14618-77-0Relevant articles and documents
β2-Homo-amino acid scan of μ-selective opioid tetrapeptide TAPP
Kosson, Piotr,Lipiński, Piotr F. J.,Misicka, Aleksandra,Tymecka, Dagmara
, (2020/08/11)
TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, μ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for μ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind μOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor μOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high μOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.
Palladium-Catalyzed Direct Arylation of C(sp3)-H Bonds of α-Cyano Aliphatic Amides
Reddy, M. Damoder,Watkins, E. Blake
, p. 11447 - 11459 (2015/12/05)
Pd(OAc)2-catalyzed arylation of C(sp3)-H bonds in α-cyano-α-methyl aliphatic amides is achieved in the presence of 8-aminoquinoline, as a removable directing group, using Mn(OAc)2 and Na2CO3. The current strategy enables the placement of an aryl/heteroaryl group at the β-position of α-cyano aliphatic acids for the first time. Wide functional group tolerance and easily accessible starting materials provide an efficient protocol for the synthesis of arylated α-cyano amides. Furthermore, the synthetic utility of the products has been demonstrated by their efficient conversions to medicinally important α,α-dialkylated acid and β-amino acid derivatives.
Cephalosporin compounds
-
, (2008/06/13)
The present invention relates to new cephalosporin compounds of the formula(I), pharmaceutically acceptable non-toxic salts thereof, and physiologically hydrolyzable esters and solvates thereof, which have potent and broad antibacterial activities STR1 wherein R1 is a C1?4 alkyl, C3?4 alkenyl, C3?4 alkynyl group, or --C(Ra)(Rb)CO2 H1 wherein Ra and Rb are the same or different, and each is a hydrogen atom or a C1?4 alkyl group, or Ra and Rb form a C3?7 cycloalkyl group with the carbon atom to which they are linked; R2 is a C1?4 alkyl, C3?4 alkenyl or C3?4 cycloalkyl group, a substituted or unsubstituted amino group, or a substituted or unsubstituted phenyl group; R3 is hydrogen or a C1?4 alkyl group; and Q is N or CH. The invention further relates to a process for preparing said compounds, and to pharamaceutical compositions containing said compounds.
