Doravirine

Not to be confused with drotaverine.

Doravirine
Systematic (IUPAC) name

3-Chloro-5-({1-[(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2-oxo-4-(trifluoromethyl)-1,2-dihydro-3-pyridinyl}oxy)benzonitrile
Clinical data
Legal status	Investigational New Drug
Routes of administration	Oral^[1]
Identifiers
CAS Number	1338225-97-0
ATC code	None
PubChem	CID 58460047
ChemSpider	28424197
UNII	913P6LK81M^Y
KEGG	D10624
ChEMBL	CHEMBL2364608
Synonyms	MK-1439
PDB ligand ID	2KW (PDBe, RCSB PDB)
Chemical data
Formula	C₁₇H₁₁ClF₃N₅O₃
Molar mass	425.75 g/mol
SMILES Cn1c(n[nH]c1=O)Cn2ccc(c(c2=O)Oc3cc(cc(c3)Cl)C#N)C(F)(F)F
InChI InChI=1S/C17H11ClF3N5O3/c1-25-13(23-24-16(25)28)8-26-3-2-12(17(19,20)21)14(15(26)27)29-11-5-9(7-22)4-10(18)6-11/h2-6H,8H2,1H3,(H,24,28) Key:ZIAOVIPSKUPPQW-UHFFFAOYSA-N

Doravirine (MK-1439) is a non-nucleoside reverse transcriptase inhibitor under development by Merck & Co. for use in the treatment of HIV/AIDS. Doravirine demonstrated robust antiviral activity and good tolerability in a small clinical study of 7-day monotherapy reported at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013. Doravirine appeared safe and generally well tolerated with most adverse events being mild-to-moderate.^[2]^[3]

References

↑ Collins, Simon; Horn, Tim. "The Antiretroviral Pipeline." (PDF). Pipeline Report. p. 10. Retrieved 6 December 2015.
↑ Safety and Antiviral Activity of MK-1439, a Novel NNRTI, in Treatment-naïve HIV+ Patients. Gathe, Joseph et al. 20th Conference on Retroviruses and Opportunistic Infections. 3–6 March 2013. Abstract 100.
↑ CROI 2013: MK-1439, a Novel HIV NNRTI, Shows Promise in Early Clinical Trials. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.

Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)

Entry/fusion inhibitors
(Discovery and development)

gp41 (Enfuvirtide (ENF, T-20))
CCR5 (Maraviroc (MVC)
Vicriviroc^†, Cenicriviroc^†, PRO 140^†)
CD4 (Ibalizumab^†)
gp120 (Fostemsavir^†)

Reverse-transcriptase
inhibitors (RTIs)

Nucleoside and nucleotide (NRTI)	Nucleoside analogues/NRTIs: Abacavir (ABC)°^# Didanosine (ddI) Emtricitabine (FTC)° Lamivudine (3TC)°^# Stavudine (d4T)^# Zidovudine (AZT, ZDV)^# Amdoxovir^† Apricitabine^† Censavudine^† Elvucitabine^† Racivir^† Stampidine^† Zalcitabine (ddC)^◊ Nucleotide analogues/NtRTIs: Tenofovir disoproxil (TDF)°^# Tenofovir alafenamide (TAF)

Non-nucleoside (NNRTI) (Discovery and development)	(1st generation) Efavirenz (EFV)°^# Nevirapine (NVP)^# Delavirdine (DLV)^◊ (2nd generation) diarylpyrimidines (Etravirine (ETR) Rilpivirine (RPV)°) Doravirine

Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))

Dolutegravir (DTG)°
Elvitegravir (EVG)°
Raltegravir (RAL)°
BI 224436^†
Globoidnan A (experimental)
Cabotegravir^†
Bictegravir^†
MK-2048^†

Maturation inhibitors

Bevirimat^†
BMS-955176^§

Protease Inhibitors (PI)
(Discovery and development)

1st generation	Amprenavir (APV)^◊ Fosamprenavir (FPV) Indinavir (IDV)^◊ Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV)^# Saquinavir (SQV)^#

2nd generation	Atazanavir (ATV)°^# Darunavir (DRV)°^# Tipranavir (TPV)

Combined formulations

Abacavir/lamivudine°^#
Abacavir/dolutegravir/lamivudine°
Abacavir/lamivudine/zidovudine
Atazanavir/cobicistat
Darunavir/cobicistat
Efavirenz/emtricitabine/tenofovir°^#
Elvitegravir/cobicistat/emtricitabine/tenofovir°
Emtricitabine/rilpivirine/tenofovir°
Lamivudine/raltegravir
Lamivudine/zidovudine^#
Lopinavir/ritonavir°^#
Tenofovir/emtricitabine°^#

Pharmacokinetic boosters

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)

Transcription inhibitors	Tat antagonists

Translation inhibitors	Trichosanthin

Other	Abzyme BIT225^† Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) KP-1461^† Foscarnet Fosdevirine^† Griffithsin Hydroxycarbamide Miltefosine Portmanteau inhibitors Scytovirin Seliciclib^† Synergistic enhancers Tre recombinase Zinc finger protein transcription factor

Failed agents	Aplaviroc Atevirdine Brecanavir Capravirine Dexelvucitabine Droxinavir Lasinavir Emivirine Lersivirine Lodenosine Loviride Mozenavir Palinavir Telinavir

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

°DHHS recommended initial regimen options. ^◊Formerly or rarely used agent.

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