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Dive into the research topics where J. Richard Heys is active.

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Featured researches published by J. Richard Heys.


Journal of Pharmacology and Experimental Therapeutics | 2009

[N-methyl-3H3]AZ10419369 Binding to the 5-HT1B Receptor: In Vitro Characterization and in Vivo Receptor Occupancy

Donna L. Maier; Cindy Sobotka-Briner; Min Ding; Mark E. Powell; Qiaoling Jiang; Geraldine Hill; J. Richard Heys; Charles S. Elmore; M. Edward Pierson; Ladislav Mrzljak

Radiotracers suitable for positron emission tomography studies often serve as preclinical tools for in vivo receptor occupancy. The serotonin 1B receptor (5-HT1B) subtype is a pharmacological target used to discover treatments for various psychiatric and neurological disorders. In psychiatry, 5-HT1B antagonists may provide novel therapeutics for depression and anxiety. We report on the in vitro and in vivo evaluation of tritiated 5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylicacid (4-morpholin-4-yl-phenyl)-amide ([N-methyl-3H3]AZ10419369), a potent 5-HT1B radiotracer. [N-methyl-3H3]-AZ10419369 showed saturable single-site high-affinity in vitro binding (guinea pig, Kd = 0.38 and human, Kd = 0.37) to guinea pig or human 5-HT1B receptors in recombinant membranes and high-affinity (Kd = 1.9 nM) saturable (Bmax = 0.099 pmol/mg protein) binding in membranes from guinea pig striatum. When [N-methyl-3H3]AZ10419369 was administered to guinea pigs by intravenous bolus, the measured radioactivity was up to 5-fold higher in brain areas containing the 5-HT1B receptor (striatum/globus pallidus, midbrain, hypothalamus, and frontal cortex) compared with the cerebellum, the nonspecific binding region. Specific uptake peaked 30 min after injection with slow dissociation from target regions, as suggested by the in vitro binding kinetic profile. Pretreatment with 6-fluoro-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid [4-(4-propionyl-piperazin-1-yl)-phenyl]-amide (AZD1134) and 2-aminotetralin (AR-A000002), 5-HT1B-selective ligands, inhibited [N-methyl-3H3]AZ10419369-specific binding in a dose-dependent manner. In the guinea pig striatum, AZD1134 (ED50 = 0.017 mg/kg) occupies a greater percentage of the 5-HT1B receptors at a lower administered dose than AR-A000002 (ED50 = 2.5 mg/kg). In vivo receptor occupancy is an essential component to build binding-efficacy-exposure relationships and compare novel compound pharmacology. [N-methyl-3H3]AZ10419369 is a useful preclinical tool for investigating 5-HT1B receptor occupancy for novel compounds targeting this receptor.


Journal of Labelled Compounds and Radiopharmaceuticals | 1996

Synthesis of I‐125 labeled photoaffinity rapamycin analogs

Arthur Y. L. Shu; Dennis S. Yamashita; Dennis Alan Holt; J. Richard Heys

Two no-carrier-added 125 I-labeled photoaffinity rapamycin analogs were prepared : 7-demethoxy-7-(4-azido-3- 125 I-benzyloxy)rapamycin (2) and its C 28 -C 29 seco analog 3. The key reactions of the synthesis were substitution of the C 7 methoxyl of rapamycin (1) with 4-azido-3-tributylstannylbenzyloxy group, exchange of tributyltin with 125 I using Na 125 I and Chloramine-T, and a ZnCl 2 mediated retro-Aldol cleavage of the C 28 -C 29 bond of rapamycin.


Tetrahedron Letters | 2000

Direct, efficient and selective tritiations of paclitaxel and photoaffinity taxoids

Arthur Y. L. Shu; J. Richard Heys

Abstract Radiolabeled paclitaxel and three photophore-bearing derivatives were prepared by organoiridium-mediated direct tritium exchange under both catalytic and stoichiometric conditions. The resulting tritiated taxoids had specific activities ranging from 53 to 195 Ci/mmol.


Journal of Labelled Compounds and Radiopharmaceuticals | 1996

Facile preparation of a 4-substituted [2,6-14C]pyridine: Synthesis of [14C]SK&F 105809

J. Richard Heys; Anthony J. Villani; Antonietta R. Mastrocola

[ 14 C]Formaldehyde was used in a nucleophile-assisted iminium ion cyclization with N-benzyl-3-butynylamine to provide N-benzyl-4-iodo-1,2,5,6-tetrahydro[2,6- 14 C 2 ]pyridine. Palladium-catalyzed coupling of this vinyl iodide with the organozinc derivative 2 gave the corresponding 4-arylated tetrahydropyridine. Treatment of this compound at elevated temperatures with Pd/Al 2 O 3 in nitrobenzene solution caused hydrogenolysis of the benzyl group and aromatization, generating the 4-substituted [2,6- 14 C 2 ]pyridine 4 in good overall radiochemical yield from [ 14 C]formaldehyde. In high yields, compound 4 was converted via the methylsulfide [ 14 C]SK&F 105561 (1b) to the methylsulfinyl compound [ 14 C]SK&F 105809 (l#). It is proposed that, during the iminium ion cyclization, randomization of label between the 2- and 6-positions of the tetrahydropyridine ring occurs as the result of rapid equilibration between alkynyl and allenyl iminium ions, prior to cyclization.


Steroids | 1982

Syntheses of E- and Z-pseudodiethylstilbestrol and Z-1-hydroxypseudodiethylstilbestrol.

J. Richard Heys; James L. Hicks; Paul H. Ruehle

Abstract The synthesis and characterization of E - and Z -3,4-bis(4-hydroxyphenyl)-2-hexene ( E - and Z -pseudo-DES) and of Z -3,4-bis(4-hydroxyphenyl)-2-hexen-1-ol ( Z -1-hydroxypseudo-DES) are described. These compounds are useful as probes in the study of hormone action.


Journal of Labelled Compounds and Radiopharmaceuticals | 2007

Organoiridium complexes for hydrogen isotope exchange labeling

J. Richard Heys


Journal of Labelled Compounds and Radiopharmaceuticals | 2010

Metal‐catalysed hydrogen isotope exchange labelling: a brief overview

William J. S. Lockley; J. Richard Heys


Journal of Labelled Compounds and Radiopharmaceuticals | 2010

Nickel‐catalyzed hydrogen isotope exchange

J. Richard Heys


Journal of Labelled Compounds and Radiopharmaceuticals | 1994

Synthesis of carbon-14 and tritiated steroidal 5α-reductase inhibitors

Arthur Y. L. Shu; J. Richard Heys


Journal of Pharmacology and Experimental Therapeutics | 1998

Binding of [3H]-SK&F 107260 and [3H]-SB 214857 to Purified Integrin αIIbβ3: Evidence for a Common Binding Site for Cyclic Arginyl-Glycinyl-Aspartic Acid Peptides and Nonpeptides

Angela Wong; Shing Mei Hwang; Kyung Johanson; James Samanen; Donald R. Bennett; Scott W. Landvatter; Wenting Chen; J. Richard Heys; Fadia E. Ali; Thomas W. Ku; William E. Bondinell; Andrew J. Nichols; David A. Powers; Jeffrey M. Stadel

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Joseph Sisko

Pennsylvania State University

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