Pyrazoloquinoline

That the benzodiazepine structure was a prerequisite for the characteristic tranquilizer profile and specific binding at the benzodiazepine receptor was a long-held belief. This has now been shown not to be the case by the discovery of a range of different compounds that bind to the benzodiazepine receptor [Figure 29-2). These include the 3-carbolines (e.g., abecarnil), the triazolo-pyridazines [e.g., GL 218,872), the imidazopyridines (e.g., zolpidem), the cyclopyrrol ones [e.g., suriclone), and the pyrazoloquinolines. 

For 3-aryl-5-aminopyrazoles 222 the direction of the multicomponent reaction with cyclic P-diketones and aromatic aldehydes is not so unequivocal. Quiroga et al. [190] found that during refluxing of these starting materials in ethanol, the reaction products were only derivatives of pyrazoloquinoline 227,... 

A regioselective synthesis of pyrazoloquinolines 225 by the multicomponent reaction of 3-aryl-5-aminopyrazole 222 with 1,3-diketones and aromatic aldehydes in ethanol in the presence of Et3N under microwave irradiation at 150°C (Scheme 3.62, reaction i) was described in [193,194]. In the presence of a strong base such as EtONa (KOH), the three-component treatment proceeded via a different pathway and led to novel and unusual reaction products—quinolizi-nones 226 (Scheme 3.62, reaction ii) [193]. The formation of only one diaster-eomeric pair from two possible ones with trans relative configuration of the... 

As it was mentioned in Section III.B.3, 6-nitroquinoline 209 reacts with arylhy-drazones giving a mixture of pyrazoloquinolines 210 and triazinoquinolines 211. The formation of the latter can be considered to involve a cascade process taking its course via intermediate nitroso compound 298, which then undergoes a base-catalyzed heterocyclization (Scheme 88) (OOOL413). 

Pyrazoloquinolines frequently possess subnanomolar affinity for the BZR, but show no subtype selectivity in their binding (396). Unlike the benzodiazepines,some pyrazoloquinolines also bind to the diazepam-insensitive receptor subtypes (a4 and 0 6). Although several compounds show partial agonist and anxio-selective profiles (e.g., C(jS9896) in preclinical models, there is no evidence to suggest any... 

Conversely two closely related pyrazoloquinolines, compounds CGS 8216 and its para-chloro analog CGS 9896 present a totally opposed activity profile on the same benzodiazepine receptor. A dramatic effect resulting from chlorine substitution is also found in the change from 3-phenyl-GABA to 3-(p-chlorophenyl)-GABA. ... 

Gee, K. W., Yamamura, H. I. A novel pyrazoloquinoline that interacts with brain benzodiazepine receptors characterization of some in vitro and in vivo properties of CGS 9896. Life Sci. 1982, 30, 2245—2252. 

In terms of structure, compounds which bind to the BZD site are generally flat, and contain a two or three-ring heterocyclic nucleus at their core. They include the BZDs mentioned previously, /I-carbolines (e.g. abecarnil, 12), imidazopyridines (e.g. alpidem, 13), pyrazoloquinolines (e.g. CGS 8216, 14), and imidazoquinoxalines (e.g. panadiplon, 15). New series of compounds with BZD site affinity are regularly reported in the medicinal chemistry literature [38-41] with similar overall structural elements. There are... 

The other angular pyrazoloquinoline derivative 327 was obtained by hydrazinolysis of 2-imino-7,7-dimethy-4-methylsulfanyl-5-oxo-5,6,7,8-tetrahydro-2H-benzopyran-3-carbonitrile (326). The reaction can be proceeded by substitution of the methylsulfanyl group by hydrazine followed by cyclization to give 327 (97JCR(S)256) (Scheme 61). 

Compound 24 forms when 23 reacts with 2-aminobenzaldehyde 17 in a normal aldol condensation where the methyl group is converted to a nucleophile. In the second step, the amino nitrogen of 17 attacks the imine carbon of 23 with subsequent loss of N-NH-Ph. Alternatively, 23 was condensed with o-nitrobenzaldehyde and reduction and thermal cyclization gave pyrazoloquinoline 25 (34J1C427), a procedure similar to that used in the synthesis of an indolinquinoline (60CIL1871). 

Pyrazolo-based organic materials belong to the most promising blue electroluminescent and transporting materials. A series of pyrazoloquinoline derivatives have been synthesized for use in LEDs. Their optical properties can be tuned by the modification of the side groups. 4-Methyl-pyr-azolo[3.4-b]quinoline emits at 440-460 nm. ... 

J. Niziol, A. Danel, E. Gondek, P. Armatys, J. Sanetra, and G. Boiteux. Pyrazoloquinolines - alternative chromophores for organic LED fabrication. Macromol. Symp., 212 473-478, April 2004. 

Z. He, A. Danel, and G. H. W. Milbum. Thin-layer photoluminescence and electroluminescence observed from pyrazoloquinoline-doped polymer matrices. J. Lumin., 122-123 605-609, January-April 2007. 

Chen CH, Wu FI, Shu CF, Chien CH, Tao [119] YT. Spirobifluorene-based pyrazoloquinolines efficient blue electrolvuninescent materials. J... 

Niziol J, Danel A, Gondek E, Armatys P, Sane-tra J, Boiteux G, et al. Pyrazoloquinolines— alternative chromophores for organic LED fabrication. Macromol Symp 2004 212 473-8. 

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