| Identification | Back Directory | [Name]
Ethanone, 2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-1-[(2R)-2-methyl-4-[2-(trifluoromethyl)-4-[2-(trifluoromethyl)-5-pyrimidinyl]-5-thiazolyl]-1-piperazinyl]- | [CAS]
1646267-59-5 | [Synonyms]
ACT-660602
Ethanone, 2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-1-[(2R)-2-methyl-4-[2-(trifluoromethyl)-4-[2-(trifluoromethyl)-5-pyrimidinyl]-5-thiazolyl]-1-piperazinyl]- | [Molecular Formula]
C20H20F6N8OS | [MOL File]
1646267-59-5.mol | [Molecular Weight]
534.48 |
| Chemical Properties | Back Directory | [Boiling point ]
611.0±65.0 °C(Predicted) | [density ]
1.60±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
3.59±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
ACT-660602 is a Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases. ACT-660602 led to significantly reduced recruitment of the CXCR3+ CD8+ T cell in the bronchoalveolar lavage compartment when administered orally at a dose of 30 mg/kg. | [Uses]
ACT-660602 is an orally active antagonist of chemokine receptor (CXCR3) with an IC50 value of 204 nM. ACT-660602 inhibits T-cell migration and shows efficacy in acute lung ingury model. ACT-660602 can be used for autoimmune diseases research[1][2]. | [in vivo]
ACT-660602 (1 μM; 6 h) intrinsic metabolic clearance (CLint) in human, rat, mouse liver microsomes (HLM, RLM, MLM)[1].
ACT-660602 (30 mg/kg; p.o.; once daily) displays anti-inflammatory activity and exerts efficacy in the mouse model of acute lung ingury[1].
Range for Pharmacokinetics of ACT-660602[1]
| Animal | Route | Dose (range) (mg/kg) | Cmax (range) (ng/mL) | Tmax (range) (h) | AUC (range) (ng?h/mL) | F (%) | CL (range) (mL/min/kg) | Vss (range) (L/kg) | T1/2 (range) (h) | | Dog | p.o. | 2 | 1380 | 1 | 20000 | 8 | 1.3 | 1.7 | 14.5 | | i.v. | 0.5 | 1300-1450 | 0.5-2.0 | 10400-32000 | / | 0.6-3.0 | 1.6-1.7 | 6.3- | | Rat | p.o. | 2 | 1520 | 0.5 | 14000 | 80 | 1.9 | 1.1 | 7.1 | | i.v. | 0.5 | 1250-1860 | 0.5-1.0 | 11600-15641 | / | 1.9-1.9 | 0.9-1.3 | 5.7-8.8 |
| Animal Model: | LPS-induced lung inflammation model (72 h post LPS challenge)[1] | | Dosage: | 30 mg/kg | | Administration: | Oral gavage; once daily | | Result: | Significantly reduced recruitment of the CXCR3+ CD8+ T cell in the bronchoalveolar lavage compartment.
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| [IC 50]
CXCR3: 204 nM (IC50) | [References]
[1] Meyer EA, et al. Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases. J Med Chem. 2022 Aug 10. DOI:10.1021/acs.jmedchem.2c00675
[2] Caroff Eva, et al. Preparation of piperazinyltriazolylethanone derivatives for use as CXCR3 receptor modulators: World Intellectual Property Organization, WO2015011099. 2015-01-29. |
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