2770-66-3

Usage

InChI:InChI=1/C10H13ClN4O2/c1-13-8-7(9(16)14(2)10(13)17)15(6-12-8)5-3-4-11/h6H,3-5H2,1-2H3

Upstream product

• 58-55-9 theophylline 
• 142-28-9 1,3-Dichloropropane 
• 109-70-6 1.3-chlorobromopropane 

Downstream Products

• 88338-88-9 γ-(theophylline-7-yl)-butyronitrile 
• 85118-43-0 7-<3-<4-(p-Fluorbenzoyl)-piperidino>-propyl>-theophyllin 
• 79730-42-0 3,7-dihydro-1,3-dimethyl-7-<3-<4-<3-(phenylthio)propyl>piperazin-1-yl>propyl>-1H-purine-2,6-dione 

Relevant academic research and scientific papers

Synthesis, toxicological and pharmacological assessment of 7-substituted derivatives of 1,3-dimethylxanthine

The synthesis of two 7-substituted theophylline derivatives from the theophylline sodium salt, dichloroalkane and N-methyl-N-cyclohexylamine is reported. The structures of the synthesized compounds were proved by microanalyses and 1H-NMR data. Acute toxicity studies of the compounds were performed on mice and rats. A comparative pharmacological study of the in vivo broncholytic effect of the derivatives and aminophylline showed that the new compounds have different bronchodilatory activity and the compound 7-[2-(N-methyl-N-cyclohexyl)-aminoethyl]-1,3-dimethylxanthine tartrate 3a was more active than 7-[3-(N-methyl-N-cyclohexyl)-aminopropyl]-1,3-dimethylxanthine hydrochloride 3b. It was demonstrated that compound 3b and aminophylline exerted the strongest inhibitory effect on the enzyme activity of phosphodiesterase in lung homogenate. Compound 3a showed a slight inhibitory effect on the enzyme activity in this homogenate. The possible mechanisms of the broncholytic effects of these compounds are discussed.

Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions

In the search for improved selective antagonist ligands of the A2B adenosine receptor, which have the potential as antiasthmatic or antidiabetic drugs, we have synthesized and screened a variety of alkylxanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions. Competition for 125I-ABOPX (125I-3-(4-amino-3-iodobenzyl)-8-(phenyl-4-oxyacetate)-1 -propylxanthine) binding in membranes of stably transfected HEK-293 cells revealed uniformly higher affinity (2B adenosine receptors. Binding to rat brain membranes expressing A1 and A2A adenosine receptors revealed greater A2B selectivity over A2A than A1 receptors. Substitution at the 1-position with 2-phenylethyl (or alkyl/olefinic groups) and at N-3 with hydrogen or methyl favored A2B selectivity. Relative to enprofylline 2b, pentoxifylline 35 was equipotent and 1-propylxanthine 3 was > 13-fold more potent at human A2B receptors. Most N-7 substituents did not enhance affinity over hydrogen, except for 7-(2-chloroethyl), which enhanced the affinity of theophylline by 6.5-fold to 800 nM. The A2B receptor affinity-enhancing effects of 7-(2-chloroethyl) vs 7-methyl were comparable to the known enhancement produced by an 8-aryl substitution. Among 8-phenyl analogues, a larger alkyl group at the 1-position than at the 3-position favored affinity at the human A2B receptor, as indicated by 1-allyl-3-methyl-8-phenylxanthine, with a Ki value of 37 nM. Substitution on the 8-phenyl ring indicated that an electron-rich ring was preferred for A2B receptor binding. In conclusion, new leads for the design of xanthines substituted in the 1-, 3-, 7-, and 8-positions as A2B receptor-selective antagonists have been identified.

Piperazine derivatives of theophylline

New compounds of the formula STR1 and the pharmaceutically acceptable acid addition salts thereof, wherein Z1 and Z2 are each independently selected from the group consisting of CH2, CHOB and C=O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z1 is CHOB; m is an integer from 0-4 but cannot be zero when Z2 is CHOB; and R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold.

Piperazine derivatives of theophylline

New compounds of the formula STR1 and the pharmaceutically acceptable acid addition salts thereof, wherein M is selected from the group consisting of hydrogen, morpholino, benzylamino, di-n-lower alkylamine, n-lower alkylamine, and aryl piperazino; Z1 and Z2 are each independently selected from the group consisting of CH2, CHOB and C=O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z1 is CHOB; m is an integer from 0-4 but cannot be zero when Z2 is CHOB, or when m is hydrogen; R1, R2 and R3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; and R4 and R5 are each independently lower alkyl, with the proviso that both R4 and R5 cannot be methyl when M is hydrogen; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold. They are also vasodilators.