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Chemical Compound Review:

COMPOUND 16 (8S,9R)-9-[4-[2-[(3R,4R)- 3,4...

Synonyms: CHEMBL183467, CHEBI:40620, CHEBI:404669, AC1L9MUR, 1xp6, ...

Youssefyeh, R.D. et al., Huang, S.T. et al., Gasparotto, V. et al., Kucharczyk, N. et al., Gopalsamy, A. et al., et al.

Marco, de los Ríos, García, Villarroya, Carreiras, Martins, Eleutério, Morreale, Orozco, Luque, Hu, Xiang, DiGrandi, Du, Ipek, Laakso, Li, Li, Rush, Schmid, Skotnicki, Tam, Thomason, Wang, Levin, Liu, Xin, Clampit, Wang, Gum, Haasch, Trevillyan, Abad-Zapatero, Fry, Sham, Liu, Cases-Thomas, Masters, Walter, Campbell, Haughton, Gallagher, Dobson, Mancuso, Bonnier, Giard, Defrance, Vanmarsenille, Ledgard, White, Ouwerkerk-Mahadevan, Brunelle, Dezutter, Herbots, Lienard, Findlay, Hayhurst, Boot, Thompson, Hemrick-Luecke, Greenfield, Grosanu, Dunlop, McIlvain, Carrick, Jow, Lu, Kowal, Williams, Butera, Gopalsamy, Lim, Ciszewski, Park, Ellingboe, Bloom, Insaf, Upeslacis, Mansour, Krishnamurthy, Damarla, Pyatski, Ho, Howe, Orlowski, Feld, O'Connell,

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Disease relevance of COMPOUND 16

In addition, compound 16 is also active against HIV replication in a monocytic cell line and in peripheral blood mononuclear cells (PBMCs) [1].
MBE(Br-77) may prove to be a more favorable agent for imaging human breast tumors than our previously described compound, 16 alpha-[77Br]bromoestradiol-17 beta [2].
Compound 16 not only failed to induce catalepsy in the rat but was quite effective in reversing the cataleptic effect of neuroleptic agents, thus indicating a low propensity for causing extrapyramidal side effects [3].
Compound 16 showed significant activity against P388 leukemia in cell culture [4].
Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration [5].

Psychiatry related information on COMPOUND 16

One water-soluble compound, 16, in which the substituent was 3-carbonylpropionate, strongly prolonged the reaction time in the mouse hot-plate test both after iv or oral administration and was devoid of degranulating activity in rat peritoneal mast cells [6].

High impact information on COMPOUND 16

The newly synthesized 7-phenyl-3H-pyrrolo[3,2-f]quinolinones 16-26 and previously 27 and 28 were assayed for their in vitro antiproliferative activity on tumor cell lines, and the lead compound 16 in vivo on a singenic hepatocellular carcinoma in Balb/c mice [7].
The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK [8].
The in vivo experimental results showed that compound 16 could inhibit 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reaction and sheep red blood cell (SRBC) induced antibody production, respectively [9].
A novel series of HCV NS5B RNA-dependent RNA polymerase inhibitors containing a pyrano[3,4-b]indole scaffold is described leading to the discovery of compound 16, a highly potent and selective inhibitor that is active in the replicon system [10].
Nonselective compound 16 and 3,9-dinitro 13, which exhibited selectivity toward leukemia tumor cell lines, were selected for in-depth evaluation, including in vivo experiments [11].

Biological context of COMPOUND 16

The nitrogen bridge was therefore introduced by cyclization of 5-fluoroisocytidine (10) to give the 2,2'-imino-bridged compound 16 [12].
Compound 16 also intragastrically inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ID50 of 0.6 mg/kg [13].
In particular, compound 16 is more potent than UK-1 against A-549 and HeLa cell lines, and compounds 15, 17, and 18 selectively exhibit potent cytotoxic activity against the BFTV-905 cells (IC50 9.6 microM), A-549 cells (IC50 6.6 microM), and MES-SA cells (IC50 9.2 microM), respectively [14].
Compound 16 showed 100% oral bioavailability in rats and demonstrated >50% inhibition of bovine cartilage degradation at 10 ng/mL [15].
A sub-G1 cell stage and DNA fragmentation in MCF-7 cells were significantly observed after 72 h incubation with selective compound 16 [16].

Anatomical context of COMPOUND 16

Furthermore, the hematopoietic synergistic activity induced by compound 16 in stromal cell cultures was blocked by an antibody known to neutralize the hematoregulatory effect of 1, indicating a common mechanistic end point [17].

Associations of COMPOUND 16 with other chemical compounds

Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs [18].
Furthermore the presence of a 4-benzyl substituent on the piperidine ring (compound 16, Ki = 3.9 nM on sigma 1 sites) caused an increase in 5-HT1A affinity (Ki < 0.14 nM) [19].
The compound (16) was found to be superior to ethambutol clinically used anti TB drug in in vitro screen [20].
Interestingly, diamino compound 16 is a 4-fold more potent inhibitor than its parent monoamino heterocyclic rimantadine 4 propably because of additional hydrogen bonding interactions with the M2 protein receptor [21].
In vitro binding affinity for the norepinephrine, dopamine and serotonin transporters and in vivo examination of a select compound (16) in a pharmacodynamic animal model for norepinephrine reuptake inhibition are presented [22].

Gene context of COMPOUND 16

When tested in vivo, compound 16 increased the median survival time of mice implanted with M5076 with an optimum %T/C of 154% and produced cures in 50% of mice implanted with Lox melanoma [23].
Compound 16 (lacking the 3-hydroxymethyl substituent) was a better substrate for human DTD than EO9, yet exhibited lesser toxicity under both aerobic and hypoxic conditions [24].
Compound 16 was identified as a potent JNK inhibitor with good cellular potency [25].
Compound (16) represents one of the most potent (IC50=85+/-5 nM) and selective inhibitors of EAAT-2 identified to date [26].
These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16) [27].

Analytical, diagnostic and therapeutic context of COMPOUND 16

Compound 16 effectively inhibited DHT production 4 h after a 3 mg/kg oral administration [28].
The major diterpenoids 1-9, 11, and 13, as well as the very abundant phenolic compound 16, were subjected to antibacterial and cytotoxic bioassays [29].

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