Diarylpyrimidines

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Diarylpyrimidines (DAPY) and diaryltriazines (DATA) are two closely related classes of molecules resembling the pyrimidine nucleotides found in DNA. They show great potency in inhibiting the activity of HIV reverse transcriptase.^[1]^[2] Several compounds in this class are currently underdevelopment as the next generation of non-nucleoside reverse transcriptase inhibitors,^[3]^[4] notably etravirine^[5] and rilpivirine.^[6]

[edit] References

^ Van Herrewege Y, Vanham G, Michiels J, Fransen K, Kestens L, Andries K, Janssen P, Lewi P (2004). "A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides". Antimicrob. Agents Chemother. 48 (10): 3684–9. doi:10.1128/AAC.48.10.3684-3689.2004. PMID 15388420.
^ Mordant C, Schmitt B, Pasquier E, Demestre C, Queguiner L, Masungi C, Peeters A, Smeulders L, Bettens E, Hertogs K, Heeres J, Lewi P, Guillemont J (2007). "Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains". Eur J Med Chem 42 (5): 567–79. doi:10.1016/j.ejmech.2006.11.014. PMID 17223230.
^ Goebel F, Yakovlev A, Pozniak AL, Vinogradova E, Boogaerts G, Hoetelmans R, de Béthune MP, Peeters M, Woodfall B (2006). "Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects". AIDS 20 (13): 1721–6. doi:10.1097/01.aids.0000242818.65215.bd. PMID 16931936.
^ Fang C, Bauman JD, Das K, Remorino A, Arnold E, Hochstrasser RM (2007). "Two-dimensional infrared spectra reveal relaxation of the nonnucleoside inhibitor TMC278 complexed with HIV-1 reverse transcriptase". Proc Natl Acad Sci U S A. doi:10.1073/pnas.0709320104. PMID 18040050.
^ Das K, Clark AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW, Ho CY, Ye H, Lichtenstein MA, Andries K, Pauwels R, De Béthune MP, Boyer PL, Clark P, Hughes SH, Janssen PA, Arnold E (2004). "Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants". J. Med. Chem. 47 (10): 2550–60. doi:10.1021/jm030558s. PMID 15115397.
^ Steve Mitchell. HIV Market To Top 10 Billion Dollars. United Press International. April 11, 2007.

v • d • e Antivirals used against HIV (HAART) (primarily J05)

Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI)	Abacavir (ABC)° • Emtricitabine° • Lamivudine (3TC)° • Tenofovir° • Didanosine • Zidovudine (AZT) • Apricitabine^† • Stampidine^† • Elvucitabine^† • Racivir^† • Amdoxovir^† • Stavudine^‡ • Zalcitabine^‡

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)	Efavirenz° • Nevirapine • Etravirine • Rilpivirine^† • Loviride^‡ • Delavirdine^‡

Protease Inhibitors (PI)	Atazanavir° • Brecanavir^§ • Fosamprenavir° • Lopinavir° • Darunavir • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir^‡ • Indinavir^‡

Entry/fusion inhibitors	Enfuvirtide • Maraviroc • Vicriviroc^† • PRO 140^† • Ibalizumab^†

Integrase inhibitors	Raltegravir • Elvitegravir^†

Maturation inhibitors	Bevirimat^† • Vivecon™^†

Combined formulations	Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom

Other & experimental agents	Foscarnet • Hydroxyurea • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A • Cyanovirin-N • Miltefosine • R-roscovitine^†

°DHHS preferred first-line agent. ^†Undergoing clinical trials, not FDA approved. ^‡Formerly or rarely used agent. ^§Development terminated.