Pyrazole derivatives as GnRH inhibitors

A compound of Formula (I),

• wherein
• A represents a direct bond or optionally substituted C1-5alkylene;
• B is a group of Formula (II):
• wherein at position (a) Formula (II) is attached to the nitrogen atom and the group X is attached to R8;
• M is —(CH2)0-2—O—;
• R1 represents hydrogen;
• optionally substituted C1-8alkyl;
• or (CH2)b—Ra, wherein
• Ra represents C3-8cycloalkyl and b is zero or an integer from 1 to 6;
• R2 represents an optionally substituted mono- or bi-cyclic aromatic ring structure wherein the optional substituents are selected from cyano, NR3R3a, optionally substituted C1-8alkyl, optionally substituted C1-8alkoxy or halo;
• R3 and R3a are independently selected from hydrogen;
• optionally substituted C1-8alkyl and optionally substituted aryl;
• R5 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 III-a;
• III-b;
• III-c;
• III-d;
• III-e;
• III-f, III-g, III-h, III-i or III-j:
• 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;
• R6 and R6a, are independently selected from hydrogen and optionally substituted C1-8alkyl;
• or R6 and R6a together represent carbonyl;
• R7 represents hydrogen or optionally substituted C1-8alkyl;
• or
• together from an optionally substituted 3- to 8-membered heterocyclic ring containing from 1 to 3 further heteroatoms independently selected from O, N and S, and R6a represents hydrogen or optionally substituted C1-8alkyl;
• X and R8 are selected from:
• (i) X represents N and R8 is selected from:
• cyano, hydrogen, hydroxy, —O—Rb, —NRbRc—C(O)O—Rb, —CONRbRc or NH—C(O)—Rb, where Rb and Rc are independently selected from hydrogen and C1-4alkyl optionally substituted with hydroxy, amino, N—C1-4alkylamino, N,N-di-C1-4alkylamino, HO—C2-4alkyl-NH— or HO—C2-4alkyl-N(C1-4alkyl)-;
• (ii) X represents CH and R8 represents NO2;
• and
• (iii) X—R8 represents —O—;
• R11 is a group of the formula:
• N(R9R10) wherein R9 represents hydrogen, optionally substituted aryl, an optionally substituted 3- to 10 membered heterocyclic ring or optionally-substituted C1-8alkyl and R10 represents hydrogen or optionally substituted C1-8alkyl;
• or
• the structure N(R9R10) represents an optionally-substituted 3- to 10 membered heterocyclic ring optionally containing from 1 to 3 further heteroatoms independently selected from O, N and S;
• R12 and R12a are independently selected from hydrogen or optionally substituted C1-8alkyl;
• or R12 and R12a together with the carbon to which they are attached form an optionally substituted 3 to 7-membered cycloalkyl ring;
• R13 and R14 are selected from:
• (i) R13 is selected from hydrogen;
• optionally substituted C1-8alkyl;
• optionally substituted aryl;
• —Rd—Ar, where Rd represents C1-8alkylene and Ar represents optionally substituted aryl;
• and optionally substituted 3 to 8 membered heterocyclic ring optionally containing from 1 to 3 further heteroatoms independently selected from O, N and S;
• and R14 is selected from hydrogen;
• optionally substituted C1-8alkyl and optionally substituted aryl;
• (ii) where R5 represents a group of formula III-a, III-b or III-i, then the group NR13(—R14) 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
• (iii) where R5 represents structure III-e, then the group
• represents an optionally substituted 3 to 8 membered heterocyclic ring optionally containing from 1 to 4 heteroatoms independently selected from O, N and S;
• or a salt, pro-drug or solvate thereof.