These are described spirolactam derivatives of formulae (Ia) and (Ib)
wherein
R represents a hydrogen atom or a conventional nitrogen protecting group;
R¹ represents a hydrogen atom or a conventional carboxyl protecting group or activating group;
R² represents the side chain of any naturally occurring amino acid;
m represents 1 or 2;
n representss 1 or 2;
the configuration at * may be (R) or (S) or a mixture thereof; with the proviso that when R represents the nitrogen protecting group R³-CO(O)- (where R³ represents (CH₃)₃C-), the group -CO₂R¹ represents the protected carboxy group -CO₂CH₃, m is 1 and n is 1 in the compounds of formula (Ib); R² may not represent an arylmethyl group;
and solvates or acid addition salts thereof.
These derivatives are of value in the preparation of spirolactam compounds which, depending on their stereochemistry, are either antagonists or agonists of substance P, and as such have a variety of therapeutic properties.
所述的是式 (Ia) 和 (Ib) 的螺内酰胺衍
生物
其中
R 代表氢原子或常规氮保护基团;
R¹ 代表氢原子或常规羧基保护基团或活化基团;
R² 代表任何天然
氨基酸的侧链;
m 代表 1 或 2
n 代表 1 或 2;
*处的构型可以是(R)或(S)或其混合物;但当R代表氮保护基团R³-CO(O)-(其中R³代表(CH₃)₃C-)时,在式(Ib)化合物中,基团-CO₂R¹代表受保护的羧基-CO₂CH₃,m为1,n为1;R²不得代表芳甲基;
及其溶剂或酸加成盐。
这些衍
生物在制备螺内酰胺化合物中具有重要价值,根据其立体
化学性质,它们可以是 P 物质的拮抗剂或激动剂,因此具有多种治疗特性。