| Identification | Back Directory | [Name]
NDT 9513727 | [CAS]
439571-48-9 | [Synonyms]
NDT 9513727
N,N-Bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-Imidazole-5-methanamine | [Molecular Formula]
C36H35N3O4 | [MDL Number]
MFCD22683794 | [MOL File]
439571-48-9.mol | [Molecular Weight]
573.68 |
| Chemical Properties | Back Directory | [Boiling point ]
723.1±62.0 °C(Predicted) | [density ]
1.23±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 100 mM; Ethanol: 100 mM | [form ]
A solid | [pka]
6.69±0.50(Predicted) | [color ]
White to yellow | [InChIKey]
ITACCRHKSPSKKL-UHFFFAOYSA-N | [SMILES]
CCCCN1C(CN(CC2=CC=C3OCOC3=C2)CC4=CC5=C(C=C4)OCO5)=C(N=C1C6=CC=CC=C6)C7=CC=CC=C7 |
| Hazard Information | Back Directory | [Description]
NDT 9513727 is a competitive antagonist of the C5a receptor (C5aR; IC50 = 11.6 nM for human recombinant receptors) that has inverse agonist activity in a GTPγ[35S] assay. It is selective for human recombinant over rat and mouse recombinant C5aRs (IC50 = >10 μM for both) but does have activity at macaque and gerbil receptors (IC50s = 7.3 and 6.4 nM, respectively). NDT 9513727 inhibits degranulation in U937 cells stimulated with C5a (IC50 = 7.1 nM). It also prevents neutropenia induced by human recombinant C5a in gerbils (ED50 = 2.2 mg/kg) and in cynomolgus macaques when administered at doses of 5 and 25 mg/kg. | [Uses]
NDT 9513727 is a selective, and potent inverse agonist of the human C5aR. NDT 9513727 has been shown to effectively inhibit C5a-induced neutropenia in gerbil and cynomolgus macaque in vivo. These results suggest that NDT 9513727 is a promising candidate for the treatment of human inflammatory diseases. | [in vivo]
NDT 9513727 (3-30 mg/kg; p.o.) exhibits a dose-dependent inhibition of hC5a-induced neutropenia[1].
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NDT 9513727 exhibits moderate oral bioavailability (rat 73%, monkey 26%) and Cmax (rat 5.98 μM, monkey 830 nM) following oral administration (rat 50, monkey 25.2 mg/kg)[1].
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NDT 9513727 exhibits moderate plasma elimination half-lives (rat 4.8, monkey 7.9 h) due to low plasma clearance (1.4 L/h/kg and 3.8 L/h/kg respectively) following oral administration (rat 50, monkey 25.2 mg/kg)[1].
| Animal Model: | Six-week-old Mongolian gerbils[1] | | Dosage: | 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg | | Administration: | Oral administration | | Result: | Significantly inhibited hC5a-induced neutropenia at 3 mg/kg, 10 mg/kg, 30 mg/kg. |
| Animal Model: | Rat[1] | | Dosage: | 50 mg/kg (Pharmacokinetic Analysis) | | Administration: | Oral administration | | Result: | Oral bioavailability (73%), Cmax (5.98 μM), T1/2 (4.8 h). |
| Animal Model: | Monkey[1] | | Dosage: | 25.2 mg/kg (Pharmacokinetic Analysis) | | Administration: | Oral administration | | Result: | Oral bioavailability (26%), Cmax (830 nM), T1/2 (7.9 h). |
| [storage]
Store at +4°C | [References]
[1] NATHAN ROBERTSON. Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727[J]. Nature, 2018, 553 7686: 111-114. DOI: 10.1038/nature25025
[2] ROBBIN M BRODBECK. Identification and characterization of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a novel, orally bioavailable C5a receptor inverse agonist.[J]. Journal of Pharmacology and Experimental Therapeutics, 2008, 327 3: 898-909. DOI: 10.1124/jpet.108.141572 |
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