Novel n- and c-terminal substituted antagonistic analogs of...

A - Human Necessities – 61 – K

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A61K 38/25 (2006.01) C07K 14/60 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2718146

There is provided a novel series of synthetic analogs of hGH-RH(1-29)NH2 (SEQ ID NO: 96) and hGH-RH(1-30)NH2. Of particular interest are those carrying PhAc, N-Me-Aib, Dca, Ac- Ada, Fer, Ac-Anic, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, or CH3{CH2)10-CO- Ada, at the N-Terminus and .beta.-Ala, Amc, Apa, Ada, AE2A, AE4P, .epsilon.-Lys(.alpha.-NH2), Agm, Lys(Oct) or Ahx, at the C- terminus. These analogs inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers through a direct effect on the cancer cells. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, result from replacement of various amino acids.

La présente invention concerne de nouvelles séries danalogues synthétiques de hGH-RH(1-29)NH2 (SEQ ID NO : 96) and hGH-RH(1-30)NH2. Ceux particulièrement intéressants sont ceux portant PhAc, N-Me-Aib, Dca, Ac-Ada, Fer, Ac-Amc, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, ou CH3-(CH2)10-CO-Ada, au bout de chaîne N et ß-Ala, Amc, Apa, Ada, AE2A, AE4P, e-Lys(a-NH2), Agm, Lys(Oct) ou Ahx, au bout de chaîne C. Ces analogues inhibent la libération dhormone de croissance du pituitaire chez des mammifères et inhibent également la prolifération de cancers humains par un effet direct sur les cellules cancéreuses. Les plus fortes activités inhibitrices des nouveaux analogues, en comparaison à des analogues décrits antérieurement, résultent du remplacement de divers acides aminés.

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