The Administrators of the Tulane Educational Fund

Tamas Janaky

Andrew V Schally

Sandor Bajusz

Attila Juhasz

Atilla Juhasz

The present invention deals with LHRH analogs which contain cytotoxic moieties, have influence on the release of gonadotropins from the pituitary in mammals (possess high agonistic or antagonistic activity) and have antineoplastic effect. The compounds of this invention are represented by Formula I: X-R,-R,-R,-Ser-R,-R,(Q)-Leu-Arg-Pro-R,-NH,, wherein R,is pGlu or D-Nal(2), R,is His or D-Phe(4Cl), R,is Trp, D-Trp or D-Pal(3), R,is Tyr or Arg, R,is D-Lys or D-Orn, R,is Gly or D-Ala, X is hydrogen or a lower alkanoyl group of 2-5 carbon atoms, Q is a cytotoxic moiety having the formula &mdash;Q,or &mdash;A(Q,) or &mdash;B(Q,),or &mdash;B(AQ,),, wherein A is &mdash;NH&mdash;(CH,),&mdash;CO&mdash; or &mdash;OC&mdash;(CH,),&mdash;CO&mdash; where n is 2-6, B is &mdash;NH&mdash;CH,&mdash;(CH,),&mdash;CH(NH)&mdash;(CH,),&mdash;CO&mdash; where m is 0 or 1, n is 0 or 1, the &mdash;CO moiety of A&mdash; and of B&mdash; being bonded to an amino group on R,, and in the group B(AQ,),, the &mdash;CO moiety of A&mdash; and of B&mdash; being bonded to the episilon or delta amino group of R,when R,is Lys or Orn respectively, and in the group B(AQ,),, the &mdash;CO moiety of A being bonded to an amino group on B, Q,is D or L-Mel, cyclopropanealkanoyl, aziridine-2-carbonyl, epoxyalkyl or 1,4-naphthoquinone-5-oxy-carbonyl-ethyl, Q,is Q,, 2-anthraquinonyl-methylenoxy or doxorubicinyl, Q,is Q,, mitomicinyl, esperamycinyl or methotrexoyl, Q,is Q,or methotrexoyl and pharmaceutically acceptable salts thereof and methods of use pertaining these compounds.

Luteinizing hormone releasing hormone analogs with cytotoxic moiety

Disclosed herein are analogues of the luteinizing hormone-releasing hormone (LH-RH), which are potent antagonists of LH-RH. These peptides inhibit the release of gonadotropins from the pituitary in mammals, including humans and possess antitumor activity. Formula I represents peptides which are within the scope of this invention:

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Szeged, Hungary

Tamas Janaky