RU2001117218A

RU2001117218A - ANTAGONISTIC ANALOGUES OF RELEASING HORMONE OF GROWTH HORMONE (GH-RH), INHIBITING INSULIN-LIKE GROWTH FACTORS (IGF-I and-II)

Info

Publication number: RU2001117218A
Application number: RU2001117218/04A
Authority: RU
Inventors: Эндрю В. ШЭЛЛИ; Джозеф ВАРГА; Марта ЗАРАНДИ
Original assignee: Дзе Администрейторс Оф Дзе Тьюлейн Эдьюкешнл Фанд
Priority date: 1998-11-25
Filing date: 1999-11-23
Publication date: 2003-05-20

Claims

1. The peptide selected from the group having the formula

XR ¹ -R ² -Asp-Ala-R ⁵ -R ⁶ -Thr-R ⁸ -R ⁹ -R ¹⁰ -Arg-R ¹² -R ¹³ -R ¹⁴ -R ¹⁵ -R ¹⁶ -Leu-R ¹⁸ -R ¹⁹ -Arg-R ²¹ -R ²² -Leu-Gln-Asp-Ile-R ²⁷ -R ²⁸ -R ²⁹ -NH ₂ ,

where X is PhAc, IndAc or Nac;

R ¹ means Tyr or His;

R ² means D-Arg;

R ⁵ means Ile or Val;

R ⁶ means Phe or Phe (Cl);

R ⁸ means Asn, Gin, Ala or D-Asn;

R ⁹ is Arg, Har, Lys, Orn, D-Arg, D-Har, D-Lys, D-Orn, Cit, Nie, Tyr (Me), Ser, Ala or Aib;

R ¹⁰ means Tyr or Tyr (Me);

R ¹² means Lys;

R ¹³ means Val or Nle;

R ¹⁴ means Leu or Nle;

R ¹⁵ means Gly, Ala, Abu, Nle or Gln;

R ¹⁶ means Gln or Arg;

R ¹⁸ means Ser or Nle;

R ¹⁹ means Ala;

R ²¹ means Lys;

R ²² means Leu, Ala or Alb;

R ²⁷ means Met, Leu, Nle, Abu or D-Arg;

R ²⁸ means Arg, D-Arg or Ser;

R ²⁹ means Arg, D-Arg, Har or D-Har,

with the proviso that when R ⁹ and R ^{28 are} Ser, R ^{29 is} not Arg or Har,

and its pharmaceutically acceptable salts.

2. The compound according to claim 1, selected from the group consisting of

[PhAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (l-29) NH ₂ peptide 1,

[IndAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (l-29) NH ₂ peptide 2,

[PhAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Har ⁹ , Tyr (Me) ¹⁰ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1-29) NH ₂ peptide 3 ,

[PhAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Tyr (Me) ¹⁰ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1-29) NH ₂ peptide 6 ,

[PhAc ⁰ , His ¹ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (l-29) NH ₂ peptide 7,

[Nac ⁰ , His ¹ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1-29) NH ₂ peptide 8.

3. The compound according to claim 1, having the formula [PhAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1-29) NH ₂ peptide 1.

4. The compound according to claim 1, having the formula [IndAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1-29) NH ₂ peptide 2.

5. The compound according to claim 1, having the formula [PhAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Har ⁹ , Tyr (Me) ¹⁰ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH- RH (1-29) NH ₂ peptide 3.

6. The compound according to claim 1, having the formula [PhAc ⁰ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Tyr (Me) ¹⁰ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH- RH (1-29) NH ₂ peptide 6.

7. The compound according to claim 1, having the formula [PhAc ⁰ , His ¹ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1 -29) NH ₂ peptide 7.

8. The compound according to claim 1, having the formula [Nac ⁰ , His ¹ , D-Arg ² , Phe (pCl) ⁶ , Arg ⁹ , Abu ¹⁵ , Nle ²⁷ , D-Arg ²⁸ , Har ²⁹ ] hGH-RH (1 -29) NH ₂ peptide 8.

9. A method of suppressing excessive GH levels in a patient in need thereof, which consists in administering to said patient an effective amount of a compound according to claim 1.

10. A method of treating a patient having a malignant tumor bearing IGF-I or -II receptors, which comprises administering to said patient an effective amount of a compound according to claim 1.

11. A method of inhibiting IGF-II levels in tumors (malignant tumors) and mRNA expression for IGF-II in the same tumors, which consists in administering to said patient an effective amount of a compound according to claim 1.