7546-52-3Relevant academic research and scientific papers
Design, synthesis, and spectroscopic study of 7-azaindolyl hydrazones with anti-breast cancer activity
Dongare, Sakharam B.,Bandgar, Babasaheb P.,Bhale, Pravin S.,Shringare, Sadanand N.,Chavan, Hemant V.
, p. 1 - 9 (2019/06/24)
A series of 7-azaindolyl hydrazones were prepared by reacting of hydrazides of 7-azaindole-3-acetic acids with aromatic aldehydes and N-substituted indolyl-3-carboxyaldehydes. Structure of all the synthesized compounds were satisfactorily correlated by IR, 1H NMR, 13C NMR and mass spectroscopic evidences. The synthesized compounds were evaluated for their possible anticancer potential against MCF-7 induced breast carcinoma. It is worth mentioning that most of the compounds were considerably active against MCF-7 cell line with GI50 values ranging from 22.3–81.0 μM. The hydrazones of N-1-substituted indole-3-carboxyaldehydes 9f, 9g, 9h, 9c, and 9j were active against MCF-7 cell line with GI50 values less than 40 μM (GI50 = 22.3 and 24.9, 29.6, 30.2 and 37.8 μM respectively) with moderate TGI values (TGI = 56.6, 59.5, 65.5, 70.7 and 94.6 μM respectively). The active compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells.
Fevipiprant selective prostaglandin DP2 (CRTh2) inhibitor treatment of asthma
Singh,Saroj,Kumar,Kuhad,Kuhad
, p. 565 - 572 (2018/09/11)
Prostaglandin D2 (PGD2), a major prostanoid, releases from activated mast cells. It activates and recruits various inflammatory cells like eosinophils and basophils through DP2 receptors to the site of inflammation and further promotes late-phase allergic reactions. For the last decade, the scientific community has extensively explored this pathway and synthesized various specific DP2 receptor antagonists for the management of asthma. About 20 compounds with DP2 antagonistic activity have reached different stages of clinical development. Among these, fevipiprant is one of the most advanced oral DP2 inhibitors as it selectively blocks the DP2 receptors. Fevipiprant has demonstrated an acceptable safety profile in phase II studies as evident from significant reduction of moderate to severe asthma exacerbations. Currently this novel antiasthmatic drug is in phase III clinical trials. This review provides a brief overview of PGD2 blockers, particularly fevipiprant and its preclinical pharmacology and clinical development, by providing a summary of completed or ongoing clinical studies assessing its safety and efficacy in asthma.
Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases
Sandham, David A.,Arnold, Nicola,Aschauer, Heinrich,Bala, Kamlesh,Barker, Lucy,Brown, Lyndon,Brown, Zarin,Budd, David,Cox, Brian,Docx, Cerys,Dubois, Gerald,Duggan, Nicholas,England, Karen,Everatt, Brian,Furegati, Marcus,Hall, Edward,Kalthoff, Frank,King, Anna,Leblanc, Catherine J.,Manini, Jodie,Meingassner, Josef,Profit, Rachael,Schmidt, Alfred,Simmons, Jennifer,Sohal, Bindi,Stringer, Rowan,Thomas, Matthew,Turner, Katharine L.,Walker, Christoph,Watson, Simon J.,Westwick, John,Willis, Jennifer,Williams, Gareth,Wilson, Caroline
supporting information, p. 6582 - 6591 (2013/10/22)
Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype derived from high throughput screening furnished a highly selective compound NVP-QAV680 with low nM functional potency for inhibition of CRTh2 driven human eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent mechanistic and allergic disease models and was suitable for clinical development.
7-Azaindole-3-acetic acid derivatives: Potent and selective CRTh2 receptor antagonists
Sandham, David A.,Adcock, Claire,Bala, Kamlesh,Barker, Lucy,Brown, Zarin,Dubois, Gerald,Budd, David,Cox, Brian,Fairhurst, Robin A.,Furegati, Markus,Leblanc, Catherine,Manini, Jodie,Profit, Rachael,Reilly, John,Stringer, Rowan,Schmidt, Alfred,Turner, Katharine L.,Watson, Simon J.,Willis, Jennifer,Williams, Gareth,Wilson, Caroline
experimental part, p. 4794 - 4798 (2010/05/18)
High throughput screening identified a 7-azaindole-3-acetic acid scaffold as a novel CRTh2 receptor antagonist chemotype, which could be optimised to furnish a highly selective compound with good functional potency for inhibition of human eosinophil shape change in whole blood and oral bioavailability in the rat.
