477775-36-3

Upstream product

• 589-15-1 1-bromomethyl-4-bromobenzene 
• 146013-28-7 N-(tert-butyl)-5-isobutylthiophene-2-sulphonamide 
• 163520-14-7 5-isobutyl-2 -(tert-butylaminosulfonyl)-3-thiopheneboronic acid 
• 477775-35-2 3-(4-imidazol-1-ylmethylphenyl)-5-isobutyl-N-tert-butylthiophene-2-sulfonamide 

Downstream Products

• 477775-14-7 MO 24 

Relevant academic research and scientific papers

Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity

Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]6-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT2R/AT1R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2, has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21.

Synthesis of 11C-labeled Sulfonyl Carbamates through a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols, and [11C]CO

We describe the development of a new methodology focusing on 11C-labeling of sulfonyl carbamates in a multicomponent reaction comprised of a sulfonyl azide, an alkyl alcohol, and [11C]CO. A number of 11C-labeled sulfonyl carbamates were synthesized and isolated, and the developed methodology was then applied in the preparation of a biologically active molecule. The target compound was obtained in 24±10 % isolated radiochemical yield and was evaluated for binding properties in a tumor cell assay; in vivo biodistribution and imaging studies were also performed. This represents the first successful radiolabeling of a non-peptide angiotensin II receptor subtype 2 agonist, C21, currently in clinical trials for the treatment of idiopathic pulmonary fibrosis.

Selective angiotensin II AT2 receptor agonists: Arylbenzylimidazole structure-activity relationships

Structural alterations in the 2- and 5-positions of the first drug-like selective angiotensin II AT2 receptor agonist (1) have been performed. The imidazole ring system was proven to be a strong determinant for the AT2 selectivity, and with few exceptions all variations gave good AT2 receptor affinities and with retained high AT 2/AT1 selectivities. On the contrary to the findings with AT1 receptor agonists, the impact of structural modifications in the 5-position of the AT2 selective compounds were less pronounced regarding activation of the AT2 receptor. The butyloxyphenyl (56) and the propylthienyl (50) derivatives were found to exert a high agonistic effect as deduced from their capacity to induce neurite elongation in neuronal cells, as does angiotensin II.

Design, synthesis, and biological evaluation, of the first selective nonpeptide AT2 receptor agonist

The first druglike selective angiotensin II AT2 receptor agonist (21) with a Ki value of 0.4 nM for the AT2 receptor and a Ki > 10 μM for the AT1 receptor is reported. Compound 21, with a bioavailability of 20-3