400641-62-5

Upstream product

• 71659-82-0 2-methyl-2-o-tolyloxypropionic acid ethyl ester 
• 598-21-0 2-Bromoacetyl bromide 
• 95-48-7 ortho-cresol 

Downstream Products

• 247073-83-2 2-(4-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxy-phenyl)-1-methyl-ethylamino]-ethyl}-2-methyl-phenoxy)-2-methyl-propionic acid ethyl ester 
• 247074-02-8 ethyl 2-[4-(2-bromoethyl)-2-methylphenoxy]-2-methylpropionate 

Relevant academic research and scientific papers

2-methylpropionic acid derivatives and pharmaceutical compositions comprising the same

The present invention provides novel 2-methylpropionic acid derivatives represented by the general formula: (wherein R1 represents a hydroxy group, a lower alkoxy group or an aralkyl group; R2 represents a hydroxy group, a lower alkyl group or a halogen atom; A represents an oxygen atom or an imino group; the carbon atom marked with (R) represents a carbon atom in R configuration; and the carbon atom marked with (S) represents a carbon atom in S configuration) and pharmaceutically acceptable salts thereof, which have excellent β3-adrenoceptor stimulating effects and are useful as agents for the prevention or treatment of obesity, hyperglycemia, the diseases caused by intestinal hypermotility, pollakiuria, urinary incontinence, depression, or the diseases caused by biliary calculi or hypermotility of biliary tract.

Beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acid.

In a search for novel analogues of beta(3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective beta(3)-AR agonist in functional assays using the ferret detrusor (beta(3)-AR), rat uterus (beta(2)-AR), and rat atrium (beta(1)-AR); beta(3): EC(50)=7.8 nM, beta(2): IC(50)=7,300 nM, beta(1): EC(20)=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved beta(3)-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED(50)=31 microg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b-e), possess beta(3)-AR agonistic activity in the absence of undesirable beta(1)- or beta(2)-AR mediated actions, and may be useful for clinical treatment and pharmacological studies.