- Structural and Biological Investigations for a Series of N-5 Substituted Pyrrolo[3,2-d]pyrimidines as Potential Anti-Cancer Therapeutics
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Pyrrolo[3,2-d]pyrimidines have been studied for many years as potential lead compounds for the development of antiproliferative agents. Much of the focus has been on modifications to the pyrimidine ring, with enzymatic recognition often modulated by C2 and C4 substituents. In contrast, this work focuses on the N5 of the pyrrole ring by means of a series of novel N5-substituted pyrrolo[3,2-d]pyrimidines. The compounds were screened against the NCI-60 Human Tumor Cell Line panel, and the results were analyzed using the COMPARE algorithm to elucidate potential mechanisms of action. COMPARE analysis returned strong correlation to known DNA alkylators and groove binders, corroborating the hypothesis that these pyrrolo[3,2-d]pyrimidines act as DNA or RNA alkylators. In addition, N5 substitution reduced the EC50 against CCRF-CEM leukemia cells by up to 7-fold, indicating that this position is of interest in the development of antiproliferative lead compounds based on the pyrrolo[3,2-d]pyrimidine scaffold.
- Cawrse, Brian M.,Robinson, Nia'mani M.,Lee, Nina C.,Wilson, Gerald M.,Seley-Radtke, Katherine L.
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- Identification and Optimization of Pyrrolo[3,2-d]pyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for the Treatment of Hepatitis B
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Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 ac
- McGowan, David C.,Herschke, Florence,Pauwels, Frederik,Stoops, Bart,Smyej, Ilham,Last, Stefaan,Pieters, Serge,Embrechts, Werner,Khamlichi, Mourad Daoubi,Thoné, Tine,Van Schoubroeck, Bertrand,Mostmans, Wendy,Wuyts, Debbie,Verstappen, Dorien,Scholliers, Annick,De Pooter, Dorien,Dhuyvetter, Deborah,Borghys, Herman,Tuefferd, Marianne,Arnoult, Eric,Hong, Jin,Fanning, Gregory,Bollekens, Jacques,Urmaliya, Vijay,Teisman, Ard,Horton, Helen,Jonckers, Tim H. M.,Raboisson, Pierre
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p. 6137 - 6151
(2017/08/02)
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- PYRROLO[3,2-D]PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS AND OTHER DISEASES
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This invention concerns pyrrolo[3,2-d]pyrimidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treatment and /or therapy of diseases.
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Page/Page column 8
(2014/05/07)
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- DIARYL-PURINE, AZAPURINES AND -DEAZAPURINES AS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS FOR TREATMENT OF HIV
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This application concerns certain 2-phenylamino-6-aryl amino-, 6-aryloxy-, and 6- arylthio- purines, -azapurines and -deazapurines. These compounds are non-nucleoside reverse transcriptase inhibitors and have potential as anti-HIV treatment.
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- Direct C-Glycosylation of Guanine Analogues: The Synthesis and Antiviral Activity of Certain 7- and 9-Deazaguanine C-Nucleosides
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C-Glycosylation of two guanine analogues, 9-deaza- and 7-deazaguanine, has been achieved under Friedel-Crafts conditions, providing a direct synthetic route to 9-deazaguanosine (4; 2-amino-7-β-D-ribofuranosyl-5H-pyrrolopyrimidin-4(3H)-one) and 8-β-
- Girgis, Nabih S.,Michael, Maged A.,Smee, Donald F.,Alaghamandan, Hassan A.,Robins, Roland K.,Cottam, Howard B.
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p. 2750 - 2755
(2007/10/02)
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