237435-16-4Relevant articles and documents
Scaffold morphing leading to evolution of 2,4-diaminoquinolines and aminopyrazolopyrimidines as inhibitors of the ATP synthesis pathway
Tantry, Subramanyam J.,Shinde, Vikas,Balakrishnan, Gayathri,Markad, Shankar D.,Gupta, Amit K.,Bhat, Jyothi,Narayan, Ashwini,Raichurkar, Anandkumar,Jena, Lalit Kumar,Sharma, Sreevalli,Kumar, Naveen,Nanduri, Robert,Bharath, Sowmya,Reddy, Jitendar,Panduga, Vijender,Prabhakar,Kandaswamy, Karthikeyan,Kaur, Parvinder,Dinesh, Neela,Guptha, Supreeth,Saralaya, Ramanatha,Panda, Manoranjan,Rudrapatna, Suresh,Mallya, Meenakshi,Rubin, Harvey,Yano, Takahiro,Mdluili, Khisi,Cooper, Christopher B.,Balasubramanian,Sambandamurthy, Vasan K.,Ramachandran, Vasanthi,Shandil, Radha,Kavanagh, Stefan,Narayanan, Shridhar,Iyer, Pravin,Mukherjee, Kakoli,Hosagrahara, Vinayak P.,Solapure, Suresh,Hameed, P.Shahul,Ravishankar, Sudha
supporting information, p. 1022 - 1032 (2016/06/08)
The success of bedaquiline as an anti-tubercular agent for the treatment of multidrug-resistant tuberculosis has validated the ATP synthesis pathway and in particular ATP synthase as an attractive target. However, limitations associated with its use in the clinic and the drug-drug interactions with rifampicin have prompted research efforts towards identifying alternative ATP synthesis inhibitors with differentiated mechanisms of action. A biochemical assay was employed to screen AstraZeneca's corporate compound collection to identify the inhibitors of mycobacterial ATP synthesis. The high-throughput screening resulted in the identification of 2,4-diaminoquinazolines as inhibitors of the ATP synthesis pathway. A structure-activity relationship for the quinazolines was established and the knowledge was utilized to morph the quinazoline core into quinoline and pyrazolopyrimidine to expand the scope of chemical diversity. The morphed scaffolds exhibited a 10-fold improvement in enzyme potency and over 100-fold improvement in selectivity against inhibition of mammalian mitochondrial ATP synthesis. These novel compounds were bactericidal and demonstrated growth retardation of Mycobacterium tuberculosis in the acute mouse model of tuberculosis infection.
5-Substituted 1H-pyrrolo[3,2-b]pyridines as inhibitors of gastric acid secretion
Palmer, Andreas Marc,Muench, Gabriela,Brehm, Christof,Zimmermann, Peter Jan,Buhr, Wilm,Feth, Martin Philipp,Simon, Wolfgang Alexander
, p. 1511 - 1530 (2008/09/18)
A series of novel 1H-pyrrolo[3,2-b]pyridines was prepared relying on a copper iodide catalyzed cyclization of 2-prop-1-ynylpyridin-3-amines. A structure-activity relationship was established focusing on the influence of the substitution pattern in position 1, 3, and 5 of the heterocycle on anti-secretory activity, lipophilicity, and pKa value. Some of the compounds proved to be potent inhibitors of the gastric acid pump.
Compounds and methods which modulate feeding behavior and related diseases
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, (2008/06/13)
There are provided compounds, compositions and methods of use thereof in the modulation of feeding behavior, obesity, diabetes, cancer (tumor), inflammatory disorders, depression, stress related disorders, Alzheimer's disease and other disease conditions.
Structure-activity relationships of a series of pyrrolo[3,2-d]pyrimidine derivatives and related compounds as neuropeptide Y5 receptor antagonists
Norman,Chen,Chen,Fotsch,Hale,Han,Hurt,Jenkins,Kincaid,Liu,Lu,Moreno,Santora,Sonnenberg,Karbon
, p. 4288 - 4312 (2007/10/03)
Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. Pharmacological data suggests that the Y5 receptor subtype contributes to the effects of NPY on appetite, and therefore a Y5 antagonist might be a useful therapeutic agent for the treatment of obesity. In attempts to identify potential Y5 antagonists, a series of pyrrolo[3,2-d]pyrimidine derivatives was prepared and evaluated for their ability to bind to Y5 receptors in vitro. We report here the synthesis and initial structure-activity relationship investigations for this class of compounds. The target compounds were prepared by a variety of synthetic routes designed to modify both the substitution and the heterocyclic core of the pyrrolo[3,2-d]pyrimidine lead 1. In addition to identifying several potent Y5 antagonists for evaluation as potential antiobesity agents, a pharmacophore model for the human Y5 receptor is presented.
