![6-METHYL-1'-(2-(5-METHYL-2-PHENYLOXAZOL-4-YL)ETHYL)SPIRO[BENZO[D][1,3]OXAZINE-4,4'-PIPERIDIN]-2(1H)-ONE structure, CAS 300816-15-3](/structures/150000/148550_1_300816_15_3.png)
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 300816-15-3 |
| Catalog No. | 2A-0148550 |
| Chinese Name | 6-甲基-1,1'-[2-(5-甲基- 2-苯基- 4-恶唑基)乙基]-螺[4H-3-1,1-苯并恶嗪- 4,4' -哌啶]-2(1H)-酮 |
| Synonyms | RS504393; RS 504393 |
| Molecular Formula | C25H27N3O3 |
| Molecular Weight | 417.50 |
| Purity | ≥98 (HPLC) |
| Density | 1.3±0.1 g/cm3 |
| Appearance | powder |
| Storage Condition | 2-8℃ |
| Application | RS 504393 is a selective CCR2 antagonist for human recombinant CCR2 and CCR1 receptors with IC50 values of 89 nM and >100 μM, respectively. |
| EINECS | 0 |
| HTC | 2934999090 |
| UN(IATA) | 0 |
| SMILES | N3(CCC4(OC(=O)Nc5c4cc(cc5)C)CC3)CCc1nc([o]c1C)c2ccccc2 |
| InChI | 1S/C25H27N3O3/c1-17-8-9-22-20(16-17)25(31-24(29)27-22)11-14-28(15-12-25)13-10-21-18(2)30-23(26-21)19-6-4-3-5-7-19/h3-9,16H,10-15H2,1-2H3,(H,27,29) |
| InChI Key | ODNICNWASXKNNQ-UHFFFAOYSA-N |
| NACRES Code | NA.77 |
| UNSPSC | 51111800 |
| Hazard Symbols | transportation |
| MSDS | msds/148550_1_300816_15_3.pdf |
| Bioactivity | RS 504393 is a selective CCR2 chemokine receptor antagonist (IC50 values are 89 nM and > 100 μM for inhibition of human recombinant CCR2 and CCR1 receptors respectively). Related Catalog Signaling Pathways >> GPCR/G Protein >> CCR Signaling Pathways >> Immunology/Inflammation >> CCR Research Areas >> Inflammation/Immunology Target CCR2:89 nM (IC50) Human α1a receptor:72 nM (IC50) Human α1d receptor:460 nM (IC50) 5HT-1a receptor:1070 nM (IC50) In Vitro RS 504393 inhibits the MCP-1-induced chemotaxis with an IC50 of 330 nM. RS 504393 treatment suppresses allergen induced β-hexosaminidase release significantly. Without allergen priming, MCP-1 induces mast cell degranulation, which is completely suppressed by RS 504393[4]. In Vivo RS504393 (0.3-3 μg) with CCL2 progressively blocks thermal hyperalgesia dose-dependently in mice[1]. RS 504393 (5 mg/kg, i.v.) supresses the elevated numbers of leukocytes and increased total protein content in BALF induced by The LPS. RS504393 significantly down regulates the LPS-induced elevation of IL-1β, PAI-1 mRNA and protein expressions. RS504393 significantly suppresses induced lung edema, protein-rich fluid, polymorphonuclear accumulation and bronchial wall thickening induced by LPS[2]. RS-504393 significantly reduces renal pathology, especially the extensive interstitial fibrosis mediated by decrease in type I collagen synthesis in a UUO model[3]. Kinase Assay Isolated mast cells are sensitized by incubation with anti-DNP IgE in RPMI1640 containing 10 ng/mL of murine recombinant IL-3, 10 ng/mL of recombinant SCF, and 5% murine serum. The cells are then washed with HBSS containing 10 ng/mL of murine recombinant IL-3, 10 ng/mL of recombinant SCF, 0.04% BSA, and 10 mM HEPES. Resuspended cells at a concentration of 2 to 8×104 cells/100 μL are transferred into triplicate wells of a 96 well U-bottom plate and allowed to equilibrate at 37°C for 10 minutes before the addition of DNP-albumin or compound 48/80. After 45 minutes, the plate is centrifuged at 290 g for 5 minutes at 4°C. The β-hexosaminidase activity of the culture supernatant is determined using a Published protocol. Fifty-μL aliquots of the supernatant are placed in wells of another 96-well plate together with 100 μL of 2.5 mM p-nitrophenyl-N-acetyl β-d glucosaminide solubilized in 0.04mol/Lcitrate buffer adjusted to pH 4.5 with disodium phosphate. After incubation at 37°C for 90 minutes, the reactions are terminated by addition of 50 μL of 0.4mol/Lglycin adjusted to pH 10.7 with sodium hydroxide. The colored product is measured at 405 nm with a reference filter of 570 nm. The relative release of β-hexosaminidase is defined as the activity in the supernatant of the tested cells divided by the activity in the positive control cell supernatant, multiplied by 100. Compound 48/80 stimulus is used for assay control. Animal Admin Male C57BL/6J mice (n=30) and male homozygote CCR1, CCR2 and CCR3 knockout mice (n=12, in each phenotype), 6-8 weeks old and weighing 20±2 g, are anesthetized with a mixture of ketamine (80 mg/kg) and xylazine (30 mg/kg) given intraperitoneally. Intranasal administration of PBS or LPS (5 mg/kg) is performed in a volume of 1 mL/kg body weight. C57BL/6J mice are treated with vehicle or RS504393 (5 mg/kg) intraperitoneally 30 min before LPS challenge. Four hours after LPS challenge, mice are terminated by an intraperitoneal injection of an overdose of pentobarbitone. The mice are kept on a 12-h light/dark cycle with access to mice chow and water ad libitum. References [1]. Baamonde, Ana., et al. Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1β in the spinal hyperalgesia evoked by the chemokine CCL2 in mice. Neuroscience Letters (2011), 502(3), 178-181. [2]. Yang, Dong., et al. Roles of CC chemokine receptors (CCRs) on lipopolysaccharide-induced acute lung injury. Respiratory Physiology & Neurobiology (2010), 170(3), 253-259. [3]. Kitagawa, Kiyoki., et al. Blockade of CCR2 ameliorates progressive fibrosis in kidney. American Journal of Pathology (2004), 165(1), 237-246. [4]. Tominaga T, et al. Blocking mast cell-mediated type I hypersensitivity in experimental allergic conjunctivitis by monocyte chemoattractant protein-1/CCR2. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5181-8. [5]. Mirzadegan T, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle. J Biol Chem. 2000 Aug 18;275(33):25562-71. Chemical & Physical Properties Density 1.3±0.1 g/cm3 Molecular Formula C25H27N3O3 Molecular Weight 417.500 Exact Mass 417.205231 PSA 67.60000 LogP 4.87 Index of Refraction 1.645 InChIKey ODNICNWASXKNNQ-UHFFFAOYSA-N SMILES Cc1ccc2c(c1)C1(CCN(CCc3nc(-c4ccccc4)oc3C)CC1)OC(=O)N2 Storage condition 2-8℃ |
| Use of | Properties Name 6-methyl-1'-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl]spiro[1H-3,1-benzoxazine-4,4'-piperidine]-2-one Synonym More Synonyms RS504393 Biological Activity Related Catalog Signaling Pathways >> GPCR/G Protein >> CCR Signaling Pathways >> Immunology/Inflammation >> CCR Research Areas >> Inflammation/Immunology CCR2:89 nM (IC50) Human α1a receptor:72 nM (IC50) Human α1d receptor:460 nM (IC50) 5HT-1a receptor:1070 nM (IC50) In Vitro RS 504393 inhibits the MCP-1-induced chemotaxis with an IC50 of 330 nM. RS 504393 treatment suppresses allergen induced β-hexosaminidase release significantly. Without allergen priming, MCP-1 induces mast cell degranulation, which is completely suppressed by RS 504393[4]. References [1]. Baamonde, Ana., et al. Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1β in the spinal hyperalgesia evoked by the chemokine CCL2 in mice. Neuroscience Letters (2011), 502(3), 178-181. [2]. Yang, Dong., et al. Roles of CC chemokine receptors (CCRs) on lipopolysaccharide-induced acute lung injury. Respiratory Physiology & Neurobiology (2010), 170(3), 253-259. [3]. Kitagawa, Kiyoki., et al. Blockade of CCR2 ameliorates progressive fibrosis in kidney. American Journal of Pathology (2004), 165(1), 237-246. [5]. Mirzadegan T, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle. J Biol Chem. 2000 Aug 18;275(33):25562-71. Chemical & Physical Properties Molecular Formula C25H27N3O3 Exact Mass 417.205231 PSA 67.60000 Index of Refraction 1.645 InChIKey ODNICNWASXKNNQ-UHFFFAOYSA-N Storage condition 2-8℃ |
| Tax Rebate | 13.0% |
| Supervision | None. MFN tariff: 6.5%. Ordinary tariff: 20.0% |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information 14.1 UN dangerous goods number European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.2 United Nations shipping name European Land Transport Dangerous Regulations: Non-dangerous goods IMDG Code: Non-dangerous goods International air transport dangerous goods regulations: non-dangerous goods 14.3 Transport hazard categories European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.4 Package group European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.5 Environmental hazards European Land Transport Danger Regulations: No International Maritime Danger Regulations International Air Transport Danger Regulations: No Marine pollutants (yes/no): No 14.6 Special reminder to users No data available |
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