RP-54745 (RP 54745) is a novel amino-dithiole-one compound that is active at micromolar concentration on the metabolism of stimulated macrophages, for example, the hexose monophosphate pathway (HMP) and the exocytosis of lysosomal enzymes. LPS-induced interleukin-1 (IL-1) production by murine peritoneal macrophages was also diminished by this compound in vitro as well as in vivo. This effect was confirmed at the mRNA level; at the concentration of 3 x 10(-6) M, the IL-1 alpha and beta mRNA signals were inhibited, whereas the TNF alpha mRNA signal was only slightly lessened. These observations were confirmed in vivo, with a dose of RP 54745 of 25 mg kg-1. These results led us to consider that RP 54745 might influence certain cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies. In all, as an inhibitor of macrophage stimulation and interleukin-1 production, RP-54745 has a potential to be used as an antirheumatic compound.
Physicochemical Properties
| Molecular Formula | C13H12NOS2CL |
| Molecular Weight | 297.82348 |
| Exact Mass | 297.005 |
| Elemental Analysis | C, 52.43; H, 4.06; Cl, 11.90; N, 4.70; O, 5.37; S, 21.53 |
| CAS # | 135330-08-4 |
| PubChem CID | 126203 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.46g/cm3 |
| Boiling Point | 411.4ºC at 760 mmHg |
| Flash Point | 202.6ºC |
| Vapour Pressure | 5.59E-07mmHg at 25°C |
| Index of Refraction | 1.707 |
| LogP | 4.011 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 18 |
| Complexity | 399 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1SSC(N2C(C)C3=C(C=CC=C3)CC2)=C1Cl |
| InChi Key | BEJJGVDFQORITE-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C13H12ClNOS2/c1-8-10-5-3-2-4-9(10)6-7-15(8)12-11(14)13(16)18-17-12/h2-5,8H,6-7H2,1H3 |
| Chemical Name | 4-Chloro-5-(3,4-dihydro-1-methyl-2(1H)-isoquinolinyl)-3H-1,2-dithiol-3-one |
| Synonyms | RP-54745; RP 54745; RP54745 |
| 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 |
| 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
| ln Vitro | LPS-induced interleukin 1 (IL-1) production by mouse peritoneal macrophages is inhibited by RP-54745 [1]. |
| ln Vivo | In various mouse models of induced arthritis, as well as in MRL/lpr mice, which are genetically predisposed to develop autoimmune pathologies including arthritis, RP-54745 (5 mg/kg) is effective at oral dosage modulation. Following three months of treatment with RP-54745, the clinical condition of MRL mice as well as some of its disturbed biochemical and immunological parameters were improved [2]. |
| References |
[1]. RP 54745, a potential antirheumatic compound. I. Inhibitor of macrophage stimulation and interleukin-1 production. Agents Actions. 1992 May;36(1-2):119-26. [2]. RP 54745, a potential antirheumatic compound. II. In vivo properties in different animal models. Agents Actions. 1992 May;36(1-2):127-35. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~62.5 mg/mL (~209.86 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.98 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 (6.98 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 | 3.3577 mL | 16.7887 mL | 33.5773 mL | |
| 5 mM | 0.6715 mL | 3.3577 mL | 6.7155 mL | |
| 10 mM | 0.3358 mL | 1.6789 mL | 3.3577 mL |