Tanaka, Nobuyuki published the artcileRelationship between Stereochemistry and the β3-Adrenoceptor Agonistic Activity of 4′-Hydroxynorephedrine Derivative as an Agent for Treatment of Frequent Urination and Urinary Incontinence, Computed Properties of 33697-81-3, the publication is Journal of Medicinal Chemistry (2003), 46(1), 105-112, database is CAplus and MEDLINE.
This report proposes a β3-adrenoceptor (AR) selective agonist, 2-[2-chloro-4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]acetic acid (I), as a novel agent for treating urinary bladder dysfunction. This compound and its relatives have a unique feature among β3-AR agonists: two chiral carbons are adjacently structured on the left side of the mol. To study the relationship between the stereoconfiguration of the vicinal chiral carbons in I and β-AR agonistic activity, the four stereoisomers were synthesized via oxazolidinone prepared by intracyclization involving inversion of the β-hydroxy group. The in vitro assays using rat atria for β1-AR, rat uteri for β2-AR, and ferret detrusor for β3-AR showed that I possessed potent β3-AR agonistic activity (EC50 = 3.85 nM) and 3700- and 1700-fold selectivity for β3-AR relative to β1– and β2-AR, resp. Comparison of the four isomers revealed that the (αS,βR)-compound (I) was not only the most potent agonist but was also the most selective for β3-AR. In the anesthetized rat, i.v. administration of I brought about a sufficient decrement of the intrabladder pressure (ED50 = 12 μg/kg), and intraduodenal administration of the Et ester of I, led to same result (ED50 = 0.65 mg/kg). Moreover, no effects on the cardiovascular system were observed in either test.
Journal of Medicinal Chemistry published new progress about 33697-81-3. 33697-81-3 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Carboxylic acid,Benzene,Phenol, name is 3-Chloro-4-hydroxyphenylacetic acid, and the molecular formula is C2H3N3, Computed Properties of 33697-81-3.
Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics