Biphenyl compounds as SOCE modulators, compositions and uses thereof

A method for treatment of a patient suffering from a disease condition depending on increased/decreased activity of SOCE, comprising administering to the patient a compound of formula (I)

• wherein
• ring Hy is selected from
• ring Hz is selected from
• A1, A2, A3, A4 and A5 are identical or different from each other and independently selected from H, CF3, Br, I, Cl, F, OH, OR1, SR1, NH2, NHR1, NR1R2, S(O)R1, S(O)2R1, NHSO2R1, CONHR1, CONR1R2, SO2NHR1, COOH, COOR1, NO2, CN, and a 5-6 membered O-heterocyclic group;
• A1 and A2, or A2 and A3, or A3 and A4, or A4 and A5 can form together a 5-6 membered O-heterocyclic group fused to the phenyl ring to which they are attached;
• B1, B2, B3, B4 and B5 are identical or different and independently selected from H, CH2COOH, COOH, COOR3, CN, CF3, Br, I, Cl, F, and 1H-tetrazol-5-yl;
• R1 and R2 are identical or different from each other and independently selected from unsubstituted or substituted C1-8 alkyl group, unsubstituted or substituted C2-8 alkenyl group, unsubstituted or substituted C2-8 alkynyl group, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic group, (CH2)n—C1-8 alkyl, (CH2)n—C2-8 alkenyl, (CH2)n—C2-8 alkynyl group, (CH2)n-cycloalkyl, (CH2)n-aryl and (CH2)n-heteroaryl, wherein n is an integer 1 to 4;
• R3 is selected from unsubstituted or substituted C1-8 alkyl group, unsubstituted or substituted C2-8 alkenyl group, unsubstituted or substituted C2-8 alkynyl group, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic group, (CH2)m—C1-8 alkyl, (CH2)m—C2-8 alkenyl, (CH2)m—C2-8 alkynyl group, (CH2)m-cycloalkyl, (CH2)m-aryl and (CH2)m-heteroaryl, wherein m is an integer 1 to 4;
• provided that at least one of A1, A2, A3, A4 and A5 is not H;
• and
• provided that at least one of B1, B2, B3, B4 and B5 is not H;
• and/or a pharmaceutically acceptable salt.

A method for treatment of a patient suffering from diseases linked to loss- or gain-of-function STIM1/Orai1 mutations, muscular dystrophies, inflammatory diseases, comprising administering to the patient a compound of formula (I)

• wherein
• ring Hy is selected from
• ring Hz is selected from
• A1, A2, A3, A4 and A5 are identical or different from each other and independently selected from H, CF3, Br, I, Cl, F, OH, OR1, SR1, NH2, NHR1, NR1R2, S(O)R1, S(O)2R1, NHSO2R1, CONHR1, CONR1R2, SO2NHR1, COOH, COOR1, NO2, CN, and a 5-6 membered O-heterocyclic group;
• A1 and A2, or A2 and A3, or A3 and A4, or A4 and A5 can form together a 5-6 membered O-heterocyclic group fused to the phenyl ring to which they are attached;
• B1, B2, B3, B4 and B5 are identical or different and independently selected from H, CH2COOH, COOH, COOR3, CN, CF3, Br, I, Cl, F, and 1H-tetrazol-5-yl;
• R1 and R2 are identical or different from each other and independently selected from unsubstituted or substituted C1-8 alkyl group, unsubstituted or substituted C2-8 alkenyl group, unsubstituted or substituted C2-8 alkynyl group, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic group, (CH2)n—C1-8 alkyl, (CH2)n—C2-8 alkenyl, (CH2)n—C2-8 alkynyl group, (CH2)n-cycloalkyl, (CH2)n-aryl and (CH2)n-heteroaryl, wherein n is an integer 1 to 4;
• R3 is selected from unsubstituted or substituted C1-8 alkyl group, unsubstituted or substituted C2-8 alkenyl group, unsubstituted or substituted C2-8 alkynyl group, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic group, (CH2)m—C1-8 alkyl, (CH2)m—C2-8 alkenyl, (CH2)m—C2-8 alkynyl group, (CH2)m-cycloalkyl, (CH2)m-aryl and (CH2)m-heteroaryl, wherein m is an integer 1 to 4;
• provided that at least one of A1, A2, A3, A4 and A5 is not H;
• and
• provided that at least one of B1, B2, B3, B4 and B5 is not H;
• and/or a pharmaceutically acceptable salt.

Pharmaceutical composition comprising at least one compound of formula (I) and a pharmaceutically acceptable carrier and/or vehicle

• wherein
• ring Hy is selected from
• ring Hz is selected from
• A1, A2, A3, A4 and A5 are identical or different from each other and independently selected from H, CF3, Br, I, Cl, F, OH, OR1, SR1, NH2, NHR1, NR1R2, S(O)R1, S(O)2R1, NHSO2R1, CONHR1, CONR1R2, SO2NHR1, COOH, COOR1, NO2, CN, a 5-6 membered O-heterocyclic group;
• A1 and A2, or Az and A3, or A3 and A4, or A4 and A5 can form together a 5-6 membered O-heterocyclic group fused to the phenyl ring to which they are attached;
• B1, B2, B3, B4 and B5 are identical or different and independently selected from H, CH2COOH, COOH, COOR3, CN, CF3, Br, I, Cl, F, 1H-tetrazol-5-yl;
• R1 and R2 are identical or different from each other and independently selected from unsubstituted or substituted C1-8 alkyl group, unsubstituted or substituted C2-8 alkenyl group, unsubstituted or substituted C2-8 alkynyl group, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic group, (CH2)n—C1-8 alkyl, (CH2)n—C2-8 alkenyl, (CH2)n—C2-8 alkynyl group, (CH2)n-cycloalkyl, (CH2)n-aryl and (CH2)n-heteroaryl, wherein n is an integer 1 to 4;
• R3 is selected from unsubstituted or substituted C1-8 alkyl group, unsubstituted or substituted C2-8 alkenyl group, unsubstituted or substituted C2-8 alkynyl group, unsubstituted or substituted C3-6 cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic group, (CH2)m—C1-8 alkyl, (CH2)m—C2-8 alkenyl, (CH2)m—C2-8 alkynyl group, (CH2)m-cycloalkyl, (CH2)m-aryl and (CH2)m-heteroaryl, wherein m is an integer 1 to 4;
• provided that at least one of A1, A2, A3, A4 and A5 is not H;
• and
• provided that at least one of B1, B2, B3, B4 and B5 is not H;
• and/or a pharmaceutically acceptable salt.