Physicochemical Properties
| Molecular Formula | C25H26CL2N4O3S |
| Molecular Weight | 533.469942569733 |
| Exact Mass | 532.11 |
| CAS # | 2411440-41-8 |
| Related CAS # | 2417323-15-8 (TFA);2411440-41-8; |
| PubChem CID | 145996525 |
| Appearance | White to light yellow solid powder |
| LogP | 5 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 35 |
| Complexity | 716 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | ClC1C=CC(=CC=1)C(C1C=CC(=CC=1)Cl)C1=CC(C)=C(C(N[C@H](C(=O)O)CCC/N=C(\N)/N)=O)S1 |
| InChi Key | OHRIKWUZKGNQKQ-IBGZPJMESA-N |
| InChi Code | InChI=1S/C25H26Cl2N4O3S/c1-14-13-20(21(15-4-8-17(26)9-5-15)16-6-10-18(27)11-7-16)35-22(14)23(32)31-19(24(33)34)3-2-12-30-25(28)29/h4-11,13,19,21H,2-3,12H2,1H3,(H,31,32)(H,33,34)(H4,28,29,30)/t19-/m0/s1 |
| Chemical Name | (2S)-2-[[5-[bis(4-chlorophenyl)methyl]-3-methylthiophene-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid |
| 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 | JR14a cells, whose IC50 ranges from 0.1 nM to 100 μM, have been shown to block C3a-induced internal Ca2+ release in human monocyte-derived macrophages[1]. An IC50 of 8 nM is observed in human LAD2 mast cells exposed to intravenous injection of JR14a (0.1 nM-100 μM) to inhibit C3a β-hexosaminidase [1]. |
| ln Vivo | JR14a (10 mg/kg; po 2 h before) induced 65% more paw swelling than controls 30 minutes after hemostatic injection in an acute state paw model of edema and edema [1]. JR14a (1 mg/kg; iv) exhibited elimination half-life (191 minutes), clearance (4.4 mL/min/kg), and AUC (3795 ng·h/mL) at shelf [1]. JR14a (10 mg/kg; po) exhibited Cmax (88 ng/mL), Tmax (300 min), and AUC (478 ng h/mL) at shelf [1]. |
| Animal Protocol |
Animal/Disease Models: Male Wister rats (8 weeks, 250-300 g) were injected with BR103[1]. Doses: 10 mg/kg Route of Administration: Oral 2 hrs (hrs (hours)) before agonist challenge Experimental Results: Inhibits C3aR-mediated inflammation. Animal/Disease Models: Male Wister rat (8 weeks, 250-300 g) [1] Doses: 1 mg/kg, intravenous (iv) (iv)injection; oral 10 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)administration and oral administration Dosing Experimental Results: IV: t1/2=191 min, clearance=4.4 mL/min/kg, AUC=3795 ng·h/mL. Po: Cmax=88 ng/mL, Tmax=300 minutes, AUC=478 ng·h/mL. |
| References |
[1]. Potent Thiophene Antagonists of Human Complement C3a Receptor with Anti-Inflammatory Activity. J Med Chem. 2020 Jan 23;63(2):529-541. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~187.45 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.69 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 25.0 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: ≥ 2.5 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (4.69 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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 | 1.8745 mL | 9.3726 mL | 18.7452 mL | |
| 5 mM | 0.3749 mL | 1.8745 mL | 3.7490 mL | |
| 10 mM | 0.1875 mL | 0.9373 mL | 1.8745 mL |