Bicyclo-pyrazoles active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
AssigneePfizer Italia S.r.l.
InventorsDeniele Fancelli, Valeria Pittala, Mario Varasi
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Abstract
Bicyclo-pyrazole compounds of formula (I), as herein defined, are useful for treating diseases linked to disregulated protein kinases.
Claims27
A bicyclo-pyrazole compound of formula (I):
- 10
- wherein
- R and R1, being the same or different, are independently a hydrogen atom or an optionally substituted group selected from R′, —COR′, —COOR′, —CONHR′, —CONR′R″, —NH—C(═NH)NHR′, —C(═NH)NER′, —SO2R′, —SO2NHR′ or —SO2NR′R″;
- wherein R′ and R″, the same or different, are independently selected from hydrogen or optionally further substituted straight or branched C1-C6 alkyl, aryl, C3-C6 cycloalkyl or aryl C1-C6 alkyl or R′ and R″ taken together form a C4-C6 alkylene chain;
- Ra, Rb, Rc and Rd, being the same or different, are independently selected among hydrogen, optionally further substituted straight or branched C1-C6 alkyl, aryl, aryl C1-C6 alkyl or —CH2OR′ groups, wherein R′ is as above defined, or Ra and Rb and/or Rc and Rd, taken together with the carbon atom to which they are bonded, form an optionally substituted C3-C6 cycloalkyl group;
- m and n, each independently, represent 0 or an integer from 1 to 2, provided that m+n is lower than, or equal to, 2 (m+n≦2);
- and the pharmaceutically acceptable salt thereof.
The use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating a disease caused by and/or associated with an altered protein kinase activity, in a patient undergoing a simultaneuous, separate or sequential anticancer treatments.
A combinatorial chemical library comprising a plurality of members of formula (V)
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- wherein
- R and R1, being the same or different, are independently a hydrogen atom or an optionally substituted group selected from R′, —COR′, —COOR′, —CONHR′, —CONR′R″, —NH—C(═NH)NHR′, —C(═NH)NHR′, —SO2R′, —SO2NHR′ or —SO2NR′R″;
- wherein R′ and R″, the same or different, are independently selected from hydrogen or optionally further substituted straight or branched C1-C6 alkyl, aryl, C3-C6 cycloalkyl or aryl C1-C6 alkyl or R′ and R″ taken together form a C4-C6 alkylene chain;
- Ra, Rb, Rc and Rd, the same or different, are selected among hydrogen, optionally further substituted straight or branched C1-C6 alkyl, aryl, aryl C1-C6 alkyl or —CH2OR′ groups, wherein R′ is as above defined or, Ra and Rb and/or Rc and Rd taken together with the carbon atom to which they are bonded, form an optionally substituted C3-C6 cycloalkyl group;
- m and n, each independently, represent 0 or an integer from 1 to 2, provided that m+n is lower than, or equal to, 2 (m+n≦2).
A method for treating a mammal, including humans, suffering from a disease caused by and/or associated with an altered protein kinase activity, by administering to said mammal in need thereof a therapeutically effective amount of a bicyclo-pyrazole compound of formula (I):
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- wherein
- R and R1, being the same or different, are independently a hydrogen atom or an optionally substituted group selected from R′, —COR′, —COOR′, —CONHR′, —CONR′R″, —NH—C(═NH)NHR′, —C(═NH)NHR′, —SO2R′, —SO2NHR′ or —SO2NR′R″;
- wherein R′ and R″, the same or different, are indenpendently selected from hydrogen or optionally further substituted straight or branched C1-C6 alkyl, aryl, C3-C6 cycloalkyl or aryl C1-C6 alkyl or R′ and R″ taken together form a C4-C6 alkylene chain;
- Ra, Rb, Rc and Rd, being the same or different, are independently selected among hydrogen, optionally further substituted straight or branched C1-C6 alkyl, aryl, aryl C1-C6 alkyl or —CH2OR′ groups, wherein R′ is as above defined, or Ra and Rb and/or Rc and Rd, taken together with the carbon atom to which they are bonded, form an optionally substituted C3-C6 cycloalkyl group;
- m and n, each independently, represents 0 or an integer from 1 to 2, provided that m+n is lower than, or equal to, 2(m+n≦2);
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.