Jump to content

Pozanicline: Difference between revisions

Page 1
Page 2
Content deleted Content added
BogBot (talk | contribs)
populated new fields in {{drugbox}} and reordered per bot approval. Report errors and suggestions to User_talk:BogBot
Oro Temp (talk | contribs)
m Removed "Making it an exciting compound". Wikipedia articles should not be suggestive.
 
(47 intermediate revisions by 28 users not shown)
Line 1: Line 1:
{{Short description|Synthetic nootropic drug}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 443472515
| Watchedfields = changed
| IUPAC_name = 2-methyl-3-([(2S)-pyrrolidin-2-yl]methoxy)pyridine
| verifiedrevid = 448113772
| image = ABT-089.png
| IUPAC_name = 2-Methyl-3-<nowiki/>{[(2''S'')-pyrrolidin-2-yl]methoxy}pyridine
| width = 240
| image = Pozanicline.svg
| width = 175


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| routes_of_administration =
| routes_of_administration =


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 161417-03-4
| CAS_number = 161417-03-4
| ATC_suffix =
| ATC_suffix = None
| PubChem = 178052
| PubChem = 178052
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = CL2002R563
| UNII = CL2002R563
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 155000


<!--Chemical data-->
<!--Chemical data-->
| C=11 | H=16 | N=2 | O=1
| C=11 | H=16 | N=2 | O=1
| molecular_weight = 192.258
| smiles = CC1=C(C=CC=N1)OC[C@@H]2CCCN2
| smiles = CC1=C(C=CC=N1)OC[C@@H]2CCCN2
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C11H16N2O/c1-9-11(5-3-6-12-9)14-8-10-4-2-7-13-10/h3,5-6,10,13H,2,4,7-8H2,1H3/t10-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = YRVIKLBSVVNSHF-JTQLQIEISA-N
}}
}}


'''Pozanicline''' ('''ABT-089''') is a drug developed by [[Abbott Laboratories|Abbott]], which acts as a [[partial agonist]] at neural [[nicotinic acetylcholine receptor]]s. It is subtype-selective, binding primarily to the [[Alpha-4 beta-2 nicotinic receptor|α4β2]] and also α6β2 [[nicotinic acetylcholine receptor#Subunits|subtypes]].<ref name="pmid19481067">{{cite journal |author=Marks MJ, Wageman CR, Grady SR, Gopalakrishnan M, Briggs CA |title=Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain |journal=Biochemical Pharmacology |volume= 78|issue= 7|pages= 795–802|year=2009 |month=May |pmid=19481067 |doi=10.1016/j.bcp.2009.05.022 |url= |pmc=2772152}}</ref><ref name="pmid19555668">{{cite journal |author=Anderson DJ, Malysz J, Grønlien JH, El Kouhen R, Håkerud M, Wetterstrand C, Briggs CA, Gopalakrishnan M |title=Stimulation of dopamine release by nicotinic acetylcholine receptor ligands in rat brain slices correlates with the profile of high, but not low, sensitivity alpha4beta2 subunit combination |journal=Biochemical Pharmacology |volume= 78|issue= 7|pages= 844–51|year=2009 |month=June |pmid=19555668 |doi=10.1016/j.bcp.2009.06.024 |url=}}</ref> It has [[nootropic]] and [[neuroprotective]] effects,<ref>Lin NH, Gunn DE, Ryther KB, Garvey DS, Donnelly-Roberts DL, Decker MW, Brioni JD, Buckley MJ, Rodrigues AD, Marsh KG, Anderson DJ, Buccafusco JJ, Prendergast MA, Sullivan JP, Williams M, Arneric SP, Holladay MW. Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties. ''Journal of Medicinal Chemistry''. 1997 Jan 31;40(3):385-90. PMID 9022806</ref><ref>Sullivan JP, Donnelly-Roberts D, Briggs CA, Anderson DJ, Gopalakrishnan M, Xue IC, Piattoni-Kaplan M, Molinari E, Campbell JE, McKenna DG, Gunn DE, Lin NH, Ryther KB, He Y, Holladay MW, Wonnacott S, Williams M, Arneric SP. ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties. ''Journal of Pharmacology and Experimental Therapeutics''. 1997 Oct;283(1):235-46. PMID 9336329</ref><ref>Decker MW, Bannon AW, Curzon P, Gunther KL, Brioni JD, Holladay MW, Lin NH, Li Y, Daanen JF, Buccafusco JJ, Prendergast MA, Jackson WJ, Arneric SP. ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys. ''Journal of Pharmacology and Experimental Therapeutics''. 1997 Oct;283(1):247-58. PMID 9336330</ref> and animal studies suggested that it might be useful for the treatment of [[ADHD]].<ref>Prendergast MA, Jackson WJ, Terry AV Jr, Decker MW, Arneric SP, Buccafusco JJ. Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys. ''Psychopharmacology (Berlin)''. 1998 Mar;136(1):50-8. PMID 9537682</ref> Subsequent human trials have shown ABT-089 to both be effective for this application,<ref>Wilens TE, Verlinden MH, Adler LA, Wozniak PJ, West SA. ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study. ''Biological Psychiatry''. 2006 Jun 1;59(11):1065-70. PMID 16499880</ref> and also to have particularly low tendency to cause side effects compared to other drugs in the class,<ref>Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP. ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders. ''CNS Drug Reviews''. 2004 Summer;10(2):167-82. PMID 15179445</ref><ref>Wilens TE, Decker MW. Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition.
'''Pozanicline''' ([[International nonproprietary name|INN]],<ref name="INN">{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 62 | url =https://www.who.int/medicines/publications/druginformation/innlists/RL62.pdf | publisher = World Health Organization | access-date = 3 January 2017 | page = 257 | url-status = live | archive-url = https://web.archive.org/web/20160518204538/http://www.who.int/medicines/publications/druginformation/innlists/RL62.pdf | archive-date = 18 May 2016 }}</ref> codenamed '''ABT-089''') is a drug developed by [[Abbott Laboratories|Abbott]], that has [[nootropic]] and [[neuroprotective]] effects.<ref>{{cite journal | vauthors = Lin NH, Gunn DE, Ryther KB, Garvey DS, Donnelly-Roberts DL, Decker MW, Brioni JD, Buckley MJ, Rodrigues AD, Marsh KG, Anderson DJ, Buccafusco JJ, Prendergast MA, Sullivan JP, Williams M, Arneric SP, Holladay MW | display-authors = 6 | title = Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties | journal = Journal of Medicinal Chemistry | volume = 40 | issue = 3 | pages = 385–90 | date = January 1997 | pmid = 9022806 | doi = 10.1021/jm960233u }}</ref><ref>{{cite journal | vauthors = Sullivan JP, Donnelly-Roberts D, Briggs CA, Anderson DJ, Gopalakrishnan M, Xue IC, Piattoni-Kaplan M, Molinari E, Campbell JE, McKenna DG, Gunn DE, Lin NH, Ryther KB, He Y, Holladay MW, Wonnacott S, Williams M, Arneric SP | display-authors = 6 | title = ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 283 | issue = 1 | pages = 235–46 | date = October 1997 | pmid = 9336329 }}</ref><ref>{{cite journal | vauthors = Decker MW, Bannon AW, Curzon P, Gunther KL, Brioni JD, Holladay MW, Lin NH, Li Y, Daanen JF, Buccafusco JJ, Prendergast MA, Jackson WJ, Arneric SP | display-authors = 6 | title = ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 283 | issue = 1 | pages = 247–58 | date = October 1997 | pmid = 9336330 }}</ref> Animal studies suggested it useful for the treatment of [[ADHD]]<ref>{{cite journal | vauthors = Prendergast MA, Jackson WJ, Terry AV, Decker MW, Arneric SP, Buccafusco JJ | title = Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys | journal = Psychopharmacology | volume = 136 | issue = 1 | pages = 50–8 | date = March 1998 | pmid = 9537682 | doi = 10.1007/s002130050538 | s2cid = 20080069 }}</ref> and subsequent human trials have shown ABT-089 to be effective for this application.<ref>{{cite journal | vauthors = Wilens TE, Verlinden MH, Adler LA, Wozniak PJ, West SA | title = ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study | journal = Biological Psychiatry | volume = 59 | issue = 11 | pages = 1065–70 | date = June 2006 | pmid = 16499880 | doi = 10.1016/j.biopsych.2005.10.029 | s2cid = 24951969 }}</ref> It binds with high affinity [[nicotinic acetylcholine receptor#Subunits|subtype-selective]] to the [[Α4β2 nicotinic receptor|α<sub>4</sub>β<sub>2</sub>]] [[nicotinic acetylcholine receptors]] and has [[partial agonist|partial agonism]] to the [[α6β2|α<sub>6</sub>β<sub>2</sub>]] subtype,<ref name="pmid19481067">{{cite journal | vauthors = Marks MJ, Wageman CR, Grady SR, Gopalakrishnan M, Briggs CA | title = Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain | journal = Biochemical Pharmacology | volume = 78 | issue = 7 | pages = 795–802 | date = October 2009 | pmid = 19481067 | pmc = 2772152 | doi = 10.1016/j.bcp.2009.05.022 }}</ref><ref name="pmid19555668">{{cite journal | vauthors = Anderson DJ, Malysz J, Grønlien JH, El Kouhen R, Håkerud M, Wetterstrand C, Briggs CA, Gopalakrishnan M | display-authors = 6 | title = Stimulation of dopamine release by nicotinic acetylcholine receptor ligands in rat brain slices correlates with the profile of high, but not low, sensitivity alpha4beta2 subunit combination | journal = Biochemical Pharmacology | volume = 78 | issue = 7 | pages = 844–51 | date = October 2009 | pmid = 19555668 | doi = 10.1016/j.bcp.2009.06.024 }}</ref> but not the [[Alpha-7 nicotinic receptor|α<sub>7</sub>]] and [[Α3β4-nAChR|α<sub>3</sub>β<sub>4</sub>]] subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class.<ref>{{cite journal | vauthors = Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP | display-authors = 6 | title = ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders | journal = CNS Drug Reviews | volume = 10 | issue = 2 | pages = 167–82 | year = 2004 | pmid = 15179445 | pmc = 6741767 | doi = 10.1111/j.1527-3458.2004.tb00011.x }}</ref><ref>{{cite journal | vauthors = Wilens TE, Decker MW | title = Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition | journal = Biochemical Pharmacology | volume = 74 | issue = 8 | pages = 1212–23 | date = October 2007 | pmid = 17689498 | pmc = 2974320 | doi = 10.1016/j.bcp.2007.07.002 }}</ref>

''Biochemical Pharmacology''. 2007 Oct 15;74(8):1212-23. PMID 17689498</ref> making it a promising candidate for clinical development.
==Synthesis==
Pozanicline is synthesized from 2-methyl-3-hydroxypyridine and Boc-L-Prolinol through a dehydration reaction followed by deprotection of the nitrogen atom of prolinol<ref>{{cite journal | vauthors = Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP | display-authors = 6 | title = ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders | journal = CNS Drug Reviews | volume = 10 | issue = 2 | pages = 167–82 | year = 2006 | pmid = 15179445 | pmc = 6741767 | doi = 10.1111/j.1527-3458.2004.tb00011.x | url = }}</ref>


== References ==
== References ==
{{Reflist|2}}
{{Reflist|2}}



{{Stimulants}}
{{Stimulants}}
{{Nootropics}}
{{Antidementia}}
{{Antihyperkinetics}}
{{Cholinergics}}


{{Nicotinic acetylcholine receptor modulators}}
[[Category:Nootropics]]

[[Category:Pyridines]]
[[Category:Nicotinic agonists]]
[[Category:Nicotinic agonists]]
[[Category:Stimulants]]
[[Category:Nootropics]]
[[Category:Phenol ethers]]
[[Category:Phenol ethers]]
[[Category:Pyridines]]
[[Category:Pyrrolidines]]
[[Category:Pyrrolidines]]
[[Category:Stimulants]]