6686-68-6Relevant academic research and scientific papers
Monna, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1
Oh, Soo-Jin,Hwang, Seok Jin,Jung, Jonghoon,Yu, Kuai,Kim, Jeongyeon,Choi, Jung Yoon,Hartzell, H. Criss,Roh, Eun Joo,Justin Lee
supporting information, p. 726 - 735 (2013/11/06)
Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a-NO2 group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC 5050 of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10～30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.
Evaluation of synthetic acridones and 4-quinolinones as potent inhibitors of cathepsins L and v
Marques, Emerson F.,Bueno, Mauro A.,Duarte, Patricia D.,Silva, Larissa R.S.P.,Martinelli, Ariani M.,Dos Santos, Caio Y.,Severino, Richele P.,Broemme, Dieter,Vieira, Paulo C.,Correa, Arlene G.
scheme or table, p. 10 - 21 (2012/08/28)
Cathepsins, also known as lysosomal cysteine peptidases, are members of the papain-like peptidase family, involved in different physiological processes. In addition, cathepsins are implicated in many pathological conditions. This report describes the synthesis and evaluation of a series of N-arylanthranilic acids, acridones, and 4-quinolinones as inhibitors of cathepsins V and L. The kinetics revealed that compounds of the classes of acridones are reversible competitive inhibitors of the target enzyme with affinities in the low micromolar range. They represent promising lead candidates for the discovery of novel competitive cathepsin inhibitors with enhanced selectivity and potency. On the other hand, 4-quinolinones were noncompetitive inhibitors and N-arylanthranilic acids were uncompetitive inhibitors.
2-(4-Methoxyphenoxy)-5-nitro-N-(4-sulfamoylphenyl)benzamide activates Kir6.2/SUR1 KATP channels
Nielsen, Flemming E.,Jacobsen, Palle,Worsaae, Anne,Arkhammar, Per O.G.,Wahl, Philip,Bondo Hansen, John
, p. 5727 - 5730 (2007/10/03)
2-(4-Methoxyphenoxy)-5-nitro-N-(4-sulfamoylphenyl)benzamide and close analogues inhibit glucose stimulated insulin release through activation of Kir6.2/SUR1 KATP channels of beta cells.
An efficient solid phase synthetic route to 1,3-disubstituted 2,4(1H,3H)-quinazolinediones suitable for combinatorial synthesis
Smith, Adrian L.,Thomson, Christopher G.,Leeson, Paul D.
, p. 1483 - 1486 (2007/10/03)
Novel, efficient solid phase chemistry has been developed for the synthesis of 1,3-disubstituted quinazolinediones. Anthranilic acids are linked to a chloroformate resin through the nitrogen, amines are coupled to the flee carboxylic acid, and thermal cyclization leads to heterocycle formation and concommitant resin release resulting in traceless linkage.
