Synthesis of 1,2,3,4-tetrahydro-1,1,2,3,3,4,4-heptamethyl-6,7-dimethoxyisoquinoline and related compounds as potential hypotensive agents

Finkelstein, Jacob N.; Chiang, Elliot; Brossi, Arnold

doi:10.1021/jm00289a007

Cited by 9 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Scheme is outlined the steps involved in the preparation of the cyclopentane derivative 4. The l-cyano-l-(3',4'-dimethoxyphenyl)cyclopentane (8) was prepared by reaction of the nitrile 7 with 1,4-diiodobutane and sodium amide in liquid NHs. The nitrile 8 was reduced to the amine 9 using LÍAIH4.…”

Section: Resultsmentioning

confidence: 99%

“…l-Cyano-l-(3',4'-dimethoxyphenyl)cyclopentane (8). To 600 ml of 0.35 M sodium amide in liquid NH3 was added in portions 3,4-dimethoxyphenylacetonitrile (Aldrich, 7,17.7 g, 0.10 mol).…”

Section: Methodsmentioning

confidence: 99%

“…was prepared according to the procedure of Finkelstein et al 8 Nitration of 1 la followed by catalytic reduction afforded the desired diamine llb. Hydrolysis of l l b with 48% HBr afforded the desired 3. by an Eschweiler-Clark methylation of 12 according to the procedure of Smissman and Nerland.10 The N,N-dimethylamine 13 was reduced catalytically and then hydrolyzed with 48% HBr to yield the N,N-dimethyl-6-NH2DA derivative 5.…”

Section: -(3'4'-dimethoxyphenyl)-3-methyl-2-aminobutane ( L L a )mentioning

confidence: 99%

See 2 more Smart Citations

Catechol O-methyltransferase. 7. Affinity labeling with the oxidation products of 6-aminodopamine

Borchardt¹,

Smissman²,

Nerland³

et al. 1976

J. Med. Chem.

View full text Add to dashboard Cite

6-Aminodopamine (6-NH2DA) and various analogs of 6-NH2DA have been evaluated for their ability to inactivate purified catechol O-methyltransferase (COMT) in vitro. The inactivation of COMT by these agents could be prevented by including an antioxidant in the preincubation mixture or by excluding oxygen; however, catalase did not protect the enzyme from inactivation. Substrate protection studies and kinetic studies suggested that the loss of enzyme activity resulted from the alkylation of an amino acid residue at the active site of COMT by the quinoid types products which were generated upon air oxidation of 6-NH2DA. In addition, we have explored in more detail the reactivity toward COMT of specific intermediates in the oxidation pathways of 6-NH2DA by using various 6-NH2DA analogs. From the above studies we have concluded that 6-aminodopamine-p-quinone (6-NH2DAQ) is perhaps the most toxic species toward COMT. However, the aminochromes which are formed from 6-NH2DAQ are also effective in inactivating COMT. The results of these studies have provided a useful model system for observing the interaction of 6-NH2DA and its oxidation products with proteins; in addition, it has provided additional insight into the topography of the active site of COMT.

show abstract

Section: Resultsmentioning

confidence: 99%

“…l-Cyano-l-(3',4'-dimethoxyphenyl)cyclopentane (8). To 600 ml of 0.35 M sodium amide in liquid NH3 was added in portions 3,4-dimethoxyphenylacetonitrile (Aldrich, 7,17.7 g, 0.10 mol).…”

Section: Methodsmentioning

confidence: 99%

Section: -(3'4'-dimethoxyphenyl)-3-methyl-2-aminobutane ( L L a )mentioning

confidence: 99%

See 1 more Smart Citation

Catechol O-methyltransferase. 7. Affinity labeling with the oxidation products of 6-aminodopamine

Borchardt¹,

Smissman²,

Nerland³

et al. 1976

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…Key intermediate 2 was obtained from 2-(3,4-dimethoxyphenyl) acetonitrile via a four-step sequence in 56% overall yield. Other synthetic routes of 2 involved harsh conditions, multistep synthesis with cumbersome workup, difficult product isolation, and unsatisfactory yields . Moreover, the original approach involved high manufacturing costs because of the application of expensive raw materials and reagents.…”

Section: Introductionmentioning

confidence: 99%

“…Our original medicinal chemistry synthesis of ZY12201 (Scheme 1), 14,15 isfactory yields. 16 Moreover, the original approach involved high manufacturing costs because of the application of expensive raw materials and reagents. The loss of significant components of the API during column chromatographic purification also attributes to the higher costs.…”

Section: ■ Introductionmentioning

confidence: 99%

Practical and Efficient Synthesis of 2-Thio-imidazole Derivative—ZY12201: A Potent TGR5 Agonist

Joshi

Sojitra

Sasane

et al. 2020

Org. Process Res. Dev.

View full text Add to dashboard Cite

Early scalable process development for the synthesis of ZY12201, a novel TGR5 receptor agonist, as a potential clinical candidate is described. A practical, efficient, and scalable synthetic route provided ZY12201 in seven steps and 32% overall yield. The key step involves an inexpensive acetic acid-mediated cyclization of thiourea 6 for the construction of 2-thio-imidazole derivative 7. The developed process demonstrated cost-effective, high-yielding, kilogram-scalable, and environmentally friendly synthesis of ZY12201. This high-yielding route enabled us to rapidly synthesize large quantities of ZY12201 in 99% purity to support in vivo and toxicity studies.

show abstract

ChemInform Abstract: SYNTHESE VON 1,2,3,4‐TETRAHYDRO‐1,1,2,3,3,4,4‐HEPTAMETHYL‐6,7‐DIMETHOXYISOCHINOLIN UND AEHNLICHEN VERBINDUNGEN ALS POTENTIELLE HYPOTENSIVE AGENTIEN

Findelstein¹,

Chiang²,

Brossi³

1971

Chemischer Informationsdienst. Organische Chemie

View full text Add to dashboard Cite

Synthesis of 1,2,3,4-tetrahydro-1,1,2,3,3,4,4-heptamethyl-6,7-dimethoxyisoquinoline and related compounds as potential hypotensive agents

Cited by 9 publications

References 0 publications

Catechol O-methyltransferase. 7. Affinity labeling with the oxidation products of 6-aminodopamine

Catechol O-methyltransferase. 7. Affinity labeling with the oxidation products of 6-aminodopamine

Practical and Efficient Synthesis of 2-Thio-imidazole Derivative—ZY12201: A Potent TGR5 Agonist

ChemInform Abstract: SYNTHESE VON 1,2,3,4‐TETRAHYDRO‐1,1,2,3,3,4,4‐HEPTAMETHYL‐6,7‐DIMETHOXYISOCHINOLIN UND AEHNLICHEN VERBINDUNGEN ALS POTENTIELLE HYPOTENSIVE AGENTIEN

Contact Info

Product

Resources

About