- Small Molecule Stimulators of Steroid Receptor Coactivator-3 and Methods of Their Use as Cardioprotective and/or Vascular Regenerative Agents
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Small molecule stimulators of steroid receptor coactivator-3 (SRC-3) and methods of their use as cardioprotective agents are provided. The small molecule stimulators are useful for promoting cardiac protection and repair and vascular regeneration after my
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Paragraph 0114-0115
(2020/03/23)
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- Thiophene bioisosteres of spirocyclic σ receptor ligands. 1. N-substituted spiro[piperidine-4,4′-thieno[3,2-c]pyrans]
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Herein, the synthesis and pharmacological evaluation of thiophene bioisosteres of the highly potent spirocyclic benzopyran 1 are detailed. The synthesis of 1-benzyl-6′-methoxy-6′,7′- dihydrospiro[piperidine-4,4′-thieno[3.2-c]pyran] (2a) was performed starting with 3-bromothiophene (3). After introduction of the acetaldehyde substructure (7), halogen metal exchange, addition of 1-benzylpiperidin-4-one, and cyclization led to the spirocyclic thienopyran 2a. The removal of the benzyl group afforded the secondary amine 2f, which was substituted with various residues. With respect to σ1 affinity the N-benzyl derivative 2a, the N-cyclohexylmethyl derivative 2d, and the N-p-fluorobenzyl derivative 2i represent the most potent compounds of this series binding with Ki values of 0.32, 0.29, and 0.62 nM, respectively. Electronic properties of the substituents have only little impact on σ1 affinity. The most potent σ1 ligands display high selectivity against σ2, 5-HT1A, 5-HT6, 5-HT7, α1A, α2, and NMDA receptors. The activity of 2a in the mouse capsaicin assay seems to indicate σ1 antagonistic activity.
- Oberdorf, Christoph,Schepmann, Dirk,Vela, Jose Miguel,Diaz, Jose Luis,Holenz, J?rg,Wünsch, Bernhard
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supporting information; experimental part
p. 6531 - 6537
(2009/10/17)
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- SPIRO [PIPERIDINE-4, 4' -THIENO [3, 2-C] PYRAN] DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE SIGMA RECEPTOR FOR THE TREATMENT OF PSYCHOSIS
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The present invention relates to compounds having pharmacological activity towards the sigma (s) receptor, and more particularly to some thieno-pyrano-pyrazole derivatives, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy and prophylaxis, in particular for the treatment of psychosis or pain.
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Page/Page column 74-75
(2009/01/23)
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- Synthesis of heteroarylpiperazines and heteroarylbipiperidines with a restricted side chain and their affinities for 5-HT1A receptor
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Heteroarylpiperazine and heteroarylbipiperidine derivatives, bearing a 4-piperidine ring instead of an alkylamino side chain to give the semi-rigidity, were prepared and evaluated for their abilities to displace [3H] 8-OH-DPAT binding to the rat hippocampal synaptic membranes. These compounds showed low to moderate affinities for 5-HT1A receptor, with Ki values ranging from 6912 nM to 232 nM. Of these compounds, 8 b and 15 e exhibited the best affinities for 5-HT1A receptor with Ki values of 232 nM and 338 nM, respectively.
- Yoo, Kyung Ho,Choi, Hyun Sik,Kim, Dong Chan,Shin, Kye Jung,Kim, Dong Jin,Song, Yun Seon,Jin, Changbae
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p. 208 - 215
(2007/10/03)
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