Heterocyclic urea

Reaction of 2-aminothiazoles with alkyl isocyanates yields 2-thiazolylureas (256) (Scheme 153) (479-483). This reaction is general and works with acyl isocyanates (484. 485). These heterocyclic ureas are also prepared by the reaction of H2O on 2-thia2olylcyanamide (486) or by action of HjOj on the corresponding thiourea (303, 481). 

Li XQK, Jiang X, Wang XZ, Li ZT. Novel multiply hydrogen-bonded heterodimers based on heterocyclic ureas. Folding and stabihty. Tetrahedron 2004 60 2063-2069. 

Urea reacts with a wide variety of reagents to give substituted linear and heterocyclic urea derivatives. Some of these reactions are summarized in Eq. (47). 

S., WaUing, T., Wild, H. (2001) Discovery of heterocyclic ureas as a new class of raf kinase inhibitors identification of a second generation lead by a combinatorial chemistry approach. Bioorg Med Chem Lett 11, 2775-2778. 

Ganellin et al. [23] have combined histamine or its sulfur analog with nitrogen containing heterocycles ( urea equivalent strategy) to prepare a unique series of potent H3 antagonists related to UCL 1283 16. Examples of compounds from these efforts are the pyridine 18 (K,= 17 nM) and UCL 1199 19 (Ki = 4.8 nM) (Figure 9). 

Smith, R. A., Barbosa, J., Blum, C. L., Bobko, M. A., Caringal, Y. V., Dally, R., et al. Discovery of Heterocyclic Ureas as a New Class of Raf Kinase Inhibitors Identification of a Second Generation Lead by a Combinatorial Chemistry Approach. Bioorg. Med. Chem. Lett. 2001,11, 2775-2778. 

In summary, triazine resistance in weeds is most commonly due to a target site alteration that confers a very high level of resistance to. y-triazinc herbicides. Although a Ser264 to Gly mutation in the D1 protein is most common, additional alterations have been identified that confer resistance to triazines and other classes of PS II inhibitors. Enhanced herbicide metabolism plays a major role in conferring resistance in only a few weed biotypes. In these biotypes, the pattern of resistance may be broader, with some cross-resistance to av-trazinones, uracils, heterocyclic ureas and phenyl ureas. The level and pattern of resistance to various herbicides in these biotypes depend, presumably, on the activity and specificity of the enzyme(s) responsible for the enhanced herbicide metabolism. 

The heterocyclic urea derivative 606 (R = OCOCHaPh or H) with an o-substituted carboxyl group, on treatment with DCC, also cychzes with formation of 607... 

Imidurea is the best known of a family of heterocyclic urea derivatives that are effective antimicrobial preservatives. Diazolidinyl urea has the greatest antimicrobial activity. 

Figure 9.3 Cuccia s heterocyclic ureas (8), Gong s diary-lureas (9), and Hamilton s dibenzoylureas (10).

Heterocyclic ureas have been introduced recently, including tebuthiuron (1974) which is a broad-spectrum herbicide for the control of herbaceous and woody plants when applied at the rate of about 7.5 kg ha" As expected, at higher concentrations it can be used as a total herbicide. The urea herbicides... 

This is a broad grouping of many different types of agrochemicals (see Table 29.13). The classes of agrochemicals previously discussed often include heterocyclic types. There are heterocyclic acid types such as picloram, heterocyclic phosphates such as diazinon, heterocyclic carbamates such as benomyl, and heterocyclic ureas such as tebuthiuron. 

Miscellaneous compounds such as biopesticides (for example. Bacillus thuringiensis and pherhormones), heterocycles (for example, atrazine), pyrethroids (for example, cypermethrin), and urea derivatives (for example, diuron). 

One of the extensively investigated applications of enamines to heterocyclic syntheses is based on the bifunctional character of enamine acylation products. Thus the vinylogous ureas and thiorueas obtained from enamines and phenylisocyanate and phenylisothiocyanate (-433) have been converted to aminopyrazoles and thiouracils with hydrazine (566) and phenylisocyanate (567). 

Use of )3-dicarbonyl compounds in heterocyclic syntheses is, of course, well established, but an interest in vinylogous amides or vinylogous ureas as reactive intermediates has been increased by the current appreciation of enamine chemistry (592-594). 

Use of bis(trimethylsilyl)acetamide and bis(trimethylsilyl)urea for protection and as control reagents in reactions with participation of heterocycles 98S357. 

Synthesis of N-heterocycles using ureas and related compounds 98UK333. 

Methylation of nitrogen at the 2 position also proves to be consistent with diuretic activity. Condensation of 160 with urea affords the heterocycle, 193. Treatment of this compound with methyl iodide and base effects alkylation on the more acidic ring nitrogen (194). Basic hydrolysis then gives the N-methylated aminosulfonamide (195). Condensation of this with chloroacetalde-... 

In a similar way, 1,3-dinitrogen systems such as diamines, amidines, guanidines, aminothiazoles, aminopyridines, ureas and thioureas react with alkynyl-carbene complexes generating the corresponding heterocycles. Of particular interest is the reaction with ureas, as the process can be applied to the easy synthesis of pyrimidine derivatives [88] (Scheme 41). 

A limited series of amide replacements have been examined including thioamides (219) [163], reverse amides (220) [164], heterocycles (221) [164], ethers (222) [165], carbamates (223), (224) [165], ureas (225) [165] and ketones (226) [166] (see Table 6.19). In general, replacement of the amide results in a loss of binding affinity compared to AEA. In some cases, replacement of the amide results in increased stability with regard to hydrolysis by FAAH [164, 165]. 

CDI and the other A /V -carbonylbisazoles of sufficiently high reactivity react with alcohols ROH to produce diesters of carbonic acid RO-CO-OR, and with amines R R2NH to give diamides of carbonic acid (ureas) R N-CO-NR 2. By use of corresponding bifunctional partners, heterocyclic systems are accessible through insertion of the carbonyl group between two heteroatoms (see Chapter 7). 

N-Aminoimidazolinones have found extensive use as synthons for such nitrofurans. Reaction of an appropriate 1,2-diamine (27, 31) with urea gives the desired heterocycle (28, 32). Nitrosation with... 

A fused heterocyclic compound (146) distantly related to the antiinflammatory agent cintazone (Chapter 12), which itself can be viewed as a cyclized derivative of phenylbutazone, retains the activity of the prototype, in the synthesis of 146, reaction of the nitroaniline 139 with phosgene gives intermediate 140, which is then reacted with ammonia to afford the substituted urea (141). Cyclization of the ortho nitrourea function by means of sodium hydroxide leads to the N-oxide (142) this last reaction represents... 

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