73733-74-1Relevant articles and documents
Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903
Sharma, Swagat H.,Pablo, Juan Lorenzo,Montesinos, Monica Suarez,Greka, Anna,Hopkins, Corey R.
supporting information, p. 155 - 159 (2018/12/11)
The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD.
Discovery of potent inhibitors of the lysophospholipase autotaxin
Shah, Pritom,Cheasty, Anne,Foxton, Caroline,Raynham, Tony,Farooq, Muddasar,Gutierrez, Irene Farre,Lejeune, Aurore,Pritchard, Michelle,Turnbull, Andrew,Pang, Leon,Owen, Paul,Boyd, Susan,Stowell, Alexandra,Jordan, Allan,Hamilton, Niall M.,Hitchin, James R.,Stockley, Martin,MacDonald, Ellen,Quesada, Mar Jimenez,Trivier, Elisabeth,Skeete, Jana,Ovaa, Huib,Moolenaar, Wouter H.,Ryder, Hamish
, p. 5403 - 5410 (2016/11/09)
The autotoxin–lysophosphatidic acid (ATX–LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active of ATX together with the occupying the LPA ‘exit’ channel.
New Antihistaminic N-Heterocyclic 4-Piperidinamines. 3. Synthesis and Antihistaminic Activity of N-(4-Piperidinyl)-3H-imidazopyridin-2-amines
Janssens, Frans,Torremans, Joseph,Janssen, Marcel,Stokbroekx, Raymond A.,Luyckx, Marcel,Janssen, Paul A. J.
, p. 1943 - 1947 (2007/10/02)
To study the bioisosteric replacement of a 2-pyridyl ring for a phenyl nucleus in astemizole, a series of N-(4-piperidinyl)-3H-imidazopyridin-2-amines was synthesised and evaluated.The title compounds were obtained starting from either 8a or 8b by four synthetic methods.The in vivo antihistamine activity was evaluated by the compound 48/80-induced lethality test in rats and the histamine-induced lethality test in guinea pigs after oral and/or subcutaneous administration.Compound 37, the isostere of astemizole, showed the most potent antihistaminic properties in the rat.However, astemizole is superior to 37 as to duration of action and total potency.
