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{{Short description|Chemical compound}} |
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{{DISPLAYTITLE:β-Chlornaltrexamine}} |
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| verifiedrevid = 409723733 |
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{{Infobox drug |
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|ImageFile=Chlornaltrexamine.svg |
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| Verifiedfields = verified |
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|ImageSize=200px |
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| Watchedfields = verified |
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|IUPACName= 6-(Bis(2-chloroethyl)amino)- 17-(cyclopropylmethyl)- 4,5-epoxy- (5-α,6-β)- morphinan- 3,14-diol |
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| verifiedrevid = 434800318 |
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|OtherNames=α-chlornaltrexamine |
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| drug_name = β-Chlornaltrexamine |
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|Section1={{Chembox Identifiers |
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| image = Chlornaltrexamine.svg |
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| CASNo=67025-94-9 |
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| width = 250px |
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| PubChem=5486190 |
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| caption = |
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| SMILES=O132(5(N(CCCl)CCCl)CC3)C4=C(C=CC(O)=C4O5)C1N(CC6CC6)CC2 |
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}} |
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<!-- Clinical data --> |
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|Section2={{Chembox Properties |
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| pronounce = |
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| Formula=C<sub>24</sub>H<sub>32</sub>Cl<sub>2</sub>N<sub>2</sub>O<sub>3</sub> |
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| MolarMass=467.43 g/mol |
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|Section3={{Chembox Hazards |
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<!-- Legal status --> |
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<!-- Pharmacokinetic data --> |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = 67025-94-9 |
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| CAS_supplemental = |
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| PubChem = 5486190 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 4588895 |
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| ChEMBL = 3228678 |
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| NIAID_ChemDB = |
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| synonyms = β-Chlornaltrexamine; Beta-Chlornaltrexamine; β-CNA; Beta-CNA; Chlornaltrexamine; CNA; 6β--17-(cyclopropylmethyl)-4,5α-epoxymorphinan-3,14-diol |
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<!-- Chemical data --> |
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| 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 |
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| C=24 | H=32 | Cl=2 | N=2 | O=3 |
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| SMILES = C1C2(3CC4=C52(CCN3CC6CC6)(1N(CCCl)CCCl)OC5=C(C=C4)O)O |
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| StdInChI = 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 |
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| StdInChIKey = OSLQQDMGHVQLCH-HRMPSQMFSA-N |
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}} |
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'''β-Chlornaltrexamine''' ('''β-CNA''') is a ] ] of the ] (MOR), the ] (DOR), and the ] (KOR), which forms a ] to the ]s of these ]s and has ultra-long-lasting ] effects.<ref name="WardPortogheseTakemori1982">{{cite journal | vauthors = Ward SJ, Portoghese PS, Takemori AE | title = Pharmacological profiles of beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) on the mouse vas deferens preparation | journal = Eur J Pharmacol | volume = 80 | issue = 4 | pages = 377–384 | date = June 1982 | pmid = 6286325 | doi = 10.1016/0014-2999(82)90083-8 | url = }}</ref> Although it is predominantly antagonistic, β-CNA also shows some irreversible ] activity at the MOR and KOR and some associated ] effects.<ref name="LeffDougall1988">{{cite journal | vauthors = Leff P, Dougall IG | title = Estimation of opioid receptor agonist dissociation constants with beta-chlornaltrexamine, an irreversible ligand which also displays agonism | journal = Br J Pharmacol | volume = 95 | issue = 1 | pages = 234–240 | date = September 1988 | pmid = 2851350 | pmc = 1854139 | doi = 10.1111/j.1476-5381.1988.tb16569.x | url = }}</ref><ref name="BroadbearSumpterBurke2000">{{cite journal | vauthors = Broadbear JH, Sumpter TL, Burke TF, Husbands SM, Lewis JW, Woods JH, Traynor JR | title = Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine | journal = J Pharmacol Exp Ther | volume = 294 | issue = 3 | pages = 933–940 | date = September 2000 | pmid = 10945843 | doi = | url = }}</ref> Its ] ] is a bis(chloroalkyl)amino-residue similar to that of the ]s.<ref>{{cite journal |doi=10.1021/jm00205a002 |vauthors=], Larson DL, Jiang JB, Takemori AE, Caruso TP |title=6β--17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan(chlornaltrexamine) a potent opioid receptor alkylating agent with ultralong narcotic antagonist activity |journal=J. Med. Chem. |volume=21 |issue=7 |pages=598–9 |date=July 1978 |pmid=209185 }}</ref><ref>{{cite journal |doi=10.1021/jm00188a008 |vauthors=Portoghese PS, Larson DL, Jiang JB, Caruso TP, Takemori AE |title=Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties |journal=J. Med. Chem. |volume=22 |issue=2 |pages=168–73 |date=February 1979 |pmid=218009 }}</ref><ref>{{cite journal |vauthors=Caruso TP, Larson DL, Portoghese PS, Takemori AE |title=Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, and antagonist, chlornaltrexamine |journal=J. Pharmacol. Exp. Ther. |volume=213 |issue=3 |pages=539–44 |date=June 1980 |pmid=6162947 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6162947}}</ref><ref>{{cite journal |doi=10.1016/0024-3205(80)90485-3 |vauthors=Caruso TP, Larson DL, Portoghese PS, Takemori AE |title=Isolation of selective 3H-chlornaltrexamine-bound complexes, possible opioid receptor components in brains of mice |journal=Life Sci. |volume=27 |issue=22 |pages=2063–9 |date=December 1980 |pmid=6259471 }}</ref> |
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'''Chlornaltrexamine''' is an irreversible mixed agonist-antagonist for ]] ], which forms a ] to the ]. It is 22 times more potent than morphine. Its alkylating group is a bis(chloroalkyl)amino-residue similar to that of the ]s.<ref>{{cite journal |doi=10.1021/jm00205a002 |author=Portoghese PS, Larson DL, Jiang JB, Takemori AE, Caruso TP |title=6β--17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan(chlornaltrexamine) a potent opioid receptor alkylating agent with ultralong narcotic antagonist actitivty |journal=J. Med. Chem. |volume=21 |issue=7 |pages=598–9 |year=1978 |month=July |pmid=209185 }}</ref> |
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<ref>{{cite journal |doi=10.1021/jm00188a008 |author=Portoghese PS, Larson DL, Jiang JB, Caruso TP, Takemori AE |title=Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties |journal=J. Med. Chem. |volume=22 |issue=2 |pages=168–73 |year=1979 |month=February |pmid=218009 }}</ref> |
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The drug was first described by 1978.<ref name="PortogheseLarsonJiang1978">{{cite journal | vauthors = Portoghese PS, Larson DL, Jiang JB, Takemori AE, Caruso TP | title = 6beta--17-(cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxymorphinan(chlornaltrexamine) a potent opioid receptor alkylating agent with ultralong narcotic antagonist actitivty | journal = J Med Chem | volume = 21 | issue = 7 | pages = 598–599 | date = July 1978 | pmid = 209185 | doi = 10.1021/jm00205a002 | url = }}</ref><ref name="PortogheseLarsonJiang1979">{{cite journal | vauthors = Portoghese PS, Larson DL, Jiang JB, Caruso TP, Takemori AE | title = Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties | journal = J Med Chem | volume = 22 | issue = 2 | pages = 168–173 | date = February 1979 | pmid = 218009 | doi = 10.1021/jm00188a008 | url = }}</ref> It should not be confused with its ] and related drug ] (α-CNA), which is likewise predominantly an irreversible antagonist of the opioid receptors but also shows some irreversible mixed agonist–antagonist activity.<ref name="SayreTakemoriPortoghese1983">{{cite journal | vauthors = Sayre LM, Takemori AE, Portoghese PS | title = Alkylation of opioid receptor subtypes by alpha-chlornaltrexamine produces concurrent irreversible agonistic and irreversible antagonistic activities | journal = J Med Chem | volume = 26 | issue = 4 | pages = 503–506 | date = April 1983 | pmid = 6300401 | doi = 10.1021/jm00358a009 | url = }}</ref> |
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<ref>{{cite journal |doi=10.1126/science.86208 |author=Caruso TP, Takemori AE, Larson DL, Portoghese PS |title=Chloroxymorphamine, and opioid receptor site-directed alkylating agent having narcotic agonist activity |journal=Science |volume=204 |issue=4390 |pages=316–8 |year=1979 |month=April |pmid=86208 |url=http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=86208}}</ref> |
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<ref>{{cite journal |author=Caruso TP, Larson DL, Portoghese PS, Takemori AE |title=Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, and antagonist, chlornaltrexamine |journal=J. Pharmacol. Exp. Ther. |volume=213 |issue=3 |pages=539–44 |year=1980 |month=June |pmid=6162947 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6162947}}</ref> |
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<ref>{{cite journal |doi=10.1016/0024-3205(80)90485-3 |author=Caruso TP, Larson DL, Portoghese PS, Takemori AE |title=Isolation of selective 3H-chlornaltrexamine-bound complexes, possible opioid receptor components in brains of mice |journal=Life Sci. |volume=27 |issue=22 |pages=2063–9 |year=1980 |month=December |pmid=6259471 }}</ref><ref>{{cite journal | journal =J. Med. Chem. | year = 1983 | volume = 26 | title =Alkylation of opioid receptor subtypes by α-chlornaltrexamine produces concurrent irreversible agonistic and irreversible antagonistic activities. | pmid =6300401 | issue = 4 | pages = 503 | doi = 10.1021/jm00358a009 | author = Sayre LM, Takemori AE, Portoghese PS}}</ref> |
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==See also== |
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==See also== |
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* ], an opioid receptor antagonist and the parent compound |
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* ], an irreversible full agonist |
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* ], an irreversible μ-] |
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* ], a related irreversible opioid receptor antagonist |
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* ], an irreversible full agonist |
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* ], an irreversible μ-opioid receptor antagonist |
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* ], an irreversible μ-opioid receptor antagonist |
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* ], an irreversible opioid receptor agonist |
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* ], an irreversible opioid receptor agonist |
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==References== |
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==References== |
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{{reflist}} |
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{{Opioid receptor modulators}} |
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{{analgesic-stub}} |
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{{Nervous-system-drug-stub}} |