Pharmacologically active derivatives

It is a prodrug with no opioid activity itself. All its pharmacological activity derives from hydrolysis to monoacetylmorphine (MAM) and then to morphine in the plasma and tissues. Diamorphine also... 

As far as the amine moiety is concerned, usual amines, such as dimethylaminc, are most commonly used. However, in particular situations requiring the preparation of pharmacologically active derivatives, bis(chlorocthyl)amine, " aziridinc, or norephedrine (this last species for the synthesis of products enhancing coronary blood flow) are employed. 

Various synthetic methods (Table 44) are applied to the modification of Mannich bases in order to obtain pharmacologically active derivatives. The carbonyl group of (3-aminoketones is frequently involved in the reaction, as is demonstrated by the elegant synthesis of Phenindamine 589 reported in Fig. 191 (see also Fig. 124, Chap. II). 

Nucleosides can be structurally modified to generate pharmacologically active derivatives that, by retaining most of the metabolic properties of the parent compounds, can be transported into the cell and metabolized. They can then interfere with nucleic acid synthesis, thus promoting either antiproliferative effects or resistance to virus replication in infected cells. This is the rationale for using nucleoside derivatives in cancer and AIDS therapies. 

Figure I. Benzophenone and xanthone biosynthesis and examples of pharmacologically active derivatives. (Adapted with permission from reference 5. Copyright 2003 Blackwell Publishing Ltd)...

Other derivatives which have been made vinyl polymerizable with lEM can be included into copolymers as an additive rather than as a latent cross-linker. For example, a variety of reagents which improve hydrophilicity as well as acid or base dyeability of acrylonitrile fibers were synthesized by Bahr et al. (40,41). Pharmacologically active derivatives of 1-adamantaneamine (42), polymeri-... 

Bagli and coworkers at Ayerst were the first to report the total synthesis of a pharmacologically active derivative of prostaglandins. Starting with ethyl 2-cyclopentanone carboxylate VI d,l-ll-desoxy-prosta-glandin Fip XII was prepared in a 12-step synthesis. Noteworthy is the... 

The appearance of the 2-(indol-3yl)ethylamine (tryptamine) unit in both tryptophan-derived natural products and in synthetic materials having potential pharmacological activity has generated a great deal of interest in the synthesis of such compounds. Several procedures which involve either direct 3-alkylation or tandem 3-functionalization/modification have been developed. Similarly, methodology applicable to preparation of tryptophan analogues has been widely explored. 

Yohimbine (104), also from the bark of C.johimbe K Schum. and from the roots of R. serpentina (1. ) Benth. has a folk history (unsubstantiated) of use as an aphrodisiac. Its use has been confirmed experimentally as a local anesthetic, with occasional employment for rehef ia angiaa pectoris and arteriosclerosis, but is frequently contraindicated by its undesired renal effects. Yohimbine and some of its derivatives have been reported as hahuciaogenic (70). In addition, its pattern of pharmacological activities ia a variety of animal models is so broad that its general use is avoided. All ten carbon atoms of secologanin (102) as well as the entire skeleton of tryptamine (98, R = H) are clearly seen as iatact portions of this alkaloid. 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

Most of the pharmacologically active indazole derivatives are useful as antiinflammatory drugs, e.g. bendazac or [(1-benzyl-l J/-indazol-3-yl)oxy]acetic acid (LDso in mice and rats of 355 and 388mgkg i.p., respectively) and benzydamine or l-benzyl-3-[3-(dimethyl-amino)propoxy]-l//-indazole (LDso in mice and rats of 110 and lOOmgkg" i.p., respectively). The last cited compound also has analgesic and antipyretic properties (B-76MI40404). 

A number of azetidines have been investigated for pharmacological activity, but no important derivatives have emerged (64HC(19-2)908, 68JMC466, 69JMC196, 79JMC183). 

Pharmacological activity spectrum and toxicological properties of benzimidazole derivatives 99KFZ(5)6. 

The pharmacological activities of other derivatives of these ring systems are examined intensively. Whereas other representatives of the above ring systems are patented as photographic sensitizers, catalysts for curing polyisocyanates, or dyes for acrylic nylon, polyester filters, and photographic material. 

The pharmacologically active and commercially important 5//-dibenz[/>,/]azepines 40 are available by base-catalyzed dehydrobromination of their 5-acyl- 10-bromo-l 0.11-dihydro derivatives 38,118 followed by hydrolysis of the isolable tV-acyl compounds 39 29.119-121... 

The pharmacological activity of the 1,5-benzothiazepine derivative diltiazem has given further impetus for synthetic routes to this ring system. A traditional preparation of the intermediate 62 by the reaction sequence shown in Scheme 12 has been subject to microwave studies, when the final product was obtained as a mixture of isomers <96TL6413>. Under optimised conditions irradiation in toluene at 390 watts for 20 minutes gave mainly the cis-isomer as the main product (cis/trans 9 1) in 75% yield. However, reaction at 490 watts in the presence of acetic acid resulted in a reversal of this ratio and a yield of 84%. The... 

Eicosanoids are derived from Cjo (eicosanoic) fatty acids synthesized from the essential fatty acids and comprise important gtoups of physiologically and pharmacologically active compounds, including the prostaglandins, thromboxanes, leukotrienes, and lipoxins. 

Coumarin and their derivatives have been found to exhibit different biological and pharmacological activities [63-66]. Owing to the widespread applications, synthetic and biological activity evaluation of coumarins and their derivatives has been a subject of intense investigations [67-69]. 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

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