Tetrahydroisoquinolines. I. 1-Alkyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines<sup>1</sup>

Craig, Paul N.; Nabenhauer, Fred P.; Williams, PG; Macko, Edward; Toner, John L.

doi:10.1021/ja01125a051

Cited by 37 publications

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“…Bronchodilator activities of 1-substituted-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines As shown in Table 1, four classes of substituents were introduced at position 1 of 6 ,7 dihydroxy-1,2,3,4-tetrahydroisoquinoline, namely 1) aryl, 2) arylmethyl, 3) 2-arylethyl, and 4) 3-arylpropyl. Although the bronchodilator activities of 1-alkyl derivatives of tetrahydroisoquinoline have already been reported briefly by Craig et al, (8), the isopropyl analogue, reported as the most active compound among them and the n-propyl analogue, reported as slightly active, were also added in the table for the comparison. Among the compounds tested, the isopropyl analogue (XVI) was as active as E, while arylmethyl analogues (VII-XI) were 0.2 to 85 times as active as E. It is worth noting that the 3, 4,5-trimethoxybenzyl analogue (IX) was 85 times as active as E and about ten times as active as Iso.…”

Section: Resultsmentioning

confidence: 99%

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Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Iwasawa

Kiyomoto

1967

Jpn.J.Pharmacol

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Section: Resultsmentioning

confidence: 99%

“…It is of great interest that structural elements that have no similarities in the chemical sense are responsible for the third site of action; for example , an alcoholic hydroxyl group in the side chain of catecholamines , and an arylmethyl, or alkyl [as shown in the Craig's paper (8)], group at position 1 of tetrahydroisoquinolines.…”

Section: Discussionmentioning

confidence: 99%

Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Iwasawa

Kiyomoto

1967

Jpn.J.Pharmacol

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“…1966; Santi et al, 1967), and within a series of related 1-substituted 6, 7-dihydroxy-1, 2, 3,4-tetrahydroisoquinolines there are several active bronchodilators (Craig et al, 1952). The most potent of these is the 1 -(3' 4' 5'-trimethoxybenzyl) derivative, trimetoquinol, which was first described by Yamato, Hirakura & Sugasawa (1966).…”

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confidence: 99%

Actions of the Sympathomimetic Bronchodilator, Trimetoquinol (Aql 208) on the Cardiac, Respiratory and Skeletal Muscle Systems in the Anaesthetized Cat, and on Cat Isolated Atrial and Tracheal Preparations

Houston

Rodger

1974

Clin Exp Pharmacol Physiol

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S U M M A R Y1. The actions of the sympathomimetic bronchodilator trimetoquinol (AQL 208) have been compared with those of laevoisoprenaline on the cardiac, respiratory and skeletal muscle systems of the cat under chloralose anaesthesia, and on cat isolated atrial and tracheal preparations.2. Trimetoquinol injected intravenously ranged in potency from two to four times less potent to about four times more potent than laevoisoprenaline in different in vivo experiments. Despite such wide variations in absolute potency the mean effective doses of trimetoquinol in both in vitro and in vivo studies were not significantly different ( P > 0.05) from those of laevoisoprenaline.3. The effect on the soleus muscle is considered to be analogous to the muscle tremor that often occurs in man, and the results suggest that systemic administration of trimetoquinol may produce muscle tremor as an unwanted side effect in some patients.4. Trimetoquinol, in the cat, shows no evidence of the selectivity for p-adrenoreceptors in different tissues reported for it in other species. It is suggested that P-receptors in the cat are less clearly differentiated and that they resemble those in man more closely than do those in other species.

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“…3,4-Dihydroisoquinolines 1a [10], 1b [10], 1c [11], 1d [12], and 8 [3] were prepared according to the references indicated. Starting Materials.…”

Section: Experimental Partmentioning

confidence: 99%

Oxidative Rearrangement of 1‐Alkylidene‐1,2,3,4‐tetrahydro‐2‐(trichloroacetyl)isoquinolines to 1,5,6,10b‐Tetrahydro‐10b‐(trichloromethyl)‐3H‐oxazolo [4,3‐a]isoquinolin‐3‐ones.

et al. 2004

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On treatment with lead tetraacetate (Pb(OAc) 4 ), the 1-(alkylidene)-1,2,3,4-tetrahydro-N-(trichloroacetyl)-isoquinolines 2a ± 2c as well as the tribromoacetyl derivative 4 undergo an oxidative cyclization with concomitant migration of the trihalogenomethyl group to afford the 1,5,6,10b-tetrahydro-10b-(trichloromethyl)-3H-oxazolo[4,3-a]isoquinolin-3-ones 3a ± 3c or the tribromomethyl derivative 6, respectively. These tricycles are also accessible via esterification of 3,4-dihydro-1-(1-hydroxy-1-methylethyl)isoquinoline 8 with either trichloroacetyl chloride or tribromoacetyl bromide, respectively. A plausible mechanistic description for these reactions involves an ± unprecedented ± −intramolecular iminoÀhaloform× rearrangement.Introduction. ± The oxidative ring expansion of −isoquinoline enamides× to tetrahydro-3-benzazepin-2-ones (i.e., I 3 II) occurs readily for different N-acyl functionalities when a) the isoquinoline ring contains electron-releasing, e.g., MeO substituents and b) the exocyclic CC bond is either unsubstituted or monoalkylsubstituted [1]. For compounds in which the exocyclic CC bond is dialkyl-substituted, the oxidation with Pb(OAc) 4 (LTA) occurs readily, but does not lead to ring expansion. Instead, phenyl tetrahydroisoquinoline-2-carboxylates cyclize to oxazoloisoquinolines (i.e., III 3 IV), while N-benzoyl or N-(trifluoroacetyl) derivatives undergo a formal oxidative rearrangement (i.e., V 3 VI) to afford the corresponding carboxylates [2] [3] (Scheme 1).In recent studies on effective routes to isoquinoline alkaloids, oxazoloisoquinolines of type IV bearing an alkyl group instead of the oxy function at C(10b) have been synthesized by intramolecular amidoalkylation of 4-hydroxyoxazolidin-2-ones [4] [5]. Here, we report on the synthesis of such compounds by LTA oxidation of appropriately substituted −isoquinoline enamides× by interconnecting the latter two reaction types in Scheme 1 accordingly.

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Tetrahydroisoquinolines. I. 1-Alkyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines¹

Cited by 37 publications

References 0 publications

Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Actions of the Sympathomimetic Bronchodilator, Trimetoquinol (Aql 208) on the Cardiac, Respiratory and Skeletal Muscle Systems in the Anaesthetized Cat, and on Cat Isolated Atrial and Tracheal Preparations

Oxidative Rearrangement of 1‐Alkylidene‐1,2,3,4‐tetrahydro‐2‐(trichloroacetyl)isoquinolines to 1,5,6,10b‐Tetrahydro‐10b‐(trichloromethyl)‐3H‐oxazolo [4,3‐a]isoquinolin‐3‐ones.

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Tetrahydroisoquinolines. I. 1-Alkyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines1

Cited by 37 publications

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Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Actions of the Sympathomimetic Bronchodilator, Trimetoquinol (Aql 208) on the Cardiac, Respiratory and Skeletal Muscle Systems in the Anaesthetized Cat, and on Cat Isolated Atrial and Tracheal Preparations

Oxidative Rearrangement of 1‐Alkylidene‐1,2,3,4‐tetrahydro‐2‐(trichloroacetyl)isoquinolines to 1,5,6,10b‐Tetrahydro‐10b‐(trichloromethyl)‐3H‐oxazolo [4,3‐a]isoquinolin‐3‐ones.

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Tetrahydroisoquinolines. I. 1-Alkyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines¹