(±)‐5′‐Nor ribofuranoside carbocyclic guanosine

Patil, Sharadbala D.; Schneller, Stewart W.

doi:10.1002/jhet.5570280351

Cited by 12 publications

(3 citation statements)

References 29 publications

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“…Synthesis of 12a (Scheme 4) was accomplished by employing a standard procedure for preparing carbocyclic nucleosides. 56 Thus, reaction of (±)-trans-2-aminocyclopentanol with 2-amino-4,6-dichloropyrimidine yielded 65, which was subjected to C-5 diazo coupling with 4-(chlorophenyl)diazonium chloride to result in 66. Completion of the preparation of 12a followed a routine sequence: 56 reduction of 66 to amine 67, ring closure with trimethyl orthoformate to prepare precursor 68, and, finally, displacement of chlorine by ammonia to give 12a.…”

Section: Chemistrymentioning

confidence: 99%

“…The residue was subjected to column chromatography on silica gel Hz, 1 H, OH-2′),5.60 (d, J = 4.1 Hz, 1 H, OH-3′), 5.60 (d, J = 7.4 Hz, 1 H, H-1′), 8.21 (s, 1 H, H-8), 8.50 (br s, 2 H, HN 6 ), 8.60 (br s, 1 H, NH-Me). Butyl)phenyl]guanidine nitrate56 (16 g, 62.99 mmol) was added to cold NaOEt in EtOH (250 mL prepared by dissolving 25 g of Na in 250 mL of absolute EtOH). This mixture was stirred at 5 °C for 10 min before diethyl allylmalonate (12.59 g, 62.95 mmol; Aldrich Chemical Co.) was added.…”

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confidence: 99%

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Search for New Purine- and Ribose-Modified Adenosine Analogs as Selective Agonists and Antagonists at Adenosine Receptors

Siddiqi

Jacobson²,

Esker³

et al. 1995

J. Med. Chem.

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108

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The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6-CH2-ring, -hydrazino, and -hydroxylamino) and the ribose moiety (2'-, 3'-, and 5'-deoxy; 2'- and 3'- O-methyl; 2'-deoxy 2'-fluoro; 6'-thio; 5'-uronamide; carbocyclic; 4'- or 3'-methyl; and inversion of configuration). (-)- and (+)-5'-Noraristeromycin were 48- and 21-fold selective, respectively, for A2a vs A1 receptors. 2-Chloro-6'-thioadenosine displayed a Ki value of 20 nM at A2a receptors (15-fold selective vs A1). 2-Chloroadenin-9-yl(beta-L-2'-deoxy-6'- thiolyxofuranoside) displayed a Ki value of 8 microM at A1 receptors and appeared to be an antagonist, on the basis of the absence of a GTP-induced shift in binding vs a radiolabeled antagonist (8-cyclopentyl-1,3-dipropyl-xanthine). 2-Chloro-2'-deoxyadenosine and 2-chloroadenin-9-yl(beta-D-6'-thioarabinoside) were putative partial agonists at A1 receptors, with Ki values of 7.4 and 5.4 microM, respectively. The A2a selective agonist 2-(1-hexynyl)-5'-(N-ethylcarbamoyl)adenosine displayed a Ki value of 26 nM at A3 receptors. The 4'-methyl substitution of adenosine was poorly tolerated, yet when combined with other favorable modifications, potency was restored. Thus, N6-benzyl-4'-methyladenosine-5'-(N-methyluronamide) displayed a Ki value of 604 nM at A3 receptors and was 103- and 88-fold selective vs A1 and A2a receptors, respectively. This compound was a full agonist in the A3-mediated inhibition of adenylate cyclase in transfected CHO cells. The carbocyclic analogue of N6-(3-iodobenzyl)adenosine-5'-(N-methyluronamide) was 2-fold selective for A3 vs A1 receptors and was nearly inactive at A2a receptors.

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Section: Chemistrymentioning

confidence: 99%

mentioning

confidence: 99%

Search for New Purine- and Ribose-Modified Adenosine Analogs as Selective Agonists and Antagonists at Adenosine Receptors

Siddiqi

Jacobson²,

Esker³

et al. 1995

J. Med. Chem.

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108

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“…exo-2-Benzyl-2-azabicyclo[2.2.1]heptan-6-ol ( 6) and exo-2-Benzyl-2-azabicyclo[2.2.1]heptan-5-ol (7). To a stirred solution of 2-benzyl-2-azabicyclo[2.2.1]hept-5-ene10 (5,10.2 g, 0.058 mol) in 115 mL of dry THF at 0 °C under an atmosphere of N2 was added dropwise a 1 M solution of BH3-THF complex (115 mL, 0.115 mol), and stirring was continued for 2 h at 0-10 °C.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and muscarinic receptor activity of ester derivatives of 2-substituted 2-azabicyclo[2.2.1]heptan-5-ol and -6-ol

Carroll¹,

Abraham²,

Chemburkar³

et al. 1992

J. Med. Chem.

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Radioligand binding affinities of four new muscarinic antagonists and six potential muscarinic agonists which possess the 2-alkyl-2-azabicyclo[2.2.1]heptane ring system have been determined in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations to examine the selectivity for subtypes of muscarinic receptor. The efficacies of the potential muscarinic agonists were determined by the ratio of binding affinities against [3H]QNB and [3H]Oxo-M. Four muscarinic antagonists which have the 2,2-diphenylpropionate side chain at either the C5 (5-endo or 5-exo) or the C6 (6-endo or 6-exo) positions did not discriminate between the subtypes of muscarinic receptors. The 2,2-diphenylpropionate 5-endo substituted compound was the most potent, showing affinities between 4.23 x 10(-10) and 1.18 x 10(-9) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. The rank order of ester potency was 5-endo greater than 5-exo greater than 6-endo greater than 6-exo. A molecular modeling study based on the pharmacophore developed for azaprophen was used to account for the relative potency of these antagonists. Six potential muscarinic agonists which have acetoxy groups in the C5 or C6 position with an N-methyl or N-benzyl substituent did not discriminate subtypes of muscarinic receptors and had affinities between 6.63 x 10(-6) and 4.76 x 10(-5) M in rat heart, rat brain, and m1- or m3-transfected CHO cell membrane preparations. exo-2-Methyl-5-acetoxy-2-azabicyclo[2.2.1]heptane was the most efficacious partial agonist.

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Diethoxymethyl Acetate

Scheeren

2001

Encyclopedia of Reagents for Organic Synthesis

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(±)‐5′‐Nor ribofuranoside carbocyclic guanosine

Cited by 12 publications

References 29 publications

Search for New Purine- and Ribose-Modified Adenosine Analogs as Selective Agonists and Antagonists at Adenosine Receptors

Search for New Purine- and Ribose-Modified Adenosine Analogs as Selective Agonists and Antagonists at Adenosine Receptors

Synthesis and muscarinic receptor activity of ester derivatives of 2-substituted 2-azabicyclo[2.2.1]heptan-5-ol and -6-ol

Diethoxymethyl Acetate

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