Analogues, structural

The polyions postulated in solution all have known structural analogues in crystalline borate salts. Investigations of the Raman (66) and B nmr (67) spectra of borate solutions have confirmed the presence of three of these species the triborate (3), B202(0H) 4, tetraborate (4), [B40 (0H) 4], and pentaborate (5) B O (OH) 4, polyanions. Skeletal stmctures were assigned based on coincidences between the solution spectra and those soHd borates for which definitive stmctural data are available (52). These same ions have been postulated to be present in alkah metal borate glasses as well. 

The general interest in the pteridines is due to their widespread occurrence in both the animal and plant kingdoms, implying potential biological activity and drug-type properties in structural analogues. 

The Pictet-Spengler reaction has been carried out on various solid support materials " and with microwave irradiation activation.Diverse structural analogues of (-)-Saframycin A have been prepared by carrying out the Pictet-Spengler isoquinoline synthesis on substrates attached to a polystyrene support. Amine 20 was condensed with aldehyde 21 followed by cyclization to give predominantly the cis isomer tetrahydroisoquinoline 22 which was further elaborated to (-)-Saframycin A analogues. 

By this approach, a wide variety of structural analogues of 2-deoxystreptamine have been used to produce a range of neomycin-like antibiotics. These structural analogues include methylated and halogenated derivatives of 2-deoxystreptamine. 

L-NAME (N-nitro-L-arginine methyl ester), like L-NMMA, is a structural analogue of L-arginine and competes with L-arginine for NO-synthase, which uses L-arginine as a substrate for the formation of NO. L-NMMA and L-NAME are very effective NO-synthesis inhibitors, both in vitro and in vivo. 

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

Probing the Intermediate ADP-P State on F-Actin Using Structural Analogues of P, AIF4 and BeFi, H2O 47... 

New organocatalysts prepared by the Jacobsen group showed that alkylation of the final amide bond increased the enantioselection (Scheme 38, compare R2 = Me, 98% ee to R2 = H, 91% ee). Thus, the reaction performed with N-allyl benzaldimine and with the dimethylamide-ending thiourea (Scheme 38 with Ri = R2 = Me) gave up to 99% ee. This compound is a structural analogue of the urea depicted in Scheme 36 [148,152,154]. 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

Sulphonamides are structural analogues of PABA. They competitively inhibit the incorporation of PABA into dihydropteroic acid and there is some evidence for their incorporation into false folate analogues which inhibit subsequent metabolism. The presence of excess PABA will reverse the inhibitory action of sulphonamides, as will thymine, adenine, guanine and methionine. However, these nutrients are not normally available at the site of infections for which the sulphonamides are used. 

This synthetic allylamine derivative inhibits the enzyme squalene epoxidase at an early stage in fungal sterol biosynthesis. Acting as a structural analogue of squalene, naffidine causes the accumulation of this unsaturated hydrocarbon, and a decrease in ergosterol in the fungal cell membrane. 

Pyrazinamide is a structural analogue of isoniazid and is converted to the active acid derivative intracellularly by a nicotinamidase. Pyrazinamide resistance has been linked to reduced levels of nicotinamidase but the genetic determinants of resistance have not been fully elucidated. 

Sedykh, A. Y., Klopman, G. A structural analogue approach to the prediction of the... 

The classic example of a peroxisome proliferator is clofibrate. This compound was developed as a drug for the treatment of hyperlipidaemia disorders. Given to rodents, it induces the proliferation in the liver of peroxisomes and, at high concentrations over a prolonged period of time, induces the development of hepatomas. A number of other compounds are now known to possess this property, many of them structural analogues of clofibrate (Reddy and Rao, 1986). 

Several groups have published on structural analogues of (382), one of the earliest being the disclosure of CP 272871 (383) from Pfizer, which displays lower affinity for the CBi receptor than (382), in addition to reduced selectivity over the CB2 receptor subtype. Both (382) and (383) have been shown to act as inverse agonists rather than neutral antagonists in vitro [265]. A recently published patent application from Sanofi-Aventis claims a series of 4-cyanopyrazole analogues of (382), with 42 specific examples [266]. 

Phenearbamide (60) is a structural analogue of acetylcholine which acts as an anticholinergic agent, possibly by serving as a false agonist. It is made by reacting N,N-diphenylcarbamoyl chloride (59) with 2-mercapto-N,N-diethylethamine. 

The affinity of platinum(II) for N-donor ligands is well established. There are numerous examples in the literature of mono-, di-, and trinuclear platinum(II)-ammine and alkylamine complexes, most of which are structural analogues of the anticancer agent, mplatin (cis- PtCl2(NH3)2]), and the corresponding trans isomer. Selected novel complexes and synthetic methods are presented below. 

Chlorpromazine is technically described as a phenothiazine, as are thioridazine and fluphenazine. Together with their structural analogues the thioxanthenes (e.g., clopenthixol) and the butyrophenones (e.g., haloperidol), the phenothiazines comprise the three major families of typical neuroleptics. They were developed in the late 1950s and early 1960s (Table 11.3). All these drugs block dopamine receptors, principally the D2 subtypes, with an affinity that correlates highly (r = +0.90) with their clinical... 

Murray, J. S., P. Evans, and P. Politzer. 1990. A Comparative Analysis of the Electrostatic Potentials of Some Structural Analogues of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and of Related Aromatic Systems. Int. J. Quant. Chem. 37, 271. 

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