[发明专利]六肽或其衍生物及其医药用途

权利要求书

1.式(I)六肽或其衍生物，其立体异构体或其药用盐

R₁-AA₁-AA₂-Val-AA₄-Leu-AA₆-R₂式(I)

其中

AA₁可为D型或L型的天然或非天然的疏水性氨基酸；

AA₂和/或AA₄可为D型或L型的天然或非天然芳香性氨基酸；

AA₄为D型或L型的天然或非天然芳香性氨基酸；

AA₆可为D型或L型的天然或非天然氨基酸；

R₁是H、Ac-、脲基-或1-10个氨基酸残基；

R₂是-OH、-NH2或1-10个氨基酸残基；

R₁和R₂可进一步选择性地被酰胺化、烷基化、酰基化、脲基化、PEG化。

2.如权利要求1所述，式(I)六肽衍生物或其立体异构体或其药用盐，其中，

AA₁为L或D型的脯氨酸、羟脯氨酸或焦谷氨酸；

AA₂和/或AA₄各自独立地为L或D型的苯丙氨酸、4-氨基苯丙氨酸、4-氯苯丙氨酸、萘丙氨酸、β-胡椒基丙氨酸、吗啉甲基苯丙氨酸或对脲基苯丙氨酸；

AA₆为甲硫氨酸、丝氨酸、谷氨酰胺、天冬氨酸、天冬酰胺、赖氨酸或精氨酸；

R1和R2中氨基酸残基为1，2，3或4个，且选自：天冬氨酸、天冬酰胺、异亮氨酸、谷氨酸或谷氨酰胺。

3.如权利要求1所述，式(I)六肽或其衍生物或其立体异构体或其药用盐选自：

(1)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-NH₂

(2)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-NH₂

(3)Ac-Pro¹-Phe²-Val³-Phe⁴-NH₂

(4)Ac-Pro¹-Phe²-Val³-NH₂

(5)Ac-Phe¹-Val²-Phe³-Leu⁴-Met⁵-NH₂

(6)Ac-Phe¹-Val²-Phe³-Leu⁴-NH₂

(7)Ac-Phe¹-Val²-Phe³-NH₂

(8)Ac-Val¹-Phe²-Leu³-Met⁴-NH₂

(9)Ac-Val¹-Phe²-Leu³-NH₂

(10)Ac-Phe¹-Leu²-Met³-NH₂

(11)Ac-D-Pro¹-D-Phe²-D-Val³-D-Phe⁴-D-Leu⁵-D-Met⁶-NH₂

(12)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Ser⁶-NH₂

(13)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Gln⁶-NH₂

(14)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Asp⁶-NH₂

(15)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Lys⁶-NH₂

(16)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Asn⁶-NH₂

(17)Ac-Pro¹-Nal²-Val³-Phe⁴-Leu⁵-Met⁶-NH₂

(18)Ac-Pro¹-Phe²-Val³-Nal⁴-Leu⁵-Met⁶-NH₂

(19)Ac-Pro¹-Nal²-Val³-Nal⁴-Leu⁵-Met⁶-NH₂

(20)Ac-Pro¹-Mop²-Val³-Phe⁴-Leu⁵-Met⁶-NH₂

(21)Ac-Pro¹-Phe²-Val³-Mop⁴-Leu⁵-Met⁶-NH₂

(22)Ac-Pro¹-Mop²-Val³-Mop⁴-Leu⁵-Met⁶-NH₂

(23)Pgl¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-NH₂

(24)Ureido-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-NH₂

(25)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-Cys⁷-OH

(26)Ac-Asp¹-Pro²-Phe³-Val⁴-Phe⁵-Leu⁶-Met⁷-NH₂

(27)Ac-Asn¹-Pro²-Phe³-Val⁴-Phe⁵-Leu⁶-Met⁷-NH₂

(28)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-Iln⁷-NH₂

(29)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-Iln⁷-Glu⁸-NH₂

(30)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-Iln⁷-Glu⁸-Gln⁹-NH₂

(31)Ac-Pro¹-Phe²-Val³-Phe⁴-Leu⁵-Met⁶-Iln⁷-Glu⁸-Gln⁹-Asn¹⁰-NH₂

(32)Ac-D-Met¹-D-Leu²-D-Phe³-D-Val⁴-D-Phe⁵-D-Pro⁶-NH₂

(33)Ac-Pro¹-D-Phe²-Val³-D-Phe⁴-Leu⁵-Met⁶-NH₂