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β-Chlornaltrexamine

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Chemical compound

Pharmaceutical compound

β-Chlornaltrexamine
Clinical data

Other names	β-Chlornaltrexamine; Beta-Chlornaltrexamine; β-CNA; Beta-CNA; Chlornaltrexamine; CNA; 6β-[Bis(2-chloroethyl)amino]-17-(cyclopropylmethyl)-4,5α-epoxymorphinan-3,14-diol
Identifiers
IUPAC name (4R,4aS,7R,7aR,12bS)-7-[bis(2-chloroethyl)amino]-3-(cyclopropylmethyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
CAS Number	67025-94-9^Y
PubChemCID	5486190
ChemSpider	4588895^Y
ChEMBL	ChEMBL3228678
CompTox Dashboard(EPA)	DTXSID90985877
Chemical and physical data
Formula	C₂₄H₃₂Cl₂N₂O₃
Molar mass	467.43 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C1C[C@]2([C@H]3CC4=C5[C@@]2(CCN3CC6CC6)[C@H]([C@@H]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
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β-Chlornaltrexamine (β-CNA) is anon-selective irreversible antagonist of theμ-opioid receptor (MOR), theδ-opioid receptor (DOR), and theκ-opioid receptor (KOR), which forms acovalent bond to thebinding sites of thesereceptors and has ultra-long-lastingopioid antagonist effects.^[1] Although it is predominantly antagonistic, β-CNA also shows some irreversiblemixed agonist–antagonist activity at the MOR and KOR and some associatedanalgesic effects.^[2]^[3] Itsalkylating group is a bis(chloroalkyl)amino-residue similar to that of thenitrogen mustards.^[4]^[5]^[6]^[7]

The drug was first described by 1978.^[8]^[9] It should not be confused with itsepimer and related drugα-chlornaltrexamine (α-CNA), which is likewise predominantly an irreversible antagonist of the opioid receptors but also shows some irreversible mixed agonist–antagonist activity.^[10]

References

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^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-[N,N-Bis(2-chloroethyl)amino]-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-[N,N-Bis(2-chloroethyl)amino]-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.