m →Synthesis: cite patent fix
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<!--Chemical data--> |
<!--Chemical data--> |
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| C=8 | H=10 | Cl=1 | N=3 | S=1 |
| C=8 | H=10 | Cl=1 | N=3 | S=1 |
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| SMILES = Clc2scc(c2N/C1=N/CCN1)C |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C8H10ClN3S/c1-5-4-13-7(9)6(5)12-8-10-2-3-11-8/h4H,2-3H2,1H3,(H2,10,11,12) |
| StdInChI = 1S/C8H10ClN3S/c1-5-4-13-7(9)6(5)12-8-10-2-3-11-8/h4H,2-3H2,1H3,(H2,10,11,12) |
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'''Tiamenidine''' ([[British Approved Name|BAN]], [[United States Adopted Name|USAN]], [[International Nonproprietary Name|INN]], also known as '''thiamenidine''', '''Hoe 440''') is an [[imidazoline]] compound that shares many of the pharmacological properties of [[clonidine]]. It |
'''Tiamenidine''' ([[British Approved Name|BAN]], [[United States Adopted Name|USAN]], [[International Nonproprietary Name|INN]], also known as '''thiamenidine''', '''Hoe 440''') is an [[imidazoline]] compound that shares many of the pharmacological properties of [[clonidine]]. It is a [[central nervous system|centrally-acting]] [[Alpha-2 adrenergic receptor|α<sub>2</sub> adrenergic receptor]] [[agonist]] ([[IC50|IC<sub>50</sub>]] = 9.1 nM).<ref name="pmid6142954">{{cite journal | vauthors = Timmermans PB, de Jonge A, Thoolen MJ, Wilffert B, Batink H, van Zwieten PA | title = Quantitative relationships between alpha-adrenergic activity and binding affinity of alpha-adrenoceptor agonists and antagonists | journal = Journal of Medicinal Chemistry | volume = 27 | issue = 4 | pages = 495–503 | date = April 1984 | pmid = 6142954 | doi = 10.1021/jm00370a011 }}</ref> It also acts as an [[Alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptor]] agonist to a far lesser extent (IC<sub>50</sub> = 4.85 μM).<ref name="pmid6142954" /> In hypertensive volunteers, like clonidine, it significantly increased sinus node recovery time and lowered [[cardiac output]].<ref>{{cite journal | vauthors = Roden DM, Nadeau JH, Primm RK | title = Electrophysiologic and hemodynamic effects of chronic oral therapy with the alpha 2-agonists clonidine and tiamenidine in hypertensive volunteers | journal = Clinical Pharmacology and Therapeutics | volume = 43 | issue = 6 | pages = 648–54 | date = June 1988 | pmid = 2897889 | doi = 10.1038/clpt.1988.90 }}</ref> It was marketed (as tiamenidine hydrochloride) by [[Sanofi-Aventis]]<ref>{{cite web|title=Pharmaceutical and healthcare online databases. Tiamenidine Hydrochloride|url=http://drugs-about.com/drugs-s/sundralen.html|website=Drugs-About.com|access-date=30 November 2015}}</ref> under the brand name '''Sundralen'''<ref>{{cite book| veditors = Ganten D, Mulrow PJ |title=Pharmacology of Antihypertensive Therapeutics|date=2013|publisher=Springer-Verlag Berlin Heidelberg|location=[S.l.]|isbn=978-3-642-74211-8|page=880|edition=1st}}</ref> for the management of [[essential hypertension]].<ref name = "Zamboulis">{{cite journal | vauthors = Zamboulis C, Hossmann V, Dollery CT, Eckert H | title = Tiamenidine, a centrally acting antihypertensive drug in essential hypertension [proceedings] | journal = British Journal of Clinical Pharmacology | volume = 8 | issue = 4 | pages = 390P | date = October 1979 | pmid = 508528 | doi = 10.1111/j.1365-2125.1979.tb04737.x | doi-access = free }}</ref> |
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==Synthesis== |
==Synthesis== |
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[[File:Tiamenidine-synthesis.svg|500px|center|thumb|Tiamenidine synthesis:<ref>{{cite patent |inventor= 0 Rippel H, Ruschig H, Linder E, Schorr M | gdate = 1973 | country = US | number = 3758476 }}</ref>]] |
[[File:Tiamenidine-synthesis.svg|500px|center|thumb|Tiamenidine synthesis:<ref>{{cite patent |inventor= 0 Rippel H, Ruschig H, Linder E, Schorr M | gdate = 1973 | country = US | number = 3758476 }}</ref>]] |
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Reaction of thiourea '''1''' with [[methyl iodide]] gives the corresponding S-methyl analogue ('''2'''), followed by heating with [[ethylenediamine]], completes the synthesis of tiamenidine ('''3'''). |
Reaction of thiourea '''1''' with [[methyl iodide]] gives the corresponding S-methyl analogue ('''2'''), followed by heating with [[ethylenediamine]], completes the synthesis of tiamenidine ('''3'''). |
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== References == |
== References == |
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{{ |
{{Reflist}} |
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{{Antihypertensives and diuretics}} |
{{Antihypertensives and diuretics}} |
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{{Adrenergic receptor modulators}} |
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{{Adrenergics}} |
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[[Category:Abandoned drugs]] |
[[Category:Abandoned drugs]] |
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[[Category:Alpha-adrenergic agonists]] |
[[Category:Alpha-1adrenergic receptor agonists]] |
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[[Category:Alpha-2 adrenergic receptor agonists]] |
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[[Category:Antihypertensive agents]] |
[[Category:Antihypertensive agents]] |
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[[Category:Chloroarenes]] |
[[Category:Chloroarenes]] |
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Trade names | Sundralen, Symcorad, Symcor |
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Elimination half-life | 2.3–5 hours[1] |
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Chemical and physical data | |
Formula | C8H10ClN3S |
Molar mass | 215.70 g·mol−1 |
3D model (JSmol) | |
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Tiamenidine (BAN, USAN, INN, also known as thiamenidine, Hoe 440) is an imidazoline compound that shares many of the pharmacological properties of clonidine. It is a centrally-acting α2 adrenergic receptor agonist (IC50 = 9.1 nM).[2] It also acts as an α1-adrenergic receptor agonist to a far lesser extent (IC50 = 4.85 μM).[2] In hypertensive volunteers, like clonidine, it significantly increased sinus node recovery time and lowered cardiac output.[3] It was marketed (as tiamenidine hydrochloride) by Sanofi-Aventis[4] under the brand name Sundralen[5] for the management of essential hypertension.[6]
Reaction of thiourea 1 with methyl iodide gives the corresponding S-methyl analogue (2), followed by heating with ethylenediamine, completes the synthesis of tiamenidine (3).
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Sympatholytics (antagonize α-adrenergic vasoconstriction) |
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