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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Chemical Compound Review

AC1LD8Y6     (4S)-4-[6-[[(2S)-2-[[(2S)-2- acetamido-6-[5...

Synonyms:
 
 
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Disease relevance of compound 11

  • Among these analogues, compound 11 exhibited excellent activity against HIV-1 HTLV-IIIB strain with an EC50 value of 0.98 microM, which is 7-fold more potent than that of HEPT [1].
  • Compound 11 was most active (ED50 value, 0.65 microM) against HIV in acutely infected H9 lymphocytes and had a therapeutic index of about 5 [2].
  • Compound 11 was found to have the most significant and selective antiviral activity against herpes simplex virus [3].
  • Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss [4].
  • When compound 11 was evaluated for its inhibitory effects on another HIV-1 strain, HTLV-IIIRE, and two HIV-2 strains, LAV-2ROD and LAV-2EHO, it proved equally inhibitory to HTLV-IIIRF, whereas both HIV-2 strains were insensitive to the compound [1].
 

High impact information on compound 11

  • Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models [5].
  • Compound 11, representative of the cyclopent[g]indole series, gave an IC50 of 10 nM for the inhibition of hnps-PLA2 in the chromogenic assay [6].
  • Compound 11 was found to bring about the increase in the activities of caspases 3 and 9 in the HL-60 cell line in a manner similar to etoposide, strongly indicating that apoptosis is the mechanism of cell death [7].
  • SAR development and the extended use of palladium-catalyzed cross-coupling reactions led to compound 11 which inhibited human PDE4D with an IC(50) value of 1 nM [8].
  • One of them (compound 11) containing a seven-membered lactam ring revealed a good affinity for GRP/BN receptors on rat pancreatic acini (K(i) value of 1.7 +/- 0.4 nM) and on Swiss 3T3 cells (K(i) value of 1.0 +/- 0.2 nM) [9].
 

Chemical compound and disease context of compound 11

  • Among the azido derivatives, compound 8 with the 3'-azido "down" was slightly more active than 2',3'-dideoxyadenosine (1) but considerably more toxic, and, of the fluorine series, compound 11, with the 2'-fluoro "up", was the most selective inhibitor of HIV, although it was less active than 1 [10].
 

Biological context of compound 11

  • Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction [11].
  • Compound 11 also caused an increase in blood pressure in anesthetized rats [12].
  • The compounds have been synthesized by the Bischler-Napieralski cyclization of corresponding amides followed by NaBH(4) reduction, and the halogens in the aromatic ring A were introduced by direct halogenation of protected compound 11 [13].
  • Whole-cell voltage-clamp electrophysiology experiments demonstrated that compound 11 blocked N-type Ca(2+) channels and Na(+) channels in superior cervical ganglion neurons at similar concentrations [14].
  • Hydrolysis of the BOC group in compound 11 using TFA afforded the desired 6beta-[(2-aminoethyl)carboxamidomethyl]estradiol 12 in 50% yield [15].
 

Anatomical context of compound 11

 

Associations of compound 11 with other chemical compounds

 

Gene context of compound 11

 

Analytical, diagnostic and therapeutic context of compound 11

  • In the case of compound 11 which has (S)- or (R)-3,7-dimethyloctyl groups, a helical organization of the molecules in the column was estimated from the peaks in the circular dichroism spectra [29].
  • To understand the origins of this improved activity, the structures of AmpC in complex with compound 10 and an analogue, compound 11, were determined by X-ray crystallography to 1.97 and 1.96 A, respectively [30].
  • Products were purified with use of reversed-phase HPLC and, in one case, diastereomeric products (compound 11) were resolved by using this procedure [31].
  • Preparative high-performance liquid chromatography of the extract resulted in the isolation of 10 brominated alkaloids (compounds 1 to 10) and one diterpene (compound 11) [32].
  • Compound 11 produces the nine-atom chain {[N(PPh2)2Se]2(mu-O)} (12) upon hydrolysis during crystallization [33].

References

  1. Synthesis and anti-HIV activity of 2-, 3-, and 4-substituted analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). Tanaka, H., Baba, M., Ubasawa, M., Takashima, H., Sekiya, K., Nitta, I., Shigeta, S., Walker, R.T., De Clercq, E., Miyasaka, T. J. Med. Chem. (1991) [Pubmed]
  2. Antitumor agents. 166. Synthesis and biological evaluation of 5,6,7,8-substituted-2-phenylthiochromen-4-ones. Wang, H.K., Bastow, K.F., Cosentino, L.M., Lee, K.H. J. Med. Chem. (1996) [Pubmed]
  3. Antiviral compounds. 1. Structure-activity relationship of some antiviral enediones derived from aldehydo sugars. Breuer, E., Melumad, D., Sarel, S., Margalith, E., Katz, E. J. Med. Chem. (1983) [Pubmed]
  4. 3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines: opioid antagonists with potent anorectant activity. Mitch, C.H., Leander, J.D., Mendelsohn, L.G., Shaw, W.N., Wong, D.T., Cantrell, B.E., Johnson, B.G., Reel, J.K., Snoddy, J.D., Takemori, A.E. J. Med. Chem. (1993) [Pubmed]
  5. Discovery of imidazo[1,2-b][1,2,4]triazines as GABA(A) alpha2/3 subtype selective agonists for the treatment of anxiety. Russell, M.G., Carling, R.W., Street, L.J., Hallett, D.J., Goodacre, S., Mezzogori, E., Reader, M., Cook, S.M., Bromidge, F.A., Newman, R., Smith, A.J., Wafford, K.A., Marshall, G.R., Reynolds, D.S., Dias, R., Ferris, P., Stanley, J., Lincoln, R., Tye, S.J., Sheppard, W.F., Sohal, B., Pike, A., Dominguez, M., Atack, J.R., Castro, J.L. J. Med. Chem. (2006) [Pubmed]
  6. Carbocyclic[g]indole inhibitors of human nonpancreatic s-PLA2. Sawyer, J.S., Beight, D.W., Smith, E.C., Snyder, D.W., Chastain, M.K., Tielking, R.L., Hartley, L.W., Carlson, D.G. J. Med. Chem. (2005) [Pubmed]
  7. Synthesis, X-ray crystal structures, stabilities, and in vitro cytotoxic activities of new heteroarylacrylonitriles. Saczewski, F., Reszka, P., Gdaniec, M., Grünert, R., Bednarski, P.J. J. Med. Chem. (2004) [Pubmed]
  8. Palladium-catalyzed cross-coupling reactions for the synthesis of 6, 8-disubstituted 1,7-naphthyridines: a novel class of potent and selective phosphodiesterase type 4D inhibitors. Hersperger, R., Bray-French, K., Mazzoni, L., Müller, T. J. Med. Chem. (2000) [Pubmed]
  9. Synthesis and biological evaluation of bombesin constrained analogues. Cristau, M., Devin, C., Oiry, C., Chaloin, O., Amblard, M., Bernad, N., Heitz, A., Fehrentz, J.A., Martinez, J. J. Med. Chem. (2000) [Pubmed]
  10. Synthesis and anti-HIV activity of various 2'- and 3'-substituted 2',3'-dideoxyadenosines: a structure-activity analysis. Herdewijn, P., Pauwels, R., Baba, M., Balzarini, J., De Clercq, E. J. Med. Chem. (1987) [Pubmed]
  11. A series of potent HIV-1 protease inhibitors containing a hydroxyethyl secondary amine transition state isostere: synthesis, enzyme inhibition, and antiviral activity. Tucker, T.J., Lumma, W.C., Payne, L.S., Wai, J.M., de Solms, S.J., Giuliani, E.A., Darke, P.L., Heimbach, J.C., Zugay, J.A., Schleif, W.A. J. Med. Chem. (1992) [Pubmed]
  12. Y1 and Y2 receptor selective neuropeptide Y analogues: evidence for a Y1 receptor subclass. Kirby, D.A., Koerber, S.C., May, J.M., Hagaman, C., Cullen, M.J., Pelleymounter, M.A., Rivier, J.E. J. Med. Chem. (1995) [Pubmed]
  13. Synthesis and human beta-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro. He, Y., Nikulin, V.I., Vansal, S.S., Feller, D.R., Miller, D.D. J. Med. Chem. (2000) [Pubmed]
  14. Synthesis of a series of 4-benzyloxyaniline analogues as neuronal N-type calcium channel blockers with improved anticonvulsant and analgesic properties. Hu, L.Y., Ryder, T.R., Rafferty, M.F., Feng, M.R., Lotarski, S.M., Rock, D.M., Sinz, M., Stoehr, S.J., Taylor, C.P., Weber, M.L., Bowersox, S.S., Miljanich, G.P., Millerman, E., Wang, Y.X., Szoke, B.G. J. Med. Chem. (1999) [Pubmed]
  15. Synthesis of 6beta-[(2'-Aminoethyl)carboxamidomethyl]estradiol and preparation of estradiol probes. Adamczyk, M., Johnson, D.D., Reddy, R.E. Bioconjug. Chem. (1998) [Pubmed]
  16. Conformationally restricted analogues of trimethoprim: 2,6-diamino-8-substituted purines as potential dihydrofolate reductase inhibitors from Pneumocystis carinii and Toxoplasma gondii. Gangjee, A., Vasudevan, A., Queener, S.F. J. Med. Chem. (1997) [Pubmed]
  17. Dihydropyridazinone cardiotonics: synthesis and inotropic activity of 5'-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)spiro[cycloalkane- 1,3'-[3H]indol]-2'(1'H)-ones. Robertson, D.W., Krushinski, J.H., Pollock, G.D., Wilson, H., Kauffman, R.F., Hayes, J.S. J. Med. Chem. (1987) [Pubmed]
  18. Synthesis and anti-melanoma activity of analogues of N-acetyl-4-S-cysteaminylphenol substituted with two methyl groups alpha to the nitrogen. Lant, N.J., McKeown, P., Timoney, M.C., Kelland, L.R., Rogers, P.M., Robins, D.J. Anticancer Drug Des. (2001) [Pubmed]
  19. Antiinflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis. Wei, B.L., Weng, J.R., Chiu, P.H., Hung, C.F., Wang, J.P., Lin, C.N. J. Agric. Food Chem. (2005) [Pubmed]
  20. Design and synthesis of novel bis(l-amino acid) ester prodrugs of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with improved anti-HBV activity. Fu, X., Jiang, S., Li, C., Xin, J., Yang, Y., Ji, R. Bioorg. Med. Chem. Lett. (2007) [Pubmed]
  21. Benzoyl nitrogen mustard derivatives of benzoheterocyclic analogues of netropsin: synthesis and biological activity. Baraldi, P.G., Romagnoli, R., Bianchi, N., Gambari, R. Bioorg. Med. Chem. (2003) [Pubmed]
  22. Synthesis and dopamine transporter binding of 2beta-isopropyl ester analogs of cocaine. El-Moselhy, T.F., Avor, K.S., Basmadjian, G.P. European journal of medicinal chemistry. (2002) [Pubmed]
  23. Binding of 2,4-disubstituted morpholines at human D4 dopamine receptors. Showell, G.A., Emms, F., Marwood, R., O'Connor, D., Patel, S., Leeson, P.D. Bioorg. Med. Chem. (1998) [Pubmed]
  24. Anti-proliferative effects of novel glyco-lipid-arsenicals (III) on MCF-7 human breast cancer cells. Wimmer, N., Robinson, J.A., Gopisetty-Venkata, N., Roberts-Thomson, S.J., Monteith, G.R., Toth, I. Medicinal chemistry (Sh⁻ariqah, United Arab Emirates) (2006) [Pubmed]
  25. Aromatase inhibition by flavonoids. Ibrahim, A.R., Abul-Hajj, Y.J. J. Steroid Biochem. Mol. Biol. (1990) [Pubmed]
  26. Structure-activity relationship studies on chalcone derivatives. the potent inhibition of chemical mediators release. Ko, H.H., Tsao, L.T., Yu, K.L., Liu, C.T., Wang, J.P., Lin, C.N. Bioorg. Med. Chem. (2003) [Pubmed]
  27. 5'-Substituted thalidomide analogs as modulators of TNF-alpha. Teubert, U., Zwingenberger, K., Wnendt, S., Eger, K. Arch. Pharm. (Weinheim) (1998) [Pubmed]
  28. 5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity. Forbes, I.T., Ham, P., Booth, D.H., Martin, R.T., Thompson, M., Baxter, G.S., Blackburn, T.P., Glen, A., Kennett, G.A., Wood, M.D. J. Med. Chem. (1995) [Pubmed]
  29. Novel superstructure of nondiscoid mesogens: uneven-parallel association of half-disk molecules, 3,4,5-trialkoxybenzoic anhydrides, to a columnar structure and its one-directionally geared interdigitation. Kishikawa, K., Furusawa, S., Yamaki, T., Kohmoto, S., Yamamoto, M., Yamaguchi, K. J. Am. Chem. Soc. (2002) [Pubmed]
  30. Structure-based optimization of a non-beta-lactam lead results in inhibitors that do not up-regulate beta-lactamase expression in cell culture. Tondi, D., Morandi, F., Bonnet, R., Costi, M.P., Shoichet, B.K. J. Am. Chem. Soc. (2005) [Pubmed]
  31. Synthesis and biological evaluation of dipeptidyl and tripeptidyl polyoxin and nikkomycin analogues as anticandidal prodrugs. Krainer, E., Becker, J.M., Naider, F. J. Med. Chem. (1991) [Pubmed]
  32. Secondary metabolites of Flustra foliacea and their influence on bacteria. Peters, L., König, G.M., Wright, A.D., Pukall, R., Stackebrandt, E., Eberl, L., Riedel, K. Appl. Environ. Microbiol. (2003) [Pubmed]
  33. Synthesis, spectroscopic, and structural investigation of the cyclic [N(PR2E)2]+ cations (E = Se, Te; R = iPr, Ph): the effect of anion and R-group exchange. Konu, J., Chivers, T., Tuononen, H.M. Inorganic chemistry (2006) [Pubmed]
 
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