Kinkaid A

General

Full name : Kinkaid Adrian

First name : Adrian

Mail : Zeneca Agrochemicals, Jealott's Hill, Bracknell, Berks

Zip Code :

City :

Country : United Kingdom

Email : adrian.kinkaid@aguk.zeneca.com

Phone : 44-1344-414627

Fax : 44-1344-413638

Website :

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References (3)

Title : A structure-based design approach to the development of novel, reversible AChE inhibitors - Doucet-Personeni_2001_J.Med.Chem_44_3203
Author(s) : Doucet-Personeni C , Bentley PD , Fletcher RJ , Kinkaid A , Kryger G , Pirard B , Taylor A , Taylor R , Taylor J , Viner R , Silman I , Sussman JL , Greenblatt HM , Lewis T
Ref : Journal of Medicinal Chemistry , 44 :3203 , 2001
Abstract : Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.
ESTHER : Doucet-Personeni_2001_J.Med.Chem_44_3203
PubMedSearch : Doucet-Personeni_2001_J.Med.Chem_44_3203
PubMedID: 11563919
Gene_locus related to this paper: torca-ACHE

Title : 4-Aminoquinolines as AChE Inhibitors -
Author(s) : Bentley PD , Earley F , Fletcher RJ , Kinkaid A , Lewis T , Pirard B , Taylor J , Viner RC
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :238 , 1998
PubMedID:

Title : Effects of Triton X100 on the Activity of Acetylcholinesterases from Drosophila Melanogaster, Musca Domestica and Torpedo Californica -
Author(s) : Kinkaid A , Earley F
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :244 , 1998
PubMedID: