Synonym
AZD-4818; AZD 4818; AZD4818.
IUPAC/Chemical Name
(S)-2-(2-chloro-5-(3-(5-chloro-3H-spiro[benzofuran-2,4'-piperidin]-1'-yl)-2-hydroxypropoxy)-4-(methylcarbamoyl)phenoxy)-
InChi Key
HVTUHSABWJPWNK-SFHVURJKSA-N
InChi Code
InChI=1S/C27H32Cl2N2O7/c1-26(2,25(34)35)37-23-12-22(19(11-20(23)29)24(33)30-3)36-15-18(32)14-31-8-6-27(7-9-31)13-16-10-17(28)4-5-21(16)38-27/h4-5,10-12,18,32H,6-9,13-15H2,1-3H3,(H,30,33)(H,34,35)/t18-/m0/s1
SMILES Code
CC(C)(OC1=CC(OC[C@@H](O)CN2CCC3(CC2)OC4=CC=C(Cl)C=C4C3)=C(C(NC)=O)C=C1Cl)C(O)=O
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, not in water
Shelf Life
>2 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:
AZD-4818 is a potent antagonist of chemokine CCR1 that can be used for researching chronic obstructive pulmonary disease (COPD).
In vitro activity:
Using membranes from HEK_CCR1Gqi5 cells, it was confirmed that AZD-4818, BX471, CCX354, CP481715 and PS899877 are all potent inhibitors of [125I]-CCL3 binding. In the case of AZD4818, CCX354 and CP481715, the affinity is significantly better with membranes from HEK_CCR1 cells than those from RPMI 8226 cells when tested using an unpaired t-test with Welch's correction (P < 0.05). Furthermore, there was a drastic shift in the rank order of potency between the membranes tested. With HEK_CCR1 membranes it was found that MLN3879 > CCX354 ≥ AZD4818 > CP481715 = BX471 > PS899877 while with membranes from RPMI 8226 cells we found MLN3879 > BX471 > CP481715 ≥ PS899877 > AZD4818 > CCX354. Incubation of cells with AZD-4818, BX471, CCX354, MLN-3897 or PS899877 reduced CCL3-mediated receptor internalization and led to a dose-dependent recovery of surface CCR1.
Reference: Br J Pharmacol. 2014 Nov;171(22):5127-38. https://pubmed.ncbi.nlm.nih.gov/24990525/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
88.11 |
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
567.46
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. Gilchrist A, Gauntner TD, Fazzini A, Alley KM, Pyen DS, Ahn J, Ha SJ, Willett A, Sansom SE, Yarfi JL, Bachovchin KA, Mazzoni MR, Merritt JR. Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, β-arrestin translocation and chemotaxis assays. Br J Pharmacol. 2014 Nov;171(22):5127-38. doi: 10.1111/bph.12835. PMID: 24990525; PMCID: PMC4253460.
In vitro protocol:
1. Gilchrist A, Gauntner TD, Fazzini A, Alley KM, Pyen DS, Ahn J, Ha SJ, Willett A, Sansom SE, Yarfi JL, Bachovchin KA, Mazzoni MR, Merritt JR. Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, β-arrestin translocation and chemotaxis assays. Br J Pharmacol. 2014 Nov;171(22):5127-38. doi: 10.1111/bph.12835. PMID: 24990525; PMCID: PMC4253460.
1: Gilchrist A, Gauntner TD, Fazzini A, Alley KM, Pyen DS, Ahn J, Ha SJ, Willett A, Sansom SE, Yarfi JL, Bachovchin KA, Mazzoni MR, Merritt JR. Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, β-arrestin translocation and chemotaxis assays. Br J Pharmacol. 2014 Nov;171(22):5127-38. doi: 10.1111/bph.12835. PubMed PMID: 24990525; PubMed Central PMCID: PMC4253460.
2: Olsson B, Borgström L, Lundbäck H, Svensson M. Validation of a general in vitro approach for prediction of total lung deposition in healthy adults for pharmaceutical inhalation products. J Aerosol Med Pulm Drug Deliv. 2013 Dec;26(6):355-69. doi: 10.1089/jamp.2012.0986. Epub 2013 Feb 19. PubMed PMID: 23421897.
3: Gladue RP, Brown MF, Zwillich SH. CCR1 antagonists: what have we learned from clinical trials. Curr Top Med Chem. 2010;10(13):1268-77. Review. PubMed PMID: 20536425.
4: Kerstjens HA, Bjermer L, Eriksson L, Dahlström K, Vestbo J. Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients. Respir Med. 2010 Sep;104(9):1297-303. doi: 10.1016/j.rmed.2010.04.010. Epub 2010 May 13. PubMed PMID: 20466530.
5: Norman P. AZD-4818, a chemokine CCR1 antagonist: WO2008103126 and WO2009011653. Expert Opin Ther Pat. 2009 Nov;19(11):1629-33. doi: 10.1517/13543770903118996. PubMed PMID: 19586423.
