- Discovery and initial optimization of 5,5′-disubstituted aminohydantoins as potent β-secretase (BACE1) inhibitors
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8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S1 to the S3 pocket.
- Nowak, Pawel,Cole, Derek C.,Aulabaugh, Ann,Bard, Jonathan,Chopra, Rajiv,Cowling, Rebecca,Fan, Kristi Y.,Hu, Baihua,Jacobsen, Steve,Jani, Minakshi,Jin, Guixan,Lo, Mei-Chu,Malamas, Michael S.,Manas, Eric S.,Narasimhan, Rani,Reinhart, Peter,Robichaud, Albert J.,Stock, Joseph R.,Subrath, Joan,Svenson, Kristine,Turner, Jim,Wagner, Erik,Zhou, Ping,Ellingboe, John W.
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scheme or table
p. 632 - 635
(2010/06/12)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- SUBSTITUTED PYRAZOLO [1,5-α] PYRIDINE COMPOUNDS AND THEIR METHODS OF USE
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The present invention is directed to substituted pyrazolo[l,5-α]pyridines and related methods for their synthesis and use.
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Page/Page column 82-83
(2010/11/29)
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- Pyrazolo[1,5-a]pyridines as p38 kinase inhibitors
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(Chemical Equation Presented) A convergent synthesis of substituted pyrazolo[1,5-a]pyridines has been achieved either via a regioselective [3 + 2] cycloaddition of N-aminopyridines with alkynes or by thermal cyclization of disubstituted azirines. Subseque
- Stevens, Kirk L.,Jung, David K.,Alberti, Michael J.,Badiang, Jennifer G.,Peckham, Gregory E.,Veal, Jim M.,Cheung, Mui,Harris, Philip A.,Chamberlain, Stanley D.,Peel, Michael R.
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p. 4753 - 4756
(2007/10/03)
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- Wrinkle-care product
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A wrinkle-care product, an aging-preventive cosmetic and a skin cosmetic each comprising a guanidine derivative of formula (I) or an acid addition salt thereof: STR1 wherein R1 represents a hydrogen atom, a lower alkyl group or --(AO)m --(BO)n --D--E ?wherein A and B may be the same or different and each represents an alkylene group having 2 to 8 carbon atoms; D represents a binding hand, --CO--, or an unsubstituted or substituted alkylene group having 1 to 6 carbon atoms; E represents a hydrogen atom, a lower alkyl group, an aralkyl group or an unsubstituted or substituted aryl group; m is a number of from 1 to 6; and n is a number of from 0 to 6!; k is a number of from 1 to 10; and G represents a hydrogen atom, a hydroxyl group, a carboxyl group, a sulfonate group or a phosphate group. These products are excellent in the effects of inhibiting wrinkling and smoothing wrinkles without damaging the physiological conditions of the skin.
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