19790-60-4Relevant articles and documents
Chiral polypropionate subunit by a chemoenzymatic approach
Bonini,Chiummiento,Funicello,Marconi,Righi
, p. 2559 - 2561 (1998)
Enzymatic desymmetrization of meso-4-methyl-3,5-syn-dioxolan- 1,3,5,7- tetrol was found to be highly enantioselective leading to both acetylated enantiomers with high enantiomeric excess.
Asymmetric synthesis of D- and L-2-deoxy-4-thioriboses
Uenishi,Motoyama,Takahashi
, p. 101 - 110 (1994)
Both D- and L-enantiomers of 2-deoxy-4-thioribose derivatives 12 and 17 were prepared stereospecifically in 12 steps from 1,3-propanediol. The key intermediary 2,3-epoxy alcohols, 8 and 15 were obtained with high enantiomeric excess by the Sharpless asymmetric epoxidation using (+)-L- diethyl tartrate and (-)-D-diethyl tartrate.
Synthesis of salicylate and salicylamide alcohols for the preparation of phosphorodiamidates and ifosfamide prodrugs
Pal, Ashutosh
, p. 295 - 301 (2021/05/19)
Prodrugs are derivatives of drugs which gives parent drug or release drug when it breaks inside the body by the presence of suitable enzyme, and then exert desired pharmacological effect. For many years, prodrug strategy has been developed enormously to solve many unwanted drug properties. In drug discovery and development, prodrugs have well-known pharmacokinetic effects of pharmacologically nimble products. Almost 10% of drugs permitted whole world are classified as prodrugs, where the application of a prodrug method during initial stages of development is an emergent fashion. Phosphorodiamidates prodrugs are well known anticancer agents particularly against leucomia. To improve the selectivity of the chemotherapeutic agents and reduce systemic toxicity, I herein report different types of salicylate and salicylamide alcohols for the preparation of phosphorodiamidates and ifosfamide prodrugs.
GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer
Liang, Jun,Zbieg, Jason R.,Blake, Robert A.,Chang, Jae H.,Daly, Stephen,Dipasquale, Antonio G.,Friedman, Lori S.,Gelzleichter, Thomas,Gill, Matthew,Giltnane, Jennifer M.,Goodacre, Simon,Guan, Jane,Hartman, Steven J.,Ingalla, Ellen Rei,Kategaya, Lorn,Kiefer, James R.,Kleinheinz, Tracy,Labadie, Sharada S.,Lai, Tommy,Li, Jun,Liao, Jiangpeng,Liu, Zhiguo,Mody, Vidhi,McLean, Neville,Metcalfe, Ciara,Nannini, Michelle A.,Oeh, Jason,O'Rourke, Martin G.,Ortwine, Daniel F.,Ran, Yingqing,Ray, Nicholas C.,Roussel, Fabien,Sambrone, Amy,Sampath, Deepak,Schutt, Leah K.,Vinogradova, Maia,Wai, John,Wang, Tao,Wertz, Ingrid E.,White, Jonathan R.,Yeap, Siew Kuen,Young, Amy,Zhang, Birong,Zheng, Xiaoping,Zhou, Wei,Zhong, Yu,Wang, Xiaojing
supporting information, p. 11841 - 11856 (2021/07/31)
Breast cancer remains a leading cause of cancer death in women, representing a significant unmet medical need. Here, we disclose our discovery efforts culminating in a clinical candidate, 35 (GDC-9545 or giredestrant). 35 is an efficient and potent selective estrogen receptor degrader (SERD) and a full antagonist, which translates into better antiproliferation activity than known SERDs (1, 6, 7, and 9) across multiple cell lines. Fine-tuning the physiochemical properties enabled once daily oral dosing of 35 in preclinical species and humans. 35 exhibits low drug-drug interaction liability and demonstrates excellent in vitro and in vivo safety profiles. At low doses, 35 induces tumor regressions either as a single agent or in combination with a CDK4/6 inhibitor in an ESR1Y537S mutant PDX or a wild-type ERα tumor model. Currently, 35 is being evaluated in Phase III clinical trials.
