Quinazoline derivatives

They also state that analytical studies of the oxidation products of dichroine-a indicate that the dichroines are quinazoline derivatives, as already indicated by Koepfli et al. for their alkaloids. With the probable exception of dichroine-a, these bases are active against malaria in chicks in the descending order dichroine-y (1), dichroine- (4) dichroidine quinazolone (40) the figures in brackets are effective doses (mgm./kilo.). There are also two neutral substances present, umbelliferone (dichrin-A) and dichrin-B, m.p. 179-181°. 

Quinazoline derivatives are used as examples in discussion of the effect of hydrogen bonding or cationization (Section II, C), of the leaving group (Section II, D), and of other substituents (Section II, E). 

Another multistep protocol that initially involves the formation of fused pyrimidines (quinazolines) has been described by Besson and coworkers in the context of synthesizing 8f-/-quinazolino[4,3-b]quinazolin-8-ones via double Niementowski condensation reactions (Scheme 6.250) [437]. In the first step of the sequence, an anthranilic acid was condensed with formamide (5.0 equivalents) under open-vessel microwave conditions (Niementowski condensation). Subsequent chlorination with excess POCl3, again under open-vessel conditions, produced the anticipated 4-chloro-quinazoline derivatives, which were subsequently condensed with anthranilic acids in acetic acid to produce the tetracyclic 8H-quinazolino[4,3-b]quinazolin-8-one target structures. The final condensation reactions were completed within 20 min under open-vessel reflux conditions (ca. 105 °C), but not surprisingly could also be performed within 10 min by sealed-vessel heating at 130 °C. 

In analogous fashion to isocyanate chemistry, isothiocyanates like 125 can be utilized to produce the corresponding quinazoline-2-thioxo-4-ones. Makino and co-workers reported the solid phase synthesis of quinazoline derivatives 126 through the reaction of polymer-bound primary amines 124 with isothiocyanates 125 <00TL8333>. 

Fig. 10.13 Effects of the quinazoline derivatives on iNOS gene expression in RAW254.7 cells (A) and vascular smooth muscle cells (B).

Fujiwara, N., Okado, A., Seo, H. G., Fujii, J., Kondo, K., Taniguchi, N., Quinazoline derivatives suppress nitric oxide production by macrophages through inhibition of NOS II gene expression, FEBS Lett. 395 (1996), p. 299-303... 

In a similar way, 3-(2-ethynylphenyl)ureas, formed in situ by deprotection of the triple bond of 3-(2-trimethylsilylethynylphenyl)ureas, afforded benzoxazine or quinazoline derivatives, as exemplified by Eqs. 47 and 48 [121]. 

For example, Gyimesi-Forras et al. [50] performed a detailed investigation on the enantiomer separation of chiral quinazoline derivatives (2-substituted... 

In addition to the amiodarone-related compounds, (81) and (82), described above, BASF has been exploring some novel heterocyclic compounds as Class III antiarrhythmic agents. A series of imidazo[l,2-c]pyrro-lo[l,2-a]quinazoline derivatives have been patented which are several times more potent than (-I- )-sotalol in lengthening QT interval of the electrocardiogram in the anaesthetized guinea-pig model [230], One of the most potent compounds is (85), which was 17-times more potent than the standard. These compounds represent one of the unique Class III structural types described to date. 

Taylor and Patel describe a quinazoline synthesis (Scheme 93) transforming the iminophosphorane of anthranonitrile with isocyanate to car-bodiimide 254. Addition of ammonia in tetrahydrofuran (THF) leads to guanidine 255, which affords with the adjacent nitrile function quinazoline derivatives 256 (91JHC1857). 

Novel quinazoline derivatives like IC87114 (compound 15, Fig. 3) have been disclosed as inhibitors of pi 105 with good selectivity over the other... 

Thioquinazolincs can also be prepared by the reaction of lithiated quinazoline derivatives with disulfides. For example, reaction of the lithio species derived from 6-bromo-4(3//)-quinazolinone 74 with tetra-iso-propylthiuram disulfide gave the 6-dithiocarbamate 75 in 81% yield <2004M323>. 

Uracil derivatives can also participate in cobalt-mediated [2-f2-f2] cycloaddition reactions with dialkynes under photochemical conditions, to give cobalt complexed dihydrobenzo[g]quinazoline derivatives 482 <1999CEJ3549>. 

Hydrolysis of reduced quinazoline derivatives has also been performed, as demonstrated by the synthesis of enantiopure 2-aminocyclohexanecarboxylic acid 560 from octahydroquinazoline 559 <2004TA3545>. 

However, perhaps the simplest route to quinazoline derivatives involves the heating of 2-aminobenzamides with formic acid to give 4(3//)-quinazolinones, where the formic acid provides the solvent, the C-2 synthon, and the acid catalysis of the ring-closure step. For example, in the synthesis of the imidazoquinazolinone 798, both the imidazo and pyrimidine rings were formed simply by heating the triamino amide 797 in formic acid for 2h <1996JME918>. 

The synthesis of quinazoline derivatives by the addition of N(3)-C(4) fragment units has not previously been a major synthetic route, but 2,4-dialkyl, alkyl/aryl, and diaryl quinazolines 865 are now readily available by a new procedure that involves activation of A -arylamides 864 with trifluoromethanesulfonic anhydride and 2-chloropyridine, and subsequent addition of nitriles <2006JA14254>. Either normal or microwave heating can be used to perform the final ring-closure step. 

The synthesis of quinazoline derivatives by ring-opening and ring-closure reactions involving isatoic anhydrides and 3,l-benzoxazin-4-ones is covered in Section 8.02.9.2. 

Substituted quinazoline derivatives can be prepared by thermal ring contraction of 3/7-1,4-benzodiazepines <1999H(51)2407>. Both 5-methoxy 981 and 5-diethylamino-3/7-l,4-benzodiazepines 983 have been converted to the analogous 4-substituted quinazolines 982 and 984. 

Several quinazoline derivatives have antihypertensive activity. Examples include prazosin 1163, doxazosin 1164, terazosin 1165, bunazosin 1166, and trimazosin 1167, which bind to Qj-adrenoreceptors, and ketanserin 1168, a serotonin 5-HT2 receptor antagonist. 

Both pyrimidine and quinazoline derivatives have been investigated as ligands for palladium-mediated reactions. Examples of ligands prepared include the phosphine-free bipyrimidine 1181, which gave the isolable palladium dichloride catalyst 1182 <2001JOM(634)39>, and the chiral oxazolinyl-quinazoline BINAP analogs 1183 and 1184 <20060L5109>. 

Brand Name(s) Cardura, Cardura XL Chemical Class-. Quinazoline derivative... 

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