- Structure–Activity Relationship Studies on 6,7-Dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline Derivatives as Multidrug Resistance Reversers
-
A series of derivatives were synthesized and studied with the aim to investigate the structure–activity relationships of the two P-glycoprotein (P-gp) modulators elacridar and tariquidar. Then, different aryl-substituted amides were inserted, and to explore the effects of varying the amide function, the corresponding isosteric ester derivatives and some alkylamine analogues were synthesized. The new compounds were studied to evaluate their P-gp interaction profile and selectivity toward the two other ABC transporters, multidrug-resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP). Investigation of the chemical stability of the amide and ester derivatives toward spontaneous or enzymatic hydrolysis showed that these compounds were stable in phosphate-buffered saline and human plasma. This study allowed us to evaluate the selectivity of the three series on the three efflux pumps and to propose the structural requirements that define the P-gp interaction profile. We identified two P-gp substrates, a P-gp inhibitor, and three ester derivatives that were active on BCRP, which opens a new scenario in the development of ligands active toward this pump.
- Teodori, Elisabetta,Dei, Silvia,Bartolucci, Gianluca,Perrone, Maria Grazia,Manetti, Dina,Romanelli, Maria Novella,Contino, Marialessandra,Colabufo, Nicola Antonio
-
-
Read Online
- COMPOUNDS AND KITS FOR PREPARING IMAGING AGENTS AND METHODS OF IMAGING
-
Compounds that include a targeting moiety bound to a regioselective leaving group are useful for preparing imaging agents. The imaging agents can be isolated from by-products derived from the leaving group based on differences in the chemical attributes (e.g., net charge or polarity) of the molecules or physical attributes of the molecules through the use of a solid support. Methods of producing an imaging agent include the steps of providing a compound that includes a targeting moiety bound to a support via a linker group that contains a site for regioselective substitution of a detectable species, contacting the compound with a solution containing the detectable species, and recovering the imaging agent. Kits which include a first container (5) having therein a solution (31) containing a detectable species and a second container (2) having therein a compound that includes a targeting moiety bound to a support (30) via a leaving group that contains a site for regioselective substitution of the detectable species are also useful for preparing imaging agents.
- -
-
-
- 2,4-diamino-6,7-dihydro-5?-cyclopentacf|pyrimidine analogues of trimethoprim as inhibitors of pneumocystis carinii and toxoplasma gondii dihydrofolate reductase
-
Three previously unreported (R,S)-2,4-diamino-5-[(3,4,5-trimethoxyphenyl)alkyl]-6,7-dihydro5.ff- cyclopenta[rf]pyrimidines 15a-c were synthesized as analogues of trimethoprim (TMP) and were tested as inhibitors of Pneumocystis carinii, Toxoplasma gondii,
- Rosowsky, Andre,Papoulis, Andrew T.,Queener, Sherry F.
-
p. 913 - 918
(2007/10/03)
-
- 5-amino-4-hydroxyhexanoic acid derivatives
-
Compounds of formula I STR1 or their hydroxy-protected derivatives, and compounds of formula I' STR2 wherein T is an acyl radical of formula Z STR3 wherein Rz is unsubstituted or substituted hydrocarbyl wherein at least one carbon atom has been replaced by a hetero atom with the proviso that a hetero atom is not bonded directly to the carbonyl to which the radical Rz is bonded, alkyl having two or more carbon atoms, lower alkenyl, lower alkynyl, aryl or unsubstituted or substituted amino, and wherein the radicals R1, B1, R2, R3, A1, A2 and NR4 R5 are as defined in the description, and precursors thereof, are described. The compounds have pharmaceutical activity, for example in the treatment of retroviral diseases, such as AIDS.
- -
-
-