- Practical synthesis of a benzophenone-based NNRT inhibitor of HIV-1
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A convergent synthesis of NNRTI 1 is described. The key step involves a direct coupling of acid chloride 4 with Grignard reagent 11 in the presence of bis[2-(N,N-dimethylamino)ethyl] ether that moderates the reactivity of the Grignard reagent to give benzophenone 7. An efficient 2-step process for the preparation of 2-fluoro-3-methyl-4-aminobenzoic acid (3) is also described.
- Wang, Xiao-Jun,Zhang, Li,Sun, Xiufeng,Lee, Heewon,Krishnamurthy, Dhileepkumar,O'Meara, Jeff A.,Landry, Serge,Yoakim, Christiane,Simoneau, Bruno,Yee, Nathan K.,Senanayake, Chris H.
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scheme or table
p. 561 - 566
(2012/07/03)
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- 4-Substituted indazoles as new inhibitors of neuronal nitric oxide synthase
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A series of halo-1-H-indazoles has been synthesized and evaluated for its inhibitory activity on neuronal nitric oxide synthase. Introduction of bromine at the C4 position of the indazole ring system provided a compound almost as potent as the reference compound, that is, 7-nitroindazole (7-NI). The importance of position 4 is further demonstrated by the synthesis and pharmacological evaluation of the 4-nitroindazole which was also a potent inhibitor of NOS activity. These compounds also exhibited in vivo NOS inhibitory activity, as attested by potent antinociceptive effects following systemic administration.
- Boulouard, Michel,Schumann-Bard, Pascale,Butt-Gueulle, Sabrina,Lohou, Elodie,Stiebing, Silvia,Collot, Valerie,Rault, Sylvain
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p. 3177 - 3180
(2008/02/04)
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- Intramolecular Selectivity of the Alkylation of Substituted Anilines by Gaseous Cations
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The intramolecular selectivity of the electrophilic reactions of Et(1+), i-Pr(1+), and Me2F(1+) cations with substituted anilines, including m-toluidine, m-anisidine, and m- and p-fluoroaniline, has been investigated in the dilute gas state at pressures ranging from 100 to 720 torr by a radiolytic technique, complemented by chemical ionization mass spectrometry.The results indicate an appreciable kinetic bias for the nitrogen atom, leading to predominant N-methylation by Me2F(1+).The reactivity of the carbenium ions is complicated by the simultaneous occurrence of proton transfer, in particular to the NH2 group, which increases the relative extent of ring alkylation.The positional selectivity is characterized, aside from the usual orienting effects of the substituents, by the enchanced reactivity of the ring positions ortho to an n-type substituent, irrespective of its activating or deactivating properties.The effect is traced to the preliminary formation of an electrostatic adduct between the aniline and the gaseous electrophile.
- Attina, Marina,Cacace, Fulvio,de Petris, Giulia
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p. 1556 - 1561
(2007/10/02)
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- 4- and 5-Substituted 2,3-dihydro-1H-isoindoles, pharmaceutical compositions and method of inhibiting phenylethanolamine N-methyltransferase
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Pharmaceutical compositions and methods of inhibiting phenylethanolamine N-methyltransferase using novel 2,3-dihydro-1H-isoindole compounds having 4- and 5-substituents.
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