Disease relevance of Compound 1

• Mechanistically, compound 1 prevents bone loss in vivo by inhibiting osteoclast-mediated bone resorption, ultimately preventing cancellous bone turnover [1].
• C1 treatment inhibited C. trachomatis but not T4SS-expressing Coxiella burnetii development in a dose-dependent manner [2].
• We therefore employed the small molecule Yersinia T3SS inhibitor N'-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide, designated compound 1 (C1), to examine the interdependence of the chlamydial T3SS and development [2].
• When dosed orally at 30 mg/kg twice a day (b.i.d.) in the chronic ovariectomy (OVX)-induced rat model of osteopenia, compound 1 also prevented bone loss [1].
• In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 microM [3].

Psychiatry related information on Compound 1

• Compound 1 is formed up to a reaction time of 13 d, and an extension of the reaction time leads to the formation of 2 [4].
• The cholinesterase inhibitory potential along with calcium-channel blocking activity of compound 1 and safe profile in human neutrophils viable assay could make it a possible drug candidate for Alzheimer's disease [5].
• Compound 1 and its xylyl derivatives tested (0.25 mumol/mouse, i.c.v.) decreased locomotor activity [6].

High impact information on Compound 1

• High concentrations of either compound (1) drastically reduced the number of primary HPP-CFC colonies and totally abolished their recloning capacity and (2) inhibited HSC proliferation [7].
• Furthermore, the compounds that contained only a stem peptide (pentapeptide, compound 1) and (DAP-PP, compound 2) as well as muramyldipeptide (compound 3) exhibited no binding indicating that the muramyltripeptide (compound 4) is the smallest peptidoglycan fragment that can be recognized by PGRP-Ialpha [8].
• Compound 1 reduced viral RNA in replicon cells with an IC(50) of approximately 0.5 microm, suggesting that the inhibitor was able to access the perinuclear membrane and inhibit the polymerase activity in the context of a replicase complex [9].
• Compound 1 is a potent inhibitor of both soluble and membrane-associated isoforms of native PKG, as well as recombinant enzyme, with an IC(50) of <1 nm [10].
• Fatty acyl-CoA oxidase (FACO) activity and mRNA were increased after treatment with either fenofibric acid or compound 1 in rat hepatocytes [11].

Chemical compound and disease context of Compound 1

• Compound 1 [1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydrochloride] selectively blocked the growth of C6 glioma leaving normal astrocytes relatively unaffected [12].
• In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day [13].
• Erythromycin A (compound 1) was inactivated by Streptomyces vendargensis ATCC 25507 in fermentation [14].
• When administered orally to animals with experimentally induced vaginal candidiasis or systemic candidiasis, compound 1 produced results approaching those produced by ketoconazole [15].
• Our in vitro assay indicated that, like compound 1, compound 16 is not an inhibitor of HIV-1 reverse transcriptase [16].

Biological context of Compound 1

• When assaying the human recombinant cPLA2 using membranes isolated from [3H]arachidonate-labeled U937 cells as substrate, 2-(2'-benzyl-4-chlorophenoxy)ethyl-dimethyl-n-octadecyl-ammonium chloride (compound 1) was found to inhibit the enzyme in a dose-dependent manner (IC50 = 5 microM) [17].
• Hence, inhibition of cholesterol esterase-catalyzed hydrolysis of p-nitrophenyl butyrate by compound 1 or 2 in the aqueous or micellar phase occurs via a carbamyl-cholesterol esterase mechanism [18].
• Thus, compound 1 represents a novel structural class of inhibitor of cPLA2 that partitions into the phospholipid bilayer and competes with the phospholipid substrate for the active site [17].
• The inhibition of cholesterol esterase by compound 1 or 2 shows saturation kinetics with increasing inhibitor concentration [18].
• Furthermore, in the absence of an in vitro-reconstituted HCV replicase assay employing viral and host proteins, the ability of compound 1 to inhibit NS5B-directed viral RNA replication was determined using the Huh7 cell-based HCV replicon system [9].

Anatomical context of Compound 1

• This discrepancy was reconciled by showing that these shorter-chained analogs did not partition into the [3H]arachidonate-labeled U937 membranes as effectively as compound 1 [17].
• Compound 1 also potently inhibited an ER-, HER-2 overexpressing breast cancer cell line [19].
• We previously reported compound 1 as a potent farnesyl protein transferase (FPT) inhibitor that exhibited reasonable pharmacokinetic stability and showed moderate in vivo activity against a variety of tumor cell lines [20].
• A HeLa cell model that mimics in vivo conditions showed that compound 1 chemically attenuates the pathogen to the advantage of the eukaryotic cell [21].
• Compound 4 is about fourfold less potent than compound 1 as an antiviral agent but is about 40-fold less toxic to the host Vero cells [22].

Associations of Compound 1 with other chemical compounds

• First-order decreases in cholesterol esterase activity effected by compound 1 or 2 are also observed in the presence of taurocholate/phosphatidylcholine micelles [18].
• In this study five derivatives of compound 1 (compounds 2-6) were selected because of their sensitivity in facilitating complex formation between the 1alpha,25(OH)(2)D(3) receptor (VDR) and the retinoid X receptor on a 1alpha,25(OH)(2)D(3) response element that was comparable to that of the natural hormone (0.2-0.9 nM) [23].
• After further pharmacological and toxicological evaluation as well as physical properties, the hydrochloride 2 (JTV-605) of compound 1 was selected for clinical studies as a potent AVP antagonist with a long duration of action [24].
• We examined interactions with purified tubulin of synthetic sarcodictyins A and B and eleutherobin (coral-derived antimitotic agents) and of compound 1, an analogue of sarcodictyin A methylated at the C-3 oxygen atom (i.e., the methyl ketal analogue of sarcodictyin A and thus structurally similar to eleutherobin but lacking the C-3 sugar moiety) [25].
• The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 microgram/ml for cidofovir and < 0.05 to 0.09 microgram/ml for compound 1 [13].

Gene context of Compound 1

• Compound 1 inhibited MIP-1alpha- and RANTES-induced migration in peripheral blood mononuclear cells in a dose-responsive manner [26].
• Compound 1, which displayed modest potency and selectivity for ERbeta vs ERalpha, was identified via high-throughput screening utilizing an ERbeta SPA-based binding assay [27].
• To elucidate its structure-function-activity relationship, we synthesized nine different analogues of ethyl 3',4',5'-trimethoxycinnamate, i.e., compounds 3-11, and compared the ICAM-1 inhibitory activity of compound 1 with those of its synthetic analogues as well as the corresponding acids 12-15 [28].
• However, using a commercial RIA and immunoblots, we showed that PRL levels increase significantly in response to treatment with the ER-alpha selective agonist, compound 1 [29].
• In this article, we report the synthesis, in vitro characterization, pharmacokinetics, and pharmacodynamics of an orally bioavailable, potent, small molecule GnRH receptor antagonist N-{4,6-dimethoxy-2-[(3-morpholin-4-ylpropyl)amino]pyrimidin-5-yl}-5-[3,3,6-trimthyl-2,3-dihydro-1H-inden-5-yl)oxy]-2-furamide (compound 1) [30].

Analytical, diagnostic and therapeutic context of Compound 1

• In addition, blood samples from 28 normal subjects, 28 cancer patients with different malignancies, and 39 patients with a variety of other than cancer ailments were screened for compound 1 on a blind basis using reverse phase ion-paired high-performance liquid chromatography [31].
• Unlike 7b and 36c, compound 1 and related 2,4,6-trimethoxyanilides (13j, 30c,d) showed poor oral activity in the rabbit bioassay [32].
• The pharmacokinetic profile of compound 1 after oral administration revealed that maximal plasma levels of compound were reached within 1 h and the half-life of the compound to be approximately 2 h in rats [33].
• In 72-hr UW-preserved kidneys, the microvessels of both cortex and medulla were completely visualized with silicon rubber compound 1 hr after reperfusion [34].
• Compound 1 possessed a straight channel, with an opening of approximately 0.5x0.8 nm, which contained the water of crystallization [35].

References