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'''Diarylpyrimidines''' (DAPY) and '''diaryltriazines''' (DATA) are two closely related classes of molecules resembling the [[pyrimidine]] [[nucleotide]]s found in [[DNA]]. They show great potency in inhibiting the activity of [[HIV]] [[reverse transcriptase]].<ref>{{cite journal |author=Van Herrewege Y, Vanham G, Michiels J, Fransen K, Kestens L, Andries K, Janssen P, Lewi P |title=A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides |journal=Antimicrob. Agents Chemother. |volume=48 |issue=10 |pages=3684–9 |year=2004 |pmid=15388420 |doi=10.1128/AAC.48.10.3684-3689.2004 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=15388420}}</ref><ref>{{cite journal |author=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 |title=Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains |journal=Eur J Med Chem |volume=42 |issue=5 |pages=567–79 |year=2007 |pmid=17223230 |doi=10.1016/j.ejmech.2006.11.014 |url=http://linkinghub.elsevier.com/retrieve/pii/S0223-5234(06)00436-3}}</ref> Several compounds in this class are currently underdevelopment as the next generation of [[non-nucleoside reverse transcriptase inhibitor]]s,<ref>{{cite journal |author=Goebel F, Yakovlev A, Pozniak AL, Vinogradova E, Boogaerts G, Hoetelmans R, de Béthune MP, Peeters M, Woodfall B |title=Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects |journal=AIDS |volume=20 |issue=13 |pages=1721–6 |year=2006 |pmid=16931936 |doi=10.1097/01.aids.0000242818.65215.bd |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00002030-200608220-00005}}</ref><ref>{{cite journal |author=Fang C, Bauman JD, Das K, Remorino A, Arnold E, Hochstrasser RM |title=Two-dimensional infrared spectra reveal relaxation of the nonnucleoside inhibitor TMC278 complexed with HIV-1 reverse transcriptase |journal=Proc Natl Acad Sci U S A |volume= |issue= |pages= |year=2007 |pmid=18040050 |doi=10.1073/pnas.0709320104 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=18040050}}</ref> notably [[etravirine]]<ref name="pmid15115397">{{cite journal |author=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 |title=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 |journal=J. Med. Chem. |volume=47 |issue=10 |pages=2550–60 |year=2004 |pmid=15115397 |doi=10.1021/jm030558s |url=http://dx.doi.org/10.1021/jm030558s |issn=}}</ref> and [[rilpivirine]].<ref>Steve Mitchell. [http://www.terradaily.com/reports/HIV_Market_To_Top_10_Billion_Dollars_999.html HIV Market To Top 10 Billion Dollars]. United Press International. April 11, 2007.</ref>
'''Diarylpyrimidines''' (DAPY) and '''diaryltriazines''' (DATA) are two closely related classes of molecules resembling the [[pyrimidine]] [[nucleotide]]s found in [[DNA]]. They show great potency in inhibiting the activity of [[HIV]] [[reverse transcriptase]].<ref>{{cite journal |author=Van Herrewege Y, Vanham G, Michiels J, Fransen K, Kestens L, Andries K, Janssen P, Lewi P |title=A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides |journal=Antimicrob. Agents Chemother. |volume=48 |issue=10 |pages=3684–9 |year=2004 |pmid=15388420 |doi=10.1128/AAC.48.10.3684-3689.2004 |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=15388420}}</ref><ref>{{cite journal |author=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 |title=Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains |journal=Eur J Med Chem |volume=42 |issue=5 |pages=567–79 |year=2007 |pmid=17223230 |doi=10.1016/j.ejmech.2006.11.014 |url=http://linkinghub.elsevier.com/retrieve/pii/S0223-5234(06)00436-3}}</ref> Several compounds in this class are currently underdevelopment as the next generation of [[non-nucleoside reverse transcriptase inhibitor]]s,<ref>{{cite journal |author=Goebel F, Yakovlev A, Pozniak AL, Vinogradova E, Boogaerts G, Hoetelmans R, de Béthune MP, Peeters M, Woodfall B |title=Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects |journal=AIDS |volume=20 |issue=13 |pages=1721–6 |year=2006 |pmid=16931936 |doi=10.1097/01.aids.0000242818.65215.bd |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00002030-200608220-00005}}</ref><ref>{{cite journal |author=Fang C, Bauman JD, Das K, Remorino A, Arnold E, Hochstrasser RM |title=Two-dimensional infrared spectra reveal relaxation of the nonnucleoside inhibitor TMC278 complexed with HIV-1 reverse transcriptase |journal=Proc Natl Acad Sci U S A |volume= |issue= |pages= |year=2007 |pmid=18040050 |doi=10.1073/pnas.0709320104 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=18040050}}</ref> notably [[etravirine]]<ref name="pmid15115397">{{cite journal |author=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 |title=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 |journal=J. Med. Chem. |volume=47 |issue=10 |pages=2550–60 |year=2004 |pmid=15115397 |doi=10.1021/jm030558s |issn=}}</ref> and [[rilpivirine]].<ref>Steve Mitchell. [http://www.terradaily.com/reports/HIV_Market_To_Top_10_Billion_Dollars_999.html HIV Market To Top 10 Billion Dollars]. United Press International. April 11, 2007.</ref>


==References==
==References==

Revision as of 09:41, 11 June 2008

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]

References

  1. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Steve Mitchell. HIV Market To Top 10 Billion Dollars. United Press International. April 11, 2007.
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