- 5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO[4,3-a]PYRAZINE DERIVATIVES AS P2X7 MODULATORS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6 R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.
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Page/Page column 78
(2010/11/17)
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- Proton mobility in 2-substituted 1,3-dichlorobenzenes: "ortho" or "meta" metalation?
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Nine 1,3-dichlorobenzene congeners were selected as model compounds to assess the relative rates of proton abstraction from 4- and 5-positions ("ortho" vs. "meta" metalation). Using lithium 2,2,6,6-tetramethylpiperidide as the basic reagent, the chlorine-adjacent 4-position underwent metalation exclusively. In contrast, attack at the chlorine-remote 5-posi" tion became significant even in the case of moderately sized 2-substituents (such as dimethylamino or ethyl) when secbutyllithium was employed. The "ortho/para" (4-/5-) ratios ranged from 80:20 to 65:35. The more pronounced "meta-orienting" effect of silicon as opposed to carbon substituents can be attributed to dissimilarities in the n polarization of the aromatic ring. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Schlosser, Manfred,Heiss, Christophe,Marzi, Elena,Scopelliti, Rosario
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p. 4398 - 4404
(2007/10/03)
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