Identification of Mineralocorticoid Receptor Modulators with Low Impact on Electrolyte Homeostasis but Maintained Organ Protection was written by Granberg, Kenneth L.;Yuan, Zhong-Qing;Lindmark, Bo;Edman, Karl;Kajanus, Johan;Hogner, Anders;Malmgren, Marcus;OMahony, Gavin;Nordqvist, Anneli;Lindberg, Jan;Taangefjord, Stefan;Kossenjans, Michael;Loefberg, Christian;Braanalt, Jonas;Liu, Dongmei;Selmi, Nidhal;Nikitidis, Grigorios;Nordberg, Peter;Hayen, Ahlke;Aagaard, Anna;Hansson, Eva;Hermansson, Majlis;Ivarsson, Ida;Jansson-Loefmark, Rasmus;Karlsson, Ulla;Johansson, Ulrika;William-Olsson, Lena;Hartleib-Geschwindner, Judith;Bamberg, Krister. And the article was included in Journal of Medicinal Chemistry in 2019.HPLC of Formula: 638-07-3 The following contents are mentioned in the article:
The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here the authors describe the structure and property driven lead generation and optimization, which resulted in identification of MR modulators (S)-1 and (S)-33. Both compounds were partial MRAs but still demonstrated equally efficacious organ protection as eplerenone after four weeks treatment in uninephrectomized rats on high salt diet and aldosterone infusion. Importantly, and in sharp contrast to eplerenone, this was achieved without substantial changes to the urine Na+/K+ ratio after acute treatment in rat, which predicts a reduced risk for hyperkalemia. This work led to selection of (S)-1 (AZD9977) as the clin. candidate for treating MR-mediated cardio-renal diseases including CKD and HF. Based on the authors’ findings the authors propose an empirical model for prediction of compounds with low risk of affecting the urinary Na+/K+ ratio in vivo. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3HPLC of Formula: 638-07-3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.HPLC of Formula: 638-07-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics