Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Teniloxazine: Difference between pages

{{Short description|Chemical compound}}

| verifiedrevid =

| IUPAC_name = 2-{[2-(thiophen-2-ylmethyl)phenoxy]methyl}morpholine

| image = Teniloxazine.svg

| width = 215

| CAS_number = 62473-79-4

| CAS_supplemental = <br />62473-80-7 ([[maleate]])

| ATC_prefix = None

| ATC_suffix =

| PubChem = 119114

| ChemSpiderID = 106426

| ChEMBL = 2105438

| smiles = O1CCNCC1COc2ccccc2Cc3sccc3

| synonyms = Y-8894

| StdInChI = 1S/C16H19NO2S/c1-2-6-16(19-12-14-11-17-7-8-18-14)13(4-1)10-15-5-3-9-20-15/h1-6,9,14,17H,7-8,10-12H2

| StdInChIKey = OILWWIVKIDXCIB-UHFFFAOYSA-N

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| pregnancy_category =

| legal_status = Rx-only

'''Teniloxazine''' ('''Lucelan''', '''Metatone'''), also known as '''sufoxazine''' and '''sulfoxazine''', is a [[drug]] which is marketed in [[Japan]].<ref name="GanellinTriggle1997">{{cite book | vauthors = Ganellin CR, Triggle DJ, Macdonald F | title = Dictionary of pharmacological agents | url = https://books.google.com/books?id=A0THacd46ZsC&pg=PA1905 | access-date=27 October 2011 | year = 1997 | publisher = CRC Press | isbn = 978-0-412-46630-4 | pages = 1905}}</ref> Though initially investigated as a [[neuroprotection|neuroprotective]] and [[nootropic]] agent for the treatment of [[cerebrovascular insufficiency]] in the 1980s,<ref name="pmid2859238">{{cite journal |vauthors=Anami K, Yamamoto Y, Setoguchi M | title = [Pharmacological studies on sufoxazine (Y-8894). (I) Effects on experimental amnesia in mice] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 85 | issue = 2 | pages = 71–7 |date=February 1985 | pmid = 2859238 | doi = 10.1254/fpj.85.71| doi-access = free }}</ref><ref name="pmid4085932">{{cite journal |vauthors=Izumi N, Yasuda H | title = [Pharmacological studies on sufoxazine (Y-8894). (II). Anti-anoxic effect] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 86 | issue = 4 | pages = 323–8 |date=October 1985 | pmid = 4085932 | doi = 10.1254/fpj.86.323| doi-access = free }}</ref><ref name="pmid3491778">{{cite journal |vauthors=Usa T, Morimoto Y, Fukuda T, Anami K, Setoguchi M, Maruyama Y | title = [Pharmacological studies on Y-8894. (III). Its effect on the abnormal electrocorticogram induced by destruction of the internal capsule] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 88 | issue = 4 | pages = 289–97 |date=October 1986 | pmid = 3491778 | doi = 10.1254/fpj.88.289| doi-access = free }}</ref><ref name="pmid3817653">{{cite journal |vauthors=Yasuda H, Izumi N, Nakanishi M, Anami K, Maruyama Y | title = [Pharmacological studies on Y-8894. (IV). Ameliorative effect on a cerebral energy metabolism disorder induced by KCN] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 88 | issue = 5 | pages = 363–7 |date=November 1986 | pmid = 3817653 | doi = 10.1254/fpj.88.363| doi-access = free }}</ref><ref name="pmid2884174">{{cite journal |vauthors=Anami K, Yamamoto Y, Setoguchi M, Maruyama Y | title = [Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 89 | issue = 3 | pages = 145–53 |date=March 1987 | pmid = 2884174 | doi = 10.1254/fpj.89.145| doi-access = free }}</ref><ref name="pmid2443434">{{cite journal |vauthors=Setoguchi M, Takehara S, Sakamori M, Anami K, Maruyama Y | title = [Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 90 | issue = 1 | pages = 41–9 |date=July 1987 | pmid = 2443434 | doi = 10.1254/fpj.90.41| doi-access = free }}</ref><ref name="pmid3443414">{{cite journal |vauthors=Yasumatsu H, Yamamoto Y, Takamuku H, etal | title = [Pharmacological studies on Y-8894. (VII). Effects on transient cerebral ischemia-induced amnesia in rats] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 90 | issue = 6 | pages = 321–30 |date=December 1987 | pmid = 3443414 | doi = 10.1254/fpj.90.321| doi-access = free }}</ref><ref name="pmid3224898">{{cite journal |vauthors=Anami K, Setoguchi M, Senoh H | title = [Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 92 | issue = 2 | pages = 113–8 |date=August 1988 | pmid = 3224898 | doi = 10.1254/fpj.92.113| doi-access = free }}</ref> it was ultimately developed and approved as an [[antidepressant]] instead.<ref name="pmid3593624">{{cite journal |vauthors=Ogura C, Kishimoto A, Kunimoto N, etal | title = Clinical pharmacology of a new antidepressant, Y-8894 in healthy young and elderly volunteers | journal = British Journal of Clinical Pharmacology | volume = 23 | issue = 5 | pages = 537–43 |date=May 1987 | pmid = 3593624 | pmc = 1386189 | doi = 10.1111/j.1365-2125.1987.tb03089.x}}</ref> It acts as a [[potency (pharmacology)|potent]] [[norepinephrine reuptake inhibitor]], with fair [[binding selectivity|selectivity]] over the [[serotonin]] and [[dopamine]] [[neurotransmitter transporter|transporter]]s, and also behaves as an [[receptor antagonist|antagonist]] of the [[5-HT2A receptor|5-HT_2A receptor]].<ref name="pmid2443434"/><ref name="pmid3593624"/><ref name="Kuriyama2009">{{cite patent|country=JP|number=2008189616A | title=Therapeutic Agent for Attention-Deficit Hyperactivity Disorder }}</ref>

==Synthesis==

[[File:Teniloxazine synthesis.svg|thumb|center|500px|[https://www.chemdrug.com/article/8/3284/16419322.html ChemDrug] Synthesis:<ref>Serradell, MN; Blancafort, P.; Castaer, J.; Y-8894. Drugs Fut 1981, 6, 7, 423.</ref><ref>Muro, Tomio; Yuki, Hiroshi; Kawakita, Takeshi; Chihara, Yasuaki; Yasumoto, Mitsuyoshi; Setoguchi, Shinro; Anami, Koretake; Setoguchi, Michihide (1986). "Syntheses and Pharmacological Activities of 2-(Substituted Phenoxymethyl) morpholine Derivatives". YAKUGAKU ZASSHI. 106 (9): 764–774. doi:10.1248/yakushi1947.106.9_764.</ref> Patents:<ref>Tomio Muro, et al. {{US patent|4005084}} (1977 to Welfide Corp).</ref><ref>Muro Tomio, Chihara Yasuaki, et al. DE2530860, (1977 to Yoshitomi Pharmaceutical).</ref> Cerebrovascular dementia usage:<ref>Michihide Setoguchi, Koretake Anami, & Hiroshi Yasuda, EP0193637 (1986 to Welfide Corp).</ref>]]

Amide formation between 1-(Benzylamino)-3-{2-[(thiophen-2-yl)methyl]phenoxy}propan-2-ol [62473-86-3] (1) and Chloroacetylchloride [79-04-9] (2) gives PC13682456 (3). In the presence of sodium metal closing of the ring morpholine occurs to give PC13682470 (4). Lactam reduction with lithium aluminium hydride affords 4-Benzyl-2-({2-[(thiophen-2-yl)methyl]phenoxy}methyl)morpholine [62473-77-2] (5). Treatment with Ethyl chloroformate [541-41-3] (6) gives the urethane and hence 4-Ethoxycarbonyl-2-[2-(2-thenyl)-phenoxymethyl]morpholine, PC21482171 (7). Hydrolysis of the carbamate in the presence of barium hydroxide completes the synthesis of Teniloxazine (8).

Alternately, base reaction between 1-[2-(2-thenyl)phenoxy]-2,3-epoxypropane [55506-46-2] (9) and 2-Aminoethyl hydrogen sulfate [926-39-6] (10) is another way to perform the synthesis.

== See also ==

* [[Bifemelane]]

* [[Indeloxazine]]

* [[Viloxazine]]

== References ==

{{Reflist|2}}

{{Antidepressants}}

{{Antidementia}}

{{Monoamine reuptake inhibitors}}

{{Serotonin receptor modulators}}

[[Category:Antidepressants]]

[[Category:Morpholines]]

[[Category:Thiophenes]]

[[Category:Phenol ethers]]