Disease relevance of Compound 17

• On the basis of the preliminary imaging and toxicity data, compound 17 was selected as a potential development candidate [1].
• Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17 [2].

Psychiatry related information on Compound 17

• Compound 17 (ip) emerged from the maximal electroshock seizure (MES) test with a 50% effective dose (ED50) of 8.25 mg/kg [3].

High impact information on Compound 17

• These processes are inhibited when photolysis is conducted in the presence of the photoinert compound 17 beta-hydroxy-5 alpha-androstan-3-one, suggesting that steroid-specific sites are involved in the reactions [4].
• The X-ray crystal structure of compound 17 bound to the enzyme revealed that the macrocycle formed a "donut"-shaped ring around the methyl group of Ala156 [5].
• In case of the compound 17, the -OH group was replaced with -CH2-CH2-OH with a resulting increase in inhibition against tyrosinase [6].
• Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA [7].
• Compound 17 also exhibited a long duration of action in the dog (inhibition of PAF-induced whole blood aggregation ex vivo was maintained for greater than 24 h following a single oral dose of 75 micrograms/kg) and was highly selective as a PAF antagonist, showing only weak affinity (IC50 = 6600 nM) for the [3H]nitrendipine binding site [8].

Biological context of Compound 17

• Potencies in the in vitro rat uterotonic, avian vasodepressor, rat pressor, and rat antidiuretic assays were determined and are as follows, respectively: for compound 17 3.01 +/- 0.14 units/mg, 4.55 +/- 0.03 units/mg, tachyphylaxis and tachyphylaxis; for compound 18 less than 0.1, less than 0.1, less than 0.05, and less thad 1.88 +/- 0.04 units/mg [9].
• Compound 17 with rapid onset caused significant relaxation (p < 0.01) of isolated rabbit femoral artery and guinea pig atrium but had no effect on heart rate [10].
• Compound 17 exhibited excellent bioavailability and a good pharmacokinetic profile in rats [11].
• Compound 2h which has no oxygen atom at the alpha-position of the amide carbonyl group and, compound 17 which has no amide carbonyl group, showed no inhibition in the rat PCA assay [12].
• In most cases loss or change in length of one of the disulfide rings eliminates paralytic activity except with compound 17, which is weakly active, IC50 = 7.0 x 10(-5) M [13].

Anatomical context of Compound 17

• Only one compound, 17 beta-N,N-diethylcarbamyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), was found to be a potent 5 alpha-R inhibitor in all tissues studied: human hair follicles, foreskin (Ki = 3 nM), genital fibroblasts (Ki = 12 nM), and prostate [14].
• The prominent compound 17 showed significant activity against the leukemia SR cell line (log GI(50)=-7.67, log TGI=-6.90 and log LC(50)=-4.77) [15].
• PEG-LE compound 17 also effectively suppressed the mobility of the larva in brain and skeletal muscle [16].
• At a concentration of 0.0084 microM (based on the IC(50) of compound 17 (seco-CBI-TMI) against the growth L1210 cells), while compounds 4 and 17 were toxic against murine bone marrow cells as judged by a colony forming study of freshly isolated murine progenitor hematopoeitic cells, compound 5, a seco-CFQ compound, was significantly less toxic [17].
• Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line [18].

Associations of Compound 17 with other chemical compounds

• The synthesis, in vitro, and in vivo evaluations of these agents, and comparative data with DPI-201-106 (compound 17) are reported [19].

Gene context of Compound 17

• Compound 17 exhibited the highest CB1 receptor affinity (Ki = 24 nM) in this series, as well as very potent CB1 antagonistic activity (pA2 = 8.8) and a high CB1/CB2 subtype selectivity (approximately 147-fold) [20].
• Another potent inhibitor in this series, compound 17, exhibited time-dependent inactivation of sulfatase when incubated at various concentrations (0.2-1.0 microM) of the inhibitor [21].
• A more effective compound (17) was obtained by esterificating repin with the paclitaxel side chain [22].
• Compound 17 was also a potent inhibitor of tubulin polymerization [23].

Analytical, diagnostic and therapeutic context of Compound 17

• Compound 17 had a higher mobility than GalA3 on paper chromatography, indicating that the putative alcohol was relatively nonpolar [24].
• Compound 17 has been taken into phase I clinical trials [25].

References