Disease relevance of COMPOUND 19

• Although some cytotoxicity was observed at these concentrations, compound 19 was active against murine cytomegalovirus in vivo [1].
• Fluorescence activated cell sorter (FACS) and cytotoxic activity analysis demonstrated the selectivity of compound 19 for melanoma cells [2].
• Compound 4 showed potent activity against HIV-1 (EC(50) 0.47mug/mL), compound 19 proved to possess remarkable activity against Mycobacterium intracellulare with an IC(50) and MIC value of 0.15 and 0.31mug/mL, while compounds 4 and 17 possessed anti-leishmanial activity with IC(50) values of 0.1 and 0.4mug/mL, respectively [3].
• Microbiological screening tests conducted in relation to 54 strains of Gram-positive and 52 strains of Gram-negative bacteria, 6 strains of yeast-like fungi and 3 strains of moulds showed significant activity of compound 19 against 52 Gram-negative bacterial strains [4].

Psychiatry related information on COMPOUND 19

• Compound 19 showed itself to be devoid of CNS depressant effects, neither modifying spontaneous motor activity nor prolonging barbiturate-sleeping time in mice at a dose of 100 mg/kg po, and is now under development [5].

High impact information on COMPOUND 19

• Lead optimization afforded highly potent CGRP antagonists, the prototype being compound 19 (BIBN4096) [6].
• Among them, compound 19 presents the highest cytotoxicity (IC50 = 0.64 +/- 0.07 micromol): this cytotoxicity was maintained in the presence of BZA-CO but decreased 8-fold compared to the control MG132 [2].
• Hydrolysis of compound 19 under acidic conditions furnished 1,6-anhydro-beta-L-idopyranose (35) in excellent yield, which was successfully transformed into the corresponding L-allo, L-altro, L-gulo, and L-ido derivatives via regioselective benzylation, benzoylation, triflation and nucleophilic substitution as the key steps [7].
• A second series of bis(4'-fluorophenyl)amine analogues have now been prepared in which the most potent DAT compound, 19 (K(i) = 8.5 nM), was selective over serotonin transporter (SERT/DAT = 94), norepinephrine transporter (NET/DAT = 63), and sigma(1) receptor binding (sigma(1)/DAT = 44) [8].
• Compound 19 bound hSSTR4 with a Ki of 100 nM [9].

Biological context of COMPOUND 19

• Furthermore, compound 19 (KW-5092) enhanced gastrointestinal motility in anesthetized rabbits along with a negligible histamine H2-receptor blocking activity [10].
• Compound 19, the most potent compound in the benzolactam series, had an IC50 = 3 nM for inhibition of binding of 125I-CCK-8 to CCK receptors in rat pancreatic tissue, and its racemic analogue 8 was found to be orally active in inhibiting CCK-induced gastric emptying in mice, with an ED50 = 2.6 mg/kg po [11].
• Compound 19, having an imide NH function had the strongest cytotoxicity towards L1210 cells and induced the largest accumulation of cells in the G2+M phases of the cell cycle [12].

Anatomical context of COMPOUND 19

• One compound (19) has shown activity between sensitive and resistant Yoshida tumours in vivo and also shows the highest activity between these two cell lines in vitro [13].
• Since all-trans-retinoic acid and compound 19 were also inhibitory, we determined whether retinobenzoic acids bind to cellular retinoic acid-binding protein (CRABP) isolated from bovine adrenal glands [14].
• Optimization of the most potent compound (19) by preparing the corresponding oxazino[3,2-a]indole ester afforded 34, which had a pIC50 of 9.5 in the guinea pig distal colon longitudinal muscle myenteric plexus preparation [15].
• Compound 19 displayed moderate H1-antihistaminic activity in the guinea-pig ileum assay (pA2 = 7.37) [16].

Associations of COMPOUND 19 with other chemical compounds

• In subsequent structure-activity studies on 7, it is shown that removing a single amide carbonyl (compound 14, IC50 = 5.2 microM) or replacing one aromatic ring system with a naphthyl ring (compound 19, IC50 = 1.1 microM) can be accomplished with little loss of inhibitory potency [17].
• Am 80 and Am 580 inhibited the specific binding of 3H-retinoic acid to CRABP, but also showed less affinity than authentic unlabeled retinoic acid and compound 19 [14].
• The mechanism(s) of inhibition of ODC induction by 7 retinobenzoic acids, Am 80, Am 81, Am 580, Am 590, Am 68, Sa 80, and Ch 55 was compared with those by all-trans-retinoic acid and the arotinoid compound 19 [14].
• Oral dosing of compound 19 to hamsters demonstrated effective reduction of both plasma total cholesterol levels and plasma triglyceride levels [18].
• Among the semisynthetic derivatives (18-25) of 13, compound 19, with an acetyl group introduced at the C-3 position in comparison to 13, demonstrated considerable growth inhibition of IL-6-dependent MH-60 cells [19].

Gene context of COMPOUND 19

• Compound 19 showed a definite selectivity to AChE over the BuChE (about 34700-fold) and, at dosages of 10-50 mg/kg, exerted a dose-dependent inhibitory effect on AChE in rat brain [20].
• Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog [21].
• In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism [22].
• Chemical combinations of trans carbapenem 13 with cis carbapenem 6 (compound 19) as well as clavulanic acid (20) with cis carbapenem 6 (compound 22) via a tetrachloroethane linker exhibited remarkable activity against beta-lactamase producing microorganisms in vitro [23].
• Against 23 strains of fungal squalene epoxidase compound 19 was found to be inactive [24].

Analytical, diagnostic and therapeutic context of COMPOUND 19

• Excellent in vitro activity against Cryptosporidium parvum was observed for both classes of isoflavones in cell cultures, and the lead compound 19, RM6427, shows high in vivo efficacy against an experimental infection [25].

References