Structure benzamides

Chemical Name N-[1 -[2-(1 H-lndol-3-yl)ethyl] -4-piperidinyl] benzamide Common Name -Structural Formula ... 

Chemical Name N-(1-Methylethyl)-4-[ (2-methylhydrazino)methyl] benzamide HCI Common Name Ibenmethyzin Structural Formula coNHCHfCHjij... 

Ring-chain tautomerism occurs in sugars (aldehyde vs. the pyranose or ftira-nose structures). In benzamide carboxaldehyde (125), whose ring-chain tautomer is... 

Derivatives of (S) N-[(l-ethyl-2-pyrrohdinyl)methyl]-6-methoxy benzamide 3 are dopamine D2 receptor antagonists. Samanta et al. obtained the following MLR QSAR for 49 derivatives with the general structure 3 [30] ... 

Figure 13 Series of de novo designed nonpeptides containing a benzamide template (exemplified by compound 12, AP21 733) designed to interact favorably with Src SH2 and specifically to displace structural waters found in complexed Src SH2 structures [14,27]. The Src SH2 binding IC50 is shown for each compound, as well as a comparative IC50 for Ac-pTyr-Glu-Glu-lle-NH2 (compound 9).

Furthermore, there are two other aspects to the extrapolation problem one structural and one statistical. An illustrative example of these various cases can be found in a dataset of benzamides (S16.1). that one of the present authors (U.N.) published some time ago [44]. If one develops a PLS model based on the same descriptors and the same, experimental design-based, training set (compounds 1-16) augmented by compound 17 (Table 16.8) in order to prove the points raised above [the prediction limit (1.502) set to two times the overall RSD of the model (0.751) which roughly gives 95% confidence interval], one can observe the following with respect to predictions on the remaining test set compounds ... 

Norinder, U., Hogberg, T., A quantitative structure-activity relationship for some dopamine D2 antagonists of benzamide type, Acta Pharm. Nord. 1992, 4, 73-78. 

The structure activity relationship (SAR) and animal model studies of biaryl benzamide MTP inhibitors 3 and 4 have also been reported. Compound 3 has an IC50 of 0.5 nM against human MTP in an in vitro assay and showed normalization of plasma lipoprotein levels in Watanabe-heritable hyperlipidemic rabbits,... 

Further divergence from classical benzamide structure is represented by the synthesis of ondansetron (GRF 38032F, (33)), a potent 5-HT3 receptor antagonist where the basic nitrogen atom is part of an imidazole ring and the aromatic ring is part of tetrahydrocarbazolone ring system [27],... 

Benzamide (43,51) crystallizes from ethanol in space group Pljc. The main features of the crystal structure (52) (Figure 5) are similar to those found in cinnamide. Hydrogen-bonded cyclic dimers are interlinked along the 5.0-A b axis to form ribbons. The ribbons are stacked along the 5.6-A a axis, in an... 

The simplest structures in this series are A-methyl- and A-ethylbenz-amide (4.73 and 4.74, respectively). When administered intraperitoneally in rats, these amides yielded methylamine and ethylamine, respectively, plus benzoic acid, which was detected in the urine as hippuric acid [47]. An alternative metabolic pathway is possible, involving A-dealkylation to the primary amide followed by hydrolysis its contribution, if any, must be minor, since benzamide levels in urine were negligible. 

Having discussed amides that carry an aromatic group on either the nitrogen or the carboxy side of the amide bond (i.e., anilides or benzamides, respectively), we continue our presentation with compounds in which the amide bond links two aromatic systems. The simplest structure in this class is A-phenylbenzamide (4.154). The influence of the nature and position of substitution on the rate of hydrolysis of a series of A-phenylbenzamides was investigated in mouse and sheep liver homogenates, with the goal of elucidating the metabolism of the anthelminthic niclosamide (4.158) [102],... 

The first case presented is that of 2-[(acyloxy)methyl]benzamides of the general structure 8.187 (Fig. 8.22) [239]. Two model compounds were examined (NRR = MeNH or morpholino, R" = Me) they reacted, as expected, to give the secondary amine and phthalide in quantitative yields. At pH 9.3 and 60°, chemical hydrolysis was 2-10 times faster than the subsequent cyclization-elimination. At pH 7.4 and 37°, the chemical hydrolysis was slow (f1/2 ca. 400 h), while hydrolysis in human plasma was fast (tm 3.2 and 1.4 h, respectively). 

One of the first HDAC inhibitors to be identified and characterized was sodium butyrate, where it was found to alter the histone acetylation state (Riggs et al, 1977), and further determined to inhibit HDAC activity both in vitro and in vivo (Candido et al, 1978). Almost a decade later trichostatin A (TSA), a fungistatic antibiotic, was found to induce murine erythroleukemia cell differentiation (Yoshida et al, 1987). To date, a wide range of molecules have been described that inhibit the activity of Class I and Class II HDAC enzymes, and with a few exceptions, can be divided into structural classes including (1) small-molecule hydroxamates, such as TSA, suberoylanilide hydroxamic acid (SAHA), scriptaid and oxamflatin (2) short-chain fatty-acids, such as sodium butyrate, sodium phenylbutyrate and valproic acid (VPA) (3) cyclic tetrapeptides, such as apicidin, trapoxin and the depsipeptide FK-228 and (4) benzamides, such as MS-275 and Cl-994 (for reviews see Remiszewski et al, 2002 Miller et al, 2003). Some of these molecules are represented in Fig. 4. 

It is important to perform both the Birch reduction of 5 and the alkylation of enolate 6 at —78 °C. Enolate 6 obtained directly from 5 at low temperatures is considered to be a kinetic enolate . A thermodynamic enolate obtained from 6 by equilibration techniques has been shown to give an opposite sense of stereoselection on alkylation. Although a comprehensive study of this modification has not been carried out, diastereoselectivities for formation of 8 were found to be greater than 99 1 for alkylations with Mel, EtI, and PhCH2Br. Thus, it should be possible to obtain both enantiomers of a target structure by utilization of a single chiral benzamide. SE... 

A structural requirement for the asymmetric Birch reduction-alkylation is that a substituent must be present at C(2) of the benzoyl moiety to desymmetrize the developing cyclohexa-1,4-diene ring (Scheme 4). However, for certain synthetic applications, it would be desirable to utilize benzoic acid itself. The chemistry of chiral benzamide 12 (X = SiMes) was investigated to provide access to non-racemic 4,4-disubstituted cyclohex-2-en-l-ones 33 (Scheme 8). 9 Alkylation of the enolate obtained from the Birch reduction of 12 (X = SiMes) gave cyclohexa-1,4-dienes 32a-d with diastereoselectivities greater than 100 1 These dienes were efficiently converted in three steps to the chiral cyclohexenones 33a-d. 

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

Further evidence for nitrogen as the site of protonation of amides in largely aqueous acid comes from studies of substituent effects on the p/Sfa Value of benzamide (Edward et al., 1960 Yates and Stevens, 1965). It has been observed that the pi g-values are correlated with a-constants of the substituents, rather than with o. This means that the structure of the dominant form of the cation is N-protonated as in [112], because resonance interactions of para-substituents in this kind of cation are similar to those in benzoic acid. The p-value (0 92)... 

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