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Chemical Compound Review

Compound 14     benzylN-[(1S)-3-methyl-1- [[(3S)-5-methyl...

Synonyms: SureCN8823930, AC1NSK38
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Disease relevance of Compound 14

  • Employing the photodependent cytotoxicity of compound 14 against HCT116 human colon cancer cells, it was demonstrated that 4-substituted-2,6-dimethylnitrobenzene analogues are useful NO donors for the time- and site-controlled NO treatment [1].
  • Of the latter compounds, compound 14 (1,3-benzodioxolane-5-carboxylic acid 4'-benzyloxy-3'-methoxybenzylidene-hydrazide) activated neutrophils at nanomolar concentrations, and Ca(2+) mobilization was inhibited by pertussis toxin and N-t-butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc-2), an antagonist of formyl peptide receptors (FPR/FPRL1) [2].
  • Compound 14 retains the in vitro toxicity associated with nitidine (1) but is devoid of antileukemic activity [3].
  • Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po) [4].
  • On the basis of the results of these studies, compound 14 is a strong candidate for clinical evaluation as a systemic agent for the treatment of picornavirus infections [5].

High impact information on Compound 14

  • In addition, compound 14 maintained potent antiviral activity against acyclovir-resistant HSV-1 strains [6].
  • Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy [6].
  • Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective K(ATP) channel openers may have utility in the treatment of overactive bladder [7].
  • In search of a backup M(2) muscarinic receptor antagonist to the previously reported compound 1, we discovered compound (+)-14, which showed superior oral efficacy in animal models [8].
  • Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14 [9].

Chemical compound and disease context of Compound 14


Biological context of Compound 14

  • The corresponding unsaturated analog of 11, compound 14, showed a slightly weaker receptor affinity (IC50 = 4.0 +/- 2.0 microM) but a significantly higher relative efficacy (50-55%) than 11 [12].
  • Hydroxymethyl compound 14 was obtained by deamination of reported 2,4-diaminopyrido[2,3-d]pyrimidine-6-methanol (12a) in refluxing 1 N NaOH [13].
  • Alkylation by compound 14, which has a vinyl linker, occurred at the A of 5'-AGTCCA-3' (site 6) and at several minor alkylation sites, including mismatch alkylation at A of 5'-TCACAA-3' (site 2) [14].
  • Although the compounds of each series had poor in vitro inhibitory potencies (IC50 >> 100 microM), most of them inhibited the EGF-dependent cellular proliferation of ER 22 cells at relatively low doses (IC50 = 1.1 microM for compound 14) [15].
  • Condensation of aldehyde (S)-(-)-17 with nitro compound (S)-(-)-27, both of which were prepared from a common precursor (S)-16, gave the alpha-hydroxynitro compound 28, which upon acetylation afforded alpha-acetoxynitro compound 14 in good yield [16].

Anatomical context of Compound 14

  • 1'-Hexylamino-9-anilinoacridine (compound 14) was the least toxic compound to human Jurkat cells, while it retained strong antileishmanial activity [17].
  • Binding at the agonist site, using3H-CP 55,940 in assays with mouse brain membranes, is inhibited byO-isopropyl dodecylfluorophosphonate (compound 2), dodecanesulfonyl fluoride (compound 14) and dodecylbenzodioxaphosphorin oxide with IC50 values of 2-11 nM [18].
  • Compounds 16 and 17 showed antimalarial activity with EC(50) values of 230 and 240ng/mL, respectively, and compound 14 exhibited an EC(50) of 0.05muM against the Leukemia cell line K-562 [19].

Associations of Compound 14 with other chemical compounds


Gene context of Compound 14

  • Compound 14 was a potent and selective inhibitor of cPLA2 and compound 4 showed a dual inhibitory profile against both types of PLA2 while no cytotoxicity at 10 microM on human neutrophils or on murine macrophage line was observed for both [22].
  • Compound 14 was 15-fold more potent in inhibiting human renin than porcine renin [23].
  • Compound 14 (MRPP) exhibited enhanced activity against L1210 in vivo, when compared to ARPP (8) [24].
  • Compound 14-inhibited CB1 in mouse brain requires about 3-4 days for recovery of 50% activity, suggesting covalent derivatization [18].
  • The most interesting compound (14) is simultaneously a highly potent H(3) receptor ligand (K(i)=4.1nM) and a highly potent HMT inhibitor (IC(50)=24nM), which makes this derivative a valuable pharmacological tool for further development [25].

Analytical, diagnostic and therapeutic context of Compound 14

  • Compounds 4, 9, 11, and 14 were most effective in the anti-angiogenesis assays run at Emory. In the assays conducted by the NCI, compound 14 was almost as potent as the anti-angiogenic drug TNP-470, which has undergone clinical trials [26].


  1. Photoinduced nitric oxide release from nitrobenzene derivatives. Suzuki, T., Nagae, O., Kato, Y., Nakagawa, H., Fukuhara, K., Miyata, N. J. Am. Chem. Soc. (2005) [Pubmed]
  2. High-throughput screening for small-molecule activators of neutrophils: identification of novel N-formyl Peptide receptor agonists. Schepetkin, I.A., Kirpotina, L.N., Khlebnikov, A.I., Quinn, M.T. Mol. Pharmacol. (2007) [Pubmed]
  3. Synthesis and biological activity of structural analogues of the anticancer benzophenanthridine alkaloid nitidine chloride. Cushman, M., Mohan, P., Smith, E.C. J. Med. Chem. (1984) [Pubmed]
  4. Piperidinyltetralin sigma ligands. Gilligan, P.J., Kergaye, A.A., Lewis, B.M., McElroy, J.F. J. Med. Chem. (1994) [Pubmed]
  5. [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating. Diana, G.D., McKinlay, M.A., Otto, M.J., Akullian, V., Oglesby, C. J. Med. Chem. (1985) [Pubmed]
  6. 4-Oxo-4,7-dihydrothieno[2,3-b]pyridines as non-nucleoside inhibitors of human cytomegalovirus and related herpesvirus polymerases. Schnute, M.E., Cudahy, M.M., Brideau, R.J., Homa, F.L., Hopkins, T.A., Knechtel, M.L., Oien, N.L., Pitts, T.W., Poorman, R.A., Wathen, M.W., Wieber, J.L. J. Med. Chem. (2005) [Pubmed]
  7. Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent K(ATP) opener that selectively inhibits spontaneous bladder contractions. Carroll, W.A., Altenbach, R.J., Bai, H., Brioni, J.D., Brune, M.E., Buckner, S.A., Cassidy, C., Chen, Y., Coghlan, M.J., Daza, A.V., Drizin, I., Fey, T.A., Fitzgerald, M., Gopalakrishnan, M., Gregg, R.J., Henry, R.F., Holladay, M.W., King, L.L., Kort, M.E., Kym, P.R., Milicic, I., Tang, R., Turner, S.C., Whiteaker, K.L., Yi, L., Zhang, H., Sullivan, J.P. J. Med. Chem. (2004) [Pubmed]
  8. Improving the oral efficacy of CNS drug candidates: discovery of highly orally efficacious piperidinyl piperidine M2 muscarinic receptor antagonists. Wang, Y., Chackalamannil, S., Hu, Z., Greenlee, W.J., Clader, J., Boyle, C.D., Kaminski, J.J., Billard, W., Binch, H., Crosby, G., Ruperto, V., Duffy, R.A., Cohen-Williams, M., Coffin, V.L., Cox, K.A., Grotz, D.E., Lachowicz, J.E. J. Med. Chem. (2002) [Pubmed]
  9. Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X-ray crystallographic analysis, and biological activities. Kim, K.S., Kimball, S.D., Misra, R.N., Rawlins, D.B., Hunt, J.T., Xiao, H.Y., Lu, S., Qian, L., Han, W.C., Shan, W., Mitt, T., Cai, Z.W., Poss, M.A., Zhu, H., Sack, J.S., Tokarski, J.S., Chang, C.Y., Pavletich, N., Kamath, A., Humphreys, W.G., Marathe, P., Bursuker, I., Kellar, K.A., Roongta, U., Batorsky, R., Mulheron, J.G., Bol, D., Fairchild, C.R., Lee, F.Y., Webster, K.R. J. Med. Chem. (2002) [Pubmed]
  10. Novel 3-(2-adamantyl)pyrrolidines with potent activity against influenza A virus-identification of aminoadamantane derivatives bearing two pharmacophoric amine groups. Stamatiou, G., Kolocouris, A., Kolocouris, N., Fytas, G., Foscolos, G.B., Neyts, J., De Clercq, E. Bioorg. Med. Chem. Lett. (2001) [Pubmed]
  11. Improved synthesis and molecular modeling of 4beta,19-dihydroxyandrost-5-en-17-one, an excellent inhibitor of aromatase. Numazawa, M., Yamada, K., Watari, Y., Ando, M. Chem. Pharm. Bull. (2002) [Pubmed]
  12. Partial GABAA receptor agonists. Synthesis and in vitro pharmacology of a series of nonannulated analogs of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. Frølund, B., Kristiansen, U., Brehm, L., Hansen, A.B., Krogsgaard-Larsen, P., Falch, E. J. Med. Chem. (1995) [Pubmed]
  13. Synthesis and antifolate evaluation of the 10-propargyl derivatives of 5-deazafolic acid, 5-deazaaminopterin, and 5-methyl-5-deazaaminopterin. Piper, J.R., Malik, N.D., Rhee, M.S., Galivan, J., Sirotnak, F.M. J. Med. Chem. (1992) [Pubmed]
  14. Molecular design of a pyrrole-imidazole hairpin polyamides for effective DNA alkylation. Bando, T., Narita, A., Saito, I., Sugiyama, H. Chemistry (Weinheim an der Bergstrasse, Germany) (2002) [Pubmed]
  15. Inhibition of the EGF-stimulated cellular proliferation of ER 22 cells by hydroxybiphenyl derivatives. Million, M.E., Boiziau, J., Parker, F., Tocque, B., Roques, B.P., Garbay, C. J. Med. Chem. (1995) [Pubmed]
  16. Bone collagen cross-links: a convergent synthesis of (+)-deoxypyrrololine. Adamczyk, M., Johnson, D.D., Reddy, R.E. J. Org. Chem. (2001) [Pubmed]
  17. 9-Anilinoacridines as potential antileishmanial agents. Mauël, J., Denny, W., Gamage, S., Ransijn, A., Wojcik, S., Figgitt, D., Ralph, R. Antimicrob. Agents Chemother. (1993) [Pubmed]
  18. Toxicological and structural features of organophosphorus and organosulfur cannabinoid CB1 receptor ligands. Segall, Y., Quistad, G.B., Sparks, S.E., Nomura, D.K., Casida, J.E. Toxicol. Sci. (2003) [Pubmed]
  19. Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity. Gul, W., Hammond, N.L., Yousaf, M., Bowling, J.J., Schinazi, R.F., Wirtz, S.S., de Castro Andrews, G., Cuevas, C., Hamann, M.T. Bioorg. Med. Chem. (2006) [Pubmed]
  20. Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives and related compounds. Takeuchi, K., Kohn, T.J., True, T.A., Mais, D.E., Wikel, J.H., Utterback, B.G., Wyss, V.L., Jakubowski, J.A. J. Med. Chem. (1998) [Pubmed]
  21. Substituted 2-(R)-methyl piperazines as muscarinic M(2) selective ligands. Kozlowski, J.A., Zhou, G., Tagat, J.R., Lin, S.I., McCombie, S.W., Ruperto, V.B., Duffy, R.A., McQuade, R.A., Crosby, G., Taylor, L.A., Billard, W., Binch, H., Lachowicz, J.E. Bioorg. Med. Chem. Lett. (2002) [Pubmed]
  22. Synthesis and enzyme inhibitory activities of a series of lipidic diamine and aminoalcohol derivatives on cytosolic and secretory phospholipases A2. Lucas, R., Ubeda, A., Payá, M., Alves, M., del Olmo, E., López, J.L., San Feliciano, A. Bioorg. Med. Chem. Lett. (2000) [Pubmed]
  23. Inhibitors of human renin. Cyclic peptide analogues containing a D-Phe-Lys-D-Trp sequence. Dutta, A.S., Gormley, J.J., McLachlan, P.F., Major, J.S. J. Med. Chem. (1990) [Pubmed]
  24. Antitumor and antiviral activity of synthetic alpha- and beta-ribonucleosides of certain substituted pyrimido[5,4-d]pyrimidines: a new synthetic strategy for exocyclic aminonucleosides. Sanghvi, Y.S., Larson, S.B., Matsumoto, S.S., Nord, L.D., Smee, D.F., Willis, R.C., Avery, T.L., Robins, R.K., Revankar, G.R. J. Med. Chem. (1989) [Pubmed]
  25. Imidazole derivatives as a novel class of hybrid compounds with inhibitory histamine N-methyltransferase potencies and histamine hH3 receptor affinities. Grassmann, S., Apelt, J., Sippl, W., Ligneau, X., Pertz, H.H., Zhao, Y.H., Arrang, J.M., Ganellin, C.R., Schwartz, J.C., Schunack, W., Stark, H. Bioorg. Med. Chem. (2003) [Pubmed]
  26. Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Adams, B.K., Ferstl, E.M., Davis, M.C., Herold, M., Kurtkaya, S., Camalier, R.F., Hollingshead, M.G., Kaur, G., Sausville, E.A., Rickles, F.R., Snyder, J.P., Liotta, D.C., Shoji, M. Bioorg. Med. Chem. (2004) [Pubmed]
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