206193-17-1Relevant articles and documents
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
Meta -Non-flat substituents: A novel molecular design to improve aqueous solubility in small molecule drug discovery
Ichikawa, Yuki,Hiramatsu, Michiaki,Mita, Yusuke,Makishima, Makoto,Matsumoto, Yotaro,Masumoto, Yui,Muranaka, Atsuya,Uchiyama, Masanobu,Hashimoto, Yuichi,Ishikawa, Minoru
supporting information, p. 446 - 456 (2021/01/29)
Aqueous solubility is a key requirement for small-molecule drug candidates. Here, we investigated the regioisomer-physicochemical property relationships of disubstituted benzenes. We found that meta-isomers bearing non-flat substituents tend to possess the lowest melting point and the highest thermodynamic aqueous solubility among the regioisomers. The examination of pharmaceutical compounds containing a disubstituted benzene moiety supported the idea that the introduction of a non-flat substituent at the meta position of a benzene substructure would be a promising approach for medicinal chemists aiming to improve the thermodynamic aqueous solubility of drug candidates, even though it might not be universally effective. This journal is
PYRAZOLYLPROPANAMIDE COMPOUNDS AND USES THEREOF FOR TREATMENT OF PROSTATE CANCER
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Paragraph 00194; 00192, (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
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
Synthesis method of nicotinate
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Paragraph 0026-0033; 0047-0055; 0068-0075, (2020/05/01)
The invention belongs to the technical field of compound preparation, and in particular, relates to (S)-1-((4-cyano-3-(trifluoromethyl)phenyl)amino)-3-(4-cyanophenoxy)-2-methyl-1-oxopropan-2-yl nicotinate and a synthesis method thereof. The method compris
ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS
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Page/Page column 145; 146, (2020/11/30)
The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.
Synthetic method of alpha-hydroxypropanamide derivatives with optical activity
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Paragraph 0023; 0024, (2019/06/05)
The invention discloses a synthetic method of alpha-hydroxypropanamide derivatives with optical activity and belongs to the field of organic synthesis. Proline taken as a chiral auxiliary, as well asmethacryloyl chloride, is subjected to acylation, bromination and chiral auxiliary removal, a product and 4-cyano-3-trifluoromethylaniline are subjected to nucleophilic substitution, and 3-bromo-2-hydroxy-2-methyl-N-[(4-cyano-3-trifluoromethyl)phenyl]propanamide is obtained and subjected to nucleophilic substitution with 4-cyanophenol, and the compound 3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethylphenyl]-2-hydroxy-2-methylpropanamide with optical activity is prepared. 3-bromo-2-hydroxy-2-methyl propionic acid and 4-nitro-3-trifluoromethylaniline are subjected to aminolysis, a product is subjected to nucleophilic substitution with paracetamol, and the compound 3-(4-acetoxyphenoxy)-N-[4-nitro-3-(trifluoromethylphenyl]-2-hydroxy-2-methylpropanamide with optical activity is prepared. The efficient synthetic method of the alpha-hydroxypropanamide derivatives with optical activity is provided.
SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF
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Paragraph 00367, (2019/12/04)
This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedys disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), 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.
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.
ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS
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Page/Page column 211; 212, (2019/12/04)
The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.