Analogs derivatization

Cyclohexyl prostaglandin analogs derivatized with 3-chloro-benzo[b]thiophen-2-yl, (V), prepared by Old (5) were effective as EP4 agonists and used in the treatment and management of glaucoma. 

The number of proposed methods for alcoholic and phenolic S-analog derivatization for GC analysis is significantly less than those for alcohols. The most objective reason for this is the lower frequency of their determinations in real analytical practice. In accordance with general recommendations, thiols and thio-phenols may be converted into TFA (PFP, HFB) esters or PFB ethers (5-TMS derivatives seems not as stable as G-TMS ethers). In addition to the optimization of chromatographic parameters, the derivatization of these compounds is necessary to prevent their oxidation by atmospheric oxygen. 

The availability of the 6,7-dehydro derivative 4.1.3.7 opened up routes to analogs derivatized at C-6 as well as to analogs with other modifications. Hydroxylation of 4.1.3.7 gave the a-diol 4.2.1.1 (167) while treatment with dimethyldioxirane gave the a-epoxide 4.2.1.2 (167, 168) a conflict between the / -stereochemistry (167) and the a-stereo-chemistry was resolved in favor of the latter by an x-ray crystal structure determination (175). 

In many cases the functional or loading capacity is expressed in mmolg" polymer. For polymer-analogous derivatization reactions the definition of the degree of functionalization (DF) is useful. It is defined as the quotient of the content of new functional groups and that of original ftmctional groups [61]. 

Another new route of synthesis for soluUe polymer supports based not on the usual polymer-analogous derivatization but on the preparation of the support by copolymerization of functional monomers was outlined and demonstrated by Geckeler and Bayer [73,104]. They used radical copolymerization of amino acid alkenyl esters, which are easily accessible by a vinyl exchange reaction with vinyl acetate, with l-vinyl-2-pyrrolidinone as solubilizing comonomer for direct preparation of a functional soluble support [104]. Thus, a carrier soluble in water as well as in many or nic solvents was obtained which already contained the first amino acid residue of the peptide ... 

The imidazolidine was prepared from an aldehyde with A/,N -dimethyl-1,2-eth-ylenediamine (benzene, heat, 78% yield) and cleaved with Mel (Et20 HjO, 92% yield). Derivatization is chemoselective for aldehydes. The imidazolidine is stable to BuLi and LDA. The diphenylimidazolidine has been prepared analogously and can be cleaved with aqueous HCl. ... 

Sanofi-Synthelabo researchers discovered pyrazole 53 and analogs to have potent Cannabinoid receptor-1 (CB-1) antagonist/inverse agonist activity and have progressed 53 into development for treatment of obesity and alcohol dependence. The synthesis of 53 was accomplished by heating the diketone sodium salt 51 with the aryl hydrazine hydrochloride in acetic acid to provide the intermediate 52, which was further derivatized... 

In saurer Losung wird Methyl-phenyl-nitrosamin an Blei zu N-Methyl-N-phenyl-hydra-zin reduziert (80% d.Th.)4. Analog verhalten sich Dialkyl-nitrosamine ( — 0,9 V, bis 82% d.Th.) in alkoholischer Salzsaure5. Zur Hcrstellung von N,N-Dimethyl-hydrazin aus dem N-Nitroso-Derivat s.ds. Handb., Bd. X/2, S. 42 (zuN,N-Dialkyl-hydrazinen s.Lit.6). 

Preparative planar chromatography is a very important step in the complicated procedures of isolation of group of compounds or pure substances from complex matrices. The method gives additional possibilities of using various adsorbents and eluent systems to achieve complete separation of stracmral analogs. The method also enables combining the various methods of sample application, plate development, and derivatization to achieve satisfactory separation of isolated plant extracts components. 

Not all drugs contain functional groups that lend themselves readily to prodrug derivatization. A case in point is the carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, and methazolamide. Although the amino functional group of their sulfonamide moiety can be methylated, the resulting analogs... 

Heterocyclic fluorophores based on the benzoxadiazole nucleous, namely 4-nitrobenz-2-oxa-l,3-diazole (NBD) 14 derivatives/analogs, have been widely used as derivatization reagents for analysis purposes. Examples include the amino- or thiol reactive 4-fluoro-7-nitrobenz-2-oxa-l,3-diazole (NBD-F) 15 and 4-chloro-7-nitrobenz-2-oxa-1,3-diazole (NBD-C1) 16 [45-50] and the thiol-reactive /V-((2-(iodoacetoxy)ethyl)-/V-methyl)amino-7-nitrobenz-2-oxa-1,3-dia-zole (IANBD ester) 17 [51] and 7-chlorobenz-2-oxa-l,3-diazole-4-sulfonate (SBD-C1) 18 [52], NBD-F and NBD-C1 derivatives can be excited at about 470 nm by using the relatively inexpensive and reliable argon ion lasers or newer diode pumped solid state (DPSS) lasers. NBD-F has been used as a labeling tag in various capillary electrophoresis (CE) experiments for amino acids [53-57] including the monitorization of in vivo dynamics of amino acids neurotransmitters [58]. 

Succinylated derivatives of nucleic acids may be prepared by reaction of the anhydride with available —OH groups. The reaction forms relatively stable ester derivatives that create car-boxylates on the nucleotide for further conjugation or modification (Figure 1.83). This method has been used in nucleic acid synthesis (Matteucci and Caruthers, 1980) and to derivatize nucleotide analogs such as AZT (Tadayoni et al., 1993). 

Iodobeads (Thermo Fisher) is an immobilized preparation of a chloramine-T analog, consisting of nonporous, polystyrene beads of diameter 1/8" that have been derivatized to contain N-chlorobenzenesulfonamide groups (as the sodium salt) (refer to US patents 4,448,764 and 4,436,718). During the manufacturing process, the hydrophobic nature of the polystyrene is changed to a rather hydrophilic surface due to the chlorosulfonamide modifications. The surface... 

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