Azaindoles: Noncovalent DprE1 Inhibitors from Scaffold Morphing Efforts, Kill Mycobacterium tuberculosis and Are Efficacious in Vivo

作者：Shirude Pravin S^*; Shandil Radha; Sadler Claire; Naik Maruti; Hosagrahara Vinayak; Hameed Shahul; Shinde Vikas; Bathula Chandramohan; Humnabadkar Vaishali; Kumar Naveen; Reddy Jitendar; Panduga Vijender; Sharma Sreevalli; Ambady Anisha; Hegde Naina; Whiteaker James; McLaughlin Robert E; Gardner Humphrey; Madhavapeddi Prashanti; Ramachandran Vasanthi; Kaur Parvinder; Narayan Ashwini; Guptha Supreeth; Awasthy Disha; Narayan Chandan; Mahadevaswamy Jyothi; Vishwas K G

来源：Journal of Medicinal Chemistry, 2013, 56(23): 9701-9708.

DOI：10.1021/jm401382v

We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-beta-D-ribose2'-epimerase (DprE1). With "drug-like" properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis.

• 出版日期2013-12-12