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Revision as of 12:11, 26 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'StdInChI', 'StdInChIKey', 'ChEBI', 'CASNo').← Previous edit Latest revision as of 11:24, 5 January 2025 edit undoPikachu.447 (talk | contribs)57 editsNo edit summaryTags: Mobile edit Mobile app edit Android app edit 
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{{Short description|Parent compound of opiates/opioids}}
{{Distinguish | 3-Methoxymorphinan}}
{{Chembox {{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 457473358
| ImageFile = Morphinan.svg | ImageFile = Morphinan.svg
| ImageSize = 170
| ImageName = Stereo structural formula of (1''R'',9''R'',10''R'')morphinan
| ImageName = Structural formula of morphinan
| PIN = Morphinan
| ImageFile1 = Morphinan molecule ball.png
| SystematicName = 17-Azatetracycloheptadeca-2(7),3,5-triene
| ImageSize1 = 180
| OtherNames = 1,2,3,9,10,10a-Hexahydro-10,4a(4''H'')-iminoethanophenanthrene
| ImageName1 = Ball-and-stick model of morphinan
| Section1 = {{Chembox Identifiers
| IUPACName = Morphinan<ref>{{cite book |author=] |date=2014 |title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 |publisher=] |pages=1522 |doi=10.1039/9781849733069 |isbn=978-0-85404-182-4}}</ref>
| CASNo = <!-- blanked - oldvalue: 468-10-0 -->
| SystematicName = (4a''R'',10''R'',10a''R'')-1,3,4,9,10,10a-Hexahydro-2''H''-10,4a-(azanoethano)phenanthrene
| PubChem1 = 614838
|Section1={{Chembox Identifiers
| PubChem1_Ref = {{Pubchemcite|correct|StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| CASNo_Ref = {{cascite|correct|CAS}}
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| CASNo = 468-10-0
| PubChem}}
| UNII_Ref = {{fdacite|correct|FDA}}
| StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| UNII = O97T9O1050
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| PubChem = 11947744 | PubChem = 11947744
| ChemSpiderID = 5256833
| PubChem_Comment = (1''R'',9''R'',10''R'')
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| PubChem_Ref = {{Pubchemcite|correct|StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| ChEBI_Ref = {{ebicite|changed|EBI}}
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| ChEBI = 35649
| PubChem}}
| SMILES = c12c(cccc1)C3NCC243CCCC4
| PubChem2 = 21176124
| InChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| PubChem2_Comment = (1''S'',9''R'',10''R'')
| InChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| PubChem2_Ref = {{Pubchemcite|correct|StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| Beilstein = 1375527
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
}}
| PubChem}}
|Section2={{Chembox Properties
| PubChem3 = 6857497
| C=16 | H=21 | N=1
| PubChem3_Comment = (1''S'',9''S'',10''R'')
| Appearance =
| PubChem3_Ref = {{Pubchemcite|correct|StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| Density = 1.58 g/cm<sup>3</sup>
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| MeltingPt =
| PubChem}}
| BoilingPt = 115±0.05&nbsp;°C (liquid oil)
| PubChem4 = 18350845
| Solubility =
| PubChem4_Comment = (hydrochloride)
| PubChem4_Ref = {{Pubchemcite|correct|StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| PubChem}}
| PubChem5 = 20678913
| PubChem5_Comment = (1''S'',9''S'',10''R''),(hydrochloride)
| PubChem5_Ref = {{Pubchemcite|correct|StdInChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2/t14-,15-,16+/m0/s1
| StdInChIKey = INAXVFBXDYWQFN-HRCADAONSA-N
| PubChem}}
| ChemSpiderID1 = 534418
| ChemSpiderID1_Ref = {{Chemspidercite|correct|ChemSpider}}
| ChemSpiderID = 5256833
| ChemSpiderID_Comment = (1''R'',9''R'',10''R'')
| ChemSpiderID_Ref = {{Chemspidercite|correct|ChemSpider}}
| ChemSpiderID2 = 10122060
| ChemSpiderID2_Comment = (1''S'',9''R'',10''R'')
| ChemSpiderID2_Ref = {{Chemspidercite|correct|ChemSpider}}
| ChEBI = <!-- blanked - oldvalue: 35649 -->
| SMILES = C1CCC23CCNC(CC4=C2C=CC=C4)C3C1
| InChI = 1S/C16H21N/c1-2-6-13-12(5-1)11-15-14-7-3-4-8-16(13,14)9-10-17-15/h1-2,5-6,14-15,17H,3-4,7-11H2
| InChIKey = INAXVFBXDYWQFN-UHFFFAOYSA-N
| Beilstein = 1375527}}
| Section2 = {{Chembox Properties
| Formula = C<sub>16</sub>H<sub>21</sub>N
| MolarMass = 227.34 g/mol
| Appearance =
| Density = 1.58 g/cm<sup>3</sup>
| MeltingPt =
| BoilingPt = 115±0.05°C (liquid oil)
| Solubility =
}} }}
| Section3 = {{Chembox Hazards |Section3={{Chembox Hazards
| MainHazards = | MainHazards =
| FlashPt = | FlashPt =
| Autoignition = | AutoignitionPt =
}} }}
}} }}
'''Morphinan''' is the prototype ] of a large ] of ]s, consisting of ] ]s, ]s, and ] ]s, among others. Typical examples include compounds such as ], ], and ] (DXM). Despite related molecular structures, the pharmacological profiles and ] between the various types of morphinan substances can vary substantially. They tend to function either as ] ] (analgesics), or ]s (dissociatives).<ref>{{cite book |doi=10.1002/14356007.a13_227.pub3 |chapter=Hydrocarbons |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2014 |last1=Schmidt |first1=Roland |last2=Griesbaum |first2=Karl |last3=Behr |first3=Arno |last4=Biedenkapp |first4=Dieter |last5=Voges |first5=Heinz-Werner |last6=Garbe |first6=Dorothea |last7=Paetz |first7=Christian |last8=Collin |first8=Gerd |last9=Mayer |first9=Dieter |last10=Höke |first10=Hartmut |pages=1–74 |isbn=978-3-527-30673-2 }}</ref>


== Structure ==
'''Morphinan''' is the base ] of a large ] of ]s, consisting of ] ]s, ]s, and ] ]s, among others.
Morphinan has a ] core structure with the ''A'' ring remaining aromatic and the ''B'' and ''C'' rings being saturated, and an additional nitrogen-containing, six-membered, saturated ring, the ''D'' ring, being attached to carbons 9 and 13 of the core, and with the nitrogen being at position 17 of the composite.


Of the major naturally occurring opiates of the morphinan type—], ] and ]—thebaine has no therapeutic properties (it causes seizures in mammals), but it provides a low-cost feedstock for the industrial production of at least four semi-synthetic opiate agonists, including ], ], ] and ], and the opioid antagonist ].
== Chemical Derivatives ==


== Structure-activity relationship ==
The physiological behavior of morphinans (naturally occurring and semi-synthetic derivatives) is thought to be associated with the aromatic ''A'' ring, the nitrogen-containing ''D'' ring and the "bridge" between these two rings formed by carbons 9, 10 and 11 of the core, with the ''D'' ring "above" the core (]).

Small groups are usually found on morphinan derivatives at carbons 3 and 6.

Many such derivatives have an epoxy group between carbons 4 and 5 (i.e., 4,5α-epoxy), thereby forming an ''E'' ring.

The substitution of certain bulky groups on nitrogen 17 converts an opioid agonist into an opioid antagonist, the most important of which is ], a non-selective opioid ] with no opioid ] properties whatsoever (]). Additionally, substitution of certain very bulky groups on carbon 6 converts naloxone into a peripherally-selective opioid antagonist with no centrally-selective antagonist properties (]).

The addition of a two-carbon bridge between carbons 6 and 14 (e.g., 6,14-ethano, or 6,14-etheno), and which significantly distorts the ''C'' ring, may increase potency 1,000 to 10,000 times, or greater, compared to morphine, as in ], and others. The relative potency is thought to be associated with the degree of distortion of the ''C'' ring, and is perhaps greatest in ], where this group is α,α-dimethyl-6,14-etheno. <em>Diprenorphine</em> (M5050) is the recommended <em>etorphine</em> (M99) antagonist, but it is not a pure opioid antagonist (i.e., it is also a weak opioid agonist), so naloxone remains a significant therapeutic tool in suspected cases of opioid overdose. See also ].

If the ''D'' ring is "below" the core (]), the analgesic and euphoric properties are eliminated or are dramatically reduced, but the cough-suppressant property is retained, as in ].

== Chemical derivatives ==
Immediate derivatives of morphinan include: Immediate derivatives of morphinan include:


* ]
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* ]
* ]
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* ] * ]
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More distant of derivatives include: More distant derivatives include:
* ]

* ] * ]
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As well as the following: As well as the following:


* ] (and analogues) * ] (and naturally occurring and semi-synthetic analogues)
[[File:Benzylisoquinoline structure in Morphine.svg|thumb|180px|Chemical structure of morphine, (5α,6α)-7,8-Didehydro-
4,5-epoxy-17-methyl'''morphinan'''-3,6-diol, perhaps the most important naturally occurring substance of the morphinan type.]]


* ]
== Chemical Relatives ==
]


* ]
The following are related to morphinan:
-4,5-epoxy'''morphinan'''-3,14-diol.]]


== Chemical relatives ==
The following structures are related to morphinan:
* ]
* ] * ]
* ] * ]


== References == == References ==
* Brunton L L, Blumenthal D K, Murri N, Dandan R H, Knollmann B C. '']''. 12th ed. New York: McGraw-Hill, 2011. {{ISBN|978-0-07-162442-8}}.
{{Reflist}}
{{Reflist|2}}

{{Analgesics}}
{{Anesthetics}}
{{Antitussants}}
{{Hallucinogens}}
{{Opioids}}


] ]
] ]

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