Phenyl-2-aminopyridines

In total, antagonizing direct upstream control over the nNOS isoform can be achieved in part by application of internal and external Ca2+ channel blockers, Ca2+ buffering agents, hyperpolarizing agents or selective nNOS inhibitors such as 6 or 7-nitroindazole, l-(2-trifluoromethylphenyl) imidazole or 6-phenyl-2-aminopyridines [131-133],... 

Phenyl-2-aminopyridines have been explored as potential nNOS inhibitors (52). These compounds have some selectivity for nNOS over eNOS. They point out that the nNOS active site appears to be less sterically hindered than the eNOS active site. When the side-chain in the compound below is quinoline, the ICgo values (joM) for NOS inhibition are 0.21 nNOS and 0.83 eNOS for the PhCOCHa side-chain, the values are 0.14 nNOS and 0.89 eNOS for the PhCHaCO side-chain the values are 0.14 nNOS and 0.69 eNOS for the PhCH2CH2 side-chain the values are 0.26 nNOS and 0.45 eNOS, demonstrating almost complete loss of isoform selectivity. For the iBu side-chain the values are 0.35 nNOS and 0.37 eNOS, demonstrating no isoform selectivity. For the... 

An unusual preparation is that of 2-(A -cyano-A -phenyl)aminopyridine (DC-52), which is obtained by heating pyridine with JV-anilino-f-butoxycarbonyl imidoyl chloride at 170 for 15 minutes. ... 

Reaction of 2-aminopyridine with ethyl 2-cyano-3-ethoxy-3-methyl-, -3-ethyl-, -3-phenylacrylates and ethyl 2-ethoxycarbonyl-3-ethoxy-3-methyl-, -3-phenylacrylates in boiling xylene yielded 2-substituted 4/f-pyrido[l,2-u]pyrimidine-3-carbonitriles and -3-carboxylates (99MI7). Similar reactions of 2-aminopyridine with 2-cyano-3-ethoxyacrylonitrile and its 3-methyl, 3-ethyl, -3-phenyl derivatives in boiling MeCN afforded 4-imino-4//-pyrido[l,2-u]-pyrimidine-3-carbonitrile and its 2-substituted derivatives. 

Substitution of a 2-pyridyl residue for the phenyl attached rectly to nitrogen affords a series of potent antihistamines, eparation of these compounds, too, is accomplished by a series alkylation reactions. It is further probable that the order the reaction can be readily interchanged. Thus, alkylation 2-aminopyridine with the chloroethyldimethylamine side chain ads to the diamine, 59. Alkylation with benzyl chloride af-rds tripelenamine (60) reaction with p-methoxybenzyl chloride ads to pyrilamine (61), °... 

The parent heterocycle of pyrido[2,3-e][l,2,4]triazine and its phenyl derivative 39 were prepared (89JHC475) by cyclization with polyphos-phoric acid of 3-acyIhydrazino-2-aminopyridines 36, obtained by reduction of the corresponding 3-acylhydrazino-2-nitropyridines 35. Compounds 35 were obtained from 3-fluoro-2-nitropyridine 34 either by reaction with benzoylhydrazine or by reaction with hydrazine and subsequent for-mylation of the initially formed 3-hydrazino-2-nitropyridine 38. Attempts to prepare 38 from 3-chloro-2-nitropyridine gave 2-hydrazino-3-chloropyridine 37. These results could be explained by semiempirical calculations (CNDO and MNDO calculations). 

BtURET, 1-PHENYL-2-THIO-, 42,87 Bromination, of 2-aminopyridine, 44,34 of l-bromo-3-phenylpropane with N-bromosuccinimide to give 1,3-dibromo-l-phenylpropane,... 

There has been considerable interest in hydroxy-3,3 -bipyridines and 3,3 -bipyridinones. Following from some very early work on the oxidation of citrazinic acid (2,6-dihydroxypyridine-4-carboxylic acid), which was considered to give some polyhydroxy-3,3 -bipyridines, it has been shown that the 3,3 -bipyridinone 59, a product of the hydrolysis of a natural blue pigment from Corynehacterium insidiosum, is obtained by oxidation of 2-hydroxy-5-aminopyridine (60) or 2,6-dihydroxypyridine-4-carboxylic acid 61) 80,83 similar oxidation of 2,6-dihydroxy-3-aminopyridine-4-carboxylic acid affords the natural product indigoidine (20). Numerous related oxidative condensations have been reported subsequently. Cyano-acetamide condensations analogous to those discussed in the synthesis of 2,3 -bipyridines afford, for example, the cyano-substituted 3,3 -bipyridinone 62 588 v, lereas condensation of 3-pyridylacetonitrile with ethyl phenyl-propiolate and ethanol affords compound 63. To complete the section on... 

Al-Jallo and Al-Biaty24 prepared 4-phenyl-2-oxo-2H-pyrido[l,2-c<]-pyrimidines from 2-aminopyridines and ethyl phenylpropiolate. When the reactions were carried out in deuterium oxide, the 3-deuterated derivatives were obtained. 2-Amino-5-nitropyridine failed to react. 

Tkachenko et al.2S prepared 4-phenyl-2-oxo-2//-pyrido[l,2-a]pyrimidine (28) starting from 2-aminopyridine and the acid chloride (24 or 25) and associated intermediates 26 or 27. 

When the 5-phenyl derivative of 43 was used, a mixture of 3-(2-phenyl-2-chloroethyl)- and 3-(2-phenylvinyl)-8-methyl-4-oxo-4H-pyrido[l,2-a]pyri-midines was obtained.49 Depending on the conditions, reaction of 2-aminopyridines with 2-acetyl-4-chloromethylbutyrolactone (47) led to a variety of bicyclic products (48-54) (Scheme 2)49,83 Reaction of 2-aminopyridines with the acid chloride (55) yielded 4-oxo-4H-pyrido[l,2-a]pyrimidines (56) and traces of the amides of type 57. From 2-amino-6-methyl-pyridine, only the amide (57 R = 6-Me) was formed.86... 

By ring closure of the acrylates (73), 3-substitu ted 4-oxo-4//-py rido [ 1,2-a] -pyrimidines with chloroacetyl, 2-ethoxycarbonylvinyl, and nitro- and 4-chlorophenylsufonyl substituents have been prepared.22145-147 Reaction of 2-aminopyridine and the enamine (84) led to the 3-phenyl derivative (85), which is presumably formed by an addition-elimination mechanism.153... 

Reaction of 2-aminopyridine and the ketene mercaptals (92) in the presence of sodium ethoxide gave the 2-methylthio derivatives (93).161,162 2-Amino-pyridine and 2-phenyl-4-ethoxymethylene-5-oxazole gave the condensation product 94, which in the presence of sodium ethoxide at room temperature isomerized to 3-benzamido-4-oxo-4H-pyrtdo[l,2-< /]pyrimidine.163... 

On being heated with 5" aqueous alkali, 3-bromo-2-phenyl-4-oxo-4//-pyrido[l,2-a]pyrimidine was transformed to 2-phenylimidazo[l,2-u]pyri-dine, whereas the 2-methyl analog in 7"0 aqueous potassium hydroxide yielded a mixture of the 3-unsubstituted- and 3-carboxy-2-methylimidazo-[l,2-u]pyridines. Under similar conditions, 3-bromo-2-chloro- and 3-bromo-4-oxo-4ff-pyrido[l,2-a]pyrimidines decomposed to 2-aminopyridine.294... 

Hydroxy-4//-pyrido[ 1,2-a]pyrimidin-4-ones were prepared from 2-aminopyridines with diethyl [4-(2-cyanophenyl)phenyl]methylmalonate at 180°C (94MI2). 

When methanol was added to the ethereal reaction mixtures of benzyli-dene derivatives of 2-aminopyridines 198 (R = H, Me R1 = Ph) and the reaction mixtures were allowed to warm up to ambient temperature and left to stand overnight, 3-chloro-2-phenyl-4//-pyrido[l,2-a]pyrimidin-4-ones 199 (R = H, Me R1 = Ph) and the methyl esters of propionic acids 201 were obtained in 5-10% and 18-32% yields, respectively (84JHC407). 

Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridine 122 has been used in the treatment of nausea and vomiting <2006W02006/002823>. 

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