586
Views
4
CrossRef citations to date
0
Altmetric
Review

Current insights into anti-HIV drug discovery and development: a review of recent patent literature (2014–2017)

, , , , , & show all
Pages 299-316 | Received 24 Dec 2017, Accepted 05 Feb 2018, Published online: 13 Feb 2018

References

  • De Clercq E. A cutting-edge view on the current state of antiviral drug development. Med Res Rev. 2013;33(6):1249–1277.
  • De Clercq E. Antivirals: past, present and future. Biochem Pharmacol. 2013;85(6):727–744.
  • Zhan P, Pannecouque C, De Clercq E, et al. Anti-HIV drug discovery and development: current innovations and future trends. J Med Chem. 2016;59(7):2849–2878.
  • Kang D, Song Y, Chen W, et al. “Old dogs with new tricks”: exploiting alternative mechanisms of action and new drug design strategies for clinically validated HIV targets. Mol Biosyst. 2014;10(8):1998–2022.
  • Zhan P, Li W, Chen H, et al. Targeting protein-protein interactions: a promising avenue of anti-HIV drug discovery. Curr Med Chem. 2010;17(29):3393–3409.
  • Zhan P, Liu X, De Clercq E. Blocking nuclear import of pre-integration complex: an emerging anti-HIV-1 drug discovery paradigm. Curr Med Chem. 2010;17(6):495–503.
  • Zhang H, Kang D, Huang B, et al. Discovery of non-peptide small molecular CXCR4 antagonists as anti-HIV agents: recent advances and future opportunities. Eur J Med Chem. 2016;114:65–78.
  • Huang B, Kang D, Zhan P, et al. Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities. Expert Opin Drug Discov. 2015;10(12):1271–1281.
  • Zhan P, Liu X. Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent review (2005–2010). Expert Opin Ther Pat. 2011;21(5):717–796.
  • Li X, Zhang L, Tian Y, et al. Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent review (2011–2014). Expert Opin Ther Pat. 2014;24(11):1199–1227.
  • Gravatt LAH, Leibrand CR, Patel S, et al. New drugs in the pipeline for the treatment of HIV: a review. Curr Infect Dis Rep. 2017;19(11):42.
  • Ju H, Zhang J, Huang B, et al. Inhibitors of influenza virus polymerase acidic (PA) endonuclease: contemporary developments and perspectives. J Med Chem. 2017;60(9):3533–3551.
  • Wang X, Gao P, Menéndezarias L, et al. Update on recent developments in small molecular HIV-1 RNase H inhibitors (2013–2016): opportunities and challenges. Curr Med Chem. 2017 Jan 13. Epub ahead of print. Available from: http://www.eurekaselect.com/149238/article
  • DeSimone RW, Currie KS, Mitchell SA, et al. Privileged structures: applications in drug discovery. Comb Chem High Throughput Screen. 2004;7(5):473–494.
  • Welsch ME, Snyder SA, Stockwell BR. Privileged scaffolds for library design and drug discovery. Curr Opin Chem Biol. 2010;14(3):347–361.
  • Li Z, Zhan P, Liu X. 1,3,4-oxadiazole: a privileged structure in antiviral agents. Mini Rev Med Chem. 2011;11(13):1130–1142.
  • Duarte CD, Barreiro EJ, Fraga CA. Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007;7(11):1108–1119.
  • Song Y, Zhan P, Liu X. Heterocycle-thioacetic acid motif: a privileged molecular scaffold with potent, broad-ranging pharmacological activities. Curr Pharm Des. 2013;19(40):7141–7154.
  • Song Y, Zhan P, Zhang Q, et al. Privileged scaffolds or promiscuous binders: a glance of pyrrolo[2,1-f][1,2,4]triazines and related bridgehead nitrogen heterocycles in medicinal chemistry. Curr Pharm Des. 2013;19(8):1528–1548.
  • Berthet M, Cheviet T, Dujardin G, et al. Isoxazolidine: a privileged scaffold for organic and medicinal chemistry. Chem Rev. 2016;116(24):15235–15283.
  • Song Y, Chen W, Kang D, et al. “Old friends in new guise”: exploiting privileged structures for scaffold re-evolution/refining. Comb Chem High Throughput Screen. 2014;17(6):536–553.
  • Han Y, Mesplède T, Wainberg MA. Investigational HIV integrase inhibitors in phase I and phase II clinical trials. Expert Opin Investig Drugs. 2017;26(11):1207–1213.
  • Cheng X, Gao P, Sun L, et al. Identification of spirocyclic or phosphate substituted quinolizine derivatives as novel HIV-1 integrase inhibitors: a patent evaluation of WO2016094197A1, WO2016094198A1 and WO2016154527A1. Expert Opin Ther Pat. 2017;27(11):1277–1286.
  • Chen YC. Beware of docking! Trends Pharmacol Sci. 2015;36(2):78–95.
  • Martin DP, Blachly PG, McCammon JA, et al. Exploring the influence of the protein environment on metal-binding pharmacophores. J Med Chem. 2014;57(16):7126–7135.
  • Embrey MW, Graham TH, Raheem IT, et al. Spirocyclic heterocycle compounds useful as HIV integrase inhibitors. WO 2016094197 A1. 2016.
  • Graham TH, Embrey MW, Walji A, et al. Spirocyclic heterocycle compounds useful as HIV integrase inhibitors. WO 2016094198 A1. 2016.
  • Yu T, Waddell ST, Mccauley JA, et al. Phosphate-substituted quinolizine derivatives useful as HIV integrase inhibitors. WO 2016154527 A1. 2016.
  • Yu T, Waddell ST, Graham TH, et al. Preparation of fused tricyclic heterocycles as HIV integrase inhibitors for the treatment and prophylaxis of HIV infection. WO 2017113288 A1. 2017.
  • Yu T, Waddell ST, Graham TH, et al. Preparation of fused tricyclic heterocycles as HIV integrase inhibitors for the treatment and prophylaxis of HIV infection. WO 2017116928 A1. 2017.
  • Song Y, Fang Z, Zhan P, et al. Recent advances in the discovery and development of novel HIV-1 NNRTI platforms (Part II): 2009–2013 update. Curr Med Chem. 2014;21(3):329–355.
  • Chen X, Zhan P, Li D, et al. Recent advances in DAPYs and related analogues as HIV-1 NNRTIs. Curr Med Chem. 2011;18(3):359–376.
  • Franck P, Heeres J, Maes B, et al. Preparation of fluoroaromatic derivatives useful as anti-HIV compounds. WO 2014072419 A1. 2014.
  • Meng Q, Liu N, Huang B, et al. Novel fluorine-containing DAPY derivatives as potent HIV-1 NNRTIs: a patent evaluation of WO2014072419. Expert Opin Ther Pat. 2015;25(12):1477–1486.
  • Mane DV, Gavade SN, Kulkarni SS, et al. Preparation of triaminotriazine picolinonitrile derivatives for treatment of hyperproliferative disease and HIV-1 infection. WO 2016059647 A2. 2016.
  • Huang B, Zhou Z, Kang D, et al. Novel diaryltriazines with a picolinonitrile moiety as potent HIV-1 RT inhibitors: a patent evaluation of WO2016059647(A2). Expert Opin Ther Pat. 2017;27(1):9–15.
  • Liu X, Zhou Z, Zhan P Preparation of diarylpyrimidines as anti-HIV agents. CN 106831605 A. 2017.
  • Liu X, Tian Y, Liu Z, et al. Preparation of substituted diaryl nicotinamide derivative for treating HIV infection. CN 106967047 A. 2017.
  • Liu X, Yang J, Zhan P, et al. Preparation of 6-substituted diarylpyridine derivatives as anti-HIV drugs. CN 105294550 A. 2016.
  • Liu X, Zhang H, Zhan P, et al. Preparation of pyrimidine derivatives for treatment of AIDS. CN 106117242 A. 2016.
  • Liu X, Li X, Zhan P Preparing method and application of N-substituted piperidine amino-4-pyrimidine derivative. CN 105968096 A. 2016.
  • Liu X, Liu Z, Zhan P Diaryl pyridine derivatives useful in treatment of human immunodeficiency virus (HIV) infection and their preparation. CN 104876860 A. 2015.
  • Liu X, Li X, Zhan P m-Diarene-pyrimidine derivatives as HIV-1 reverse transcriptase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of HIV infection. CN 103483272 A. 2014.
  • Liu X, Zhang L Preparation of 2-(N-arylmethylpiperidine-4-ylamino)-4-(substituted-phenoxy)benzene derivatives as HIV-1 inhibitors. CN 103497146 A. 2014.
  • Liu X, Li X, Zhan P Preparation of pyrimidine mercapto-acetamides derivatives. CN 104016927 A. 2014.
  • Yang J, Chen W, Kang D, et al. Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket. Eur J Med Chem. 2016;109:294–304.
  • Li X, Chen W, Tian Y, et al. Discovery of novel diarylpyrimidines as potent HIV NNRTIs via a structure-guided core-refining approach. Eur J Med Chem. 2014;80:112–121.
  • Zhang L, Zhan P, Chen X, et al. Design, synthesis and preliminary SAR studies of novel N-arylmethyl substituted piperidine-linked aniline derivatives as potent HIV-1 NNRTIs. Bioorg Med Chem. 2014;22(1):633–642.
  • Pelly SC, Van O, Willem AL, et al. Trisubstituted indoles and their use as non-nucleoside reverse transcriptase inhibitors for treatment of HIV infection or AIDS. WO 2015044928 A1. 2015.
  • Li X, Gao P, Zhan P, et al. Substituted indoles as HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent evaluation (WO2015044928). Expert Opin Ther Pat. 2016;26(5):629–635.
  • Liu X, Li X, Zhan P Indole aryl sulfone derivative useful in treatment of HIV infection and its preparation. CN 105968095 A. 2016.
  • Li X, Gao P, Huang B, et al. Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement. Eur J Med Chem. 2017;126:190–201.
  • Hazuda D, Miller MD, Grobler JA, et al. Methods for treatment and prophylaxis of HIV and AIDS. WO 2017139519 A1. 2017.
  • Zhao H. Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective. Drug Discov Today. 2007;12(3–4):149–155.
  • Bajorath J. Computational scaffold hopping: cornerstone for the future of drug design? Future Med Chem. 2017;9(7):629–631.
  • Sun H, Tawa G, Wallqvist A. Classification of scaffold-hopping approaches. Drug Discov Today. 2012;17(7–8):310–324.
  • Christ F, Debyser Z. HIV-1 integrase inhibition: looking at cofactor interactions. Future Med Chem. 2015;7(18):2407–2410.
  • Demeulemeester J, Chaltin P, Marchand A, et al. LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006–2014). Expert Opin Ther Pat. 2014;24(6):609–632.
  • Fader LD, Malenfant E, Parisien M, et al. Discovery of BI 224436, a noncatalytic site integrase inhibitor (NCINI) of HIV-1. ACS Med Chem Lett. 2014;5(4):422–427.
  • Fenwick C, Amad M, Bailey MD, et al. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Antimicrob Agent Chemother. 2014;58(6):3233–3244.
  • Christ F, Voet A, Marchand A, et al. Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat Chem Biol. 2010;6(6):442–448.
  • Feng L, Sharma A, Slaughter A, et al. The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem. 2013;288(22):15813–15820.
  • Kadow JF, Naidu BN, Patel M, et al. Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication. WO 2017195113 A1. 2017.
  • Kadow JF, Naidu BN, Wang T, et al. Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication. WO 2017195112 A1. 2017.
  • Kadow JF, Naidu BN, Wang T, et al. Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication. WO 2017195111 A1. 2017.
  • Eastman KJ, Kadow JF, Parcella KE, et al. 5-(N-Benzyltetrahydroisoquinolin-6-yl)pyridin-3-ylacetic acid derivatives as inhibitors of human immunodeficiency virus replication and their preparation. WO 2017025917 A1. 2017.
  • Kadow JF, Naidu BN, Wang T, et al. 5-(N-Aryltetrahydroisoquinolin-6-yl)pyridin-3-ylacetic acid derivatives as inhibitors of human immunodeficiency virus replication and their preparation. WO 2017025916 A1. 2017.
  • Kadow JF, Naidu BN, Wang T, et al. 5-(N-Substituted tetrahydroisoquinolin-6-yl)pyridin-3-ylacetic acid derivatives as inhibitors of human immunodeficiency virus replication and their preparation. WO 2017025914 A1. 2017.
  • Johns BA, Velthuisen EJ, Weatherhead JG Preparation of isoindoline derivatives for the treatment of viral infections. WO 2017093937 A1. 2017.
  • Johns BA, Velthuisen EJ, Weatherhead JG Preparation of isoindoline derivatives for the treatment of viral infections. WO 2017093932 A1. 2017.
  • Johns BA, Velthuisen EJ, Weatherhead JG Preparation of isoindoline derivatives for the treatment of viral infections. WO 2017093930 A1. 2017.
  • Johns BA, Velthuisen EJ, Weatherhead JG Preparation of tetrahydroisoquinoline derivatives as antivirals agents for the treatment of HIV infection. WO 2017093938 A1. 2017.
  • Johns BA, Suwandi LS, Velthuisen EJ, et al. Preparation of benzoazepine derivatives as antiviral agents. WO 2017046707 A1. 2017.
  • Naidu BN, Manoj P, Sd A, et al. Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication. WO 2015126376 A1. 2015.
  • Naidu BN, Michael AW, Margaret ES, et al. Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication. WO 2015126737 A1. 2015.
  • Kyle JE, Kyle EP, Kevin P, et al. Inhibitors of human immunodeficiency virus replication. WO 2015126765 A1, 2015.
  • Kevin P, Wang Z, David RL, et al. Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication. WO 2015123182 A1. 2015.
  • Kevin P, Wang Z, John FK, et al. Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication.US 20150232480 A1. 2015.
  • Kadow JF, Naidu BN, Patel M, et al. Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication and their preparation. WO 2017025913 A1. 2017.
  • Giordanetto F, Kihlberg J. Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties? J Med Chem. 2014;57(2):278–295.
  • Sun L, Gao P, Zhan P, et al. Pyrazolo[1,5-a]pyrimidine-based macrocycles as novel HIV-1 inhibitors: a patent evaluation of WO2015123182. Expert Opin Ther Pat. 2016;26(9):979–986.
  • Liu X, Liang X, Zhan P Imidazopyrazine derivatives as antiviral agents and their preparation, pharmaceutical compositions and use in the treatment of HIV infection. CN 104016990 A. 2014.
  • Tian Y, Du D, Rai D, et al. Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives. Bioorg Med Chem. 2014;22(7):2052–2059.
  • Wang L, Tian Y, Chen W, et al. Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 2: discovery of novel [1,2,4]Triazolo[1,5-a]pyrimidines using a structure-guided core-refining approach. Eur J Med Chem. 2014;85:293–303.
  • Huang B, Li C, Chen W, et al. Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches. Eur J Med Chem. 2015;92:754–765.
  • Huang B, Liang X, Li C, et al. Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 4: design, synthesis and biological evaluation of novel imidazo[1,2-a]pyrazines. Eur J Med Chem. 2015;93:330–337.
  • Liu X, Kang D, Zhan P, et al. Thieno[3,2-d]pyrimidine HIV-1 reverse transcriptase inhibitors and their preparation method and application in preparing anti-HIV drugs. CN 106831814 A. 2017.
  • Liu X, Kang D, Zhan P, et al. Preparation of thienopyrimidine derivatives and for treating HIV infection. WO 2016197589 A1. 2016.
  • Liu X, Fang Z, Kang D, et al. Preparation of thieno[3,2-d]pyrimidines as antiHIV agents. CN 104530078 A. 2015.
  • Liu X, Kang D, Zhan P, et al. Preparation of thienopyrimidine derivatives and for treating HIV infection. CN 104926829 A. 2015.
  • Liu X, Kang D, Zhan P, et al. Diaryl thienopyrimidines as HIV-1 reverse transcriptase inhibitor and its preparation. CN 106866699 A. 2017.
  • Kang D, Fang Z, Li Z, et al. Design, synthesis, and evaluation of thiophene[3,2-d]pyrimidine derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors with significantly improved drug resistance profiles. J Med Chem. 2016;59(17):7991–8007.
  • Kang D, Fang Z, Huang B, et al. Structure-based optimization of thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors with improved potency against resistance-associated variants. J Med Chem. 2017;60(10):4424–4443.
  • Kang D, Ding X, Wu G, et al. Discovery of Thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs targeting the tolerant region I of NNIBP. ACS Med Chem Lett. 2017;8(11):1188–1193.
  • Jansa P, Kvasnica M, Mackman RL Preparation of fused pyrimidines as HIV reverse transcriptase inhibitors useful in treatment and prevention of HIV infection. WO 2016105532 A1. 2016.
  • Jansa P, Mackman RL, Hu YE, et al. Preparation of isoquinoline compounds as HIV Reverse transcriptase inhibitors useful in treatment and prevention of HIV infection. WO 2016105534 A1. 2016.
  • Jansa P, Simon T, Lansdon E, et al. Preparation of quinazoline derivatives for the treatment of HIV infection. WO 2016105564 A1. 2016.
  • Kang D, Huo Z, Wu G, et al. Novel fused pyrimidine and isoquinoline derivatives as potent HIV-1 NNRTIs: a patent evaluation of WO2016105532A1, WO2016105534A1 and WO2016105564A1. Expert Opin Ther Pat. 2017;27(4):383–391.
  • Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012;75(3):311–335.
  • Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79(3):629–661.
  • Li G, Lou HX. Strategies to diversify natural products for drug discovery. Med Res Rev. 2017; Oct 24. [Epub ahead of print].
  • Ríos JL, Máñez S. New pharmacological opportunities for betulinic acid. Planta Med. 2017; Dec 4. [Epub ahead of print]
  • Dorr CR, Yemets S, Kolomitsyna O, et al. Triterpene derivatives that inhibit human immunodeficiency virus type 1 replication. Bioorg Med Chem Lett. 2011;21(1):542–545.
  • Regueiro-Ren A, Liu Z, Chen Y, et al. Discovery of BMS-955176, a second generation HIV-1 maturation inhibitor with broad spectrum antiviral activity. ACS Med Chem Lett. 2016;7(6):568–572.
  • Nowicka-Sans B, Protack T, Lin Z, et al. BMS-955176: identification and characterization of a second-generation HIV-1 maturation inhibitor with improved potency, anti-viral spectrum and gag polymorphic coverage. Antimicrob Agent Chemother. 2016;60(7):3956–3969.
  • Swidorski JJ, Liu Z, Sit SY, et al. Inhibitors of HIV-1 maturation: development of structure-activity relationship for C-28 amides based on C-3 benzoic acid-modified triterpenoids. Bioorg Med Chem Lett. 2016;26(8):1925–1930.
  • Zhao Y, Gu Q, Morris-Natschke SL, et al. Incorporation of privileged structures into bevirimat can improve activity against wild-type and bevirimat-resistant HIV-1. J Med Chem. 2016;59(19):9262–9268.
  • Reddy BP, Reddy KR, Krupadanam GLD, et al. Preparation of C-3 triterpenone derivatives as HIV inhibitors. WO 2017115329 A1. 2017.
  • Reddy BP, Reddy KR, Krupadanam GLD, et al. Preparation of C-3 novel triterpenones with C-28 urea derivatives as HIV inhibitors. WO 2017064628 A1. 2017.
  • Johns BA Preparation of triterpene compounds with HIV maturation inhibitory activity. WO 2017051355 A1. 2017.
  • Reddy BP, Reddy KR, Krupadanam GLD, et al. Prepartion of novel C(28)-amides with C(3)-modifications of triterpene derivatives as HIV inhibitors. WO 2017025899 A1. 2017.
  • Reddy BP, Reddy KR, Krupadanam GLD, et al. Preparation of triterpene-amide compounds as HIV inhibitors. WO 2017021922 A1. 2017.
  • Reddy BP, Reddy KR, Reddy AP, et al. Preparation of novel substituted betulinic amide derivatives as HIV inhibitors. WO 2017017630 A1. 2017.
  • Johns BA Preparation of betulin derivatives for preventing or treating HIV infections. WO 2017017609 A1. 2017.
  • Johns BA Preparation of betulin derivatives for preventing or treating HIV infections. WO 2017017607 A1. 2017.
  • Huang B, Kang D, Yang J, et al. Novel diarylpyrimidines and diaryltriazines as potent HIV-1 NNRTIs with dramatically improved solubility: a patent evaluation of US20140378443A1. Expert Opin Ther Pat. 2016;26(2):281–289.
  • Meier C. Nucleoside diphosphate and triphosphate prodrugs - an unsolvable task? Antivir Chem Chemother. 2017;25(3):69–82.
  • Pertusati F, Serpi M, McGuigan C. Medicinal chemistry of nucleoside phosphonate prodrugs for antiviral therapy. Antivir Chem Chemother. 2012;22(5):181–203.
  • Thornton PJ, Kadri H, Miccoli A, et al. Nucleoside phosphate and phosphonate prodrug clinical candidates. J Med Chem. 2016;59(23):10400–10410.
  • Pradere U, Garnier-Amblard EC, Coats SJ, et al. Synthesis of nucleoside phosphate and phosphonate prodrugs. Chem Rev. 2014;114(18):9154–9218.
  • Mehellou Y. The protides boom. Chem Med Chem. 2016;11(11):1114–1116.
  • Chapman T, McGavin J, Noble S. Tenofovir disoproxil fumarate. Drugs. 2003;63(15):1597–1608.
  • Walji AM, Sanchez RI, Clas SD, et al. Discovery of MK-8970: an acetal carbonate prodrug of raltegravir with enhanced colonic absorption. Chem Med Chem. 2015;10(2):245–252.
  • Sampath R, Zeuli J, Rizza S, et al. Tenofovir alafenamide fumarate for the treatment of HIV infection. Drugs Today (Barc). 2016;52(11):617–625.
  • Bhatia HK, Singh H, Grewal N, et al. Sofosbuvir: a novel treatment option for chronic hepatitis C infection. J. Pharmacol Pharmacother. 2014;5:278–282.
  • Cahn P, Rolon MJ, Gun AM, et al. Preclinical and first in human phase I clinical evaluation of stampidine, a potent anti-HIV pharmaceutical drug candidate. J AIDS Clinic Res. 2012;3:1000138.
  • NB1011 in Treating Patients With Metastatic or Recurrent Colorectal Cancer. [cited 2017 Dec 18]. Available from: https://clinicaltrials.gov/ct2/show/NCT00031616.
  • Blagden S, Suppiah P, O’Shea D, et al. Final results from the first in human Phase I/II study of NUC-1031 in patients with solid tumours. ASCO Annual Meeting (2015) Poster, Abstract No: 2514.
  • Blagden SP, Slusarczyk M, Serpi M, et al. Abstract CT028: first in human Phase I study of NUC-3373, a nucleotide analogue designed to overcome fluoropyrimidine drug resistance mechanisms. Cancer Res. 2016;76(14 Supplement):CT028–CT028.
  • Vachal P, Raheem I, Guo Z, et al. Preparation of acyclic nucleotide β-amino acid ester phosphodiamides as antiviral agents. WO 2017027434 A1. 2017.
  • Vachal P, Guo Z Preparation of phosphodiamide compounds as antiviral agents. WO 2017007701 A1. 2017.
  • Raheem IT, Hartingh TJ, Schreier J et al. Antiviral phosphodiamide prodrugs of tenofovir. WO 2017100108 A1. 2017.
  • Fu W, Guo Z, Qi N, et al. Antiviral oxime phosphoramide compounds. WO 2017106069 A1. 2017.
  • Dimova D, Bajorath J. Rationalizing promiscuity cliffs. Chem Med Chem. 2017; Oct 11. doi: 10.1002/cmdc.201700535.  [Epub ahead of print]
  • Stumpfe D, Hu Y, Dimova D, et al. Recent progress in understanding activity cliffs and their utility in medicinal chemistry. J Med Chem. 2014;57(1):18–28.
  • Tazi J, Mahuteau F, Najman R, et al. Compounds useful for treating AIDS. WO 2012080953 A1. 2012.
  • Tazi J, Mahuteau-Betzer F, Najman R, et al. Bicyclic compounds useful for treating diseases caused by retroviruses. WO 2015001518 A1. 2015.
  • Scherrer D, Garcel A, Campos N, et al. Quinoline derivatives for use in the treatment or prevention of viral infection. WO 2016135055 A1. 2016.
  • Scherrer D, Garcel A, Campos N, et al. Preparation of a new glucuronosylquinoline derivative for use in the treatment and prevention of viral infections. WO 2016135052 A1. 2016.
  • Rabe S, Albrecht W Process for preparing quinolin-2-yl-phenylamine derivatives and their salts for the treatment of HIV infection. WO 2017158201 A1. 2017.
  • Tazi J, Mahuteau F, Roux P, et al. Preparation of quinoline and quinoxaline compounds for preventing, inhibiting, or treating cancer, AIDS and/or premature aging. US 20170226095 A1. 2017.
  • Berkhout B. van der Velden YU. ABX464: a good drug candidate instead of a magic bullet. Retrovirology. 2015;12:64.
  • Campos N, Myburgh R, Garcel A, et al. Long lasting control of viral rebound with a new drug ABX464 targeting rev - mediated viral RNA biogenesis. Retrovirology. 2015;12:30.
  • Steens JM, Scherrer D, Gineste P, et al. Safety, pharmacokinetics, and antiviral activity of a novel HIV antiviral, ABX464, in treatment-naive HIV-infected subjects in a Phase 2 randomized, controlled study. Antimicrob Agent Chemother. 2017;61(7). pii: e00545-17.
  • Scherrer D, Rouzier R, Noel Barrett P, et al. Pharmacokinetics and tolerability of ABX464, a novel first-in-class compound to treat HIV infection, in healthy HIV-uninfected subjects. J Antimicrob Chemother. 2017;72(3):820–828.
  • Chen B. HIV capsid assembly, mechanism and structure. Biochemistry. 2016;55(18):2539–2552.
  • Campbell EM, Hope TJ. HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat Rev Microbiol. 2015;13(8):471–483.
  • Le Sage V, Mouland AJ. Valiente-Echeverrmultifaceted key player in HIV-1 infection. Infection, in Healthy H Virus Res. 2014;193:116–129.
  • Bender JA, Lopez OD, Nguyen VN, et al. Preparation of bis(amino acid) derivatives as inhibitors of human immunodeficiency virus replication and use for the treatment of HIV infection. WO 2016172425 A1. 2016.
  • Pendri A, Li G, Bender JA, et al. Preparation of sulfonylaminocarbonyl amino acid amides as inhibitors of human immunodeficiency virus replication and use for the treatment of HIV infection. WO 2015061518 A1. 2015.
  • Bender JA, Gentles RG, Pendri A, et al. Preparation of sulfonylureas as inhibitors of human immunodeficiency virus replication. WO 2016172424 A1. 2016.
  • Bondy SS, Chou CH, Link JO, et al. Indazole derivatives as antiviral and their preparation and use for the treatment of HIV infection. WO2015130964A1. 2015.
  • Chen P, Zhou D, Shao S, et al. Preparation of amino acid amides as antiviral agents. WO2013006792A1. 2013.
  • Bondy SS, Cannizzaro CE, Chou C-H, et al. Preparation of macroheterocyclic compounds for the treatment of viral infections. WO2014110296A1. 2014.
  • Brizgys G, Chou C-H, Halcomb RL, et al. Preparation of (hetero)arylacetamide derivatives as antiretroviral agents. WO2014110297A1. 2014.
  • Bondy SS, Cannizzaro CE, Chou C-H; et al. Preparation of 5-membered heteroaryl compounds useful in treatment of viral infections. WO2014110298A1. 2014.
  • Perrier M, Bertine M, Le Hingrat Q, et al. Prevalence of gag mutations associated with in vitro resistance to capsid inhibitor GS-CA1 in HIV-1 antiretroviral-naive patients. J Antimicrob Chemother. 2017;72(10):2954–2955.
  • Jarvis LM. Conquering HIV’s capsid. Chem. Eng. News. 2017;95:23–25.
  • Archin NM1, Margolis DM. Emerging strategies to deplete the HIV reservoir. Curr Opin Infect Dis. 2014;27(1):29–35.
  • Spivak AM, Planelles V. Novel latency reversal agents for HIV-1 cure. Annu Rev Med. 201
  • Kohlhof H, Groeppel M, Vitt D (E)-N-(2-aminophenyl)-3-(1-((4-(1-methyl-1H-pyrazol-4-yl)phenyl)sulfonyl)-1H-pyrrol-3-yl)acrylamide for the treatment of latent infections. WO 2017060524 A1. 2017.
  • Badley AD, Sainski AM, Kaufmann SH, et al. Methods and materials for killing HIV-infected cells using Bcl-2 inhibitors alone or in combination with agents capable of reactivating HIV. WO 2016172194 A1. 2016.
  • Ott M, Boehm D Anti-HIV compositions and methods for reactivating latent immunodeficiency virus using a SMYD2 inhibitor. WO 2016061131 A1. 2016.
  • Gramatica A, Greene WC Compositions and methods for reactivating latent human immunodeficiency virus using an Akt activator. WO 2017096161 A1. 2017.
  • Zhang L, Wang P, Ma Z, et al. Ingenol compounds and use thereof in anti-HIV latency treatment. WO 2017113489 A1. 2017.
  • Planelles V, Bosque-Pardos A, Ireland CM, et al. Triazol-1-ol analogs anti-retroviral latency drugs. WO 2014201426 A2. 2014.
  • Zhang L, Ma Z, Zeng H, et al. Uses of licoricone or derivatives thereof in treating AIDS. WO 2015165409 A1. 2015.
  • Badley AD Methods and materials for treating human immunodeficiency virus infections by administering proteasome inhibitors in combination with antiretroviral agent. WO 2016137844 A1. 2016.
  • Laird GM, Siliciano R, Bullen CK Drug combinations for the treatment of human immunodeficiency virus 1 (HIV) infection. WO 2016134202 A1. 2016.
  • Zhan P, Itoh Y, Suzuki T, et al. Strategies for the discovery of target-specific or isoform-selective modulators. J Med Chem. 2015;58(19):7611–7633.
  • Wang X, Huang B, Liu X, et al. Discovery of bioactive molecules from CuAAC click-chemistry-based combinatorial libraries. Drug Discov Today. 2016;21(1):118–132.
  • Gao P, Sun L, Zhou J, et al. Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach. Expert Opin Drug Discov. 2016;11(9):857–871.
  • Connors WH, Hale SP, Terrett NK. DNA-encoded chemical libraries of macrocycles. Curr Opin Chem Biol. 2015;26:42–47.
  • Wang S, Sun H, Liu H, et al. ADMET evaluation in drug discovery. 16. Predicting hERG blockers by combining multiple pharmacophores and machine learning approaches. Mol Pharm. 2016;13(8):2855–2866.
  • Gleeson MP1, Hersey A, Montanari D, et al. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat Rev Drug Discov. 2011;10(3):197–208.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.