R1487 HCl is a novel, potent, orally bioavailable, and highly selective inhibitor of p38α mitogen-activated protein kinase. IIt was discovered during the development of a new series of p38α inhibitors and advanced into a phase 2 clinical trial for rheumatoid arthritis. The pharmacokinetic characteristics of R1487 are good.
Physicochemical Properties
| Molecular Formula | C19H19CLF2N4O3 |
| Molecular Weight | 424.833 |
| Exact Mass | 424.111 |
| Elemental Analysis | C, 53.72; H, 4.51; Cl, 8.34; F, 8.94; N, 13.19; O, 11.30 |
| CAS # | 449808-64-4 |
| Related CAS # | 449808-64-4 |
| PubChem CID | 54580957 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 3.213 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 29 |
| Complexity | 602 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1C(OC2=CC=C(F)C=C2F)=CC3=CN=C(NC4CCOCC4)N=C3N1C.Cl |
| InChi Key | RQHSAIGGUWVOBG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C19H18F2N4O3.ClH/c1-25-17-11(10-22-19(24-17)23-13-4-6-27-7-5-13)8-16(18(25)26)28-15-3-2-12(20)9-14(15)21;/h2-3,8-10,13H,4-7H2,1H3,(H,22,23,24);1H |
| Chemical Name | 6-(2,4-difluorophenoxy)-8-methyl-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one;hydrochloride |
| Synonyms | R-1487 HCl; R1487 HCl; R 1487 HCl |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | p38α (Kd = 0.2 nM); p38β (Kd = 29 nM) |
| ln Vitro |
R1487 Hydrochloride exhibits IC50 values of 200 nM for the inhibition of TNF-induced IL-1β production and 10 nM for the inhibition of p38α[1]. R1487 (Compounds 2a) inhibits LPS-induced production of IL-1β in human whole blood (HWB) and TNFα production by human monocytic cells (THP-1)[1]. |
| ln Vivo |
R1487 (Compounds 2a, orally) demonstrably inhibits serum TNFα and IL-1β in a dose-dependent manner[1]. In rat, dog, and monkey, the oral bioavailability of 10 mg/kg R1487 (Compounds 2a) was 51.6%, 29.3%, and 10.3%, respectively[1]. |
| References |
[1]. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-on. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~20.8 mg/mL (~49.0 mM) H2O: < 0.1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3539 mL | 11.7694 mL | 23.5388 mL | |
| 5 mM | 0.4708 mL | 2.3539 mL | 4.7078 mL | |
| 10 mM | 0.2354 mL | 1.1769 mL | 2.3539 mL |