biological activity of novel SARDs that could potentially be used for the treatment of a wide spectrum of PCs including castration-resistant, Enz-R, and/or AR SV-dependent advanced PCs that are often untreatable with known hormone therapies are discussed.
SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF
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, (2016/11/17)
This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.
SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF
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, (2016/11/14)
This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic and/or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.
Novel pathway for the synthesis of arylpropionamide-derived selective androgen receptor modulator (SARM) metabolites of andarine and ostarine
Schragl, Katharina M.,Forsdahl, Guro,Gmeiner, Guenter,Enev, Valentin S.,Gaertner, Peter
supporting information, p. 2239 - 2242 (2013/05/09)
O-Dephenylandarine and O-dephenylostarine, two SARM metabolites relevant for doping control analysis, were synthesized in their endogenous (S)-forms as well as in terms of their racemates. The enantiopure (S)-metabolites were obtained after six steps in 20% and 23% overall yield, the slightly modified racemic route provided the compounds in 28% and 31% total yield, respectively.
Facile radiosynthesis of new carbon-11-labeled propanamide derivatives as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging
Gao, Mingzhang,Wang, Min,Miller, Kathy D.,Zheng, Qi-Huang
experimental part, p. 1505 - 1512 (2011/11/06)
The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[11C] methoxyphenoxy)-2-methylpropanamide ([11C]8a), (S)-2-hydroxy-3-(2- [11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl) propanamide ([11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2- hydroxy-3-(4-[11C]methoxyphenoxy)-2-methylpropanamide ([ 11C]8c) and (S)-2-hydroxy-3-(4-[11C]methoxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([11C]8g), were prepared by O-[11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2- hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy) -2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4- nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5).
AMIDE DERIVATIVES
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Page/Page column 53, (2008/06/13)
The invention concerns amide compounds of Formula (I) wherein groups R1, R2, R3, Q1, X, R4, R5, R6, and R7 are as defined in the description. The present invention als
Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators
Bohl, Casey E.,Wu, Zengru,Chen, Jiyun,Mohler, Michael L.,Yang, Jun,Hwang, Dong Jin,Mustafa, Suni,Miller, Duane D.,Bell, Charles E.,Dalton, James T.
supporting information; experimental part, p. 5567 - 5570 (2009/06/30)
Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.
