β-Chlornaltrexamine - Misplaced Pages

(Redirected from B-CNA) Chemical compound Pharmaceutical compound

β-Chlornaltrexamine
Clinical data

Other names	β-Chlornaltrexamine; Beta-Chlornaltrexamine; β-CNA; Beta-CNA; Chlornaltrexamine; CNA; 6β--17-(cyclopropylmethyl)-4,5α-epoxymorphinan-3,14-diol
Identifiers
IUPAC name (4R,4aS,7R,7aR,12bS)-7--3-(cyclopropylmethyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuroisoquinoline-4a,9-diol
CAS Number	67025-94-9
PubChem CID	5486190
ChemSpider	4588895
ChEMBL	ChEMBL3228678
CompTox Dashboard (EPA)	DTXSID90985877
Chemical and physical data
Formula	C₂₄H₃₂Cl₂N₂O₃
Molar mass	467.43 g·mol
3D model (JSmol)	Interactive image
SMILES C1C2(3CC4=C52(CCN3CC6CC6)(1N(CCCl)CCCl)OC5=C(C=C4)O)O
InChI InChI=1S/C24H32Cl2N2O3/c25-8-11-27(12-9-26)17-5-6-24(30)19-13-16-3-4-18(29)21-20(16)23(24,22(17)31-21)7-10-28(19)14-15-1-2-15/h3-4,15,17,19,22,29-30H,1-2,5-14H2/t17-,19-,22+,23+,24-/m1/s1 Key:OSLQQDMGHVQLCH-HRMPSQMFSA-N
(verify)

β-Chlornaltrexamine (β-CNA) is a non-selective irreversible antagonist of the μ-opioid receptor (MOR), the δ-opioid receptor (DOR), and the κ-opioid receptor (KOR), which forms a covalent bond to the binding sites of these receptors and has ultra-long-lasting opioid antagonist effects. Although it is predominantly antagonistic, β-CNA also shows some irreversible mixed agonist–antagonist activity at the MOR and KOR and some associated analgesic effects. Its alkylating group is a bis(chloroalkyl)amino-residue similar to that of the nitrogen mustards.

The drug was first described by 1978. It should not be confused with its epimer and related drug α-chlornaltrexamine (α-CNA), which is likewise predominantly an irreversible antagonist of the opioid receptors but also shows some irreversible mixed agonist–antagonist activity.

References

Ward SJ, Portoghese PS, Takemori AE (June 1982). "Pharmacological profiles of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) on the mouse vas deferens preparation". Eur J Pharmacol. 80 (4): 377–384. doi:10.1016/0014-2999(82)90083-8. PMID 6286325.
Leff P, Dougall IG (September 1988). "Estimation of opioid receptor agonist dissociation constants with beta-chlornaltrexamine, an irreversible ligand which also displays agonism". Br J Pharmacol. 95 (1): 234–240. doi:10.1111/j.1476-5381.1988.tb16569.x. PMC 1854139. PMID 2851350.
Broadbear JH, Sumpter TL, Burke TF, Husbands SM, Lewis JW, Woods JH, Traynor JR (September 2000). "Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine". J Pharmacol Exp Ther. 294 (3): 933–940. PMID 10945843.
Portoghese PS, Larson DL, Jiang JB, Takemori AE, Caruso TP (July 1978). "6β--17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan(chlornaltrexamine) a potent opioid receptor alkylating agent with ultralong narcotic antagonist activity". J. Med. Chem. 21 (7): 598–9. doi:10.1021/jm00205a002. PMID 209185.
Portoghese PS, Larson DL, Jiang JB, Caruso TP, Takemori AE (February 1979). "Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties". J. Med. Chem. 22 (2): 168–73. doi:10.1021/jm00188a008. PMID 218009.
Caruso TP, Larson DL, Portoghese PS, Takemori AE (June 1980). "Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, and antagonist, chlornaltrexamine". J. Pharmacol. Exp. Ther. 213 (3): 539–44. PMID 6162947.
Caruso TP, Larson DL, Portoghese PS, Takemori AE (December 1980). "Isolation of selective 3H-chlornaltrexamine-bound complexes, possible opioid receptor components in brains of mice". Life Sci. 27 (22): 2063–9. doi:10.1016/0024-3205(80)90485-3. PMID 6259471.
Portoghese PS, Larson DL, Jiang JB, Takemori AE, Caruso TP (July 1978). "6beta--17-(cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxymorphinan(chlornaltrexamine) a potent opioid receptor alkylating agent with ultralong narcotic antagonist actitivty". J Med Chem. 21 (7): 598–599. doi:10.1021/jm00205a002. PMID 209185.
Portoghese PS, Larson DL, Jiang JB, Caruso TP, Takemori AE (February 1979). "Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties". J Med Chem. 22 (2): 168–173. doi:10.1021/jm00188a008. PMID 218009.
Sayre LM, Takemori AE, Portoghese PS (April 1983). "Alkylation of opioid receptor subtypes by alpha-chlornaltrexamine produces concurrent irreversible agonistic and irreversible antagonistic activities". J Med Chem. 26 (4): 503–506. doi:10.1021/jm00358a009. PMID 6300401.