e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4, 6-dimethyl-5-pyrimidinyl) carbonyl]-4-[4-{2-methoxy-1 (R)-4-(trifluoromethyl) phenyl} …

…, K Cox, J Lachowicz, G Varty, R Watkins

Index: Tagat, Jayaram R.; McCombie, Stuart W.; Nazareno, Dennis; Labroli, Marc A.; Xiao, Yushi; Steensma, Ruo W.; Strizki, Julie M.; Baroudy, Bahige M.; Cox, Kathleen; Lachowicz, Jean; Varty, Geoffrey; Watkins, Robert Journal of Medicinal Chemistry, 2004 , vol. 47, # 10 p. 2405 - 2408

Full Text: HTML

Citation Number: 167

Abstract

The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailability in rats and monkeys. Compound 30 (Sch-417690/Sch-D), a potent inhibitor of HIV-1 entry into target cells, is currently in ...

METHYLMAGNESIUM BROMIDE Structure

METHYLMAGNESIUM...

tert-butyl 4-cyano-4-((S)-4-((R)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-methylpiperazin-1-yl)piperidine-1-carboxylate Structure

tert-butyl 4-cy...

~75%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

2-Methoxy-1-[4-(trifluoromethyl)phenyl]ethanone Structure

2-Methoxy-1-[4-...

~%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

N-(tert-Butoxycarbonyl)-4-piperidone Structure

N-(tert-Butoxyc...

~%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

(S)-2-methoxy-1-(4-trifluoromethylphenyl)ethanol Structure

(S)-2-methoxy-1...

~%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

(S)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl methanesulfonate Structure

(S)-2-methoxy-1...

~%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

(s)-1-[(r)-2-methoxy-1-(4-trifluoromethyl-phenyl)-ethyl]-2-methyl-piperazine Structure

(s)-1-[(r)-2-me...

~%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

(S)-tert-butyl 4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazine-1-carboxylate Structure

(S)-tert-butyl ...

~%

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

p-Fluorobenzotrifluoride Structure

p-Fluorobenzotr...

N-METHOXY-N-METHYL-2-METHOXYACETAMIDE Structure

N-METHOXY-N-MET...

~74%

2-Methoxy-1-[4-(trifluoromethyl)phenyl]ethanone Structure

2-Methoxy-1-[4-...

2-Methoxy-1-[4-(trifluoromethyl)phenyl]ethanone Structure

2-Methoxy-1-[4-...

~%

(S)-tert-butyl 4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazine-1-carboxylate Structure

(S)-tert-butyl ...

(S)-2-methoxy-1-(4-trifluoromethylphenyl)ethanol Structure

(S)-2-methoxy-1...

~%

(S)-tert-butyl 4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazine-1-carboxylate Structure

(S)-tert-butyl ...

tert-butyl 4-((S)-4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazin-1-yl)-4-Methylpiperidine-1-carboxylate Structure

tert-butyl 4-((...

~98%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

2-Methoxy-1-[4-(trifluoromethyl)phenyl]ethanone Structure

2-Methoxy-1-[4-...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

N-(tert-Butoxycarbonyl)-4-piperidone Structure

N-(tert-Butoxyc...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

(S)-2-methoxy-1-(4-trifluoromethylphenyl)ethanol Structure

(S)-2-methoxy-1...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

(S)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl methanesulfonate Structure

(S)-2-methoxy-1...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

(s)-1-[(r)-2-methoxy-1-(4-trifluoromethyl-phenyl)-ethyl]-2-methyl-piperazine Structure

(s)-1-[(r)-2-me...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

(S)-tert-butyl 4-((R)-2-Methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-Methylpiperazine-1-carboxylate Structure

(S)-tert-butyl ...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...

tert-butyl 4-cyano-4-((S)-4-((R)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-methylpiperazin-1-yl)piperidine-1-carboxylate Structure

tert-butyl 4-cy...

~%

(S)-1-[(R)-2-METHOXY-1-(4-TRIFLUOROMETHYL-PHENYL)-ETHYL]-2-METHYL-4-(4-METHYL-PIPERIDIN-4-YL)-PIPERAZINE Structure

(S)-1-[(R)-2-ME...