Benzodiazepine receptor binding activity of 8-substituted-9-(3-substituted-benzyl)-6-(dimethylamino)-9H-purines

Abstract

A series of 8-substituted analogues of 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (8) were synthesized and tested for their ability to bind to the benzodiazepine receptor (BZR) in rat brain tissue. The most active compound was the 8-bromo-9-(3-formamidobenzyl) analogue 16 (IC50 = 0.011 microM), which was 1000-fold more active than the parent 9-benzyl-6-(dimethylamino)-9H-purine (1) and nearly as active as diazepam. Although substitution of a m-formamido group and an 8-bromo substituent on 1 imparted potent BZR binding activity, neither 16 nor 11 analogues exhibited significant anxiolytic activity on a modified Geller-Seifter conflict schedule.

Synthesis of 6-Substituted 9-Benzyl-8-hydroxypurines with Potential Interferon-Inducing Activity

“…12,13) The activity is indicated by MEC (minimum effective concentration), which is the concentration of the test compounds required for more than 1 IU/ml induction of IFN. The 6-unsubstituted and 6-substituted purines (2)(3)(4)(5)(6)(7)(8)14) were inactive at the maximum concentration tested (10 mM), while lead compound 1 showed MEC of 10 mM. 6) In conclusion, we have synthesized various 6-substituted 9-benzyl-8-hydroxypurine derivatives and evaluated their IFN-inducing activities.…”

“…8-Hydroxypurine derivatives have been reported to have a wide range of biological activities, such as corticotropin-releasing hormone receptor antagonism, 1,2) anti-rhinovirus activity, 3) xanthine oxidase inhibiting activity 4) and excellent binding affinity to a benzodiazepine receptor. 5) Recently, we found a novel type of lead compound, 9-benzyl-8-hydroxyadenine (1), possessing potent interferon (IFN)-inducing activity and conducted substituent modifications at the 2-, 8and 9-positions of 1 to clarify the structure-activity relationships. 6) Consequently, we found that the 8-hydroxyl and 9benzyl groups of 1 are required for the expression of IFN-inducing activity and the introduction of an appropriate alkylchain substituent at the 2-position of 1 remarkably increases the activity.…”

“…6) The focus of our attention was turned to the effect of the 6-amino group of 1 on the IFN-inducing activity. In this report, the synthesis of various 6-substituted 9-benzyl-8-hydroxypurines (2)(3)(4)(5)(6)(7)(8) shown in Fig. 1 and evaluation of their IFN-inducing activity are described.…”

2D-QSAR of non-benzodiazepines to benzodiazepines receptor (BZR)

“…The imidazo-[1,2-a]-pyrimidines inhibit binding of [ 3 H] flunitrazepam from rat brain preparations. Series D: This series contains 31 derivatives of 6,9-disubstituted purines with their observed binding affinities to the rat brain tissue (Kelley et al, 1989(Kelley et al, , 1990Saha et al, 1991) as reported in Table 4.…”

Ag Loaded on SiO2 as an Efficient and Recyclable Heterogeneous Catalyst for the Synthesis of Chloro‐8‐substituted‐9H‐purines

“…These are also useful intermediates for chemical industrial products, and also, purine derivatives are also used as agrochemicals like fungicides, insecticides, and herbicides . In consequence, the synthesis of substituted purine molecules has attracted many researchers, and many strategies have been pursued with catalysts, such as acetic anhydride , ethanesulfonic acid , NaH , FeCl 3 –SiO 2 , PPA , Pd(OAc) 2 –CuI , CsCO 3 , H 2 S/base , H 2 S/S 8 , Pd 2 dba 3 , cellulose sulfuric acid , pyridine , and microwave condition .…”