3-aminoalkyl-2-aryl-indole derivatives and their use as GnRH antagonists

A compound of formula I or a salt, pro-drug or solvate thereof

• wherein
• for A, either:—
• (i) A represents hydrogen or optionally substituted C1 to C8 alkyl;
• or
• (ii) the structure N—A(—R4) represents an optionally substituted 3- to 8-membered heterocyclic ring optionally containing from 1 to 3 further heteroatoms independently selected from O, N and S;
• B represents a direct bond or optionally substituted C1 to C5 alkylene;
• C represents a mono- or bi-cyclic aromatic ring structure optionally having at least one substituent selected from CN, NR5R6, an optionally substituted C1 to C8 alkyl, optionally substituted C1 to C8 alkoxy or halo;
• D represents hydrogen;
• optionally substituted C1 to C8 alkyl;
• or (CH2)b—Ra, wherein Ra is C3 to C8 cycloalkyl and b represents zero or an integer from 1 to 6;
• E is selected from an optionally substituted 3- to 8-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from O, N and S;
• or a group of formula II;
• III;
• IV;
• V;
• VI, VII or VIII
• wherein het represents an optionally substituted 3- to 8-membered heterocyclic ring containing from 1 to 4 heteroatoms independently selected from O, N and S;
• for X and Y, either:—
• (iii) X represents N and Y represents CN;
• hydrogen or —CONRbRc where Rb and Rc are independently selected from hydrogen and C1 to C8 alkyl;
• (iiia) X represents CH and Y represents NO2;
• or
• (iv) X—Y represents O;
• For R1 and R2, either:—
• (v) R1 and R2 are independently selected from hydrogen and optionally substituted C1 to C8 alkyl;
• or
• (vi) R1 and R2 together represent carbonyl;
• or
• (vii)
• represents an optionally substituted 3- to 8-membered heterocyclic ring containing from 1 to 3 further heteroatoms independently selected from O, N and S, and R2 meets the definition in option (v);
• R3 meets the definition in option (vii) or represents hydrogen or optionally substituted C1 to C8 alkyl;
• R4 meets the definition in option (ii), or when A meets the definition in option (i) R4 represents hydrogen or optionally substituted C1 to C8 alkyl;
• R5 and R6 are independently selected from hydrogen;
• optionally substituted C1 to C8 alkyl and optionally substituted aryl;
• for R7 and R7a, either:—
• (viii) R7 and R7a are independently selected from hydrogen or optionally substituted C1 to C8 alkyl;
• or
• (ix)
• represents an optionally substituted 3 to 7-membered cycloalkyl ring;
• for R8 and R9, either:—
• (x) R8 is selected from hydrogen;
• optionally substituted C1 to C8 alkyl;
• optionally substituted aryl;
• —Rd—Ar, where Rd represents C1 to C8 alkylene and Ar represents optionally substituted aryl;
• and an optionally substituted 3- to 8-membered heterocyclic ring optionally containing from 1 to 3 further heteroatoms independently selected from O, N and S;
• and
• R9 is selected from hydrogen;
• optionally substituted C1 to C8 alkyl and optionally substituted aryl;
• (xi) wherein E represents a group of formula II or III, then the group NR8(—R9) represents an optionally substituted 3- to 8-membered heterocyclic ring optionally containing from 1 to 3 further heteroatoms independently selected from O, N and S;
• or
• (xii) wherein E represents structure VI,
• represents an optionally substituted 3- to 8-membered heterocyclic ring optionally containing from 1 to 4 heteroatoms independently selected from O, N and S;
• with the proviso that:
• when A is C1 to C8 alkyl or the structure N—A(—R4) represents an optionally-substituted 3- to 8-membered heterocyclic ring containing from 1 to 3 heteroatoms independently selected from O, N and S;
• X represents N and Y represents CN or hydrogen, X represents CH and Y represents NO2 or X—Y represents O;
• then the optional substituents on A are not selected from optionally substituted phenyl or an optionally-substituted 3- to 8-membered heterocyclic ring.