Carboxamides 7-hydroxy

A[,A/-diethyl-l,3,4,6,7,ll -hexaliydro-2-hydroxy-9,10-dimethoxy-2Ff-ben2o-(i7)-quinoli2ine-3-carboxamide acetate hydrochloride) (16) may be made by the method described in Reference 14. 

The use of selective P-antagonists for treatment of CHF has included the P -blocker metoprolol (Table 1) and results of clinical trials suggest long-term beneficial effects. Selective P -antagonists have also been tested, an example of which is xamoterol [81801 -12-9], C2 H25N20, which is (i)-A/-(2-hydroxy-3-(4-hydroxyphenoxy)propylamino)ethylmorphine-4-carboxamide. Xamoterol exhibits approximately 50% of the activity of isoproterenol, and serves to provide modest inotropic effects (128,129). 

Pyridazines with a hydroxy group at an a- or y-position to a ring nitrogen atom, i.e. 3-and 4-hydroxypyridazines (4) and (5), exist predominantly in the oxo form. This conclusion is based on spectroscopic evidence from UV spectra of unsubstituted compounds and their A-methyl and O-methyl derivatives in alkaline, neutral and acidic solutions. In some instances, as for example for 6-oxo-l,6-dihydropyridazine-3-carboxamide, there is also evidence from X-ray analysis <54AX199, 63AX318). Maleic hydrazide and substituted maleic hydrazides exist in the monohydroxymonooxo form (6). 

Pyrazolo-5-carboxamide, 4-hydroxy-3-/3-D-ribofuranosyl-occurrence, 5, 303 Pyrazolodiazepines synthesis, 5, 321... 

Pyrrole-2-carboxamide, N,N-dimethyl-conformation, 4, 194 Pyrrole-3-carboxamide, N,N-dimethyl-conformation, 4, 194 Pyrrolecarboxamides synthesis, 4, 242 Pyrrole-2-carboxamides synthesis, 4, 148, 360 Pyrrolecarboxylhydrazides Curtius degradation, 4, 362 Pyrrole-2-carboxylic acid, l-benzyl-3-hydroxy-ethyl ester... 

Reaction of 2-amino-3-hydroxypyridine and cyclohexanone 433 in boiling AcOH yielded N, 1 -diphenyl-6-hydroxy-3-methyl-11 -0x0-1,2-dihydro-11 //-pyrido[2,l-Z)]quinazoline-2-carboxamide (434) (98MI2, 99USP5908840, 99USP5914327). 

Fluorophenyl)-l ]-hydroxy-2,3,4,1 ]-tetrahydro-6/7-pyrimido[],2-Z)]-isoquinolin-6-one was obtained in the reaction of l-(4-fluorophenyl)-3-oxo-],3-dihydro-2-benzofuran-l-carboxamide and 1,3-diaminopropane in boiling toluene (01BMCL339). 

Catalytic hydrogenation of 9-(3-hydroxy-l-propynyl)-A-(4-chloroben-zyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- 7e]-l,4-benzoxazine-6-carboxamide over 5%) Pd/C in a 1 1 mixture of THE and MeOH afforded a mixture of... 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

Ethyl 1 -substituted 7-hydroxy-5-oxo-1,2,3,5-tetrahydropyrido[ 1,2,3-<7e] quinoxaline-6-carboxylates were reacted with A- [3,5-bis(trifluoromethyl)-phenyl]methyl methylamine to yield carboxamides (01MIP12). 

A solution of 2-chloro-Ar-(2-hydroxy-4-tolyl)-5-nitropyridine-3-carboxamide (6.3 g, 20 mmol) in pyridine (100 mL) was heated under argon at 90°C for 2.5 h and then cooled. Addition of H20 precipitated the crude product, which was collected and washed successively with hot H20, EtOH and Et20 yield 4.08 g (75%) mp 285-288JC. 

Inhibitors for proteases plasmepsin I and II of the malaria parasite Plasmodium falciparum, with a good plasmepsin/human protease cathepsin D selectivity, have been identified via library construction involving rapid microwave-accelerated Suzuki reactions [57]. The phenyl ring of the biphenyl unit in the lead compound M-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-phenyl-benzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methylpropyl)pyridine-2-carboxamide has been altered by performing Suzuki reactions on N-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-bromobenzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methyl-propyl)pyridine-2-carboxamide (Scheme 37). In particular, a 2-benzofuryl moiety proved to be interesting since a Ki value of 13 nM for plasmepsin I and... 

CN [8p(S)]-9,10-didehydro-N-(2-hydroxy-1 -methylethyl)-6-methylergoline-8-carboxamide maleate (1 1)... 

CN 4-hydroxy-2-methyl-//-(5-methyl-3-isoxazolyl)-2/7-1,2-benzothiazine-3-carboxamide 1,1-dioxide... 

S)-(L-osparoginylamino)-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyldecahydro-(4aS,8aS)-isoquinaline-3(S)-carboxamide (XII)... 

Reduction of 3-benzyl-8-chloro-4-oxo-4//-pyrido[l,2- ]pyrimidine-2-carboxylate <2004W004/064741> and 2-methyl-4-oxo-4//-pyrido[l,2-tf]pyrimidine-3-carboxylate <2003T4123> with DIBAL-H afforded 2- and 3-formyl derivatives, respectively. Reduction of /V-(4-fluorobenzyl)-3-hydroxy-8-[methoxy(methyl)amino]-4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2- ]pyrimidine-2-carboxamide with Zn-dust in aqueous AcOH afforded the 8-methylamino derivative, which was acylated with AcOH in the presence of Hiinig s base, HOBt, and l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide-HCl <2004W004/058756>. 3-(Perhydropyrido[l,2- ]pyrimidin-2-yl)propylamine was obtained by catalytic hydrogenation of 2-(perhydropyrido[l,2- ]pyrimidin-2-yl)propionitrile over a Pt02 catalyst <2003FRP1275647>. 

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