26954-85-8Relevant articles and documents
Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins
Chen,Zhu,Liu,Lu,Xie,Ling
, p. 4001 - 4010 (2007/10/03)
Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (>100 nM) this large pool of IGF is biologically inactive because of its association with six distinct binding proteins which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants which bind to IGFBPs but not the IGF-I receptor have been shown to be potent IGF/IGFBP inhibitors small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by 1 and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.
A CONVENIENT PREPARATION OF DIBENZOCYCLOOCTATRIENE USING FRIEDEL-CRAFTS INTRAMOLECULAR ACYLATION
Yamato, Takehiko,Inoue, Hisataka,Fukumoto, Maki,Tashiro, Masashi
, p. 495 - 498 (2007/10/02)
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BENZOPHENANTHRIDINES. I. SYNTHESIS OF 7,12-DIACETOXY-2,3,9,10-TETRAMETHOXY-5,6-DIMETHYLBENZOPHENANTHRIDINIUM PERCHLORATE
Khokhlov, V. A.,Sladkov, V. I.,Kurkovskaya, L. N.,Kuleshova, E. F.,Suvorov, N. N.
, p. 538 - 543 (2007/10/02)
The synthesis of a structural isomer of the highly active antileukemia benzophenathridine alkaloids, i.e., 7,12-diacetoxy-2,3,9,10-tetramethoxy-5,6-dimethylbenzophenanthridinium perchlorate, was realized from 2-hydroxy-3-(3,4-dimethoxyphenyl)-6,7-di
