SR 142948 dihydrochloride

• CAT Number: I041435
• Molecular Formula: C39H53Cl2N5O6
• Molecular Weight: 758.77
• Purity: ≥95%
• Synonyms: 2-[[5-(2,6-dimethoxyphenyl)-1-[4-[3-(dimethylamino)propyl-methylcarbamoyl]-2-propan-2-ylphenyl]pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid;dihydrochloride
• InChI: InChI=1S/C39H51N5O6.2ClH/c1-23(2)29-21-26(37(46)43(5)15-9-14-42(3)4)12-13-31(29)44-32(35-33(49-6)10-8-11-34(35)50-7)22-30(41-44)36(45)40-39(38(47)48)27-17-24-16-25(19-27)20-28(39)18-24;;/h8,10-13,21-25,27-28H,9,14-20H2,1-7H3,(H,40,45)(H,47,48);2*1H
• InChIKey: AQJKZKHTPLUIAD-UHFFFAOYSA-N
• SMILES: CC(C)C1=C(C=CC(=C1)C(=O)N(C)CCCN(C)C)N2C(=CC(=N2)C(=O)NC3(C4CC5CC(C4)CC3C5)C(=O)O)C6=C(C=CC=C6OC)OC.Cl.Cl

SR 142948 dihydrochloride is an orally active and selective non-peptide neurotensin receptor (NT) antagonist with IC50s of 1.19 nM, 0.32 nM, 3.96 nM in h-NTR1-CHO cells, HT-29 cells, and adult rat brain, respectively. SR 142948 dihydrochloride antagonizes NT-induced inositol monophosphate formation in HT-29 cells with an IC50 of 3.9 nM. SR 142948 dihydrochloride blocks hypothermia, analgesia and steering behavior induced by NT in vivo. SR 142948 dihydrochloride shows blood-brain permeability and can be used in study of psychiatric disorders[1][2].
SR 142948 (1 µM; 90 min) dihydrochloride inhibits expression of c-fos and krox24 in CHO-hNT1-R cells[1].
SR 142948 (0-1 µM; 1 h) dihydrochloride exhibits good antagonistic activity by inhibiting [125I-Tyr3]NT binds to h-NTR1-CHO and HT 29 cell membranes, with IC50s of 1.19 and 0.32 nM, respectively[2].
SR 142948 (0-1 µM; 30 min) dihydrochloride antagonizes production of IP1 stimulated by NT both in h-NTR1-CHO and HT 29 cells, in a concentration-dependent manner[2].
SR 142948 (1, 10 nM; 60-80 s) dihydrochloride antagonizes intracellular calcium mobilization stimulated by NT in h-NTR1-CHO cells[2].
SR 142948 (2 µg/kg; p.o.; single) dihydrochloride inhibits the turning behavior induced by NT (10 pg/mouse)[2].
SR 142948 (0.01, 0.03, 0.3 mg/kg; i.p.; single) dihydrochloride prevents the enhancement of ACh release produced by NT (100 nM), in a dose-dependent manner[2].
SR 142948 (0-10 mg/kg; p.o.; single) dihydrochloride partially but significantly blocks NT-induced hypothermia (53% at 2 mg/kg in rats and 54% at 4 mg/kg in mice)[2].

Reference

[1]. M Portier, et al. neurotensin antagonists SR Neurotensin type 1 receptor-mediated activation of krox24, c-fos and Elk-1: preventing effect of the 48692 and SR 142948. FEBS Lett. 1998 Jul 31;432(1-2):88-93.
 [Content Brief]

[2]. D Gully, et al. Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist. J Pharmacol Exp Ther. 1997 Feb;280(2):802-12.
 [Content Brief]