The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Chemical Compound Review

AC1L4VNW     3-acetamido-5-(ethanoyl- methyl-amino)-2,4...

Synonyms: AC1Q4PBE, AR-1C5894, A823048
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Compound 18

  • Compound 18 showed the most potent antiviral activity against hepatitis C virus (55% inhibition at 1.0 microM) [1].
  • In vivo, compound 18 was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 8.8 mg/kg, po) and demonstrated a significant reduction in emetic side effects (ferret, 20% emesis at 30 mg/kg, po) [2].
  • Modifications on the initial compound were then made on the basis of its cocrystal structure with HIV Pr and inhibition data, resulting in compounds with enhanced potency against the enzyme (compound 18, Ki = 0.48 microM) [3].
  • Compound 18 showed weak inhibition of lymphoma cell growth (IC50 = 42 microM) and of AICAR formylTF (IC50 = 17 microM) [4].
  • The prominent compound 18 showed significant activity against cell lines of colon cancer (HCT-116), renal cancer (786-0) and melanoma (M14) (GI50 in the range 0.33-1.08 microM) as well as good selectivity toward non-small cell lung cancer (HOP-62) cells (GI50 = 0.05 microM, TGI = 0.38 microM and LC50 = 4.83 microM) [5].
 

High impact information on Compound 18

 

Biological context of Compound 18

  • Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg [11].
  • Compound 18 demonstrated a dose-related (3-30 mg/kg) decrease in blood pressure that was sustained for greater than 24 h [12].
  • Compound 18 (Cys[psi CH2NH]Ile[psi CH2NH]Ile-homoserine lactone) reduced the extent of Ras farnesylation by 50% in NIH3T3 fibroblasts in culture at a concentration of 50 microM [13].
  • The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated [14].
  • The basic hydrolysis of the 10-acetyl group in compound 18 took place with concomitant intramolecular conjugated addition of the alkoxide to the butenolide moiety to give ether 19 [15].
 

Anatomical context of Compound 18

 

Gene context of Compound 18

  • Naphthyloxy compound 18 (beta3 EC50 = 78 nM) did not activate the beta1 and beta2 ARs at 10 microM, and showed >1000-fold selectivity over binding to the beta1 and beta2 ARs [19].
  • Attempts to discover newer compounds with improved selectivity over the prototypical SB compound 203580 (1), led to the discovery of a new sub-class of p38 inhibitors typified by compound 18 at Merck [20].
 

Analytical, diagnostic and therapeutic context of Compound 18

References

  1. Synthesis and antiviral activity of helioxanthin analogues. Yeo, H., Li, Y., Fu, L., Zhu, J.L., Gullen, E.A., Dutschman, G.E., Lee, Y., Chung, R., Huang, E.S., Austin, D.J., Cheng, Y.C. J. Med. Chem. (2005) [Pubmed]
  2. Biarylcarboxylic acids and -amides: inhibition of phosphodiesterase type IV versus [3H]rolipram binding activity and their relationship to emetic behavior in the ferret. Duplantier, A.J., Biggers, M.S., Chambers, R.J., Cheng, J.B., Cooper, K., Damon, D.B., Eggler, J.F., Kraus, K.G., Marfat, A., Masamune, H., Pillar, J.S., Shirley, J.T., Umland, J.P., Watson, J.W. J. Med. Chem. (1996) [Pubmed]
  3. Structure-based design and synthesis of substituted 2-butanols as nonpeptidic inhibitors of HIV protease: secondary amide series. Reich, S.H., Melnick, M., Pino, M.J., Fuhry, M.A., Trippe, A.J., Appelt, K., Davies, J.F., Wu, B.W., Musick, L. J. Med. Chem. (1996) [Pubmed]
  4. 5,10-Methylenetetrahydro-5-deazafolic acid and analogues: synthesis and biological activities. Gangjee, A., Patel, J., Kisliuk, R.L., Gaumont, Y. J. Med. Chem. (1992) [Pubmed]
  5. Synthesis, molecular structure, and in vitro antitumor activity of new 4-chloro-2-mercaptobenzenesulfonamide derivatives. Sławiński, J., Gdaniec, M. European journal of medicinal chemistry. (2005) [Pubmed]
  6. FK506-binding protein ligands: structure-based design, synthesis, and neurotrophic/neuroprotective properties of substituted 5,5-dimethyl-2-(4-thiazolidine)carboxylates. Zhao, L., Huang, W., Liu, H., Wang, L., Zhong, W., Xiao, J., Hu, Y., Li, S. J. Med. Chem. (2006) [Pubmed]
  7. Design of potent and selective 2-aminobenzimidazole-based p38alpha MAP kinase inhibitors with excellent in vivo efficacy. de Dios, A., Shih, C., López de Uralde, B., Sánchez, C., del Prado, M., Martín Cabrejas, L.M., Pleite, S., Blanco-Urgoiti, J., Lorite, M.J., Nevill, C.R., Bonjouklian, R., York, J., Vieth, M., Wang, Y., Magnus, N., Campbell, R.M., Anderson, B.D., McCann, D.J., Giera, D.D., Lee, P.A., Schultz, R.M., Li, L.C., Johnson, L.M., Wolos, J.A. J. Med. Chem. (2005) [Pubmed]
  8. Synthesis and antitumor activity of new benzoheterocyclic derivatives of distamycin A. Baraldi, P.G., Romagnoli, R., Beria, I., Cozzi, P., Geroni, C., Mongelli, N., Bianchi, N., Mischiati, C., Gambari, R. J. Med. Chem. (2000) [Pubmed]
  9. Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues. Högberg, M., Sahlberg, C., Engelhardt, P., Noréen, R., Kangasmetsä, J., Johansson, N.G., Oberg, B., Vrang, L., Zhang, H., Sahlberg, B.L., Unge, T., Lövgren, S., Fridborg, K., Bäckbro, K. J. Med. Chem. (1999) [Pubmed]
  10. Improved P1/P1' substituents for cyclic urea based HIV-1 protease inhibitors: synthesis, structure-activity relationship, and X-ray crystal structure analysis. Nugiel, D.A., Jacobs, K., Cornelius, L., Chang, C.H., Jadhav, P.K., Holler, E.R., Klabe, R.M., Bacheler, L.T., Cordova, B., Garber, S., Reid, C., Logue, K.A., Gorey-Feret, L.J., Lam, G.N., Erickson-Viitanen, S., Seitz, S.P. J. Med. Chem. (1997) [Pubmed]
  11. Derivatives of 2-[[N-(Aminocarbonyl)-N-hydroxyamino]methyl]-1,4- benzodioxan as orally active 5-lipoxygenase inhibitors. Satoh, Y., Powers, C., Toledo, L.M., Kowalski, T.J., Peters, P.A., Kimble, E.F. J. Med. Chem. (1995) [Pubmed]
  12. Nonpeptide angiotensin II receptor antagonists. 2. Design, synthesis, and structure-activity relationships of 2-alkyl-4-(1H-pyrrol-1-yl)-1H-imidazole derivatives: profile of 2-propyl-1-[[2'-(1H-tetrazol-5-yl)-[1,1' -biphenyl]-4-yl]-methyl]-4-[2-(trifluoroacetyl)-1H-pyrrol-1-yl]-1H- imidazole-5-carboxylic acid (CI-996). Sircar, I., Hodges, J.C., Quin, J., Bunker, A.M., Winters, R.T., Edmunds, J.J., Kostlan, C.R., Connolly, C., Kesten, S.J., Hamby, J.M. J. Med. Chem. (1993) [Pubmed]
  13. Pseudopeptide inhibitors of Ras farnesyl-protein transferase. Graham, S.L., deSolms, S.J., Giuliani, E.A., Kohl, N.E., Mosser, S.D., Oliff, A.I., Pompliano, D.L., Rands, E., Breslin, M.J., Deana, A.A. J. Med. Chem. (1994) [Pubmed]
  14. Synthesis of 3'-deoxy-3'-difluoromethyl azanucleosides from trans-4-hydroxy-l-proline. Qiu, X.L., Qing, F.L. J. Org. Chem. (2005) [Pubmed]
  15. Stereoselective synthesis of 7,11-guaien-8,12-olides from santonin. Synthesis of podoandin and (+)-zedolactone A. Blay, G., Bargues, V., Cardona, L., García, B., Pedro, J.R. J. Org. Chem. (2000) [Pubmed]
  16. Congener derivatives and conjugates of histamine: synthesis and tissue and receptor selectivity of the derivatives. Khan, M.M., Melmon, K.L., Marr-Leisy, D., Verlander, M.S., Egli, M., Lok, S., Goodman, M. J. Med. Chem. (1987) [Pubmed]
  17. Synthesis and sulfatase inhibitory activities of non-steroidal estrone sulfatase inhibitors. Li, P.K., Milano, S., Kluth, L., Rhodes, M.E. J. Steroid Biochem. Mol. Biol. (1996) [Pubmed]
  18. Investigation into the mast cell stabilizing activity of nature-identical and synthetic indanones. Frankish, N., Farrell, R., Sheridan, H. J. Pharm. Pharmacol. (2004) [Pubmed]
  19. Tetrahydroisoquinoline derivatives containing a benzenesulfonamide moiety as potent, selective human beta3 adrenergic receptor agonists. Parmee, E.R., Brockunier, L.L., He, J., Singh, S.B., Candelore, M.R., Cascieri, M.A., Deng, L., Liu, Y., Tota, L., Wyvratt, M.J., Fisher, M.H., Weber, A.E. Bioorg. Med. Chem. Lett. (2000) [Pubmed]
  20. P38 MAP kinase inhibitors: evolution of imidazole-based and pyrido-pyrimidin-2-one lead classes. Natarajan, S.R., Doherty, J.B. Current topics in medicinal chemistry. (2005) [Pubmed]
  21. Investigation of the effect of varying the 4-anilino and 7-alkoxy groups of 3-quinolinecarbonitriles on the inhibition of Src kinase activity. Boschelli, D.H., Ye, F., Wu, B., Wang, Y.D., Barrios Sosa, A.C., Yaczko, D., Powell, D., Golas, J.M., Lucas, J., Boschelli, F. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
 
WikiGenes - Universities