6-aryl-7-substituted-3-(1h-pyrazol-5-yl)-7h-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines as inhibitors of the stat3 pathway with anti-proliferative activity

A compound represented by the following formula:

• wherein:
• R is selected from the group consisting of a C1-C6 alkyl or aryl, optionally substituted by one or more selected from the group consisting of —OR′, —NR′R″,
• and an optionally substituted phenyl, wherein
• (1) R′ and R″ are each independently selected from —H, C1-C6 alkyl and C1-C6 alkyl substituted by one or more fluro groups, and when R′ and R″ are each alkyl they may form a ring,
• (2) Y is selected from C1-C6 alkyl, —OR′, and —NR′R″, wherein when the optionally substituted phenyl contains a substituent, the substituent is selected from —OR′, —NR′R″, and
• R1 is
• wherein
• (1) each Z is independently selected from halogen, C1-C6 alkyl, C1-C6 alkyl substituted by one or more fluro groups, —OR′, —NR′R″,
• (2) a is an integer of 0 to 4,
• (3) Y′ is selected from C1-C6, alkyl, C1-C6 alkyl substituted by one or more fluro groups, —OR′, and —NR′R″,
• wherein R and R1 may form a ring;
• X is
• phenyl optionally substituted by one or more halogen,
• wherein
• (1) R2 is phenyl optionally substituted by one or more halogen and R3 is hydrogen or a halogen, or R2 and R3 form a 5 or 6-membered ring comprising sp3 carbon atoms, and optionally one heteroatom selected from S, NR* and O, wherein R* is H, C1-C6 alkyl or benzyl,
• (2) R5 is phenyl optionally substituted by one or more halogen and R4 is hydrogen or a halogen, or R5 and R4 form a 5 or 6-membered ring comprising carbon atoms, and optionally one heteroatom selected from S, NR* and O, wherein R* is H, C1-C6 alkyl or benzyl,
• (3) Z′ is halogen, benzyl, C1-C6 alkyl, and C1-C6 alkyl substituted by one or more fluro groups,
• (4) b is an integer from 0 to 4,
• (5) R′″ is hydrogen, C1-C6 alkyl, benzyl,
• wherein the benzyl may be substituted by one or more halogen, C1-C6 alkyl, or C1-C6 alkyl substituted by one or more fluro groups —OR′,
• (6) R″″ is hydrogen, C1-C6 alkyl, benzyl, or
• wherein the benzyl may be substituted by one or more halogen, C1-C6 alkyl, or C1-C6 alkyl substituted by one or more fluro groups —OR′,
• or a pharmaceutically acceptable solvate or salt thereof, and
• wherein when R and R1 are both unsubstituted phenyl, then R2 cannot be unsubstituted phenyl.