Synonym
AM-679, AM679, AM 679
IUPAC/Chemical Name
1-Pentyl-3-(2-iodobenzoyl)indole
InChi Key
GAJBHYUAJOTAEW-UHFFFAOYSA-N
InChi Code
1S/C20H20INO/c1-2-3-8-13-22-14-17(15-9-5-7-12-19(15)22)20(23)16-10-4-6-11-18(16)21/h4-7,9-12,14H,2-3,8,13H2,1H3
SMILES Code
CCCCCn1cc(c2c1cccc2)C(=O)c3ccccc3I
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
AM679 is a potent, selective 5-lipoxygenase-activating protein (FLAP) inhibitor with an IC50 of 2 nM in a human FLAP membrane binding assay.
In vitro activity:
ll of the biaryl compounds 34 to 39 (AM679) showed excellent in vitro inhibition against FLAP. Of particular note was compound 39 with an excellent hWB IC50 potency of 154 nM. This compound also showed an improved CYP inhibition profile (IC50 3A4 = 16.7 μM, 2C9 = 3.7 μM, 2D6 >30 μM), no time dependent inhibition against CYP3A4 (0.003 min−1 vs 0.057 min−1 for troleandomycin control @ 10 μM) and no CYP3A4 induction. The pharmacokinetic properties of 39 had also significantly improved over the chlorobenzyl derivative 20, showing reasonable bioavailability, low clearance and improved AUC (10 mg/kg sodium carboxylate salt in rat po F = 29%, Cl = 11 mL/min/kg, Cmax = 1.6 μM, AUC = 4.6 h μg/mL, T½ = 6.8 h).
Reference: Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. https://pubmed.ncbi.nlm.nih.gov/19914828/
In vivo activity:
To determine if a FLAP LT synthesis inhibitor can ameliorate eye inflammation following RSV infection, this study treated one eye of drug-treated mice with 60 ng AM679 in 2 μl sterile saline (or one eye of control mice with 2 μl sterile saline only) 40 min after inoculation with 106 PFU RSV and then every day afterward for 13 more days. The RSV-infected eyes from control mice showed ocular inflammation, mucus, and conjunctivitis that peaked 6 to 8 days after infection and largely resolved by 14 days (Fig. 3). The FLAP inhibitor AM679-treated mouse eyes showed significant protection from RSV-induced pathology as early as 2 days continuing to 14 days postinfection. At 6 to 8 days the FLAP inhibitor-treated eyes showed greater then 70% reduction in total pathological scores. Representative eyes from both control and AM679-treated mice through days 2 to 6 clearly demonstrate the reduced inflammation and mucus in the drug-treated animals (Fig. 3).
Reference: Clin Vaccine Immunol. 2009 Nov; 16(11): 1654–1659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772391/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
57.0 |
136.60 |
|
| DMF |
10.0 |
23.96 |
|
| Ethanol |
10.0 |
23.96 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
417.29
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Stock N, Baccei C, Bain G, Broadhead A, Chapman C, Darlington J, King C, Lee C, Li Y, Lorrain DS, Prodanovich P, Rong H, Santini A, Zunic J, Evans JF, Hutchinson JH, Prasit P. 5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. doi: 10.1016/j.bmcl.2009.10.131. Epub 2009 Oct 31. PMID: 19914828.
2. Musiyenko A, Correa L, Stock N, Hutchinson JH, Lorrain DS, Bain G, Evans JF, Barik S. A novel 5-lipoxygenase-activating protein inhibitor, AM679, reduces inflammation in the respiratory syncytial virus-infected mouse eye. Clin Vaccine Immunol. 2009 Nov;16(11):1654-9. doi: 10.1128/CVI.00220-09. Epub 2009 Sep 16. PMID: 19759251; PMCID: PMC2772391.
In vitro protocol:
1. Stock N, Baccei C, Bain G, Broadhead A, Chapman C, Darlington J, King C, Lee C, Li Y, Lorrain DS, Prodanovich P, Rong H, Santini A, Zunic J, Evans JF, Hutchinson JH, Prasit P. 5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. doi: 10.1016/j.bmcl.2009.10.131. Epub 2009 Oct 31. PMID: 19914828.
In vivo protocol:
1. Stock N, Baccei C, Bain G, Broadhead A, Chapman C, Darlington J, King C, Lee C, Li Y, Lorrain DS, Prodanovich P, Rong H, Santini A, Zunic J, Evans JF, Hutchinson JH, Prasit P. 5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. doi: 10.1016/j.bmcl.2009.10.131. Epub 2009 Oct 31. PMID: 19914828.
2. Musiyenko A, Correa L, Stock N, Hutchinson JH, Lorrain DS, Bain G, Evans JF, Barik S. A novel 5-lipoxygenase-activating protein inhibitor, AM679, reduces inflammation in the respiratory syncytial virus-infected mouse eye. Clin Vaccine Immunol. 2009 Nov;16(11):1654-9. doi: 10.1128/CVI.00220-09. Epub 2009 Sep 16. PMID: 19759251; PMCID: PMC2772391.
1: Stock N, Baccei C, Bain G, Broadhead A, Chapman C, Darlington J, King C, Lee C, Li Y, Lorrain DS, Prodanovich P, Rong H, Santini A, Zunic J, Evans JF, Hutchinson JH, Prasit P. 5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5 -methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. doi: 10.1016/j.bmcl.2009.10.131. Epub 2009 Oct 31. PubMed PMID: 19914828.
2: Musiyenko A, Correa L, Stock N, Hutchinson JH, Lorrain DS, Bain G, Evans JF, Barik S. A novel 5-lipoxygenase-activating protein inhibitor, AM679, reduces inflammation in the respiratory syncytial virus-infected mouse eye. Clin Vaccine Immunol. 2009 Nov;16(11):1654-9. doi: 10.1128/CVI.00220-09. Epub 2009 Sep 16. PubMed PMID: 19759251; PubMed Central PMCID: PMC2772391.
