N-[2-(4-Methylphenyl)Ethyl]-N′-[2-(5-Bromopyridyl)]-Thiourea as a Potent Inhibitor of NNRTI-Resistant and Multidrug-Resistant Human Immunodeficiency Virus Type 1

Abstract

0.007 µM, which is equal to the IC 50 value of trovirdine. Notably, HI-244 was 20 times more effective than trovirdine against the multidrugresistant HIV-1 strain RT-MDR with a V106A mutation (as well as additional mutations involving the RT residues 74V, 41L and 215Y) and seven times more potent than trovirdine against the NNRTIresistant HIV-1 strain A17 with a Y181C mutation.

Non‐Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Past, Present, and Future

“…Yet, newer classes of NNRTIs described in the past five years include the thieno [3,4- [27], the imidazole derivative S-1153 (AG1549, capravirine) [28], (À)-6-chloro-2-{[1-(furo[2,3-c]pyridin-5-yl)ethyl]thio}pyrimidin-4-amine (PNU-142721) [29], N-[2-(5-bromopyridyl]-N'-[2-(2,5dimethoxyphenyl)ethyl]thiourea (HI-236) [30], the pyrido[1,2-a]indole derivative BCH-1 [31], the 4-(cyclopropylalkenyl)-3,4-dihydro-4-trifluoromethyl)quinazolin-2(1H)-ones DPC 082 and DPC 083 [32], the thiophene-ethylthiourea (TET) derivative HI-443 [33], the (cyclohexenyl)ethylthiourea derivatives HI-346 and HI-445 [34], the cis-cyclopropyl urea-PETT derivatives [35], the (alkenyl)(diaryl)methane (ADAM) series of compounds [36 ± 38], the pyrrolobenzoxazepinone (PBO) derivatives [39], the (quinoxalinylethyl)pyridylthioureas (QXPTs) [40], the MKC-442 (emivirine) derivative SJ-3366 [41], the 3,4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DA-BOs) [42], the dianilinopyrimidine (DAPY) derivatives (i.e., TMC125) [43], 4,4disubstituted 1H,3H-2,1,3-benzothiadiazine 2,2-dioxides [44], N-(5-bromopyridin-2-yl)-N'-[2-(4-methylphenyl)ethyl]thiourea [45], (quinoxalinylethyl)pyridylthioureas [46], 2,3-diaryl-1,3-thiazolidin-4-ones [47], 2-amino-6-(arylsulfanyl)benzonitriles [48], 6substituted 2-(arylsulfanyl)benzonitriles [49], 2-(methylsulfanyl)-1H-imidazoles [50], N-aminoimidazole derivatives structurally analogous to capravirine [51], and acylthiocarbamates structurally related to (phenethyl)thiazolylthiourea [52].…”

Therapeutic innovations against HIV

“…, is a rationally designed thiophene thiourea NNRTI with potent activity against NRTI-resistant, NNRTI-resistant and multi-drug resistant HIV-1 [84,85].…”

A Review of Recent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Research Activity

“…The same group also published a paper describing the use of computer modeling to design additional PEPT analogs [58]. Additional PETT analogs were prepared in an effort to improve their resistance profile and N- [2-(4-methylphenyl)ethyl]-N'-[2-(5-bromopyridyl)]thiourea (HI-244) was identified [59]. HI-244 maintained activity against RT-MDR, a HIV-1 strain that contains the NNRTI V106A mutation, along with several NRTI mutations.…”