Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 13, 2009, Pages 3669-3673

  Charrier, Nicolas ^a   Clarke, Brian ^a   Demont, Emmanuel ^a   Dingwall, Colin ^a   Dunsdon, Rachel ^a   Hawkins, Julie ^a   Hubbard, Julia ^a   Hussain, Ishrut ^a   Maile, Graham ^a   Matico, Rosalie ^a   Mosley, Julie ^a   Naylor, Alan ^a   O'Brien, Alistair ^a   Redshaw, Sally ^a   Rowland, Paul ^a   Soleil, Virginie ^a   Smith, Kathrine J ^a   Sweitzer, Sharon ^a   Theobald, Pam ^a   Vesey, David ^a   Walter, Daryl S ^a   Wayne, Gareth ^a   more..

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Alzheimer; Aspartic protease; BACE 1; Hydroxyethylamine

Indexed keywords

BETA SECRETASE; BETA SECRETASE INHIBITOR; GSK 188909; SULFONAMIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG MECHANISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANIMALS; ASPARTIC ENDOPEPTIDASES; BINDING SITES; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; ETHYLAMINES; HUMANS; MICE; PROTEASE INHIBITORS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZINES;

ANIMALIA;

EID: 66349123508     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.03.150     Document Type: Article

References (7)

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2. Beswick P., Charrier N., Clarke B., Demont E., Dingwall C., Dunsdon R., Faller A., Gleave R., Hawkins J., Hussain I., Johnson C.N., MacPherson D., Maile G., Milner P., Naylor A., O'Brien A., Redshaw S., Riddell D., Rowland P., Skidmore J., Soleil V., Smith K., Stanway S., Stemp G., Stuart A., Theobald P., Vesey D., Walter D.S., Ward J., and Wayne G. Bioorg. Med. Chem. Lett. 18 (2008) 1022
3. Clarke B., Demont E., Dingwall C., Dunsdon R., Faller A., Hawkins J., Hussain I., MacPherson D., Maile G., Matico R., Milner P., Mosley J., Naylor A., O'Brien A., Redshaw S., Riddell D., Rowland P., Soleil V., Smith K.J., Stanway S., Stemp G., Sweitzer S., Theobald P., Vesey D., Walter D.W., Ward J., and Wayne G. Bioorg. Med. Chem. Lett. 18 (2008) 1022 1017
4. Clarke B., Demont E., Dingwall C., Dunsdon R., Faller A., Hawkins J., Hussain I., MacPherson D., Maile G., Matico R., Milner P., Mosley J., Naylor A., O'Brien A., Redshaw S., Riddell D., Rowland P., Soleil V., Smith K.J., Stanway S., Stemp G., Sweitzer S., Theobald P., Vesey D., Walter D.W., Ward J., and Wayne G. Bioorg. Med. Chem. Lett. 18 (2008) 1022 1011
5. Charrier N., Demont E., Dunsdon R., Maile G., Naylor A., O'Brien A., Redshaw S., Theobald P., Vesey D.S., and Walter D.W. Synthesis (2006) 3467
6. 50 < 10 nM, the FRET assay was considered as not reliable for SAR, which was then driven by cellular activity; All compounds tested had purity > 95% by LC-MS and/or NMR.
7. free = 0.217).