Multicyclic compounds and methods of their use

a technology of multicyclic compounds and active ingredients, applied in the field of multicyclic compounds, to achieve the effect of improving cognitive performan

Inactive Publication Date: 2006-11-16
LEXICON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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[0009] Another embodiment encompasses methods of improving cognitive performance, and of tre...

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  • Multicyclic compounds and methods of their use
  • Multicyclic compounds and methods of their use
  • Multicyclic compounds and methods of their use

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[0249] 6.1. SLC6A7-Deficient Mice

[0250] To determine the effect of inhibiting the Na+-dependent proline transporter, mice homozygous for a genetically engineered mutation in the murine ortholog of the human SLC6A7 gene (“knockout” or “KO” mice) were generated using correspondingly mutated ES cell clones from the OMNIBANK collection of mutated murine ES cell clones (see generally U.S. Pat. No. 6,080,576).

[0251] Mice that were heterozygous, homozygous, or wildtype for the mutated allele were produced by breeding heterozygous animals capable of germline transmission of the mutant allele. The mutated allele assorted according to standard Mendelian genetics. The mice were subjected to a battery of medical and behavioral tests, including those described below. [0252] 6.1.1. Trace Conditioning

[0253] Trace aversive conditioning measures a form of classical conditioning with temporal separation between the end of a conditioned stimulus (CS) (in this case an 80 db tone) and the onset of an...

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Abstract

This invention relates to multicyclic compounds, pharmaceutical compositions comprising them, and methods of their use in, for example, the treatment of cognitive disorders.

Description

[0001] This application claim priority to U.S. provisional application No. 60 / 680,501, filed May 13, 2005.FIELD OF THE INVENTION [0002] This invention relates to multicyclic compounds, pharmaceutical compositions comprising them, and methods of their use. BACKGROUND OF THE INVENTION [0003] The amino acid L-proline reportedly plays a role in regulating synaptic transmission in the mammalian brain. See, e.g., Crump et al., Molecular and Cellular Neuroscience, 13: 25-29 (1999). For example, a synaptosomal bisynthetic pathway of L-proline from ornithine has been reported, and high affinity Na+-dependent synaptosomal uptake of L-proline has been observed. Yoneda et al., Brain Res., 239: 479-488 (1982); Balcar et al., Brain Res., 102: 143-151 (1976). [0004] In general, neurotransmitter systems typically have mechanisms that inactivate signaling, many of which work through the action of a Na+-dependent transporter. In this case, a Na+-dependent transporter for proline has been described, a...

Claims

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Application Information

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IPC IPC(8): A61K31/496A61K31/4545C07D403/02C07D401/02
CPCC07D239/42C07D277/42C07D401/04C07D401/12C07D487/04C07D403/04C07D417/04C07D451/02C07D471/08C07D401/14A61P25/00A61P25/28A61P43/00A61K31/506
Inventor BARBOSA, JOSEPHDONG, LIFINK, CYNTHIA ANNEWANG, JIANCHENGZIPP, G. GREGORY
Owner LEXICON PHARM INC
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