111631-72-2Relevant articles and documents
Synthesis of σ Receptor Ligands with a Spirocyclic System Connected with a Tetrahydroisoquinoline Moiety via Different Linkers
Bergkemper, Melanie,Schepmann, Dirk,Wünsch, Bernhard
, p. 1184 - 1197 (2021)
With the aim to develop new σ2 receptor ligands, spirocyclic piperidines or cyclohexanamines with 2-benzopyran and 2-benzofuran scaffolds were connected to the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety by variable linkers. In addition to flexible alkyl chains, linkers containing an amide as functional group were synthesized. The 2-benzopyran and 2-benzofuran scaffold of the spirocyclic compounds were synthesized from 2-bromobenzaldehyde. The amide linkers were constructed by acylation of amines with chloroacetyl chloride and subsequent nucleophilic substitution, the alkyl linkers were obtained by LiAlH4 reduction of the corresponding amides. For the development of σ2 receptor ligands, the spirocyclic 2-benzopyran scaffold is more favorable than the ring-contracted 2-benzofuran system. Compounds bearing an alkyl chain as linker generally show higher σ affinity than acyl linkers containing an amide as functional group. A higher σ1 affinity for the cis-configured cyclohexanamines than for the trans-configured derivatives was found. The highest σ2 affinity was observed for cis-configured spiro[[2]benzopyran-1,1′-cyclohexan]-4′-amine connected to the tetrahydroisoquinoline system by an ethylene spacer (cis-31, Ki (σ2)=200 nM; the highest σ1 affinity was recorded for the corresponding 2-benzofuran derivative with a CH2C=O linker (cis-29, Ki (σ1)=129 nM).
Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents
Sharma, Pankaj,Srinivasa Reddy,Thummuri, Dinesh,Senwar, Kishna Ram,Praveen Kumar, Niggula,Naidu,Bhargava, Suresh K.,Shankaraiah, Nagula
, p. 608 - 621 (2016)
A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50value of 11.46?±?1.46?μM on A549 lung cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung cancer cells (A549) have been used to know the mechanism of cell growth inhibition and apoptosis inducing effect with compound 11p. The treatment of A549?cells with 11p showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of apoptosis in A549 cells by compound 11p.
Synthesis and pharmacological evaluation of piperidinoalkanoyl-1,2,3,4- tetrahydroisoquinoline derivatives as novel specific bradycardic agents
Kubota, Hideki,Watanabe, Toshihiro,Kakefuda, Akio,Masuda, Noriyuki,Wada, Kouichi,Ishii, Noe,Sakamoto, Shuichi,Tsukamoto, Shin-Ichi
, p. 3049 - 3052 (2007/10/03)
A series of piperidinoalkanoyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized, and their bradycardic activities were investigated in the isolated right atria of guinea pigs and in conscious rats. These efforts identified the achiral compound 2f, which exhibited potent and long-lasting bradycardic activity with minimal effects on mean blood pressure in conscious rats.
