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3. Seroprevalence of Adeno-Associated Virus Neutralizing Antibodies in Males with Duchenne Muscular Dystrophy

Author

Verma, Sumit, primary, Nwosu, Stella N., additional, Razdan, Raj, additional, Upadhyayula, Saila R., additional, Phan, Han C., additional, Koroma, Abubakarr A., additional, Leguizamo, Isai, additional, Correa, Natalie S., additional, Kuipa, Michael, additional, Lee, David, additional, Vanderford, Thomas H., additional, and Gardner, Matthew R., additional

Published
2022
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23. Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): Identification of neutralizing and antibodies reactive to S, N, M and E viral proteins

Author

Tripp, Ralph A., Haynes, Lia M., Moore, Deborah, Anderson, Barbara, Tamin, Azaibi, Harcourt, Brian H., Jones, Les P., Yilla, Mamadi, Babcock, Gregory J., Greenough, Thomas, Ambrosino, Donna M., Alvarez, Rene, Callaway, Justin, Cavitt, Sheana, Kamrud, Kurt, Alterson, Harold, Smith, Jonathan, Harcourt, Jennifer L., Miao, Congrong, Razdan, Raj, Comer, James A., Rollin, Pierre E., Ksiazek, Thomas G., Sanchez, Anthony, Rota, Paul A., Bellini, William J., and Anderson, Larry J.

Published
2005
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24. Dibenzcycloheptatrienes (Part I) ; A new molecular rearrangement effected by aluminium chloride (Part 2)

Author

Razdan, Raj Kumar

Subjects
547
Abstract

A: Dibenzcycloheptatrienes. 2:3-Dimethoxy-9-and -10-mefhylphenanthrenes were synthesised and, by expansion of the central ring in each, were converted into dihenzocycloheptatrienones. Thereby 13:14-dimethoxy-3:4-5:6-dihenzocyclohepta-1:3:5-triene was isolated and fully characterised hut the isomeric triene was less well defined and attempted interconversion of the two gave results which were not free of ambiguity. B: A New Molecular Rearrangement effected by Aluminium Chloride. It is shown that through being heated with aluminium chloride chromanone is rearranged to 7-hydroxyindanone and dihydrocoumarin to 4-hydroxyindanone. Further applications of this type of rearrangement are described and discussed. In particular it is employed to prepare 6-hydroxyperinaphthen-7-one, the corresponding 8:9-dihydride and 6-hydroxy-perinaphthen-9-one. A comparative study of these three compounds is made to evaluate the chemical effects which are associated with the strong hydrogen-bonding present in the first of them. An improved method for the synthesis of chromanones has been developed.

Published
1954

45. Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol

Author

Ghafouri, Nazdar, Tiger, Gunnar, Razdan, Raj K, Mahadevan, Anu, Pertwee, Roger G, Martin, Billy R, and Fowler, Christopher J

Subjects
Dose-Response Relationship, Drug, Arachidonic Acids, CHO Cells, Monoacylglycerol Lipases, Amidohydrolases, Glycerides, Rats, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Cerebellum, Cricetinae, Papers, Animals, lipids (amino acids, peptides, and proteins), Enzyme Inhibitors, Endocannabinoids, Pain Measurement
Abstract

The pharmacology of monoacylglycerol lipase (MAGL) is not well understood. In consequence, the abilities of a series of analogues of 2-arachidonoylglycerol (2-AG) to inhibit cytosolic 2-oleoylglycerol and membrane-bound anandamide hydolysis by MAGL and fatty acid amide hydrolase (FAAH), respectively, have been investigated. 2-AG and its 1-regioisomer (1-AG) interacted with MAGL with similar affinities (IC(50) values 13 and 17 mum, respectively). Shorter homologues of 2-AG (2-linoleoylglycerol and 2-oleoylglycerol) had affinities for MAGL similar to 2-AG. This pattern was also seen when the arachidonoyl side chain of arachidonoyl trifluoromethylketone was replaced by an oleoyl side chain. Arachidonoyl serinol (IC(50) value 73 microM) was a weaker inhibitor of MAGL than 2-AG. The IC(50) values of noladin ether towards MAGL and FAAH were 36 and 3 microM, respectively. Arachidonoyl glycine interacted with FAAH (IC(50) value 4.9 microM) but only weakly interacted with MAGL (IC(50) value100 microM). alpha-Methyl-1-AG had similar potencies towards MAGL and FAAH (IC(50) values of 11 and 33 microM, respectively). O-2203 (1-(20-cyano-16,16-dimethyl-eicosa-5,8,11,14-tetraenoyl) glycerol) and O-2204 (2-(20-hydroxy-16,16-dimethyl-eicosa-5,8,11,14-tetraenoyl) glycerol) were slightly less potent, but again affected both enzymes equally. alpha-Methyl-1-AG, O-2203 and O-2204 interacted only weakly with cannabinoid CB(1) receptors expressed in CHO cells (K(i) values 1.8, 3.7 and 3.2 microM, respectively, compared with 0.24 microM for 1-AG) and showed no evidence of central cannabinoid receptor activation in vivo at doses up to 30 mg kg(-1) i.v. It is concluded that compounds like alpha-Methyl-1-AG, O-2203 and O-2204 may be useful as leads for the discovery of selective MAGL inhibitors that lack direct effects upon cannabinoid receptors.

Published
2004

47. Separation of cannabinoid receptor affinity and efficacy in delta-8-tetrahydrocannabinol side-chain analogues

Author

Griffin, Graeme, Williams, Stephanie, Aung, Mie Mie, Razdan, Raj K, Martin, Billy R, and Abood, Mary E

Subjects
Male, organic chemicals, Receptors, Drug, Cell Membrane, Carboxylic Acids, CHO Cells, In Vitro Techniques, Cyclohexanols, Rats, Rats, Sprague-Dawley, Radioligand Assay, Structure-Activity Relationship, Guanosine 5'-O-(3-Thiotriphosphate), Cerebellum, Cricetinae, mental disorders, Papers, Animals, Dronabinol, Receptors, Cannabinoid
Abstract

1. The activities of a number of side-chain analogues of delta-8-tetrahydrocannabinol (Delta(8)-THC) in rat cerebellar membrane preparations were tested. 2. The affinities of each compound for the CB(1) receptor were compared by their respective abilities to displace [(3)H]-SR141716A and their efficacies compared by stimulation of [(35)S]-GTPgammaS binding. 3. It was found that the affinities varied from 0.19+/-0.03 nM for 3-norpentyl-3-[6'-cyano,1',1'-dimethyl]hexyl-Delta(8)-THC to 395+/-66.3 nM for 5'-[N-(4-chlorophenyl)]-1',1'-dimethyl-carboxamido-Delta(8)-THC. 4. The efficacies of these compounds varied greatly, ranging from the very low efficacy exhibited to acetylenic compounds such as 1'-heptyn-Delta(8)-THC and 4'-octyn-Delta(8)-THC to higher efficacy compounds such as 5'-(4-cyanophenoxy)-1',1'-dimethyl-Delta(8)-THC and 5'-[N-(4-aminosulphonylphenyl)]-1',1' dimethyl-carboxamido Delta(8)-THC. All agonist activities were antagonized by the CB(1)-selective antagonist SR141716A. 5. It was found that a ligand's CB(1) affinity and efficacy are differentially altered by modifications in the side-chain. Decreasing the flexibility of the side-chain reduced efficacy but largely did not alter affinity. Additionally, the positioning of electrostatic moieties, such as cyano groups, within the side-chain also has contrasting effects on these two properties. 6. In summary, this report details the characterization of a number of novel Delta(8)-THC analogues in rat cerebellar membranes. It provides the first detailed pharmacological analysis of how the inclusion of electrostatic moieties in the side-chain and also how alteration of the side-chain's flexibility may differentially affect a CB(1) cannabinoid receptor ligand's affinity and efficacy.

Published
2001

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