843. Isothiazoles. Part VII. Quaternary isothiazoles

Chaplen, P.; Slack, Robert J.; Wooldridge, K. R. H.

doi:10.1039/jr9650004577

Cited by 6 publications

(4 citation statements)

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“…Subsequent treatment with hydrobromic acid (33% in acetic acid) furnished the commonly used alkylating agent 7 . 11 , 21 Alkylation of intermediate 10 with agent 7 gave cyanopyrimidine 1 in a satisfactory 40% yield. The synthesis of 2 was started from the commercially available cyanuric chloride 11 .…”

Section: Resultsmentioning

confidence: 99%

“…Then, 2-bromomethylimidazole ( 7 ) was synthesized by reducing the commercially available 2-imidazolecarboxaldehyde with sodium borohydride in absolute ethanol. Subsequent treatment with hydrobromic acid (33% in acetic acid) furnished the commonly used alkylating agent 7 . , Alkylation of intermediate 10 with agent 7 gave cyanopyrimidine 1 in a satisfactory 40% yield. The synthesis of 2 was started from the commercially available cyanuric chloride 11 .…”

Section: Resultsmentioning

confidence: 99%

“…The precipitate formed in the mixture was collected by filtration, washed with H 2 O (25 mL × 3), and dried under reduced pressure to give 19 in good yield (232 mg, 1.02 mmol, 53%). 1 2-(1-Phenylethylidene)malononitrile (21). 25 The synthesis of this compound was adapted from the conditions previously described by Longstreet et al 25 A mixture of acetophenone 20 (2.80 mL, 24 mmol, 1.0 equiv), malononitrile (1.586 g, 24.00 mmol, 1 equiv), and ammonium acetate (0.370 g, 4.80 mmol, 0.2 equiv) in toluene (20 mL) was heated at reflux under Dean−Stark conditions for 5 h. The reaction progress was monitored by TLC.…”

Section: ■ Discussion and Conclusionmentioning

confidence: 99%

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Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A_2A Receptor

et al. 2021

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In this study, we determined the crystal structure of an engineered human adenosine A 2A receptor bound to a partial agonist and compared it to structures cocrystallized with either a full agonist or an antagonist/inverse agonist. The interaction between the partial agonist, belonging to a class of dicyanopyridines, and amino acids in the ligand binding pocket inspired us to develop a small library of derivatives and assess their affinity in radioligand binding studies and potency and intrinsic activity in a functional, label-free, intact cell assay. It appeared that some of the derivatives retained the partial agonist profile, whereas other ligands turned into inverse agonists. We rationalized this remarkable behavior with additional computational docking studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: ■ Discussion and Conclusionmentioning

confidence: 99%

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Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A_2A Receptor

et al. 2021

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“…2-Bromomethylimidazole was synthesized by reducing the commercially available 2-imidazole carboxaldehyde with LiAlH 4 in THF. The resulting alcohol function was then substituted for bromine through the action of a solution of hydrobromic acid in glacial acetic acid according to literature procedures . The final step was the reaction of the free thiol with 2-bromomethylimidazole in the presence of NaHCO 3 in DMF at room temperature to give 16 − 20 in modest yields.…”

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confidence: 99%

New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A_2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine

Beukers¹,

Chang²,

Künzel³

et al. 2004

J. Med. Chem.

150

162

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The adenosine A(2B) receptor is the least well characterized of the four known adenosine receptor subtypes because of the absence of potent, selective agonists. Here, we present five non-adenosine agonists. Among them, 2-amino-4-(4-hydroxyphenyl)-6-(1H-imidazol-2-ylmethylsulfanyl)pyridine-3,5-dicarbonitrile, 17, LUF5834, is a high-efficacy partial agonist with EC(50) = 12 nM and 45-fold selectivity over the adenosine A(3) receptor but lacking selectivity versus the A(1) and A(2A) subtypes. Compound 18, LUF5835, the 3-hydroxyphenyl analogue, is a full agonist with EC(50) = 10 nM.

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1,2-Azoles: pyrazoles, isothiazoles and isoxazoles: reactions and synthesis

Joule¹,

Mills²,

Smith³

1995

Heterocyclic Chemistry

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843. Isothiazoles. Part VII. Quaternary isothiazoles

Cited by 6 publications

References 0 publications

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A_2A Receptor

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A_2A Receptor

New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A_2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine

1,2-Azoles: pyrazoles, isothiazoles and isoxazoles: reactions and synthesis

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843. Isothiazoles. Part VII. Quaternary isothiazoles

Cited by 6 publications

References 0 publications

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2A Receptor

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2A Receptor

New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine

1,2-Azoles: pyrazoles, isothiazoles and isoxazoles: reactions and synthesis

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Product

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About

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A_2A Receptor

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A_2A Receptor

New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A_2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine