Substituent

About: Substituent is a research topic. Over the lifetime, 42877 publications have been published within this topic receiving 516716 citations. The topic is also known as: side chain & side group.

Substituent effects and transition structures for Diels-Alder reactions of butadiene and cyclopentadiene with cyanoalkenes

Abstract: Etude theorique des etats de transitions pour les reactions du butadiene-1,3 avec l'ethylene, l'acrylonitrile, le maleonitrile, le fumaronitrile et le dicyano-1,1 ethylene, et pour les reactions du cyclopentadiene avec l'ethylene et l'acrylonitrile

Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors

Abstract: Novel hydrosoluble 3-arylidene-2-oxindole derivatives, having tyrosine kinase inhibitor activity, encompassed by general formula (I), wherein m is zero, 1 or 2; A is a bicyclic ring chosen from tetralin, naphthalene, quinoline and indole; R1 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl; one of R2 and R3 independently is hydrogen and the other is a substituent selected from: a C1-C6 alkyl group substituted by 1, 2 or 3 hydroxy groups; -SO3R4 in which R4 is hydrogen or C1-C6 alkyl unsubtituted or substituted by 1, 2 or 3 hydroxy groups; -SO2NHR5 in which R5 is as R4 defined above or a -(CH2)n-N(C1-C6 alkyl)2 group in which n is 2 or 3; -COOR6 in which R6 is C1-C6 alkyl unsubtituted or substituted by phenyl or by 1, 2 or 3 hydroxy groups or phenyl; -CONHR7 in which R7 is hydrogen, phenyl or C1-C6 alkyl substituted by 1, 2 or 3 hydroxy groups or by phenyl; -NHSO2R8 in which R8 is C1-C6 alkyl or phenyl unsubtituted or substituted by halogen or by C1-C4 alkyl; -N(R9)2, -NHR9 or -OR9 wherein R9 is C2-C6 alkyl substituted by 1, 2 or 3 hydroxy groups; -NHCOR10, -OOCR10 or -CH2OOCR10 in which R10 is C1-C6 alkyl substituted by 1, 2 or 3 hydroxy groups; -NHCONH2; -NH-C(NH2)=NH; -C(NH2)=NH; -CH2NHC(NH2)=NH; -CH2NH2; -OPO(OH)2; -CH2OPO(OH)2; -PO(OH)2; or (a), (b), (c), or (d) group, wherein p is 1, 2 or 3 and Z is -CH2-, -O- or (e), in which R11 is hydrogen or is as R9 defined above; and the pharmaceutically acceptable salts thereof, are disclosed.

Design, synthesis, and biological evaluation of analogues of the antitumor agent, 2-(4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469).

Abstract: 2-(4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469) is among the most highly and broadly active antitumor agents to have been evaluated in our laboratories and is currently scheduled to enter clinical trials in 2001. The mechanism or mechanisms of action of XK469 remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogues of XK469 and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions-I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chemical alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of XK469 showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-(4-[(2-quinoxalinyl)oxy]phenoxy)propionic acid, generated the most highly and broadly active antitumor agents. A methyl, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of 1 was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of XK469 (region III), i.e., CONH2, CONHCH3, CON(CH3)2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

Total Synthesis of Indotertine A and Drimentines A, F, and G

Abstract: The pyrroloindoline alkaloids attract wide interest from the fields of chemistry, biosynthesis, and biology. From a structural perspective, they can be divided into several classes that vary in the substituent on C3a of the pyrroloindoline core, including heteroatoms, arenes, aliphatic groups, and another pyrroloindoline motif. Accordingly, a series of strategies have been developed for the synthesis of the above pyrroloindoline classes. Notably, a structurally complex aliphatic side chain linked to the C3a position is rather rare. The drimentine alkaloids (1–4, Scheme 1), which exhibit anticancer, antibacterial, antifungal, and anthelmintic properties, possess the latter substitution mode. A stereocontrolled method to form the C10b–C12 bond of the drimentine scaffold is highly desired for the synthesis of these compounds. Indotertine A (5, Scheme 1) with an unprecedented, but biosynthetically relevant, skeleton was recently discovered. The biosynthetic relationship between 3 and 5 is postulated in Scheme 1. Acidic activation of the germinal diamine moiety of 3 may generate an iminium species 6, which could undergo an iminium–olefin cyclization followed by a proton elimination of the cationic intermediate 7. Herein, we report the first total synthesis of drimentines A, G, and F (1–3), exploiting a photocatalyzed radical conjugate addition to address the problem of the C10b–C12 bond formation; a synthesis of indotertine A (5), guided by the above biosynthetic hypothesis, is also described. We first undertook a retrosynthetic analysis of drimentine G (Scheme 2). Disassembly of the diketopiperazine motif at the amide bonds followed by cleavage of the exocyclic C=C bond simplifies this molecule to core structure 8. Disconnection of the C10b–C12 bond leads to a pair of precursors (9 and 10) for an intermolecular radical conjugate addition. The former is readily available from bis(Boc-l-tryptophan) methyl ester (Boc= tert-butoxycarbonyl), whereas the latter could be derived from commercially available (+)-sclareolide (11). Scheme 1. Representative drimentine alkaloids and the postulated biosynthetic relationship between drimentine F and indotertine A.