TY - JOUR
T1 - iso-Lactam and reduced amide analogues of the peptidomimetic dopamine receptor modulator 3(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide
AU - Dolbeare, Kristine
AU - Pontoriero, Giuseppe F.
AU - Gupta, Suresh K.
AU - Mishra, Ram K.
AU - Johnson, Rodney L.
N1 - Funding Information:
This work was supported in part by a NIH grant (NS20036) to R.L.J.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - An analogue of the highly potent γ-lactam Pro-Leu-Gly-NH2 peptidomimetic, 3(R)-[(2(S)-pyrrolidinylcarbonyl) amino]-2-oxo-1-pyrrolidineacetamide (2), 4(R)-[[2(S)-pyrrolidinylcarbonyl]amino]-2-oxo-1-pyrrolidineacetamide (3), in which the lactam carbonyl moiety has been placed in a different position with respect to the 3-amino group was synthesized. Also, a series of analogues of 2, compounds 4-6, were synthesized in which each of the amide bonds of 2 were systematically replaced with a reduced amide bond surrogate. The analogues were tested for their ability to enhance the binding of [ 3H]N-propylnorapomorphine to dopamine receptors in a functional in vitro assay utilizing bovine striatal membranes. Peptidomimetic 3 was shown to be more potent than 2, while 4 and 5 were significantly less effective than 2. Peptidomimetic 6 had a pharmacological profile similar to that of 2.
AB - An analogue of the highly potent γ-lactam Pro-Leu-Gly-NH2 peptidomimetic, 3(R)-[(2(S)-pyrrolidinylcarbonyl) amino]-2-oxo-1-pyrrolidineacetamide (2), 4(R)-[[2(S)-pyrrolidinylcarbonyl]amino]-2-oxo-1-pyrrolidineacetamide (3), in which the lactam carbonyl moiety has been placed in a different position with respect to the 3-amino group was synthesized. Also, a series of analogues of 2, compounds 4-6, were synthesized in which each of the amide bonds of 2 were systematically replaced with a reduced amide bond surrogate. The analogues were tested for their ability to enhance the binding of [ 3H]N-propylnorapomorphine to dopamine receptors in a functional in vitro assay utilizing bovine striatal membranes. Peptidomimetic 3 was shown to be more potent than 2, while 4 and 5 were significantly less effective than 2. Peptidomimetic 6 had a pharmacological profile similar to that of 2.
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U2 - 10.1016/S0968-0896(03)00396-1
DO - 10.1016/S0968-0896(03)00396-1
M3 - Article
C2 - 12927872
AN - SCOPUS:0042090281
SN - 0968-0896
VL - 11
SP - 4103
EP - 4112
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 18
ER -