دورية أكاديمية
Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo.
| العنوان: | Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo. |
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| المؤلفون: | Shirude PS; Department of Medicinal Chemistry, IMED Infection, AstraZeneca India , Bellary Road, Hebbal, Bangalore 560024, India., Shandil R, Sadler C, Naik M, Hosagrahara V, Hameed S, Shinde V, Bathula C, Humnabadkar V, Kumar N, Reddy J, Panduga V, Sharma S, Ambady A, Hegde N, Whiteaker J, McLaughlin RE, Gardner H, Madhavapeddi P, Ramachandran V, Kaur P, Narayan A, Guptha S, Awasthy D, Narayan C, Mahadevaswamy J, Vishwas KG, Ahuja V, Srivastava A, Prabhakar KR, Bharath S, Kale R, Ramaiah M, Choudhury NR, Sambandamurthy VK, Solapure S, Iyer PS, Narayanan S, Chatterji M |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2013 Dec 12; Vol. 56 (23), pp. 9701-8. Date of Electronic Publication: 2013 Nov 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Antitubercular Agents/*pharmacology , Bacterial Proteins/*antagonists & inhibitors , Indoles/*chemical synthesis , Mycobacterium tuberculosis/*drug effects , Oxidoreductases/*antagonists & inhibitors, Alcohol Oxidoreductases ; Animals ; Antitubercular Agents/pharmacokinetics ; Antitubercular Agents/therapeutic use ; Drug Discovery ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/pharmacokinetics ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/therapeutic use ; Indoles/pharmacokinetics ; Indoles/pharmacology ; Indoles/therapeutic use ; Mice ; Rats ; Tuberculosis, Multidrug-Resistant/drug therapy |
| مستخلص: | 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-β-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. |
| المشرفين على المادة: | 0 (Antitubercular Agents) 0 (Bacterial Proteins) 0 (Enzyme Inhibitors) 0 (Indoles) EC 1.- (Oxidoreductases) EC 1.1.- (Alcohol Oxidoreductases) EC 1.1.- (DprE1 protein, Mycobacterium tuberculosis) |
| تواريخ الأحداث: | Date Created: 20131113 Date Completed: 20140304 Latest Revision: 20141120 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1021/jm401382v |
| PMID: | 24215368 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/jm401382v |