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Volumn 20, Issue 18, 2010, Pages 5434-5438

The discovery of a series of N-substituted 3-(4-piperidinyl)-1,3- benzoxazolinones and oxindoles as highly brain penetrant, selective muscarinic M1 agonists

Author keywords

Allosteric; Benzoxazolinone; Central nervous system penetration; Cognitive enhancer; Muscarinic M1 agonist; Oxidole

Indexed keywords

2 BENZOXAZOLONE DERIVATIVE; INDOLE DERIVATIVE; MUSCARINIC M1 RECEPTOR AGONIST;

EID: 77956177282     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.07.097     Document Type: Article
Times cited : (22)

References (27)
  • 20
    • 77956181282 scopus 로고    scopus 로고
    • For full experimental procedures and NMR and LC/MS characterisation see Cooper, D. G.; Forbes, I. T.; Garzya, V.; Johnson, D. J.; Stevenson, G. I.; Wyman, P. A. WO2009/037294
    • For full experimental procedures and NMR and LC/MS characterisation see Cooper, D. G.; Forbes, I. T.; Garzya, V.; Johnson, D. J.; Stevenson, G. I.; Wyman, P. A. WO2009/037294.
  • 21
    • 77956174415 scopus 로고    scopus 로고
    • 4 cells also stably express Gqi5 chimaeric G-protein. 11 point concentration-response curves were generated. Values are average of at least five experiments
    • 4 cells also stably express Gqi5 chimaeric G-protein. 11 point concentration-response curves were generated. Values are average of at least five experiments.
  • 22
    • 77956181096 scopus 로고    scopus 로고
    • Antagonist selectivity was not investigated due to agonist induced desensitisation of the FLIPR assay
    • Antagonist selectivity was not investigated due to agonist induced desensitisation of the FLIPR assay.
  • 26
    • 77956176678 scopus 로고    scopus 로고
    • For a full list of assays tested see
    • For a full list of assays tested see http://www.cerep.fr/cerep/users/ pages/catalog/Profiles/catalog.asp.
  • 27
    • 77956177099 scopus 로고    scopus 로고
    • note
    • The novel object recognition (NOR) model was used to assess the effects on recognition memory in rats. Ennaceur and Delacour (Behavioural Brain. Res., 1988, 31, 47) and is a non-rewarded test of spontaneous behaviour based on the differential exploration of novel and familiar objects. The NOR test comprised of two sessions, T1 and T2, each lasting 3 min. On the first test day (T1), following a 3 min habituation to the empty test box, the rat was placed into the annex and 2 identical objects were placed into the test arena. The rat was then returned to the test area and allowed to freely explore the objects for 3 min. On the second day (T2), a similar protocol was adopted, except that one of the 'familiar' objects was substituted for a novel one of the same colour, material and similar size but different shape. In order to detect a potential cognition-enhancing effect an inter-trial interval (ITI) of 24 h between T1 and T2 was used to induce a performance deficit. The objects comprised of black hardened plastic geometric shapes, such as towers and pyramids, that were approximately 6.5 cm high × 6 cm diameter. Exploration was scored as time spent sniffing or licking the objects. Sitting on or climbing over the objects was not considered to be exploratory behaviour. Between trials, objects were cleaned with 70% ethanol to remove olfactory cues. All trials were recorded via camera. Exploration was scored retrospectively by an experimenter blind to the novel object. The presentation of objects was balanced across days, trials and box position (left/right) to minimise bias. Data were expressed as a d1 index (time spent exploring novel object - time spent exp exploring familiar object) and d2 index ([time exploring novel object - time exploring familiar object]/total exploration time). T1 exploration times were also considered since hyperactivity or sedation may confound the results. The d1 and d2 index scores were analyzed using a two-way analysis of variance (ANOVA, object × treatment) followed by planned comparisons for between groups analysis using Statistica version 6 (Statsoft Inc., Tulsa). Data are expressed as mean ± SEM and were considered significant when p <0.05.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.