Potential neuroleptic agents. 2,6-Dialkoxybenzamide derivatives with potent dopamine receptor blocking activities

Florvall, Lennart; Oegren, S.-O.

doi:10.1021/jm00353a003

Cited by 93 publications

(30 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[12] Reaction of carboxylic acid 26 with 2.0 equivalents of Br 2 in dioxane furnished compound 27, in 84 % yield, containing a bromine atom in the ortho position to the methoxy substituent. [13] As intended, the carboxylic acid at C-1 in 26 was successful in directing the bromination and this functionality subsequently needed to be "unmasked" as the phenol to allow the introduction of two ortho-hydroxymethyl units. [14] This transformation first required an acid to aldehyde reduction, which was achieved in 2 steps by initial treatment of 27 with LiAlH 4 to give the alcohol 28 in 72 % yield and subsequent oxidation with MnO 2 to afford aldehyde 29 in 87 % yield.…”

Section: Resultsmentioning

confidence: 99%

Towards a Total Synthesis of the New Anticancer Agent Mensacarcin: Synthesis of the Carbocyclic Core

Tietze¹,

Stewart²,

Polomska³

et al. 2004

Chemistry A European J

View full text Add to dashboard Cite

A synthesis of the carbocyclic core associated with the new anticancer agent mensacarcin (1) is reported. The strategy involves the synthesis of several novel highly substituted aromatic compounds, such as 12 and 23. The lithium derivative of 12 readily engages in a nucleophilic addition to benzaldehyde 4 to provide the diphenylcarbinol rac-15. The analogous benzyl ether rac-16 undergoes an intramolecular Heck reaction to provide the required tetrahydroanthracene rac-17, which can be transformed into the key tricyclic methyl ether rac-20. In a second approach, the lithium derivative of 21 is added to the hexasubstituted benzaldehyde 23 to give the diphenylcarbinol rac-35. Subsequent methylation to rac-36 followed by an intramolecular Heck reaction provides tricycle rac-37. Similarly, the oxidised compound 40 provides an electronically more suitable intramolecular Heck partner to afford compound 41. Further transformations of these substrates leads to rac-43, which incorporates the core structure of mensacarcin (1).

show abstract

Section: Resultsmentioning

confidence: 99%

Towards a Total Synthesis of the New Anticancer Agent Mensacarcin: Synthesis of the Carbocyclic Core

Tietze¹,

Stewart²,

Polomska³

et al. 2004

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…The noradrenergic input seems to be peripheral as phentolamine, a non-selective and mainly peripherally acting a-adrenoceptor antagonist, was also a potent inhibitor of the response (Renyi, 1985). Remoxipride, a selective dopamine-receptor antagonist (Florvall & Ogren, 1982), did not antagonize the 5-MeODMTinduced ejaculatory response.…”

Section: Discussionmentioning

confidence: 94%

“…Remoxipride, a selective dopamine2-receptor antagonist (Florvall & Ogren, 1982), had no significant effect even at a large dose (Table 1).…”

Section: Drugsmentioning

confidence: 99%

The effect of selective 5‐hydroxytryptamine uptake inhibitors on 5‐methoxy‐N,N‐dimethyltryptamine‐induced ejaculation in the rat

Rènyi

1986

British J Pharmacology

View full text Add to dashboard Cite

1The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-' i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective EDM values for uptake inhibition. 2 Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment ofthe rats with the postsynaptic 5-HT receptor antagonist methergoline. 3 An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. 4 Acute doses ofalaproclate and citalopram significantly blocked the ejaculatory response at I h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. 5 It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions.

show abstract

“…For 1 h, 5-bromo-2,3-dimethoxybenroyl chloride [l] (3.8 mmol) was reacted with (S)-l-tritylpyrrolidine-2-methylamine [25] (1.35 g, 3.9 mmol) in 10 ml of CH,CI, at r.t. The solvent was evaporated and the residue treated with 10 ml of EtOH and 0.1 ml ofconc.…”

Section: + J-( S)-5-bromo-23-dimethoxy-n-[pyrrolidin-2-yljmethyljbenmentioning

confidence: 99%

Potential antipsychotic agents. Part 8. Antidopaminergic properties of a potent series of 5‐substituted (−)‐(S)‐N‐[(1‐ethylpyrrolidin‐2‐yl)methyl]‐2,3‐dimethoxybcnzaimides. Synthesis via common lithio intermediates

Högberg

Ström

Hall

et al. 1990

Helvetica Chimica Acta

View full text Add to dashboard Cite

A series of 5-substituted (-)-(S)-N-[( l-ethylpyrrolidin-2-yl)methyl]-2,3-dimethoxybenzamideswere made by reaction of the corresponding benzoyl chlorides with (S)-l-ethylpyrrolidine-2-methylamine (+ 14-16, 18-21). The acids required were prepared in a regiospecific manner from 5-bromo-2,3-dimethoxybenzoic acid which was protected as dihydrooxazole (+ U ) , metalated, reacted with various electrophiles (MeI, EtI, BuBr, CC13CC13 or MeSSMe), and hydrolyzed (+ 9-13). Alternatively, (-)-(S)-S-bromo-N-[( 1 -ethylpyrrolidin-2-yI)methyl]-2,3-dimethoxybenzamide was treated with KH followed by BuLi and an electrophile (I2 or Me3SiC1) to give the 5-iodo and 5-(trimethylsilyl) derivatives 17 and 22, respectively. All 5-substituted amides were highly potent inhibitors of [3H]spiperone binding in rat striatal membranes with IC,, values of 0.5 to 5 nM (Table 3 ) . Thus, a relatively large steric bulk can be accomodated in the positionpara to the 2-Me0 group. This work also supports the notion that a positive as well as negative electrostatic potential can be located in this position. A selected number of derivatives were also investigated in uiuo and found to inhibit apomorphine-induced behavioural responses in the same dose range as haloperidol and raclopride (Table 4 ) . This new group of benzamides is suitable for investigations of dopamine D-2 receptors in labelled or unlabelled form.

show abstract

Potential neuroleptic agents. 2,6-Dialkoxybenzamide derivatives with potent dopamine receptor blocking activities

Cited by 93 publications

References 8 publications

Towards a Total Synthesis of the New Anticancer Agent Mensacarcin: Synthesis of the Carbocyclic Core

Towards a Total Synthesis of the New Anticancer Agent Mensacarcin: Synthesis of the Carbocyclic Core

The effect of selective 5‐hydroxytryptamine uptake inhibitors on 5‐methoxy‐N,N‐dimethyltryptamine‐induced ejaculation in the rat

Potential antipsychotic agents. Part 8. Antidopaminergic properties of a potent series of 5‐substituted (−)‐(S)‐N‐[(1‐ethylpyrrolidin‐2‐yl)methyl]‐2,3‐dimethoxybcnzaimides. Synthesis via common lithio intermediates

Contact Info

Product

Resources

About