Synonym
JNJ27141491; JNJ 27141491; JNJ-27141491
IUPAC/Chemical Name
3-[(1S)-1-(3,4-Difluorophenyl)propyl]-2,3-dihydro-5-(5-isoxazolyl)-2-thioxo-1H-imidazole-4-carboxylic acid methyl ester
InChi Key
SYARXICKXVXWNA-LBPRGKRZSA-N
InChi Code
InChI=1S/C17H15F2N3O3S/c1-3-12(9-4-5-10(18)11(19)8-9)22-15(16(23)24-2)14(21-17(22)26)13-6-7-20-25-13/h4-8,12H,3H2,1-2H3,(H,21,26)/t12-/m0/s1
SMILES Code
O=C(C1=C(C2=CC=NO2)NC(N1[C@H](C3=CC=C(F)C(F)=C3)CC)=S)OC
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
>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:
Potent and selective human CCR2 antagonist.
In vitro activity:
JNJ-27141491 strongly suppressed hCCR2-mediated in vitro functions, such as MCP-1-induced guanosine 5'-O-(3-[(35)S]thio)triphosphate binding; MCP-1, -3, and -4-induced Ca(2+) mobilization; and leukocyte chemotaxis toward MCP-1 (IC(50) = 7-97 nM).
Reference: J Pharmacol Exp Ther. 2008 Oct;327(1):1-9. https://pubmed.ncbi.nlm.nih.gov/18599682/
In vivo activity:
Furthermore, treatment with JNJ-27141491 (20 mg/kg q.d.) significantly delayed the onset and temporarily reduced neurological signs in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Taken together, these results identify JNJ-27141491 as a noncompetitive, functional antagonist of hCCR2, capable of exerting oral anti-inflammatory activity in transgenic hCCR2-expressing mice.
Reference: J Pharmacol Exp Ther. 2008 Oct;327(1):1-9. https://pubmed.ncbi.nlm.nih.gov/18599682/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
379.38
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. Buntinx M, Hermans B, Goossens J, Moechars D, Gilissen RA, Doyon J, Boeckx S, Coesemans E, Van Lommen G, Van Wauwe JP. Pharmacological profile of JNJ-27141491 [(S)-3-[3,4-difluorophenyl)-propyl]-5-isoxazol-5-yl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxyl acid methyl ester], as a noncompetitive and orally active antagonist of the human chemokine receptor CCR2. J Pharmacol Exp Ther. 2008 Oct;327(1):1-9. doi: 10.1124/jpet.108.140723. Epub 2008 Jul 3. PMID: 18599682.
In vitro protocol:
1. Buntinx M, Hermans B, Goossens J, Moechars D, Gilissen RA, Doyon J, Boeckx S, Coesemans E, Van Lommen G, Van Wauwe JP. Pharmacological profile of JNJ-27141491 [(S)-3-[3,4-difluorophenyl)-propyl]-5-isoxazol-5-yl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxyl acid methyl ester], as a noncompetitive and orally active antagonist of the human chemokine receptor CCR2. J Pharmacol Exp Ther. 2008 Oct;327(1):1-9. doi: 10.1124/jpet.108.140723. Epub 2008 Jul 3. PMID: 18599682.
In vivo protocol:
1. Buntinx M, Hermans B, Goossens J, Moechars D, Gilissen RA, Doyon J, Boeckx S, Coesemans E, Van Lommen G, Van Wauwe JP. Pharmacological profile of JNJ-27141491 [(S)-3-[3,4-difluorophenyl)-propyl]-5-isoxazol-5-yl-2-thioxo-2,3-dihydro-1H-imidazole-4-carboxyl acid methyl ester], as a noncompetitive and orally active antagonist of the human chemokine receptor CCR2. J Pharmacol Exp Ther. 2008 Oct;327(1):1-9. doi: 10.1124/jpet.108.140723. Epub 2008 Jul 3. PMID: 18599682.
1: Zweemer AJ, Bunnik J, Veenhuizen M, Miraglia F, Lenselink EB, Vilums M, de Vries H, Gibert A, Thiele S, Rosenkilde MM, IJzerman AP, Heitman LH. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2. Mol Pharmacol. 2014 Oct;86(4):358-68. doi: 10.1124/mol.114.093328. Epub 2014 Jul 14. PubMed PMID: 25024169.
2: Buntinx M, Hermans B, Goossens J, Moechars D, Gilissen RA, Doyon J, Boeckx S, Coesemans E, Van Lommen G, Van Wauwe JP. Pharmacological profile of JNJ-27141491 [(S)-3-[3,4-difluorophenyl)-propyl]-5-isoxazol-5-yl-2-thioxo-2,3-dihydro-1H-imida zole-4-carboxyl acid methyl ester], as a noncompetitive and orally active antagonist of the human chemokine receptor CCR2. J Pharmacol Exp Ther. 2008 Oct;327(1):1-9. doi: 10.1124/jpet.108.140723. Epub 2008 Jul 3. PubMed PMID: 18599682.
