Pyrazole - pyrimidines, Pharmaceutical composition, process and use in myelodysplastic syndrome, myeloproliferative disorders, and cancer

摘要

1: A responsive compound (1) or an acceptable salt for pharmaceutical use, wherein: cycloa is selected from six members of phenyl and isopropyl acyl, in which five or six members of phenyl and isopropyl acyl are replaced by one or more r5s; and X is from - NH -.- that is...Y-S-R1 se selecciona entre H -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo de 3 a 5 miembros heterociclilo de 5 miembros -OR1a - SR1a -N (R1a) 2 -N (R1a) C (O) R1b N And C (R1a) = n (or1a),In this case, C1-6, c2-6, c2-6, c2-6 tar, carbon thyroid of 3-5 members and isomerized oil of 5 members are replaced by one or more R10; R1a is selected from h, C1-6 tar, carbon thyroid of 3-5 members and isomerized oil of 5 members, among which C1-6 tar, One or more R10 can be selected to replace 3 to 5 members' carbohydrates and 5 members' non bicycles; in each case, r1b is selected from C1-6, alquenilo c2-6, c2-6 tar, 3 to 5 members' carbohydrates and 5 members' non bicycles, Among them, No. C1-6 asphalt,C2-6 alquenilo c2-6, c12-6 asphalt, 3-5 members' carbon thyroid, and 5 members' isomers can be replaced by one or more R10 respectively; R2 can be selected separately between halo-cn, C1-6 asphalt, c2-6 alquenilo c2-6, c2-6 asphalt, carbocyclo, isopropyl-or2a and sr2a. (2) 2) 2A (r22a (R2A (or (R2A) 2) s (o) 2r2b, - C (R2A) = n (R2A),y -C (R2a) 3DN (OR2a)wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R20; R2a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more R20; R2b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl,y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms R20 R3 se selecciona entre H halo -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -OR3a -SR3a -N (R3a) 2 - y -C (R3a) 3DN (OR3a)wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R30; R3a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more R30; R3b in each case is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl ,,carbociclilo y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms R30 R4 se selecciona entre -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -N (R4a) C (O) R4b N ( y -C (R4a) 3DN (OR4a)wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R40; R4a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more R40; R4b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl,y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms R40 R5 en cada caso se selecciona en forma independiente entre halo -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -OR5a -SR5a -N y -C (R5a) 3DN (OR5a)wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally substituted with one or more R50; R5a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more R50; R5b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl,y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms R50 R10 en cada caso se selecciona en forma independiente entre halo -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -OR10a -SR10a -N y -C (R10a) 3DN (OR10a)wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more Ra; R10a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more Ra; R10b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl,y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms Ra R20 en cada caso se selecciona en forma independiente entre halo -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -OR20a -SR20a -N y -C (R20a) 3DN (OR20a)wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more Rb; R20a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more Rb; R20b in each case is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl,y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms Rb R30 en cada caso se selecciona en forma independiente entre halo -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -OR30a -SR30a -N And C (r30a) = n (r30a),wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more Rc; R30a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, carbocyclyl, and heterocyclyl are independently and optionally substituted with one or more Rc; R30b in each case is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, carbocyclyl,y heterociclilo en cada caso y en forma independiente est n opcionalmente sustituidos con uno oms Rc R40 en cada caso se selecciona en forma independiente entre halo -CN alquilo C1-6 alquenilo C2-6 alquinilo C2-6 carbociclilo heterociclilo -OR40a SR40a -N ( y -C (R40a) 3DN (OR40a)There they said