Synthesis and Antiovulatory Activities in Rats of Analogs of the Luteinizing Hormone Releasing Hormone Having a Moiety of /?-(3-Quinolyl)-D-a-alanine in Positions 3 and 6

Abstract

<jats:title>Abstract</jats:title><jats:p> Analogs of the luteinizing hormone releasing hormone (LHRH) having a moiety (D-Qal-) of β-(3-quinolyl)-D-α-alanine were synthesized toward more effective inhibitors of ovulation. [N-Ac-pCl-D-Phe<jats:sup>1,2</jats:sup>, D-3-Pal<jats:sup>3</jats:sup>, D-3-Qal<jats:sup>6</jats:sup>, D-Ala<jats:sup>10</jats:sup>]-LHRH was the most effective, and had an antiovulatory activity of 40% at 1 μg/rat. D-3-Qal<jats:sup>6</jats:sup> was as effective as D-Trp<jats:sup>6</jats:sup> in combination with N-Ac-<jats:sup>3</jats:sup>⊿Pro<jats:sup>1</jats:sup>, pF-D-Phe<jats:sup>2</jats:sup>, D-Trp<jats:sup>3</jats:sup>. D-Arg<jats:sup>6</jats:sup> was superior to D-3-Qal<jats:sup>6</jats:sup>) in combination with N-Ac-pCl-D-Phe<jats:sup>1,2</jats:sup>, D-Trp<jats:sup>3</jats:sup> (or D-3-Pal<jats:sup>3</jats:sup>), D-Ala<jats:sup>10</jats:sup>. The introduction of D-3-Qal<jats:sup>3</jats:sup>, D-His<jats:sup>3</jats:sup> and D-Arg<jats:sup>3</jats:sup> in comparable analogs caused substantial loss of activities. </jats:p>

Enantioselective Synthesis of (2-Pyridyl)alanines via Catalytic Hydrogenation and Application to the Synthesis of l-Azatyrosine

“…Pyridylalanines have been used as replacements of histidine and shown to function as antagonists of phenylalanines . Additionally, the pyridylalanine derivative have also been studied as antiinflammatory and antitumor−antibiotic agents 7 and for other pharmaceutical applications . A number of methods have been developed for synthesis of pyridylalanines, e.g., enzymatic separation of racemates, organometallic coupling reactions, diastereoselective alkylation, and by catalytic asymmetric hydrogenation .…”