Bicyclic molecule

About: Bicyclic molecule is a research topic. Over the lifetime, 29587 publications have been published within this topic receiving 451252 citations. The topic is also known as: bicyclic molecule.

Effect of bridge region variation on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines

Abstract: Variation of the bridge linking the heterocyclic ring and p-aminobenzoyl-L-glutamate portions of our previously descibed classical 2,4-diaminofuro[2,3-d]pyrimidines 1 and 2 are reported as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) and as antitumor agents. Specifically -CH 2 CH 2 - and -CH 2 NHCH 2 - bridged analogues, N-[4-[2-(2,4-diamino-furo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid (3) and N-[4-[[N-[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)methyl]amino]methyl]benzoyl]-L-glutamic acid (4), respectively, were synthesized. Compound 3 was obtained via a Wittig reaction of the tributylphosphonium salt of 2,4-diamino-5-(chloromethyl)furo[2,3-d]pyrimidine (5) and methyl 4-formylbenzoate (6) followed by reduction and coupling with the diethyl ester of L-glutamic acid. Compound 4 was synthesized by the nucleophilic displacement of 5 with diethyl N-[4-(aminomethyl)benzoyl]-L-glutamate (15) and saponification. Both analogues were evaluated in vitro as inhibitors of DHFRs from (recombinant) human, human CCRF-CEM cells, and Lactobacillus casei. Compound 3 showed moderate activity (IC 50 10 -6 -10 -7 M). Compound 4 was essentially inactive (IC 50 10 -5 M, CCRF-CEM). The compounds were also evaluated against TS from (recombinant) human and L. casei and were of low activity (IC 50 10 -5 M). The three-atom-bridged analogue 4 was somewhat more inhibitory to human TS than methotrexate (MTX). Compound 3 inhibited the growth of tumor cells in culture (IC 50 10 -7 M) while 4 showed a low level of growth inhibitory activity. The inhibition of the growth of leukemia CCRF-CEM cells by both compounds parallels their inhibition of CCRF-CEM DHFR. Analogue 3 was a good substrate for human folylpolyglutamate synthetase (FPGS) derived from CCRF-CEM cells (K m 8.5 μM). Further evaluation of the growth inhibitory activity of 3 against the MTX-resistant subline of CCRF-CEM cells (R30dm) with decreased FPGS indicated that poly-γ-glutamylation was important for its action. Protection studies with 3 in the FaDu squamous cell carcinoma cell line indicated that inhibition was completely reversed by leucovorin [(6R,S-5-formyltetrahydrofolate] or by a combination of thymidine and hypoxanthine, suggesting an antifolate effect directed at DHFR

Catalytic Intramolecular Palladium‐Ene Reactions. Preliminay Communication

Abstract: Syntheses du methylene-3 vinyl-4 cyclopentanedicarboxylate-1,1 de dimethyle a partir de l'acetoxy-8 octadiene-1,6 dicarboxylate de dimethyle et du ditosyl-1,1 methylene-4 vinyl-3 cyclohexane a partir du ditosyl-5,5 nonadiene-2,8 ol-1

Novel adenine compound and use thereof

Abstract: A drug for topical administration which is effective as an antiallergic agent. The drug for topical administration contains as an active ingredient either an adenine compound represented by the general formula (1): (1) [wherein ring A represents a 6- to 10-membered, mono- or bicyclic, aromatic carbocycle or a 5- to 10-membered, mono- or bicyclic, aromatic heterocycle containing one to three heteroatoms selected among zero to two nitrogen atoms, zero or one oxygen atom, and zero or one sulfur atom; n is an integer of 0 to 2; m is an integer of 0 to 2; R represents halogeno, (un)substituted alkyl, etc.; X1 represents oxygen, sulfur, NR1 (R1 represents hydrogen or alkyl), or a single bond; Y1 represents a single bond, alkylene, etc.; Y2 represents a single bond, alkylene, etc.; Z represents alkylene; and at least either of Q1 and Q2 represents -COOR10 (wherein R10 represents (un)substituted alkyl, etc.), etc.] or a pharmaceutically acceptable salt of the compound.