黑色素皮質激素受體七肽類激動劑及其製備方法和用途的製作方法

2023-07-07 19:26:06 1

/>IVVVI(Mpca)各個R5獨立地為R1、-NR1R2、-NHC(O)NR1R2、-C(O)NR1R2、-NH-C(O)R1，其中R1和R2的定義同前；S4為D型的Z，Z的定義同前；S6為L或D型的Trp或Z，Z的定義同前，所述「芳基」為6-14元單環或雙環芳香基團，如苯基或萘基，其未被取代或被獨立地選自滷素、硝基、羧基或C1-C4烷基的取代基單取代或二取代或三取代；「雜芳基」為含有1-5個獨立地選自N、O和S的雜原子的4-10元單環或雙環芳香基團，如吡咯基、呋喃基、吡啶基等，其未被取代或被獨立地選自滷素、硝基、羧基或C1-C4烷基的取代基單取代或二取代；「雜環基」為其環結構中含1-5個、優選1-3個獨立地選自N、O和S的雜原子的3-8元非芳香環狀基團，如吡喃基、哌啶基等，其未被取代或被獨立地選自滷素、硝基、羧基或C1-C4烷基的取代基單取代或二取代或三取代。2、根據權利要求1的化合物，其中R為AC-、-C0NH2、-CON(CH3)2、No-。3、根據權利要求l的化合物，4、根據權利要求l的化合物，5、根據權利要求l的化合物，6、根據權利要求1的化合物，或D-Upa。其中B為-NH2或-0H。其中Sz為Asp。其中S3為L或D型的His或Tic。其中S4為D-Tic、D-Mob、D-Fpa7、根據權利要求1的化合物，其選自以下七肽衍生物，或其立體異構體或無生理毒性的鹽(1)Ac-Nle-Asp-His-D-Tic-Arg-Trp-Lys-NH2(2)Ac-N1e-Asp-His-D-Tic-Arg-Tic-Lys-NH2(3)Ac-N1e_Asp-His-D-Tic-Arg-Tca-Lys-NH2(4)Ac-Nle-Asp-His-D-Mob-Arg-Trp-Lys-NH2(5)Ac-N1e_Asp-His-D-Mob-Arg-Tic-Lys-NH2(6)Ac-Nle-Asp-His-D-Mob-Arg-Tca-Lys-NH2(7)Ac-Nle-Asp-His-D-Fpa-Arg-Trp-Lys-NH2(8)Ac-N1e-Asp-His-D-Fpa-Arg-Tic-Lys-NH2(9)Ac-Nle-Asp-His-D-Fpa-Arg-Tca-Lys-NH2(10)Ac-N1e-Asp-His-D-Upa-Arg-Trp-Lys-NH2(11)Ac-Nle-Asp-His-D-Upa-Arg-Tic-Lys-NH2(12)Ac-Nle-Asp-His-D-Upa-Arg-Tca-Lys-NH2(13)Ac-Nle-Asp-Tic-D-Tic-Arg-Trp-Lys-NH2(14)Ac-N1e-Asp-Tic-D-Tic-Arg-Tic-Lys-NH2(15)Ac-N1e-Asp-Tic-D-Tic-Arg-Tca-Lys-NH2(16)Ac-N1e-Asp-Tic-D-Mob-Arg-Trp-Lys-NH2(17)Ac-N1e-Asp-Tic-D-Mob-Arg-Tic-Lys-NH2(18)Ac-N1e-Asp-Tic-D-Mob-Arg-Tca-Lys-NH2(19)Ac-Nle-Asp-Tic-D-Fpa-Arg-Trp-Lys-NH2(20)Ac-Nle-Asp-Tic-D-Fpa-Arg-Tic-Lys-NH2(21)Ac-Nle-Asp-Tic-D-Fpa-Arg-Tca-Lys-NH2(22)Ac-Nle-Asp-Tic-D-Upa-Arg-Trp-Lys-跳(23)Ac-N1e-Asp-Tic-D-Upa-Arg-Tic-Lys-NH2(24)Ac-Nle-Asp-Tic-D-Upa-Arg-Tca-Lys-NH2(25)Ac-N1e-Asp-His-D-Tic-Arg-Trp-Lys-OH(26)Ac-N1e-Asp-His-D-Tic-Arg-Tic~Lys-OH(27)Ac-N1e-Asp-His-D-Tic一Arg-Tca-Lys-OH(28)Ac-N].e--Asp-HLS.-D-Mob-Arg-Trp-Lys--OH(29)Ac-N].e--Asp-H]LS--D-Mob-Arg-Tic一Lys--OH(30)Ac-N.e--Asp-H[s--D-Mob-Arg-Tca-Lys--OH(31)Ac-N].e--Asp-H[s.-D-Fpa-Arg-Trp-Lys--OH(32)Ac-N].e--Asp-HLS--D-Fpa-Arg-Tic一Lys--OH(33)Ac-N].e--Asp-H1LS--D-Fpa-Arg-Tca-Lys--OH(34)Ac-N].e--Asp-HLS--D-Upa-Arg-Trp-Lys--OH(35)Ac-N]e--Asp-H〗LS--D-Upa-Arg-Tic一Lys--OH(36)Ac-NJ■e--Asp-H]LS--D-Upa-Arg-Tca-Lys--OH(37)Ac-N]■e--Asp-T]LC-陽D-Tic-Arg-Trp-Lys--OH(38)Ac-N].e--Asp-T〗LC--D-Tic-Arg-Tic-Lys--OH(39)Ac-N]e--Asp-TiLC--D-Tic-Arg-Tca-Lys--OH(40)Ac-Ne--Asp-TiLC--D-Mob-Arg-Trp-Iyys--OH(41)Ac-NL6--Asp-TilC--D-Mob-Arg-Tic一Lys國-OH(42)Ac-Nl6--Asp-Ti.c--D-Mob-Arg-Tca-Lys--OH(43)Ac-N6-陽Asp-Tic--D-Fpa-Arg-Trp-Lys-OH(44)Ac-N.6--Asp-Ti.c--D-Fpa-Arg-Tic一Lys隱-OH(45)Ac-N6--Asp-Tic-畫D-Fpa-Arg-Tca-Lys--OH(46)Ac-N6誦隱Asp-Tic--D-Upa-Arg-Trp-Lys--OH(47)Ac-N.6--Asp-H.c--D-Upa-Arg-Tic-Lys-OH(48)Ac-N.6--Asp-Tic--D-Upa-Arg-Tca-Lys-OH(49)NH2C0-Nle-Asp-His-D-Tic-Arg-Trp-Lys-NH(50)NH2CO-Nle-Asp-His-D-Tic-Arg-Tic-Lys-NH(51)NH2CO-Nle-Asp-His-D-Tic-Arg-Tca-Lys-NH(52)NH2CO-Nle-Asp-His-D-Mob-Arg-Trp-Lys-NH:(53)NH2CO-Nle-Asp-His-D-Mob-Arg-Tic-Lys-NH:(54)NH2C0-Nle-Asp-His-D-Mob-Arg-Tca-Lys-NH(55)NH2C0-Nle-Asp-His-D-Fpa-Arg-Trp-Lys-NH(56)NH2CO-Nle-Asp-His-D-Fpa-Arg-Tic-Lys-NH:(57)NH2CO-Nle-Asp-His+Fpa-Arg-Tca-Lys-NH2(58)NH2CO-Nle-Asp-His-D-Upa-Arg-Trp-Lys-NH2(59)NH2C0-N1e-Asp-His-D-Upa-Arg-Tic-Lys-NH2(60)NH2CO-Nle-Asp-His-D-Upa-Arg-Tca-Lys-NH2(61)NH2CO-Nle-Asp-Tic-D-Tic-Arg-Trp-Lys-NH2(62)NH2C0-N1e-Asp-Tic-D-Tic-Arg-Tic-Lys-NH2(63)NH2CO-Nle-Asp-Tic-D-Tic-Arg-Tca-Lys-NH2(64)NH2CO-Nle-Asp-Tic-D-Mob-Arg-Trp-Lys-NH2(65)NH2C0-N1e-Asp-Tic-D-Mob-Arg-Tic-Lys-NH2(66)NH2CO-Nle-Asp-Tic-D-Mob-Arg-Tca-Lys-NH2(67)NH2CO-Nle-Asp-Tic-D-Fpa-Arg-Trp-Lys-NH2(68)NH2CO-Nle-Asp-Tic-D-Fpa-Arg-Tic-Lys-NH2(69)NH2CO-Nle-Asp-Tic-D-Fpa-Arg-Tca-Lys-NH2(70)NH2CO-Nle-Asp-Tic-D-Upa-Arg-Trp-Lys-NH2(71)NH2CO-Nle-Asp-Tic-D-Upa-Arg-Tic-Lys-NH2(72)NH2C0-N1e-Asp-Tic-D-Upa-Arg-Tca-Lys-NH2(73)NH2CO-Nle-Asp-His-D-Tic-Arg-Trp-Lys-OH(74)NH2C0-N1e-Asp-His-D-Tic-Arg-Tic-Lys-OH(75)NH2CO-Nle-Asp-His-D-Tic-Arg-Tca-Lys-OH(76)NH2CO-Nle-Asp-His-D-Mob-Arg-Trp-Lys-OH(77)NH2C0-N1e-Asp-His-D-Mob-Arg-Tic-Lys-OH(78)NH2CO~Nle-Asp-His-D-Mob-Arg-Tca-Lys一OH(79)NH2CO-Nle-Asp-His-D-Fpa-Arg-Trp-Lys-OH(80)NH2C0-Nle-Asp-His-D-Fpa-Arg-Tic-Lys-0H(81)NH2CO-Nle-Asp-His+Fpa-Arg-Tca-Lys-OH(82)NH2CO-Nle-Asp-His-D-Upa-Arg-Trp-Lys-OH(83)NH2CO-Nle-Asp-His-D-Upa-Arg-Tic-Lys-OH(84)NH2CO-Nle-Asp-His-D-Upa-Arg-Tca-Lys-OH(85)NH2C0-N1e-Asp-Tic-D-Tic-Arg-Trp-Lys-OH86)觀C0-N1e-Asp-Tic-D-Tic-Arg-Tic-Lys-0H87)NH2CO-Nle-Asp-Tic-D-Tic-Arg-Tca-Lys-OH88)NH2CO-Nle-Asp-Tic-D-Mob-Arg-Trp-Lys-OH89)NH2C0-N1e-Asp-Tic-D-Mob-Arg-Tic-Lys-OH90)NH2CO-Nle-Asp-Tic-D-Mob-Arg-Tca-Lys-OH91)NH2CO-Nle-Asp_Tic+Fpa-Arg-Trp-Lys-OH92)NH2CO-Nle-Asp-Tic+Fpa-Arg-Tic-I>ys-OH93)NH2CO_N1e-Asp-Tic-D-Fpa-Arg-Tca-Lys-OH94)NH2CO-Nle-Asp-Tic-D-Upa-Arg-Trp-Lys-OH95)NH2CO-N1e-Asp-Tic-D-Upa-Arg-Tic-Lys-OH96)NH2CO-N1e-Asp-Tic-D-Upa-Arg-Tca-Lys-OH97)(CH3)2NCO-N1e-Asp-His-D-Tic-Arg-Trp-Lys-NH98)(CH3)2NCO-Nle-Asp-His-D-Tic-Arg-Tic-Lys-NH99)(CH3)2NCO-Nle-Asp-His-D-Tic-Arg-Tca-Lys-NH100)(CH3)2NCO-Nle-Asp-Hi.s--D-Mob-Arg-Trp-Lys-NH2101)(CH3)2腦-N1e-Asp-Hi.s--D-Mob-Arg-Tic-Lys-NH2102)(CH3)2NCO-Nle-Asp-His--D-Mob-Arg-Tca-Lys-NH2103)(CH3)2NCO-Nle-Asp-Hi-S-陽D-Fpa-Arg-Trp-Lys-NH2104)(CH3)2NCO-Nle-Asp-His-陽D-Fpa-Arg-Tic-Lys-NH2105)(CH3)2NCO-Nle-Asp-His-隱D-Fpa-Arg-Tca-Lys-NH2106)(CH3)2NCO-Nle-Asp-Hi.s-隱D-Upa-Arg-Trp-Lys-NH2107)(CH3)2NC0-N1e-Asp-HiLS-陽D-Upa-Arg-Tic-Lys-NH2108)(CH3)2NC0-N1e-Asp-HiLS國-D-Upa-Arg-Tca-tys-NH2109)(CH3)2NCO-Nle-Asp-TiLC--D-Tic-Arg-Trp-Lys-NH2110)(CH3)2NCO-Nle-Asp-TiLC--D-Tic_Arg-Tic-Lys-NH2111)(CH3)2NCO-Nle-Asp-TiLC--D-Tic-Arg-Tca-Lys-NH2112)(CH3)2NCO-Nle-Asp-T〗LC-陽D-Mob-Arg-Trp-Lys-NH2113)(CH3)2NCO-Nle-Asp-TiLC-畫D-Mob-Arg-Tic-Lys-NH2114)(CH3)2NCO-Nle-Asp-TiLC--D-Mob-Arg-Tca-Lys-NH2(115)線)2腦-N16--Asp-Tic畫-D-Fpa-Arg-Trp-Lys誦-NH2(116)(CH3)2NC0-N16--Asp-Tic--D-Fpa-Arg-Tic-Lys--NH2(117)(CH3)2NC0-N16_-Asp-Tic--D-Fpa-Arg-Tca-Lys--NH2(118)(CH3)2NC0-N16_-Asp-Tic--D-Upa-Arg-Trp-Lys--NH2(119)(CH3)2NC0-N16--Asp-Tic--D-Upa-Arg-Tic一Lys--NH2(120)(CH3)2NC0-N16-陽Asp-Tic--D-Upa-Arg-Tca-Lys--NH2(121)(CH3)2NC0-N16--Asp-His--D-Tic一Arg-Trp-:Lys--OH(122)(CH3)2NC0-N16_-Asp-His--D-Tic-Arg-Tic-Lys--OH(123)(CH3)2NC0-N16--Asp-His-匿D-Tic-Arg-Tca-Lys--OH(124)(CH3)2NC0-N16_-Asp-His--D-Mob-Arg-Trp-Lys--OH(125)(CH3)2NC0-N16--Asp-His--D-Mob-Arg-Tic-Lys誦國OH(126)(CH3)2NC0-N16_-Asp-His誦-D-Mob-Arg-Tca-Lys--OH(127)(CH3)2NC0-N16--Asp-His--D-Fpa-Arg-Trp-Lys誦國OH(128)(CH3)2NC0-N16_-Asp-His-曙D-Fpa-Arg-Tic-Lys-國OH(129)(CH3)2腦-N16_-Asp-His--D-Fpa-Arg-Tca-!Lys--OH(130)(CH3)2歸-N16_-Asp-His--D-Upa-Arg-Trp-Lys誦-OH(131)(CH3)2腦-N〗.6--Asp-Hi.s-陽D-Upa-Arg-Tic-Lys-OH(132)(CH3)2NCO-Ne--Asp-HiLS--D-Upa-Arg-Tca-!Lys--OH(133)(CH3)2歸-N.e-國Asp-TiLC-畫D-Tic-Arg-Trp-Lys--OH(134)(CH3)2NCO-N]L6--Asp-"HLC--D-Tic-Arg-Tic-Lys--OH(135)(CH3)2NCO-N.e--Asp-TiLC--D-Tic-Arg-Tca-Lys--OH(136)(CH3)2NCO-N.e--Asp-T〗LC.-D-Mob-Arg-Trp-!Lys--OH(137)(CH3)2NCO-N]e--Asp-TLC-隱D-Mob-Arg-Tic-Lys--OH(138)(CH3)2NC0-N].e--Asp-T.c--D-Mob-Arg-Tca-Lys--OH(139)(CH3)2NCO-N].e-陽Asp-T〗ic--D-Fpa-Arg-Trp-Lys--OH(140)(CH3)2NC0-NLe--Asp-Tic--D-Fpa-Arg-Tic-Lys-OH(141)(CH3)2NC0-NLe--Asp-Tle--D-Fpa-Arg-Tca-Lys.-OH(142)(CH3)2NC0-NLe--Asp-Tlc--D-Upa-Arg-Trp-Lys--OH(143)(CH3)2NC0-NLe--Asp-TLc--D-Upa-Arg-Tic一:Lys--OH144)(CH3)2NCO-Nle-Asp-Tic-D-Upa-Arg-Tca-Lys-OH145)Ac-隱N].e--環(Asp-H]ls--D-Tic-Arg-Trp-Lys〕-NH2146)Ac--N].e--環(Asp-H]ls--D-Tic-Arg-Tic-Lys〕-NH2147〕Ac--N].e--環(Asp-Hls--D-Tic-Arg-Tca-Lys〕-NH2148)Ac--N].e--環(Asp-H]ls.-D-Mob-Arg-Trp-Lys)-NH2149〕Ac--N〕.e--環(Asp-H]ls.-D-Mob-Arg-Tic-Lys〕-NH2150)Ac-隱N].e-陽環(Asp-H〗LS--D-Mob-Arg-Tca-Lys〕-NH2151)Ac誦-N].e--環(Asp-Hils.-D-Fpa-Arg-Trp"Lys〕-NH2152)Ac--N〗e曙-環(Asp-HiLS.-D-Fpa-Arg-Tic-:Lys)-NH2153〕Ac-隱N].e--環(Asp-H〗ls--D-Fpa-Arg-Tca-Lys〕-NH2154)Ac-國N.e--環(Asp-H〗ls--D-Upa-Arg-Trp-Lys)-NH2155)Ac國-N]e-國環(Asp-H〗ls--D-Upa-Arg-Tic-Lys)-NH2156)Ac-陽N].e--環(Asp-Hils--D-Upa-Arg-Tca-Lys)-NH2157)Ac--N]e--環(Asp-T〗LC--D-Tic-Arg-Trp-Lys)-NH2158)Ac誦-N,e--環(Asp-Ti.c--D-Tic-Arg-Tic-Lys)-NH2159)Ac--N]L6誦-環(Asp-Tic--D-Tic-Arg-Tca-Lys)-匪2160)Ac--Ne--環(Asp-TilC--D-Mob-Arg-Trp-Lys)-NH2161)Ac--Ne-陽環(Asp-TiLC--D-Mob-Arg-Tic-Lys)-NH2162)Ac--NJe誦國環(Asp-TiLC--D-Mob-Arg-Tca-Lys)-NH2163)Ac-國Ne--環(Asp-T〗LC.-D-Fpa-Arg-Trp-Lys)-NH2164)Ac--N.e-國環(Asp-TiLC--D-Fpa-Arg-Tic-Lys)-NH2165)Ac誦國N〗e誦國環(Asp-TiLC--D-Fpa-Arg-Tca-Lys)-NH2166)Ac-隱N.e-陽環(Asp-TiLC--D-Upa-Arg-Trp"Lys)-NH2167)Ac--N.e-畫環(Asp-Tilc--D-Upa~Arg-Tic一Ly5)-NH2168)Ac誦國N]e誦畫環(Asp-Tilc-D-Upa-Arg-Tca-Lys)-NH2169)Ac-陽N〗e-陽環(Asp-Hils--D-Tic-Arg-Trp-Lys)-OH170)Ac--N.e-畫環(Asp-H3ls--D-Tic-Arg-Tic-Lys)-OH171)Ac-畫N]e-畫環(Asp-Hils--D-Tic-Arg-Tca-Lys)-OH172)Ac--NJe誦畫環(Asp-Hils--D-Mob-Arg-Trp"Lys)-OHformulaseeoriginaldocumentpage10(202)NH2CO-Nle-環(Asp-His--D-Upa-Arg-Trp-Lys)-NH2(203)NH2C0-Nle-環(Asp-His--D-Upa-Arg-Tic-Lys)-NH2(204)NH2CO-Nle-環(Asp-His--D-Upa-Arg-Tca-Lys)-NH2(20)NH2CO-Nle-環(Asp-Tic-D-Tic-Arg-Trp-Lys)畫-NH2(206)冊2CO-Nle-環(Asp-Ti,c--D-Tic-Arg-Tic-Lys)-NH2(207)NH2CO-Nle-環(Asp-Ti-C--D-Tic-Arg-Tca-Lys)-NH2(208)NH2CO-Nle-環(Asp-TiLC--D-Mob-Arg-Trp-Lys)-NH2(209)NH2CO-Nle-環(Asp-T,c--D-Mob-Arg-Tic~Lys)-NH2(210)NH2C0-Nle-環(Asp-TiLC--D-Mob-Arg-Tca-Lys)-NH2(211)NH2CO-Nle-環(Asp-TiLC--D-Fpa-Arg-Trp-Lys)-NH2(212)NH2CO-Nle-環(Asp-TiLC--D-Fpa-Arg-Tic-Lys)-NH2(213)冊2C0-Nle-環(Asp-TiLC--D-Fpa-Arg-Tca-Lys)-NH2(214)NH2CO-Nle-環(Asp-TiLC-畫D-Upa-Arg-Trp-Lys)-NH2(215)NH2CO-Nle-環(Asp-Ti-D-Upa-Arg-Tic-Lys)-NH2(216)NH2CO-Nle-環(Asp-Tic--D-Upa-Arg-Tca-Lys)-匪2(217)NH2CO-Nle-環(Asp-HiLS國隱D-Tic-Arg-Trp-Lys)-OH(218)冊2CO-Nle-環(Asp-Hi.s-國D-Tic-Arg-Tic-Lys)-OH(219)冊2C0-Nle-環(Asp-HiLS-曙D-Tic-Arg-Tca-Lys)-OH(220)NH2CO-Nle-環(Asp-HiLS--D-Mob-Arg-Trp-Lys)-OH(221)NH2CO-Nle-環(Asp-HiLS-畫D-Mob-Arg-Tic-Lys)-OH(222)NH2CO-Nle-環(Asp-HLS-國D-Mob-Arg-Tca-Iiys)-OH(223)NH2C0-Nle-環(Asp-HLS-陽D-Fpa-Arg-Trp-Lys)-OH(224)NH2CO-Nle-環(Asp-HiLS.-D-Fpa-Arg-Tic-Lys)-OH(225)NH2CO-Nle-環(Asp-HiLS-國D-Fpa-Arg-Tca-Lys)-OH(226)NH2CO-Nle-環(Asp-H〗LS--D-Upa-Arg-Trp-Lys)-OH(227)NH2CO-Nle-環(Asp-H〗LS--D-Upa-Arg-Tic-Lys)-OH(228)NH2CO-Nle-環(Asp-H〗LS--D-Upa-Arg-Tca-Lys)-OH(229)NH2CO-Nle-環(Asp-Tic-D-Tic-Arg-Trp-Lys)-OH(230)NH2C0-N1e-環(Asp-Tic-D-Tic-Arg-Tic-Lys)一OH(231)NH2C0-Nle-環(Asp-Tic-D-Tic-Arg-Tca-Lys)-OH(232)NH2CO-Nle-Sf(Asp-Tic-D-Mob-Arg-Trp-Lys)-OH(233)NH2C0-Nle;(Asp-Tic+Mob-Arg-Tic-Lys)-OH(234)NH2C0-Nle-環(Asp-Tic-D-Mob-Arg-Tca-Lys)-OH(235)NH2C0-Nle-環(Asp-Tic-D-Fpa-Arg-Trp-Lys)-OH(236)NH2C0-Nle-環(Asp-Tic-D-Fpa-Arg-Tic-Lys)-OH(237)NH2C0-Nle-環(Asp-Tic-D-Fpa-Arg-Tca-Lys)-OH(238)NH2C0-Nle-環(Asp-Tic-D-Upa-Arg-Trp-Lys)-OH(239)NH2C0-N1e-環(Asp-Tic-D-Upa-Arg-Tic-Lys)-OH(240)冊2-環(Asp-Tic-D-Upa-Arg-Tca-Lys)-OH(241)(CH3)2NCO-N1e-環(Asp-His-D-Tic-Arg-Trp-Lys)-冊2(242)(CH3)2NCO-N1e-環(Asp-His-D-Tic-Arg-Tic-Lys)-NH2(243)(CH3)2NCO-Nle-環(Asp-His-D-Tic—Arg-Tca-Lys)-NH2(244)(CH3)2NCO-Nle-環(Asp-His-D-Mob-Arg-Trp-Lys)-NH2(245)(CH3)2NCO-N1e-環(Asp-His-D-Mob-Arg-Tic-Lys)-匪2(246)(CH3)2NC0-Nle-環(Asp-His-D-Mob-Arg-Tca-Lys)-NH2(247)(CH3)2NC0-Nle-環(Asp-His-D-Fpa-Arg-Trp-Lys)-匪2(248)(CH3)2NCO-N1e-環(Asp-His-D-Fpa-Arg—Tic-Lys)-冊2(249)(CH3)2腦-Nle-環(Asp-His-D-Fpa-Arg-Tca-Lys)-冊2(250)(CH3)2NC0-Nle-環(Asp-His-D-Upa-Arg-Trp-Lys)-NH2(251)(CH3)2NCO-Nle-環(Asp-His-D-Upa-Arg-Tic-Lys)-亂(252)(CH3)2NCO-Nle-環(Asp-His-D-Upa-Arg-Tca-Lys)-NH2(253)(CH3)2NCO-Nle-環(Asp-Tic-D-Tic-Arg-Trp-Lys)-NH2(254)(CH3)2NC0-Nle-環(Asp-Tic-D-Tic-Arg-Tic-Lys)-NH2(255)(CH3)2NC0-Nle-環(Asp-Tic-D-Tic-Arg-Tca-Lys)-NH2(256〕(CH3)2NCO-Nle-環(Asp-Tic-D-Mob-Arg-Trp-Lys)-NH2(257)(CH3)2NC0-Nle-環(Asp-Tic-D-Mob-Arg-Tic-Lys)-NH2(258〕(CH3)2NC0-Nle-環(Asp-Tic-D-Mob-Arg-Tca-Lys)-NH2(259〕(CH3)2NC0-N1e-環(Asp-Tic-D-Fpa-Arg-Trp-Lys)-NH2(260)(CH3〕2腳-Nle-環(Asp-T]LC--D-Fpa-Arg-Tic-Lys〕-NH2(261)(CH3〕2腳-Nle-環(Asp-TLC--D-Fpa-Arg-Tca-Lys〕-NH2(262)線〕2NC0-Nle-環(Asp-TLC.-D-Upa-Arg-Trp-Lys〕-NH2(263)線〕2NCO-Nle-環(Asp-TLC.-D-Upa-Arg-Tic-Lys〕-NH2(264)(CH3〕2NC0-Nle-環(Asp-T〗LC--D-Upa-Arg-Tca-Lys〕-NH2(265)(CH3〕2NC0-Nle-環(Asp-H〗LS--D-Tic-Arg-Trp-Lys〕-OH(266)(CH3〕2NC0-Nle-環(Asp-H〗LS--D-Tic-Arg-Tic-Lys〕-OH(267)(CH3〕2NC0-Nle-環(Asp-HLS.-D-Tic-Arg-Tca"Lys〕_0H(268)(CH3)2NC0-Nle-環(Asp-HiLS--D-Mob-Arg-Trp"Lys)-OH(269)(CH3〕2NC0-Nle-環(Asp-HLS--D-Mob-Arg-Tic"Lys)-OH(270)線)2NC0-Nle-環(Asp-HiLS--D-Mob-Arg-Tca-Lys)-OH(271)(CH3)2腳-Nle-環(Asp-HiLS--D-Fpa-Arg-Trp-Lys)-OH(272)(CH3)2腳-Nle-環(Asp-HiLS國-D-Fpa-Arg-Tic-Lys)-OH(273)(CH3)2NC0-Nle-環(Asp-His--D-Fpa-Arg-Tca"Lys)-OH(274)(CH3)2NC0-Nle-環(Asp-HiS誦-D-Upa-Arg-Trp-:Lys)-OH(275)(CH3)細-Nle-環(Asp-H〗s--D-Upa-Arg-Tic"Lys)-OH(276)(CH3)2腳-Nle-環(Asp-His--D-Upa-Arg-Tca-Lys)-OH(277)(CH3)2NC0-Nle-環(Asp-Tic--D-Tic-Arg-Trp-Lys)-OH(278)(CH3)2腳-Nle-環(Asp-Tic-陽D-Tic-Arg-Tic-Lys)-OH(279)(CH3)2NC0-Nle-環(Asp-Tic國陽D-Tic-Arg-Tca-Lys)-OH(280)(CH3)2NC0-Nle-環(Asp-Ti.c誦畫D-Mob-Arg-Trp-Lys)-OH(281)(CH3)2NC0-Nle-環(Asp-T〗c-畫D-Mob-Arg-Tic-Lys)-OH(282)(CH3)2NC0-Nle-環(Asp-Ti.c--D-Mob-Arg-Tca-Lys)-OH(283)(CH3)2NC0-Nle-環(Asp-Tic-畫D-Fpa-Arg-Trp-Lys)-OH(284)(CH3)2NC0-Nle-環(Asp-Tic-陽D-Fpa-Arg-Tic-Lys)-OH(285)(CH3)2NC0-Nle-環(Asp-Tic-隱D-Fpa-Arg-Tca-Lys)-OH(286)(CH3)2腳-Nle-環(Asp-Tic-陽D-Upa-Arg-Trp-Lys)-OH(287)(CH3)2NC0-Nle-環(Asp-Tic--D-Upa-Arg-Tic-Lys)-OH(288)(CH3)2NC0-Nle-環(Asp-Tic--D-Upa-Arg-Tca-Lys)-OH(289)No-Nle-環(Asp-Tic-D-Tic-Arg-Trp-Lys)-NH2。8、藥物組合物，其含有至少一種權利要求l-7任一項的化合物以及可藥用載體或賦形劑。9、權利要求1-7任一項的化合物用於製備治療肥胖及相關疾病(如高血壓)或性功能障礙的藥物的用途。10、權利要求1-7任一項的化合物用於製備MC-Rs激動劑的用途。全文摘要本發明涉及具有MC3R/MC4R受體激動活性的七肽衍生物，其製備方法，含有它們的藥物組合物，以及它們用於製備治療肥胖及相關疾病以及性功能障礙等的藥物的用途。文檔編號A61P9/12GK101302246SQ20081009672公開日2008年11月12日申請日期2008年5月9日優先權日2007年5月9日發明者馮思良,劉克良,寧周,孫彭利,梁遠軍,許笑宇,郄建坤,寒韓申請人:中國人民解放軍軍事醫學科學院毒物藥物研究所