SUBSTITUTED PYRAZOLE ANALOGS As RAR ANTAGONISTS

A compound according to formula II

• wherein:
• R is selected from C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl-C3-6 cycloalkyl, phenyl, and C1-5 alkylphenyl;
• A is CH or N;
• X is CH or N
• R1 is selected from:
• —C(O)N(R3)2, and —C(O)R4;
• R2 is selected from:
• —C3-4 alkyl, —OCH(CH3)2, and —SCH(CH3)2;
• each R3 is independently selected from:
• H and —CH3;
• R4 is selected from:
• 4-morpholinyl, 1-piperidinyl, 4-thiomorpholinyl, —NH(CH2)3OH, and 4-methyl-1-piperazinyl;
• and
• provided that when one of A or X is N, the other one of A or X is CH;
• or a pharmaceutically acceptable salt thereof.

A process of preparing a compound of formula I or a pharmaceutically acceptable salt thereof,

• wherein:
• A is CH or N;
• X is CH or N;
• R1 is selected from:
• —C(O)N(R3)2, and —C(O)R4;
• R2 is selected from:
• —C3-4 alkyl, —OCH(CH3)2, and —SCH(CH3)2;
• each R3 is independently selected from:
• H and —CH3;
• R4 is selected from:
• 4-morpholinyl, 1-piperidinyl, 4-thiomorpholinyl, —NH(CH2)3OH, and 4-methyl-1-piperazinyl;
• and
• provided that when one of A or X is N, the other one of A or X is CH;
• said method comprising de-esterifying a compound of formula II;
• wherein R1 to R4 is as above;
• and
• R is selected from C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkyl-C3-6 cycloalkyl, phenyl, and C1-5 alkylphenyl to provide a compound of formula I, or a pharmaceutically acceptable salt thereof.

A compound which is 4-[5-(3,5-Di-tert-butylphenyl)-1-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyrazol-3-yl]benzoic acid in crystalline form characterized by an X-ray powder diffraction pattern obtained from a CuKα source (λ=1.54056 Å) which comprises peaks at:

• a) 5.4, 7.5, 14.6, and 19.9+/−0.2 in 2θ;
• or
• b) 5.4, 7.5, 14.6, 16.0, 19.4, and 19.9+/−0.2 in 2θ;
• or
• c) 5.4, 7.5, 14.6, 15.7, 16.0, 19.4, 19.9 and 22.1+/−0.2 in 2θ.