1262447-58-4Relevant articles and documents
TETRAHYDRO-β-CARBOLINE DERIVATIVES, SYNTHESIS AND USE THEREOF
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Example 28, (2011/06/19)
Certain 2-halophenyl, 2,4-dihalophenyl (e.g. 2,4-dichlorophenyl), 3,4- dichlorophenyl (e.g.3,4-dichlorophenyl), 2,6-dichlorophenyl (2,6-dichlorophenyl) and 2,5-diakoxyphenyl (e.g. 2,5-dimethoxyphenyl) derivatives of tetrahydro-β-carbolines are provided, along with their pharmaceutically acceptable salts; prodrugs and solvates, and compositions containing the compounds. The compounds are useful for the prevention and treatment of cancer, and other indications where PDE5 inhibitors have shown benefits including erectile dysfunction, pulmonary hypertension, enhancing cognitive function, cystic fibrosis, or enhancing the activity of conventional chemotherapeutic drugs. Methods for fabricating the compounds are also provided.
Synthesis and molecular modeling of novel tetrahydro-β-carboline derivatives with phosphodiesterase 5 inhibitory and anticancer properties
Mohamed, Heba A.,Girgis, Nancy M. R.,Wilcken, Rainer,Bauer, Matthias R.,Tinsley, Heather N.,Gary, Bernard D.,Piazza, Gary A.,Boeckler, Frank M.,Abadi, Ashraf H.
, p. 495 - 509 (2011/04/15)
New derivatives based upon the tetrahydro-β-carboline-hydantoin and tetrahydro-β-carboline-piperazinedione scaffolds were synthesized. All compounds were evaluated for their ability to inhibit PDE5 in vitro, and numerous compounds with IC50 values in the low nanomolar range were identified including compounds derived from l-tryptophan. Compounds with high potency versus PDE5 were then evaluated for inhibitory activity against other PDEs to assess isozyme selectivity. Compound 5R,11aS-5-(3,4-dichlorophenyl)-2- ethyl-5,6,11,11a-tetrahydro-1H-imidazo[1′,5′:1,6]pyrido[3,4-b] indole-1,3(2H)dione 14 showed a selectivity index of >200 for cGMP hydrolysis by PDE5 versus PDE11. Meanwhile, 6R,12aR-6-(2,4-dichlorophenyl)-2-ethyl-2,3,6, 7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4dione 45 demonstrated strong potency for inhibition of PDE11 with an IC50 value of 11 nM, representing the most potent PDE11 inhibitor thus far reported. Docking experiments differentiated between active and inactive analogues and revealing the conformational, steric, and lipophilic necessities for potent PDE5 inhibition. Many derivatives, including potent PDE5 inhibitors, were able to inhibit the growth of the MDA-MB-231 breast tumor cell line with low micromolar potency.
