- PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS FOR USE IN THE TREATMENT OF PARKINSON'S DISEASE
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Compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3 and A are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease
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Page/Page column 44
(2013/11/19)
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- Synthesis of 1,4-dioxa-2λ5-phosphorinanes by insertion of triphenylalkylidenephosphoranes into the peroxide bond of 1,2-dioxetanes: Thermolysis, hydrolysis, and wittig olefination
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The reaction of the methyl-substituted 1,2-dioxetanes 1-3 with triphenylalkylidenephosphoranes 4-7 was investigated. By nucleophilic attack of the negatively charged phosphorane carbon atom at the peroxide bond of the 1,2-dioxetanes, the dipolar phosphoni
- Adam, Waldemar,Harrer, Heinrich M.,Treiber, Alexander
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p. 7581 - 7587
(2007/10/02)
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- Chelates as intermediates in nucleophilic additions to alkoxy ketones according to Cram's rule (cyclic model)
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Chelates have been considered intermediates in the often highly stereoselective reactions of α-alkoxy and similarly substituted ketones for over 30 years,10 but without mechanistic evidence. It is now shown, by stop-flow ("rapid injection") NMR kinetics,15 that the specific rates of reaction of ketones C6H5COCH(OR)CH3 with Me2Mg, where R = (i-Pr)3 ("TIPS"), t-BuPh2Si, t-BuMe2Si, Et3Si, Me3Si, and Me, parallel the diastereoselectivity of the reaction; i.e., the fastest reacting compound (R = Me) is the one which gives the highest proportion of the product predicted by Cram's chelate rule. The major product of the slowest reacting compound (R = TIPS) is not in accord with Cram's chelate rule, and this compound reacts at the same specific rate as the parent, C6H5COCH2CH3. This is in accord with earlier work indicating that TIPSO does not chelate. Compounds intermediate in the series react at intermediate rates and give the two diastereomeric products in proportions which can be calculated by assuming two competing reactions (cf. Figure 2): one proceeding via the chelated transition states giving the product predicted by the chelate rule and one not involving chelation which gives the same product composition as the R = TIPS compound. Direct steric effects on carbonyl reactivity due to the remote bulky silyloxy substituents have been excluded by the study of carbon analogues bearing similar bulky groups. Thus, the kinetic effect in the above series appears to be due to steric hindrance to chelation; hence, the parallel of specific rate and stereoselectivity demonstrates that high stereoselectivity is associated with strong chelation, as postulated by Cram and Kopecky in 1959.10.
- Chen, Xiangning,Hortelano, Edwin R.,Eliel, Ernest L.,Frye, Stephen V.
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p. 1778 - 1784
(2007/10/02)
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