Indazole 6- nitro

Dzoljic, M. R., de Vries, R. van Leeuwen, R. (1996). Sleep and nitric oxide effects of 7-nitro indazole, inhibitor of brain nitric oxide synthase. Brain Res. 718, 145-50. 

Z., Hart, S. L., Babbedge, R. C., Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles antinociceptive and cardiovascular effects, Br. J. Pharmacol. 110 (1993), p. 219-224... 

S. L., 7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse... 

Motzko D, Glade U, Tober C, Flohr H. 7-Nitro indazole enhances methohexital anesthesia. Brain Res 1998 788(1-2) 353-5. 

Nitroindazole and 3-bromo-7-nitro indazole reduced the LEG power density in all frequency bands in the rat (Dzoljic et al. 1997). This effect of 7-nitroindazole was more prominent during the day than during the night, indicating a circadian variation in the NOS response to NOS inhibitors. 

LiCl (12 mEq/kg i.p.) and tacrine (5mg/kg i.p.) enhanced the expression of nNOS, but not eNOS, enzyme protein in the rat hippocampus during the preconvulsive period and this triggered seizures and hippocampal damage (Bagetta etal. 2002). Systemic administration of 7-nitro indazole (50 mg/ kg given i.p. 30 min before tacrine), a selective inhi-... 

Raman, C.S., Li, H., Martasek, P., Southan, G., Masters, B. S. S., Poulos, and Thomas, L. (2001), Crystal Structure of Nitric Oxide Synthase Bound to Nitro Indazole Reveals a Novel Inactivation Mechanism, Biochemistry 40 13448-13455. 

Indazoles. - The photochemical amination of nitro-indazoles has been reported thus 1-methyl-4-nitroindazole yields the 3-amino-derivative (272). 10-Diazoanthrone adds 4-methylbenzyne to form a mixture of the... 

Six articles cover general aspects of heterocyclic chemistry 1,3-dipolar cycloreversions, syntheses with arylnitrenes and a-metallated isocyanides, and photo-oxygenation of nitrogen heterocycles,while others deal with more specialized subjects, i.e. preparation and use of halogeno-lactones, aspects of the chemistry of furan, 1-hydroxy-indoles, ring-opening of azoles by the action of amines, " the use of 2-chlorobenzoxazolium (1) and other heterocyclic onium salts for dehydration and condensation reactions," the synthesis of monosub-stituted tetrathiafulvalenes (2), cycloadditions of azoles containing three heteroatoms,sydnone imines (3), the conversion of acyl-benzofuroxans into nitro-indazoles (cf. p. 199), and advances in the chemistry of pyrrolizidine " and indolizine." ... 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

From UV studies of 4-phenyl-, 4-nitro- and 4-nitroso-pyrazoles, Habraken et al. (67RTC1249,72JHC939) conclude that the 4-pyrazolyl group acts as an electron-donating group. UV spectra of pairs of 1-aryl- and 2-aryl-indazoles and their utility in the determination of isomeric structures are discussed in (67BSF2619) many other UV data on indazole derivatives can be found in (71PMH(3)67). 

Although the conventional mass spectra of the five C- nitro derivatives of indazole are nearly identical, the corresponding metastable peak shapes associated with the loss of NO-can be used to differentiate the five isomers (790MS114). The protonation and ethylation occurring in a methane chemical ionization source have been studied for a variety of aromatic amines, including indazoles (80OMS144). As in solution (Section 4.04.2.1.3), the N-2 atom is the more basic and the more nucleophilic (Scheme 5). 

The basicities of indazole (1.31), 1-methyl (0.42) and 2-methyl (2.02) derivatives and of eight other substituted indazoles have been measured (67BSF261 The effect of substituents in the 3-position is similar in pyrazoles and indazoles with Api values as follows Me, 0.80 and 0.86 Cl, -3.01 and -2.98 Br, -2.85 and -2.82, respectively. A nitro group in the homocycle has an expected base-weakening effect of -2 pK units, whether it is at the 5- or the 6-position. 

Studies of the alkylation of indazoles (67HC(22)1) have been updated by Nunn (73JCS(PD2371) and Palmer (75JCS(P1)1695). The ratio of methylation at positions 1 and 2 is relatively sensitive to the steric effect of substituents at positions 3 and 7 as shown by the results obtained in basic medium for unsubstituted indazole (55 45) and its 3-phenyl (74 26) and7-nitro derivatives (29 71). 

In the section dealing with electrophilic attack at carbon some results on indazole homocyclic reactivity were presented nitration at position 5 (Section 4.04.2.1.4(ii)), sulfon-ation at position 7 (Section 4.04.2.1.4(iii)) and bromination at positions 5 and 7 (Section 4.04.2.1.4(v)). The orientation depends on the nature (cationic, neutral or anionic) of the indazole. Protonation, for instance, deactivates the heterocycle and directs the attack towards the fused benzene ring. A careful study of the nitration of indazoles at positions 2, 3, 5 or 7 has been published by Habraken (7UOC3084) who described the synthesis of several dinitroindazoles (5,7 5,6 3,5 3,6 3,4 3,7). The kinetics of the nitration of indazole to form the 5-nitro derivative have been determined (72JCS(P2)632). The rate profile at acidities below 90% sulfuric acid shows that the reaction involves the conjugate acid of indazole. 

The creation of the N—N bond as the last step of the ring synthesis is common in indazoles and very rare in pyrazoles. In indazoles this method is well known (type B synthesis (67HC(22)l), for example, the dehydration of oximes (570) with acetic anhydride yields 1-acetylindazoles (571), and in basic medium the indazole 1-oxides (573) are formed from the nitro derivatives (572). 

In the search for new structures with antiinflammatory activities some 1-substituted 3-dimethylaminoalkoxy-lJ/-indazoles (704) have been synthesized and pharmacologically tested (66JMC38). Doses of 20-40 mg g i.p. produced sedation, muscle relaxation and motor incoordination, whereas doses of 80-100 mg kg produced depression. Toxicity was fairly constant in all series, varying from 120 to 150 mg kg i.p., with the exception of compounds possessing a nitro group or an amino group in the indazole nucleus, which provoked cyanosis. 

Anthranil, 7-nitro-synthesis, 6, 407 Anthranil, 3-phenyl-thermolysis, S, 91 Anthranilonitriles indazoles from, S, 274 Anthranils... 

So erhalt man aus 4-Formyl-benzofurazan-l-oxid mit primaren Aminen die entsprechenden 2-Alkyl-7-nitro- und 2-Aryl-7-nitro-2H-indazole (s.Bd.E8b)270 ... 

Formyl-3-methyl-2-( 2-methoxy-4-nitro-anilino)-2,3-dihydro-indazol wenig (bei pH = 6 42%)... 

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