Recent advances in the development of next generation non-nucleoside reverse transcriptase inhibitors.
Since their discovery, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have become one of the cornerstones of highly active anti-retroviral therapy (HAART). Currently, three NNRTI agents, efavirenz, nevirapine and delavirdine are commercially available. Efavirenz and nevirapine, used in combination with nucleoside reverse transcriptase inhibitors (NRTIs), provide durable regimens with efficacy comparable to protease inhibitor (PI) containing therapies. When virological failure occurs following treatment with an NNRTI, the resistance mutations can confer reduced sensitivity to the entire agent class. Therefore, the strategy for the development of next generation NNRTIs has been to focus on compounds which have improved potencies against the clinically relevant viral mutants. Agents with improved virological profiles and which maintain the ease of administration and favorable safety profiles of the current agents should find use in anti-retroviral naïve patients as well as in components of salvage regimens in the anti-retroviral experienced patient. This review summarizes the recent developments with compounds in clinical trials as of January 2002 as well as to summarize information on new agents appearing in the primary and patent literature between January 2001 and December 2002.
Tarby
Christine M
CM
Bristol-Myers Squibb Company, Discovery Chemistry, P.O. Box 4000, Princeton, NJ 08543, USA. christine.tarby@bms.com
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D007093:Imidazoles; D015394:Molecular Structure; D009570:Nitriles; D010330:Patents as Topic; D039681:Pyranocoumarins; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013457:Sulfur Compounds
D019380:Anti-HIV Agents; D003374:Coumarins; C430648:DPC 083; D007093:Imidazoles; D009570:Nitriles; D039681:Pyranocoumarins; D011724:Pyridazines; D011743:Pyrimidines; D011799:Quinazolines; D018894:Reverse Transcriptase Inhibitors; D013457:Sulfur Compounds; C451734:etravirine; D054303:HIV Reverse Transcriptase; C075959:calanolide A; C481671:Dapivirine; C433874:capravirine