Benzoyl Moiety Research Articles

Synthesis and bioactivity of some fluorine‐containing benzoyl arylureas. Part II: Insecticidal products in which the aryl group bears a polyfluoroalkoxy or (polyfluoroalkoxy)alkoxy side chain

AbstractThis paper reports the synthesis and insecticidal activities of benzoyl arylureas in which the aryl group bears a polyfluoroalkoxy or (polyfluoroalkoxy)alkoxy side‐chain. The activity of these compounds has been evaluated against larvae of S. littoralis, A. aegypti and L. decemlineata.The effects have been studied of varying (a) the substituents, R1 and R2 in the 2‐and 6‐positions of the benzoyl moiety; (b) the polyfluoroalkoxy chain R1 in the 4‐position of the aryl moiety; and (c) the other substituent(s), R3, on this ring.In general, the highest activities were achieved against S. littoralis when R1, R2 = F, R3 = 2‐F and R1 = OCF2CFHOCF3 or R1 = Cl and R2 = H. R3 = 2‐Cl and R1 = OCF2CFHOCF3; against A. aegypti when R1, R2 = F. R3 = 3‐F and R1 = OCF2CFHOCF3 or R1 = Cl and R2 = H. R3 = 3‐F and R1 = OCF2CFHOCF3; and against L. decemlineata by compounds in which R1 = Cl and R2 = H. R3 = 3. 5‐CI and R1 = OCF2CFHOCF3, R1, R2 = F, R3 = 3.5‐Cl and R1 = OCF2CFHOCF2CF3, R1, R2 = F, R3 = 3‐CI and R1 = OCF2CFHOCF2CF2CF3. The greatest overall insecticidal activities were achieved when R1, R2 = F, R3 = 2‐F and R1 = OCF2CFHOCF3 and when R1, R2 = F, R3 = 3‐Cl and R1 = OCF2CFHOCF3.

Effects of benzoylphenyl ureas on growth of B16 melanoma cells in vitro and in vivo

New analogs of diflubenzuron, a benzoylphenyl urea, are tested on their in vitro cytostatic activity against B16 melanoma cells. The following structure-activity relationship was established: substitution by a hydroxylated function at the ortho, meta or para position or by a dimethylamino function at the ortho position of the benzoyl moiety appeared to be necessary for cytostatic activity in vitro. Acetoxy functions at the ortho position or hydroxy functions at the para position of the aniline ring resulted also in active compounds. A number of these benzoylphenyl ureas are selected for in vivo evaluation of antitumor activity on B16 melanoma growing s.c.. Although many of the tested benzoylphenyl ureas delayed tumor growth during the first ten days of drug treatment, only a few increased animal life span. The best results (% T/C) were obtained with compounds 5 (127%), 7 (147%), 13 (135%) and 16 (135%), which all have hydroxylated functions in the benzoyl moiety.

(Benzoylphenyl)piperidines: a new class of immunomodulators

A series of (benzoylphenyl)piperidines has been synthesized and evaluated for activity as immunomodulators. Several of these compounds show good activity in primary screening on the basis of the lymphocytes mitogenic response to Con A, PHA, and PWM. A chloro group in position 4 of the benzoyl moiety as well as an amino group (or a carbamate derivative) para to the piperidine nucleus seems to be essential for activity. The depicted compounds may be considered as the first examples of a new series of immunomodulators.

Anodic oxidation of some substituted benzoylacetanilides in non-aqueous media

Anodic oxidation of three series of benzoylacetanilides has been investigated in benzonitrile at a platinum electrode. Series I contains substituents on the benzoyl moiety, series II has the substituents on the anilide moiety and series III has substituents on both benzoyl and anilide moieties. All these compounds are oxidized in two irreversible one-electron processes following the ECEC mechanism leading to the formation of the corresponding substituted 2,4-dioxo-1 -phenyl-1,2,3,4-tetrahydroquinoline. A good linearity is obtained when the E½ values are plotted against the σ substituent constants of the substituents in the different series (I–III).

Theoretische Untersuchungen zur Molekülgeometrie, zum elektronischen Spektralverhalten und intramolekularen Donor‐Akzeptorvermögen ausgewählter Diphenylchalkone

Theoretical Investigations on the Molecular Geometry, the Electronic Spectral Behaviour and the Intramolecular Donor‐Acceptor Properties of Selected Diphenyl ChalconesTheoretical completely‐optimized S0 and S1 molecular geometries of diphenylpropenone are presented. On this basis the influence of donor substituents within the styryl and/or benzoyl moieties on the electronic spectral behaviour and the intramolecular donor‐acceptor properties has been studied. The theoretical results are interpreted in context with the experimental data.

New bioactive heptenes from melodorum fruticosum (annonaceae)

By guiding fractionation with brine shrimp lethality, three novel compounds, with cytotoxic activities against human tumor cell lines, have been isolated from the bark of Melodorum fruticosum Lour.(Annonaccae). These compounds have benzoyl moieties in common with a c 7 dienone or lactone terminal which appears to arise from a heptose or the equivalents. They were named melodienone, isomelodienone, and acetylmelodorinol.

Quantitative structure-activity studies of benzoylphenylurea larvicides: VI. Comparison of substituent effects among activities against different insect species

The larvicidal activity of a number of substituted benzoylphenylureas was measured against the silkworm, Bombyx mori, and the common cutworm, Spodoptera litura, under various synergistic conditions. The effects of substituents at the anilide moiety on the activity were analyzed quantitatively using physicochemical parameters and regression analysis, and compared with those on the activity against the rice stem borer, Chilo suppressalis, analyzed previously. The effects of structural variations at the benzoyl moiety were also quantitatively compared among activities against these insect species. The results indicated that the effects of substituents at the benzoyl moiety are much the same, but the electronic substituent effect at the anilide moiety is quite different among species, being attributable to differences in the participation of the metabolic transformation in the apparent activity. The specific larvicidal spectra of certain compounds in this series were suggested to be due to innate differences in the metabolic mechanism besides differences in the physicochemical substituent effects on the ultimate activity.

Studies of the inhibition of aldose reductase: Evidence for multiple site inhibitor binding

1. 1. Comparison of structure-inhibition relationships and kinetic data between the N-{[(4-benzoylamino) phenyl]sulfonyl}amino acids (BAPS-amino acids) and phenylsulfonylamino acids (PS-amino acids) suggests that the additional benzoyl moiety present in the BAPS-amino acids enhances inhibition by direct interaction with aldose reductase (EC 1.1.1.21) without altering the mode of interaction with the enzyme. 2. 2. Also the 2-, 3- and 4-nitro regioisomers of BAPS-glycine (NBAPSG) display parallel structureinhibition relationships with the 2-, 3- and 4-nitrobenzaldehyde substrates and the 2-, 3- and 4-nitroacetophenone competitive inhibitors. 3. 3. Competition studies and multiple inhibition analyses demonstrate that the 4-nitrobenzoyl group of 4. 4-NBAPSG binds at the substrate site of aldose reductase, while the PS-glycine moiety of 4-NBAPSG binds cooperatively at a distinct site.

The biosynthesis of the benzoyl moiety of cocaine

[carboxyl- 13C, 14C]Benzoic acid,[carbonyl- 13C, 14C]-and [4- 3H]-benzoic acid, S-(2-acetamidoethyl)ester served as precursors of the benzoyl moiety of cocaine when fed, by leaf painting, to Erythroxylum coca plants. The high (10.5%) specific incorporation, of the 13C-labelled thioester was established by 13C NMR. Aqueous Tween 80 was found to have a significant effect on the degree of incorporation of the benzoic acid, presumably facilitating the transport of the labelled compound through the leaf wax. A major component of the leaf wax is hentriacontane.

Quantitative structure-activity studies of benzoylphenylurea larvicides: III. Effects of substituents at the benzoyl moiety

The larvicidal activity of 2-substituted- and 2,6-disubstituted-(4-chlorophenyl)ureas against rice stem borers ( Chilo suppressalis) and silkworms ( Bombyx mori) was measured by topical application under conditions in which oxidative metabolism was eliminated using piperonyl butoxide. The substituent effects at the benzoyl moiety on the activity were analyzed quantitatively using physicochemical parameters and regression analysis. The substituent parameter for the electron withdrawal from the side chain was estimated taking into consideration the steric inhibition of the resonance of ortho substituents. The results indicated that the larvicidal activity was enhanced by electron-withdrawing and hydrophobic substituents and lowered by bulky groups. The effect of substituents at the benzoyl moiety on activity was about the same for rice stem borers and silkworms. In vitro inhibition of the same series of compounds against new cuticle formation was also measured using cultured pieces of integument of diapause larvae of the rice stem borer. In vitro activity was linearly related to in vivo activity after allowing for the hydrophobic factor that may contribute to transport.

Quantitative structure-activity studies of benzoylphenylurea larvicides: IV. Benzoyl Ortho substituent effects and molecular conformation

The effect of ortho substituents at the benzoyl moiety of benzoylphenylurea derivatives was studied by infrared spectra, using the corresponding benzamides as model compounds. The stretching frequency of the amide carbonyl was quantitatively analyzed with the electronic and steric parameters of the ortho substituents. We found that di- ortho substitutions, but not mono- ortho substitutions, twist the amide group from the coplanar conformation, inhibiting resonance interaction with the benzene ring. Intramolecular hydrogen bonding between amide NH and hydrogen acceptor ortho substituents was detected by examining the NH stretching bands. The possibility of stacking interaction between two aromatic rings in an aqueous environment was studied by comparing the 1-octanol/water partition coefficients of benzoylphenylureas with those of related aliphatic acylalkylureas. Using the additive and constitutive principles in partition coefficients for compounds without intramolecular interactions, we propose an extended conformation for benzoylphenylureas.

Application of the ORMUCS Method to Structure‐Activity Studies on the Fungicidal Activity of Mepronil Derivatives

AbstractApplication of the ORMUCS method, proposed by the authors in the previous work, to structure‐activity studies is discussed in comparison with the Hansch approach. Using this method, the correlation between chemical structures of a series of mepronil derivatives and their fungicidal activity were examined with rating score data obtained by green house tests (in vivo test). The activity was highly correlated with the largest width and hydrogen accepting property of a substituent on the benzoyl moiety. This is consistent with the best QSAR equation obtained from Hansch analysis using in vitro data for mycelial growth inhibition on the same series.

2,3-Dehydrococaine: not a direct precursor of cocaine in Erythroxylum coca.

(+/-)-3-[4(-3)H]Benzoyloxy-2-[carbonyl-13C, 14C]carbomethoxy-2-tropene (2,3-dehydrococaine) was synthesized from Ba [13C, 14C]CO3 and [4(-3)H]benzoic acid. This labeled compound (3H/14C 0.65) was administered to Erythroxylum coca plants for 3 and 15 days. After these times, cocaine was isolated and was found to have a 3H/14C ratio quite different from the administered dehydrococaine (3.0 and 10.6 for the 3- and 15-day feeding experiments, respectively). Degradations of the cocaine indicated that tritium was all located in the 4-position of its benzoyl moiety. 13C-nmr spectroscopy indicated enrichment of the carbomethoxy group of cocaine, consistent with the observed specific incorporation of the 14C. From the 3-day feeding experiment unmetabolized dehydrococaine was isolated having the same specific activity and 3H/14C ratio as the administered compound. Also from this feeding experiment 2-carbomethoxy-3-tropinone was isolated having about 1/3 the specific activity (14C) of the administered dehydrococaine and having a (-) optical rotation. These results indicate that cocaine is not formed by the direct reduction of dehydrococaine. The results indicate that cocaine is not formed by the direct reduction of dehydrococaine. The results are rationalized by proposing initial hydrolysis of the dehydrococaine to benzoic acid and 2-carbomethoxy-3-tropinone. The latter compound is then reduced to methyl ecgonine, which is then esterified with benzoic acid to yield cocaine. The change in the 3H/14C ratio is due to the fact that only the (+) enantiomer of 2-carbomethoxy-3-tropinone is converted to cocaine, and that different pool sizes of the non-labeled intermediates exist in the plant.

Structural features of various proglumide-related cholecystokinin receptor antagonists

Thirteen proglumide derivatives that varied in the length of the di-n-alkyl group and in the substitutions on the benzoyl moiety were tested for their ability to interact with guinea pig pancreatic cholecystokinin (CCK) receptors. Each derivative was more potent than proglumide. There was a close correlation between their abilities to inhibit CCK-stimulated amylase release and to inhibit binding of 125I-CCK. For the di-n-alkyl derivatives the relative potency was n-pentyl greater than n-hexyl greater than n-butyl greater than n-propyl. For the benzoyl moiety, adding two electron-withdrawing groups increased potency more than adding a single electron-withdrawing group or adding electron-donating groups. The 3,4-dichloro-di-n-pentyl derivative of proglumide was 1,300 times more potent than proglumide, and its action was specific, competitive, and it functioned as a CCK receptor antagonist in rat, mouse, and guinea pig pancreas. For all proglumide derivatives there was a good correlation (r = 0.84, P less than 0.001) between their abilities to inhibit CCK-stimulated amylase release and that previously reported for their abilities to inhibit CCK-induced gallbladder contraction. However, certain proglumide derivatives had a much higher affinity for the pancreatic CCK receptor than for the CCK receptor mediating gallbladder contraction. For other proglumide derivatives the pattern was reversed. These results demonstrate that both the di-n-alkyl group and the substitution on the benzoyl moiety of proglumide are equally important determinants of affinity and that derivatives such as the di-n-pentyl 3,4-dichloro analogue can be produced that are 1,300 times more potent than proglumide.(ABSTRACT TRUNCATED AT 250 WORDS)

The Dissociation Constants of Some 1,5,5‐Trisubstituted Barbituric Acids

AbstractThe pKa, values of 15 N‐substituted 5,5‐diethylbarbituric acids containing phenyl, benzyl and benzoyl moieties have been determined. The qualitative and quantitative effects of substitution at the N‐1 atom on the pKa, value are discussed.

Proglumide analogues: potent cholecystokinin receptor antagonists

Proglumide [N-(benzoyl)-L-glutamic acid-1-di-n-propylamide] is a specific cholecystokinin receptor antagonist. In the present study we synthesized various analogues of proglumide and used pancreatic acini from guinea pig pancreas to examine the abilities of these analogues to function as cholecystokinin receptor antagonists. Each analogue inhibited cholecystokinin octapeptide-stimulated amylase secretion but did not stimulate amylase secretion when present alone. There was a close correlation between the ability of a particular analogue to inhibit the action of cholecystokinin on acinar cell function and its ability to inhibit binding of 125I-cholecystokinin. Structure-function studies demonstrated that neither the dipropylamide nor the benzoyl moieties are essential for inhibiting the action of cholecystokinin but that both groups are important in determining the inhibitory potency. Replacing the dipropylamide group with a hydroxyl group caused a 13-fold decrease in potency. Replacing the benzoyl moiety by an acetyl group caused a 30- to 40-fold decrease in inhibitory potency, whereas replacing the benzoyl moiety by a p-chlorophenoxyacetyl or phenoxyacetyl moiety caused a 75-fold increase in potency. Replacing both the dipropylamide moiety with a hydroxyl group and the benzoyl moiety with a phenoxyacetyl group resulted in a 5-fold decrease in inhibitory potency. Inhibition of cholecystokinin-stimulated amylase release by both the phenoxyacetyl and p-chlorophenoxyacetyl analogues was competitive in nature, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on potential antiviral compounds, XXIII. 2-(substituted benzoylamino)-3,5-dichloropyridines and isosteric benzamides.

AbstractNovel 2‐(substituted benzoylamino)‐3,5‐dichloropyridines and isosteric benzamides were synthesized and tested in vitro against the MP strain of herpes simplex virus type 1 [HSV‐1(MP)]. The introduction of methoxy groups at the 2‐ and 6‐positions of the benzoyl moiety yielded compounds which significantly inhibit HSV‐1(MP) growth. Substitution with fluorine at the 4‐position of the benzoyl group resulted in inactive compounds and on the whole led to enhanced cell toxicity. 2‐(3‐Bromo‐2,6‐dimethoxybenzoylamino)‐3,5‐dichloropyridine (11) was the most active compound (2.06 log10 units > 99% inhibition at 100μg/ml).

Aromatic rearrangements in the benzene series. Part 3. Rearrangement of isotopically labelled phenyl benzoates: intermolecularity of the ortho-directed rearrangement. Criteria for determining the intra-/inter-molecularity of aromatic rearrangements

The rearrangement of a mixture of Ph13COOPh and PhCO18OPh (with some unlabelled ester) catalysed by anhydrous AlBr3 in homogeneous solution in chlorobenzene has been examined. Contrary to expectations, more of the 2-hydroxybenzophenone is formed intermolecularly than of the 4-hydroxybenzophenone at the beginning of the reaction, contradicting earlier views that a high ortho : para ratio in such reactions indicates the operation of an intramolecular mechanism. A mechanism is proposed for this stage of the rearrangement involving a cyclic six-membered transition state originating from one molecule of phenyl benzoate and one of Ph–C(OPh)=[graphic omitted]–ĀlBr3, allowing C-acylation by the benzoyl moiety of the catalyst–ester complex to compete with bimolecular ester interchange. This C-acylation can only occur at the ortho-position of the phenoxy-ring of the (uncomplexed) ester molecule, because of steric requirements. This step of the rearrangement is thus necessarily intermolecular. Criteria for judging the intra- or inter-molecularity of aromatic rearrangements are also briefly discussed.

Evaluation of the intramolecular stacking of the fluorosulfonylbenzoyl derivatives of 1,N6-ethenoadenosine, adenosine, and guanosine.

The differences in conformation in solution of fluorosulfonylbenzoyl nucleosides were analyzed by fluorescence and proton nuclear magnetic resonance spectroscopy. The quantum yield of 5'-p-fluorosulfonylbenzoyl-1,N6-ethenoadenosine (5'-FSB epsilon A) in aqueous solution is low (ø = 0.01) as compared to that of its parent nucleoside, ethenoadenosine (ø = 0.54), and increases approximately 5-fold when measured in a series of solvents of decreasing dielectric constant. The quantum yield of 5'-p-sulfonylbenzoyl-1,N6-ethenoadenosine covalently bound to glutamate dehydrogenase and pyruvate kinase is also 0.01, suggesting that the analogue may exist in the same conformation when enzyme-bound as when free in solution. In D2O, the resonances of the purine ring protons on 5'-FSB epsilon A, 5'-p-fluorosulfonylbenzoyl adenosine (5'-FSBA), and 5'-p-fluorosulfonylbenzoyl guanosine (5'-FSBG) are shifted upfield by about 0.1-0.3 ppm relative to the corresponding protons of their parent nucleosides. The calculated difference in chemical shift (delta delta) decreases as the dielectric constant of the solvent decreases. The delta delta decreases with increasing temperature. These data indicate that 5'-FSB epsilon A, 5'-FSBA, and 5'-FSBG exist in aqueous solution in a conformation in which the purine ring is intramolecularly stacked with the benzoyl moiety. From the magnitude of change in delta delta for 5'-FSB epsilon A, 5'-FSBA, and 5'-FSBG as a function of solvent, it appears that the three analogues differ in their sensitivity to disruption of stacking. The solution conformation of these three fluorosulfonylbenzoyl nucleoside analogues may be an important determinant of their reaction with various enzymes and may explain differences among the analogues in their reaction with a single enzyme.

Biosynthesis of cocaine and cuscohygrine from [1- 14C]acetate and [4- 3H]phenylalanine in erythroxylon coca

A mixture of sodium [1- 14C]acetate and DL-[4- 3H]phenylalanine ( 3H/ 14C  1.0) was administered to Erythroxylon coca plants by painting an aqueous solution of these compounds on the leaves. The leaves were removed after two weeks and yielded labeled cocaine ( 3H/ 14C  11.4)and cuscohygrine. A systematic degradation of the cocaine indicated that 96% of the 3H was located in the para-position of its benzoyl moiety, and the 14C was located in the ecgonine residue at positions in accord with the accepted biosynthesis of this alkaloid. The cuscohygrine, containing a negligible amount of 3H, was found to have 67% of its 14C located on the carbonyl carbon. Cocaine, isolated from a second crop of leaves, harvested 10 weeks after the initial feeding, was still labeled at specific positions.