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

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Chemical Compound Review:

CHEMBL182980 (8S,9R)-9-[4-[2-[(3S,4S)- 3,4...

Synonyms: CHEBI:404752, AC1L9MUP, 1xp1, AIH

Kuo, G.H. et al., Shen, D.M. et al., Clark, E.R. et al., Henke, B.R. et al., Viala, A. et al., et al.

Mach, Huang, Freeman, Wu, Vangveravong, Luedtke, Murugesan, Tellew, Gu, Kunst, Fadnis, Cornelius, Baska, Yang, Beyer, Monshizadegan, Dickinson, Panchal, Valentine, Chong, Morrison, Carlson, Powell, Moreland, Barrish, Kowala, Macor, Rashad, Ali, Cabeza, Heuze, Bratoeff, Murillo, Ramirez, Lira, Kuo, Wang, Emanuel, Deangelis, Zhang, Connolly, Murray, Gruninger, Sechler, Fuentes-Pesquera, Johnson, Middleton, Jolliffe, Chen, Shen, Zhang, Brady, Candelore, Dallas-Yang, Ding, Dragovic, Feeney, Jiang, McCann, Mock, Qureshi, Saperstein, Shen, Tamvakopoulos, Tong, Tota, Wright, Yang, Zheng, Chapman, Zhang, Tata, Parmee,

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 15

Compound 15 represents a new approach to treating hypertension [1].
Compound 15 showed activity against Staphylococcus aureus and Bacillus subtilis with MIC of 64 and 32 microg/mL, respectively [2].
Compound 15, in particular, is the most effective cyclic inhibitor in hand to inhibit FIV replication in tissue culture at a concentration of 1.0 micro g/mL (1.2 microM) [3].
Compound 15 showed the highest effect on HSV-1 than the other three compounds, while the four tested compounds did not show any activity against HAV [4].
These include 3 junctional, 7 compound, 15 intradermal and 8 SPitz naevi; 6 superficial type, 2 lentigo maligna and 6 nodular melanomata [5].

High impact information on COMPOUND 15

Compound 15 was shown to interact with the active site by x-ray crystallography [6].
Compound 15 has an IC50 of 320 nM for 17beta-HSD1 and is selective for 17beta-HSD1 over 17beta-HSD2 [7].
Compound 15 also displayed high inhibitory potency on VEGF-stimulated human umbilical vein endothelial cell (HUVEC) proliferation (IC(50) = 0.005 microM) and good selectivity against cell lines such as HUVEC, human aortic smooth muscle cells, and MRC5 lung fibroblasts [8].
On the other hand, compound 15 exhibited more than 100-fold selectivity against calmodulin kinase 2; casein kinase-1 and -2; CDK1 and -4; mitogen-activated protein kinase; and protein kinase A, Cbeta2, and Cgamma (IC(50) >10 microM) [8].
Compound 15 exhibited remarkable cytotoxic activity against several other human solid tumor cell lines [9].

Biological context of COMPOUND 15

Compound 15 inhibited the human cancer cell growth of KB, MKN45, H460, HT29, and TSGH, as well as one human-resistant cancer line of KB-vin 10, with an IC50 of 9.6, 8.8, 9.4, 8.6, 10.8, and 8.9 nM, respectively [10].
The results of this structure-activity relationship study identified one compound, 15, that bound with high affinity (K(i) value=2nM) and moderate selectivity (30-fold) for D3 compared to D2 receptors [11].

Anatomical context of COMPOUND 15

In the most sensitive species, the dog, both of these compounds achieved good plasma levels; however, compound 9f caused adrenal necrosis, whereas compound 15 had no effect on the adrenal gland [12].
A single bolus dose of compound 15, administered intravenously following permanent occlusion of middle cerebral artery (MCA) in the rat, reduced the size of infarcted tissue by 57% [13].
The nonsubstituted benzoyloxy ester (compound 15) showed a lower antiandrogenic activity as measured in the seminal vesicles model than the p-substituted benzoyloxy compounds [14].
The compound 15 containing 5-(trifluoromethyl)uracil showed marked inhibitory activity against all human malignant cell lines (IC(50): 5.6-12.8 microM) except on human T-lymphocytes [15].

Associations of COMPOUND 15 with other chemical compounds

At a molar ratio of 10 compound 14 failed to suppress the uterine weight response of immature rats to 17beta-estradiol, whereas compound 15, at a molar ratio of 200, produced a significant increase in the uterine weight of immature rats but not of immature mice even at a molar ratio of 1000 [16].
The heterocyclic nitrogen atoms of 13 and 16 facilitate planarisation of the system, compared to 14, which is in agreement with X-ray structural data obtained for 5-bromo-2-phenylpyrimidine 6, 2,5-diphenylpyrimidine 7 and compound 15 [17].

Gene context of COMPOUND 15

In addition, the X-ray crystal structure of compound 15 complexed with the ligand binding domain of ERbeta has been solved and was utilized in the design of more conformationally restrained analogues such as 31 in an attempt to increase selectivity for the ERbeta subtype [18].
By utilizing a key discriminatory compound (compound 15) that potently inhibits TNF-alpha convertase but not alpha-secretase, we show that TNF-alpha convertase is not involved in the regulated shedding of APP from human neuronal cells [19].
Preliminary studies have revealed that compound 15 is an orally active human glucagon receptor antagonist in a transgenic murine pharmacodynamic model at 10 and 30 mpk [20].
Compound 15 is orally bioavailable in several preclinical species and shows selectivity toward cardiac ion channels and other family B receptors, such as hGIP1 and hGLP [20].
Compound 15 inhibited ODC at 3 times lower concentrations than 6a and 3-(aminooxy)propanamine (APA), and it was superior to APA as an antiproliferative agent in inhibiting the growth of human T24 bladder carcinoma cells in vitro [21].

Analytical, diagnostic and therapeutic context of COMPOUND 15

The gas chromatographic procedures are the most sensitive for the quantitative determination fo the unchanged compound: 15 and 35 ng/ml in plasma and 5 and 10 ng/ml in urine; the detection limit for thin-layer chromatography is about 100 ng [22].

References

Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and endothelin A receptor antagonists. Murugesan, N., Tellew, J.E., Gu, Z., Kunst, B.L., Fadnis, L., Cornelius, L.A., Baska, R.A., Yang, Y., Beyer, S.M., Monshizadegan, H., Dickinson, K.E., Panchal, B., Valentine, M.T., Chong, S., Morrison, R.A., Carlson, K.E., Powell, J.R., Moreland, S., Barrish, J.C., Kowala, M.C., Macor, J.E. J. Med. Chem. (2002) [Pubmed]
Synthesis and antibiotic activity of the tricyclic furo[3,2-c] isochromen-2-trione unit of the pyranonaphthoquinones. Bianchi, D.A., Sutich, E.G., Kaufman, T.S. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
Design and synthesis of broad-based mono- and bi- cyclic inhibitors of FIV and HIV proteases. Mak, C.C., Brik, A., Lerner, D.L., Elder, J.H., Morris, G.M., Olson, A.J., Wong, C.H. Bioorg. Med. Chem. (2003) [Pubmed]
Synthesis and antiviral screening of some thieno[2,3-d]pyrimidine nucleosides. Rashad, A.E., Ali, M.A. Nucleosides Nucleotides Nucleic Acids (2006) [Pubmed]
Patterns of staining for neurone specific enolase in benign and malignant melanocytic lesions of the skin. Dhillon, A.P., Rode, J. Diagnostic histopathology / published in association with the Pathological Society of Great Britain and Ireland. (1982) [Pubmed]
Tripeptide mimetics inhibit the 20 S proteasome by covalent bonding to the active threonines. Braun, H.A., Umbreen, S., Groll, M., Kuckelkorn, U., Mlynarczuk, I., Wigand, M.E., Drung, I., Kloetzel, P.M., Schmidt, B. J. Biol. Chem. (2005) [Pubmed]
Modification of estrone at the 6, 16, and 17 positions: novel potent inhibitors of 17beta-hydroxysteroid dehydrogenase type 1. Allan, G.M., Lawrence, H.R., Cornet, J., Bubert, C., Fischer, D.S., Vicker, N., Smith, A., Tutill, H.J., Purohit, A., Day, J.M., Mahon, M.F., Reed, M.J., Potter, B.V. J. Med. Chem. (2006) [Pubmed]
Synthesis and discovery of pyrazine-pyridine biheteroaryl as a novel series of potent vascular endothelial growth factor receptor-2 inhibitors. Kuo, G.H., Wang, A., Emanuel, S., Deangelis, A., Zhang, R., Connolly, P.J., Murray, W.V., Gruninger, R.H., Sechler, J., Fuentes-Pesquera, A., Johnson, D., Middleton, S.A., Jolliffe, L., Chen, X. J. Med. Chem. (2005) [Pubmed]
Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the dihydrothieno[2,3-b]naphtho-4,9-dione system. Gomez-Monterrey, I., Santelli, G., Campiglia, P., Califano, D., Falasconi, F., Pisano, C., Vesci, L., Lama, T., Grieco, P., Novellino, E. J. Med. Chem. (2005) [Pubmed]
7-aroyl-aminoindoline-1-sulfonamides as a novel class of potent antitubulin agents. Chang, J.Y., Hsieh, H.P., Chang, C.Y., Hsu, K.S., Chiang, Y.F., Chen, C.M., Kuo, C.C., Liou, J.P. J. Med. Chem. (2006) [Pubmed]
Conformationally-flexible benzamide analogues as dopamine D3 and sigma 2 receptor ligands. Mach, R.H., Huang, Y., Freeman, R.A., Wu, L., Vangveravong, S., Luedtke, R.R. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
alpha-Substituted malonester amides: tools to define the relationship between ACAT inhibition and adrenal toxicity. Sliskovic, D.R., Picard, J.A., O'Brien, P.M., Liao, P., Roark, W.H., Roth, B.D., Anderson, M.A., Mueller, S.B., Bocan, T.M., Bousley, R.F., Hamelehle, K.L., Homan, R., Reindel, J.F., Stanfield, R.L., Turluck, D., Krause, B.R. J. Med. Chem. (1998) [Pubmed]
Design and synthesis of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid (EAA-090), a potent N-methyl-D-aspartate antagonist, via the use of 3-cyclobutene-1,2-dione as an achiral alpha-amino acid bioisostere. Kinney, W.A., Abou-Gharbia, M., Garrison, D.T., Schmid, J., Kowal, D.M., Bramlett, D.R., Miller, T.L., Tasse, R.P., Zaleska, M.M., Moyer, J.A. J. Med. Chem. (1998) [Pubmed]
New progesterone esters as 5alpha-reductase inhibitors. Cabeza, M., Heuze, I., Bratoeff, E., Murillo, E., Ramirez, E., Lira, A. Chem. Pharm. Bull. (2001) [Pubmed]
The novel pyrimidine and purine derivatives of l-ascorbic acid: synthesis, one- and two-dimensional 1H and 13C NMR study, cytostatic and antiviral evaluation. Gazivoda, T., Plevnik, M., Plavec, J., Kraljević, S., Kralj, M., Pavelić, K., Balzarini, J., De Clercq, E., Mintas, M., Raić-Malić, S. Bioorg. Med. Chem. (2005) [Pubmed]
Potential steroidal antiestrogens. Clark, E.R., Omar, A.M., Prestwich, G. J. Med. Chem. (1977) [Pubmed]
New pyrimidine- and fluorene-containing oligo(arylene)s: synthesis, crystal structures, optoelectronic properties and a theoretical study. Hughes, G., Wang, C., Batsanov, A.S., Fearn, M.J., Frank, S., Bryce, M.R., Perepichka, I.F., Monkman, A.P., Lyons, B.P., Fern, M. Org. Biomol. Chem. (2003) [Pubmed]
A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta. Henke, B.R., Consler, T.G., Go, N., Hale, R.L., Hohman, D.R., Jones, S.A., Lu, A.T., Moore, L.B., Moore, J.T., Orband-Miller, L.A., Robinett, R.G., Shearin, J., Spearing, P.K., Stewart, E.L., Turnbull, P.S., Weaver, S.L., Williams, S.P., Wisely, G.B., Lambert, M.H. J. Med. Chem. (2002) [Pubmed]
Structure-activity relationship of hydroxamate-based inhibitors on the secretases that cleave the amyloid precursor protein, angiotensin converting enzyme, CD23, and pro-tumor necrosis factor-alpha. Parkin, E.T., Trew, A., Christie, G., Faller, A., Mayer, R., Turner, A.J., Hooper, N.M. Biochemistry (2002) [Pubmed]
Discovery of novel, potent, and orally active spiro-urea human glucagon receptor antagonists. Shen, D.M., Zhang, F., Brady, E.J., Candelore, M.R., Dallas-Yang, Q., Ding, V.D., Dragovic, J., Feeney, W.P., Jiang, G., McCann, P.E., Mock, S., Qureshi, S.A., Saperstein, R., Shen, X., Tamvakopoulos, C., Tong, X., Tota, L.M., Wright, M.J., Yang, X., Zheng, S., Chapman, K.T., Zhang, B.B., Tata, J.R., Parmee, E.R. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
2-substituted 3-(aminooxy)propanamines as inhibitors of ornithine decarboxylase: synthesis and biological activity. Stanek, J., Frei, J., Mett, H., Schneider, P., Regenass, U. J. Med. Chem. (1992) [Pubmed]
Qualitative and quantitative determination of metapramine and its metabolites in biological materials. Viala, A., Cano, J.P., Durand, A., Monjanel, S. J. Chromatogr. (1979) [Pubmed]

Contributions to this collaborative article are from individual authors of WikiGenes or mined by the WikiGenes Data Mining Engine from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

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.