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

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• 作者：Pravin S. Shirude ; Radha Shandil ; Claire Sadler ; Maruti Naik ; Vinayak Hosagrahara ; Shahul Hameed ; Vikas Shinde ; Chandramohan Bathula ; Vaishali Humnabadkar ; Naveen Kumar ; Jitendar Reddy ; Vijender Panduga ; Sreevalli Sharma ; Anisha Ambady ; Naina Hegde ; James Whiteaker ; Robert E. McLaughlin ; Humphrey Gardner ; Prashanti Madhavapeddi ; Vasanthi Ramachandran ; Parvinder Kaur ; Ashwini Narayan ; Supreeth Guptha ; Disha Awasthy ; Chandan Narayan ; Jyothi Mahadevaswamy ; KG Vishwas ; Vijaykamal Ahuja ; Abhishek Srivastava ; KR Prabhakar ; Sowmya Bharath ; Ramesh Kale ; Manjunatha Ramaiah ; Nilanjana Roy Choudhury ; Vasan K. Sambandamurthy ; Suresh Solapure ; Pravin S. Iyer ; Shridhar Narayanan ; Monalisa Chatterji
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：December 12, 2013
• 年：2013
• 卷：56
• 期：23
• 页码：9701-9708
• 全文大小：397K
• 年卷期：v.56,no.23(December 12, 2013)
• ISSN：1520-4804

文摘

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-尾-d-ribose2鈥?epimerase (DprE1). With 鈥渄rug-like鈥?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.