Imidazopyridine

Imtdazo[4,5-c]pyridtne, 4,5,6,7-tetrahydro-synthesis, 5, 623, 640, 641 Imidazo[4,5-c]pyridine-6-carboxylic acid, 4,5,6,7-tetrahydro-synthesis, 5, 623, 641 Imidazopyridines as anthelmintic, 1, 202 synthesis, 5, 462 Imidazo[l,2-n]pyridines deuterium exchange, 5, 611 diazo coupling, 5, 614 Dimroth rearrangement, 5, 613 halogenation, 5, 611 hydrogenation, 5, 614 Mannich reaction, 5, 612 nitration, 5, 612 1-oxides... 

Treatment of a 3-aminotriazolopyridine with acid gave the imidazopyridine 242 (81T1787), also obtained from the 3-nitro derivative by catalytic reduction (83AHC79). Quaternary salts derived from compound 2, when treated with tri-ethylamine and subsequently heated give 2-pyridylcyanamides 243 or 2-(oxazol-l-yl)pyridines 244 depending on the alkyl group (86H(24)2563) the ylides are presumably intermediates (see also Section IV.I). 

The narrow therapeutic range of digitalis related cardiotonic agents has resulted in an extensive effort to identify compounds in other structural classes which will improve cardiac function. The discovery of the heterocyclic cardiotonic drug, amrinone, led to research on other heterocyclic compounds for that indication. The imidazopyridine, isomazole (57), is representa-... 

It was known that the K+ -competitive imidazopyridine compound, SCH28080, inhibits acid secretion. Then, many reversible inhibitors were developed. These contain protonatable nitrogens but have a variety of core structures such as imidazopyiidines, piperidinopyr-idines, substituted 4-phenylaminoquinolines, pyrrolo [3,2-c]quinolines, guanidinothiazoles, and 2,4-diamino-pyrimidine derivatives. Several reversible inhibitors have been in clinical trials. 

Fig. 3.10 Recognition of the DNA minor groove with benzimidazole derivatives, (a) Structure of the dimeric core for Py-benzimi-dazole (Bi), Py-hydroxybenzimidazole (Hz) and Py-imidazopyridine (Ip) (left) in comparison with the five-membered ring system (right). H-bonding surfaces along the recogni-...

The term benzodiazepine refers to a specific chemical structure. Numerous benzodiazepine-receptor ligands exist which have different structures. These include the jS-carbolines (e.g. methyl-6,7-dimethoxy-4-ethyl-jS-carboline 3-carboxylate DMCM), triazolopyridazines (e.g. CL 218872), imidazopyridines (e.g. zolpidem), and pyrazolo-quinolinones (e.g. CGS 8216). In experimental animals these compounds produce... 

Figure 19.6 The chemical structure of the imidazopyridine and benzodiazepine (BZi) receptor ligand, zolpidem, and the cyclopyrrolone, zopiclone...

In 2007, Fernandez et al. demonstrated that transition-metal complexes with heterobidentate S/C ligands based on imidazopyridin-3-ylidene and thioether functionalities could be readily prepared from the corresponding azolium salts by reaction with Ag20 and transmetalation of the resulting silver carbenes with appropriate metal sources. The cationic Pd(allyl)(carbene-S) complexes have proven to be active catalysts in the test reaction, reaching enantioselectivities of... 

The group at Johnson and Johnson has published several reports on their efforts to find potent H3 antagonists. High-throughput screening using the recombinant human receptor identified the imidazopyridine RWJ-20085 (30) as a weak H3 receptor ligand K — 4 pM). Medicinal chemistry efforts then led to the discovery of the piperidine propyloxy compound (31) [100]. This imidazopyridine has a A) at the human H3 receptor of 2nM and... 

In efforts designed to replace the imidazopyridine ring system, indolizi-dines such as (32) [101] (human H3 if = 13 nM), and related heterocycles [102-104] were identified as potent H3 antagonists. Indolizidine (32) suffered from rapid metabolism in human liver microsomes, however, substitution on the indolizidine ring suppresses this liability. 

Lund R., Riither E., Wober W Hippius, H. (1988). Effects of Zolpidem (10 and 20 mg), lormetazepam, triazolam and placebo on night sleep and residual effects during the day. In Sauvanet J. P., Langer S. Z., Morselli P. L (eds.), Imidazopyridines in Sleep Disorders. New York, NY Raven Press, pp. 193-203. 

Ketal 219 undergoes intramolecular cyclization to intermediate imidazopyridine 220 which is a precursor to amide 221 (Scheme 9) <2004TL553>. 

Potent IRAK-4 inhibitors have been reported by several groups including some structurally related benzimidazoles (e.g., 34-36) as well as alternative fused heterocycles such as the imidazopyridine (37) and imidazopyridazine (38) [102-107]. Such compounds are... 

The pyridotriazines 21 and 22 were obtained (84JHC1765) by the cycliza-tion of the 2-chlorolpropargyl pyridinium bromide 20 with methylhydra-zine or 1,2-dimethylhydrazine, respectively. On the other hand, when hydrazine or acetylhydrazine were used in the reaction, imidazopyridin-ium salts were formed. 

A large number of patent applications has been filed, most recently describing imidazothiazoles [70], oxazolopyridines [71], benzimidazoles [72], benzothiazoles [73] and imidazopyridines [74] as sirtuin modulators, however it is not yet possible to determine which compound classes will prove most promising. Overall, due to their potential applications as new drug candidates for various indications, the class III HDAC inhibitors are currently a rapidly growing field of interest. 

Amino-2,3-dimethyl-3//-imidazo[4,5-fc]pyridine was reacted with EMME in boiling toluene for 2 hr to afford 7V-(imidazopyridin-5-yl)amino-methylenemalonate (91) in 84% yield (86EUP174832). The reaction of 3-amino-4,6-dimethyl- l//-pyrazolo[3,4-6]pyridine and EMME yielded N-(4,6- dimethyl -1 //- pyrazolo[3,4 - 6]py ridin- 3 - y l)aminomet hy lenemalonate (92) (87MI5). 

As with the reaction of pyrroles, diazoles and triazoles react with propargyl bromide to yield TV-substituted products and, depending upon the base strength, either TV-prop-2-ynylazoles or allenic derivatives are formed [30]. Generally, with potassium carbonate under soliddiquid two-phase conditions at room temperature in the absence of a solvent, the prop-2-ynyl compounds are formed as sole products, whereas with solid potassium hydroxide at elevated temperatures the allenes are obtained as the major products. Benztriazole produces a mixture of the N1- and N2-prop-2-ynyl, and N2-allenic derivatives, whereas with potassium hydroxide only the N -allenic derivative is obtained. The alkynes readily isomerize to the allenes in the presence of base and the quaternary ammonium salt, or upon treatment with methanolic sodium hydroxide. A series of l-(alk-2-ynyl)imidazoles have been prepared, as intermediates in the synthesis of imidazopyridines [31 ] and the reaction of 3-hydroxymethylpyrazoles with propargyl bromide leads to pyrazolooxazines [32]. 

Zolpidem is an imidazopyridine but not a benzodiazepine however, it acts on the same receptors as benzodiazepines. Zolpidem has a short duration of action and is indicated for patients who have difficulty sleeping. It does not have any hangover effects. The dose of Zolpidem should be reduced in patients with hepatic impairment and it should be avoided in cases of severe hepatic impairment. 

Zolpidem (an imidazopyridine) and zopiclone (a cyclopyrrolone) are hypnotics that, despite their different chemical structure, possess agonist activity at the benzodiazepine receptor (p. 226). 

The search for viable partial agonists or subtype selective ligands has led to the development of a variety of compounds representing diverse structural types including imidazoquinoxalines, benzodiazepines, imidazopyridines and -carbolines. In an effort to identify replacement candidates for the partial agonist pandiplon U 78875 206 [289], which was removed from clinical trials due to... 

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