Interferon inducing activities of derivatives of 1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazolo[3,4-b]quinoline and related compounds

Abstract

Syntheses and interferon inducing acitivites are reported for 137 relatives of 1,3-dimethyl-4-(3-dimethylamino-propylamino)-1H-pyrazolo[3,4-b]quinoline (1). Three different generalized synthetic schemes for the preparation of pyrazolo[3,4-b]quinolines are presented and limitations contrasted. Other heterocyclic nuclei containing the 3-dimethylaminopropylamino side chain include pyridine, quinoline, acridine, pyrazolo[3,4-b]pyridine, pyrazolo[3,4-B][1,8]naphthyridine, pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine, dipyrazolo[3,4-b:4',3'-e]pyridine, pyrrolo-[2,3-b]quinoline, isothiazolo[5,4-b]quinoline, and pyrido[2,3-h]pyrazolo[3,4-b]quinoline. Structural requirements for interferon induction in this series are discussed and two of the more active compounds (172 and 196) are compared directly with tilorone.

Reactions of 4-alkylidene (arylidene)-1-phenylpyrazolidine-3,5-dione

“…Attempted cyclization of 2d using sodium borohydride/methanol and Pd/C or fusion of 11 to get pyrazolo [3,4-b]quinoline derivative 12 with expected interferon-eliciting activity [8][9][10][11] failed. This may be due to the spatial geometry of 11.…”

Substituted Pyrazolo[3,4-B]Pyridin-3-Ones and Pyrazolo[3,4-B]Pyridine-5- Carbaldehyde, New One-Pot Synthesis Strategy Amelioration Using Vinamidinium Salts, Antibacterial and Antifungal Activities Promising Environmental Protection

“…Fused heterocyclic containing pyrazolopyridine systems have been described associated with several biological and medicinal activities including anxiolytic [26], antiviral [27,28], antileishmanial [29] and anti-inflammatory [30] profiles [31]. However, pyrazolo [3,4-b] pyridine derivatives have been studied as antiviral [32], potential antimalarial agents [33], compounds inhibiting cholesterol formation [34], for the treatment of Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction and infertility [35]. They have also been reported as potent and selective inhibitors of A1 adenosine receptors [36] and phosphodiesterase 4 (PDE4) inhibitors in immune and inflammatory cells [37].…”

Three-component one-pot synthesis of dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridines

“…Among the various fused systems, pyrazolopyridines show promising biological activities as antibacterial [2], antitumor [3], antiviral [4] and anti-inflammatory [5] agents, and antagonists of corticotropin-releasing factor 1 (CRF 1 ) [6], chemokine receptor type 1 (CCR1) [7] and dopamine D3 receptors antagonists [8]. They are also known to be cholesterol forming [9], acetyl-CoA carboxylase (ACC) [10], HIV reverse transcriptase [11], phosphodiesterase 3/4 (PDE3/4) cyclin-dependent 1 (CDK1) [12], and B-Raf kinase inhibitors [13].…”