AM-1220: Difference between revisions
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'''AM-1220''' is a drug which acts as a potent and moderately selective [[agonist]] for the [[cannabinoid receptor]] [[Cannabinoid receptor 1|CB<sub>1</sub>]], with around 19x selectivity for CB<sub>1</sub> over the related [[Cannabinoid receptor 2|CB<sub>2</sub>]] receptor.<ref name="WO 2001 28557 A1">{{Ref patent2 | country = WO | number = 200128557 | status = granted | title = Cannabimimetic indole derivatives | pubdate = 2001-04-26 | gdate = 2001-06-07 | pridate= 1999-10-18 | inventor = Makriyannis A, Deng H | assign1= }}</ref> It was originally invented in the early 1990s by a team led by Thomas D'Ambra at [[Sterling Winthrop]],<ref name="US 5068234">{{Ref patent2 | country = US | number = 5068234 | status = granted | title = 3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles | pubdate = | gdate = 1991-11-26 | pridate= 1990-02-26 | inventor = Thomas E. D'Ambra et al | assign1= }}</ref> but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two [[enantiomer]]s with quite different potency, the (R) enantiomer having a [[Dissociation constant|K<sub>i</sub>]] of 0.27nM at CB<sub>1</sub> while the (S) enantiomer has a much weaker K<sub>i</sub> of 217nM.<ref>{{Cite doi|10.1016/0960-894X(95)00560-G}}</ref> A number of related compounds are known with similar potent cannabinoid activity, with modifications such as substitution of the indole ring at the 2- or 6- positions, the naphthoyl ring substituted at the 4- position or replaced by substituted benzoyl rings or other groups, or the 1-(N-methylpiperidin-2-ylmethyl) group replaced by similar heterocyclic groups such as N-methylpyrrolidin-2-ylmethyl or N-methylmorpholin-3-ylmethyl.<ref name=liganDesign>[http://proquest.umi.com/pqdlink?did=726066941&Fmt=7&clientId=79356&RQT=309&VName=PQD Hongfeng Deng. Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs. PhD Dissertation, University of Connecticut, 2000.]</ref><ref>{{Cite doi|10.1021/jm0502743}}</ref><ref name="US 7820144">{{Ref patent2 | country = US | number = 7820144 | status = granted | title = Receptor selective cannabimimetic aminoalkylindoles | pubdate = | gdate = 2010-10-26 | pridate= 2007-01-05 | inventor = Alexandros Makriyannis et al | assign1= }}</ref> |
'''AM-1220''' is a drug which acts as a potent and moderately selective [[agonist]] for the [[cannabinoid receptor]] [[Cannabinoid receptor 1|CB<sub>1</sub>]], with around 19x selectivity for CB<sub>1</sub> over the related [[Cannabinoid receptor 2|CB<sub>2</sub>]] receptor.<ref name="WO 2001 28557 A1">{{Ref patent2 | country = WO | number = 200128557 | status = granted | title = Cannabimimetic indole derivatives | pubdate = 2001-04-26 | gdate = 2001-06-07 | pridate= 1999-10-18 | inventor = Makriyannis A, Deng H | assign1= }}</ref> It was originally invented in the early 1990s by a team led by Thomas D'Ambra at [[Sterling Winthrop]],<ref name="US 5068234">{{Ref patent2 | country = US | number = 5068234 | status = granted | title = 3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles | pubdate = | gdate = 1991-11-26 | pridate= 1990-02-26 | inventor = Thomas E. D'Ambra et al | assign1= }}</ref> but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two [[enantiomer]]s with quite different potency, the (R) enantiomer having a [[Dissociation constant|K<sub>i</sub>]] of 0.27nM at CB<sub>1</sub> while the (S) enantiomer has a much weaker K<sub>i</sub> of 217nM.<ref>{{Cite doi|10.1016/0960-894X(95)00560-G}}</ref> A number of related compounds are known with similar potent cannabinoid activity, with modifications such as substitution of the indole ring at the 2- or 6- positions, the naphthoyl ring substituted at the 4- position or replaced by substituted benzoyl rings or other groups, or the 1-(N-methylpiperidin-2-ylmethyl) group replaced by similar heterocyclic groups such as N-methylpyrrolidin-2-ylmethyl or N-methylmorpholin-3-ylmethyl.<ref name=liganDesign>[http://proquest.umi.com/pqdlink?did=726066941&Fmt=7&clientId=79356&RQT=309&VName=PQD Hongfeng Deng. Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs. PhD Dissertation, University of Connecticut, 2000.]</ref><ref>{{Cite doi|10.1021/jm0502743}}</ref><ref name="US 7820144">{{Ref patent2 | country = US | number = 7820144 | status = granted | title = Receptor selective cannabimimetic aminoalkylindoles | pubdate = | gdate = 2010-10-26 | pridate= 2007-01-05 | inventor = Alexandros Makriyannis et al | assign1= }}</ref> |
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[[Image:AM1220heterocycles.png|240px|thumb|left|1-(N-methylpyrrolidin-2-ylmethyl) and 1-(N-methylmorpholin-3-ylmethyl) derivatives]]{{clear-left}} |
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==See also== |
==See also== |
Revision as of 04:57, 2 July 2011
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Formula | C26H26N2O |
Molar mass | 382.497 g/mol g·mol−1 |
3D model (JSmol) | |
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AM-1220 is a drug which acts as a potent and moderately selective agonist for the cannabinoid receptor CB1, with around 19x selectivity for CB1 over the related CB2 receptor.[1] It was originally invented in the early 1990s by a team led by Thomas D'Ambra at Sterling Winthrop,[2] but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two enantiomers with quite different potency, the (R) enantiomer having a Ki of 0.27nM at CB1 while the (S) enantiomer has a much weaker Ki of 217nM.[3] A number of related compounds are known with similar potent cannabinoid activity, with modifications such as substitution of the indole ring at the 2- or 6- positions, the naphthoyl ring substituted at the 4- position or replaced by substituted benzoyl rings or other groups, or the 1-(N-methylpiperidin-2-ylmethyl) group replaced by similar heterocyclic groups such as N-methylpyrrolidin-2-ylmethyl or N-methylmorpholin-3-ylmethyl.[4][5][6]
See also
References
- ^ WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07
- ^ US patent 5068234, Thomas E. D'Ambra et al, "3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles", granted 1991-11-26
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/0960-894X(95)00560-G, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/0960-894X(95)00560-G
instead. - ^ Hongfeng Deng. Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs. PhD Dissertation, University of Connecticut, 2000.
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1021/jm0502743, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1021/jm0502743
instead. - ^ US patent 7820144, Alexandros Makriyannis et al, "Receptor selective cannabimimetic aminoalkylindoles", granted 2010-10-26