联苯缬氨酸衍生物及其在制备预防和/或治疗高血压的药物中的用途

摘要

本发明涉及一种新型的联苯缬氨酸衍生物及其在制备预防和/或治疗高血压的药物中的用途。本发明联苯缬氨酸衍生物是较为理想的血管紧张素II受体拮抗剂，为AT1非竞争性拮抗作用，可作为一种良好的降压药物，具备有效降压作用和靶器官保护作用，而且耐受性良好，副作用小。

主权项

1.具有通式(I)的联苯缬氨酸衍生物：式(I)中：R₀₁、R₀₂、R₀₃、R₀₄、R₀₅、R₀₆、R₀₇、R₀₈、R₀₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆独立地为氢或氘；R_N为式(II)，式(III)或式(IV)所表示的基团：上述的式(II)、式(III)中的Ra为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX，CH₂C₆H₂NX₂，O，OC_nH_2n+1，OCH₂CF₃，OCH₂CF₂C_nH_2n+1，OCH₂C₆H₅，OCH₂C₆H₄X，OCH₂C₆H₃X₂，OCH₂C₆H₄N，OCH₂C₆H₃NX或OCH₂C₆H₂NX₂；或者，上述的R_a为式(a-1)、式(a-2)、式(a-3)、式(a-4)、式(a-5)、式(a-6)、式(a-7)、式(a-8)、式(a-9)、式(a-10)、式(a-11)、式(a-12)、式(a-13)、式(a-14)之一所表示的基团：其中，R_N1为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX，CH₂C₆H₂NX₂，OC_nH_2n+1，OCH₂CF₃，OCH₂CF₂C_nH_2n+1，OCH₂CHFC_nH_2n+1，OCH₂C₆H₅，OCH₂C₆H₄X，OCH₂C₆H₃X₂，OCH₂C₆H₄N，OCH₂C₆H₃NX，OCH₂C₆H₂NX₂或N(C_nH_2n+1)₂；R_N2为H或C_nH_2n+1；R_N3为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX，CH₂C₆H₂NX₂，COC_nH_2n+1或COOC_nH_2n+1；R_N4为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX，CH₂C₆H₂NX₂，COC_nH_2n+1或COOC_nH_2n+1；R_N5为H或C_nH_2n+1；R_N6为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX或CH₂C₆H₂NX₂；R_N7为H或C_nH_2n+1；R_N8为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX，CH₂C₆H₂NX₂，COC_nH_2n+1或COOC_nH_2n+1；R_N9为H，C_nH_2n+1；R_N10为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX或CH₂C₆H₂NX₂；R_N11，R_N12独立地为H或C_nH_2n+1；R_N13为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFCnH₂n+₁，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX，CH₂C₆H₂NX₂，COC_nH_2n+1或COOC_nH_2n+1；R_N14为H或C_nH_2n+1；R_N15为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX或CH₂C₆H₂NX₂；R_N16、R_N17独立地为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX或CH₂C₆H₂NX₂；R_N18为H或C_nH_2n+1；R_N19、R_N20独立地为H，C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX或CH₂C₆H₂NX₂；上述的式(I)中的R_c和式(IV)中的R_b独立地为C_nH_2n+1，CH₂CF₃，CH₂CF₂C_nH_2n+1，CH₂CHFC_nH_2n+1，CH₂C₆H₅，CH₂C₆H₄X，CH₂C₆H₃X₂，CH₂C₆H₄N，CH₂C₆H₃NX或CH₂C₆H₂NX₂；或者，上述的R_c和R_b独立地为上述的式(a-4)、式(a-5)、式(a-6)、式(a-7)、式(a-8)、式(a-12)、式(a-13)、式(a-14)之一所表示的基团；以上化学式中，X代表F，Cl，Br，OC_nH_2n+1，SC_nH_2n+1或NC_nH_2n+1；Y代表C_nH_2n+1；n代表1-6之间的整数。