- New serotonin 5-HT1A receptor agonists with neuroprotective effect against ischemic cell damage
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We report the synthesis of new compounds 4-35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational β2-based homology models of the ligand-receptor complexes were used to explain the observed structure-affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4-dihydro-2H- chromen-2-ylmethyl)amino]hexyl}tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H) -dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (Ki = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.
- Marco, Isabel,Valhondo, Margarita,Martín-Fontecha, Mar,Vázquez-Villa, Henar,Del Río, Joaquín,Planas, Anna,Sagredo, Onintza,Ramos, José A.,Torrecillas, Iván R.,Pardo, Leonardo,Frechilla, Diana,Benhamú, Bellinda,López-Rodríguez, María L.
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p. 7986 - 7999
(2012/01/13)
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- CHROMANE AND CHROMENE DERIVATIVES AND USES THEREOF
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Methods of preparing compounds of formula (I) or pharmaceutically acceptable salts thereof are provided wherein each of R1, R2, R3, R4, x, m, n, and Ar are as defined, and described in classes and subclasses herein, which are agonists or partial agonists of the 2C subtype of brain serotonin receptors. The compounds, and compositions containing the compounds, can be used to treat a variety of central nervous system disorders such as schizophrenia.
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- METHOD FOR PRODUCING CHROMANE DERIVATIVES THAT ARE DEVOID OF ENANTIOMERS AND ARE SUBSTITUTED IN POSITION 2
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The invention relates to a method for producing chromane derivatives that are devoid of enantiomers and are substituted in position 2, from corresponding chromane-2-carboxylic acid esters.
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Page/Page column 11-12
(2008/06/13)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE CHROMAN DERIVATIVE AND INTERMEDIATE
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A process for easily producing various optically active chroman derivatives that are useful as pharmaceutical intermediates from inexpensive starting materials is provided. Cyclic hemiacetal (1) obtained from dihydrocoumarin through one step is asymmetric
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- CHROMANONE DERIVATIVES
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Chromanone derivatives of the formula I in which R1 to R4 are each, independently of one another, H, A, CN, Hal, OR5, COOR5, CF3, OCF3, NO2, Ar, OAr, N(R5)2 /sub
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- A concise stereospecific synthesis of repinotan (BAYx3702)
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A concise synthesis of the 2-[aminomethyl]chroman derivative BAYx3702 (3), a potent 5-hydroxytryptamine (5-HT1A) antagonist is described. Utilization of a Mitsunobu reaction of phenol (11) with the non-racemic allylic alcohol (12) and consequen
- Gross, Jonathan L.
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p. 8563 - 8565
(2007/10/03)
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- [(benzodioxan, benzofuran or benzopyran) alkylamino] alkyl substituted guanidines
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The present invention is concerned with vasoconstricive [(benzodioxan, benzofuran or benzopyran)alkylamino]alkyl substituted guanidines having the formula STR1 the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric
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