Method for producing megakaryocytes and/or platelets from pluripotent stem cells

A method for producing a megakaryocyte, a platelet, or both, comprising:

• culturing a hematopoietic progenitor cell derived from a pluripotent stem cell ex vivo in the presence of a compound of formula (I), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof;
• and
• differentiating the hematopoietic progenitor cell into a megakaryocyte, a platelet, or both,
• wherein W is a substituent of formula (Ia) or a carboxy group:
• R1, R2, R3 and R4 are each independently a C1-10 alkyl group which may be substituted with a halogen atom or a hydrogen atom,
• n is an integer of 0, 1, 2 or 3,
• R5 is a C2-14 aryl group which may be substituted with a substituent independently represented by V1, where when n is 2, R5 is not an unsubstituted pyridyl group,
• R6 is a C1-10 alkyl group which may be substituted with a halogen atom or a hydrogen atom,
• R7 is a C2-14 aryl group which may be substituted with a substituent independently represented by V2,
• Ar1 is a C2-14 arylene group which may be substituted with a substituent independently represented by V3,
• X is —OR20,
• Y and Z are ach independently an oxygen atom or a sulfur atom,
• V1 is —(CH2)m1M1NR8R9, —(CH2)m6NR16R17, -M2NR18(CH2)m7R19 or —C(═O)-(piperazine-1,4-diyl)-U,
• V2, V3 and V4 are each independently a hydroxy group, a protected hydroxy group, an amino group, a protected amino group, a thiol group, a protected thiol group, a nitro group, a cyano group, a halogen atom, a carboxy group, a carbamoyl group, a sulfamoyl group, a sulfo group, a formyl group, a C1-3 alkoxy group which may be substituted with a halogen atom, a C1-10 alkyl group which may be substituted with a halogen atom, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-10 alkylcarbonyloxy group, a C1-10 alkoxycarbonyl group, a C1-10 alkoxy group, a C1-10 alkylcarbonyl group, a C1-10 alkylcarbonylamino group, a mono- or di-C1-10 alkylamino group, a C1-10 alkylsulfonyl group, a C1-10 alkylaminosulfonyl group, a C1-10 alkylaminocarbonyl group, a C1-10 alkylsulfonylamino group or a C1-10 thioalkyl group,
• M1 and M2 are each independently —(C═O)— or —(SO2)—,
• m1 is an integer of 0, 1 or 2,
• m2, m3, m4, m5, m6 and m7 are each independently an integer of 1 or 2,
• R8 is a hydrogen atom or a C1-3 alkyl group,
• R9 and U are each independently —(CH2)m2OR16 or —(CH2)m4NR11R12, provided that when m1 is 1 or 2, R9 may be any of those mentioned above or a hydrogen atom,
• R10 is a hydrogen atom, a C1-3 alkyl group or —(CH2)m3T,
• R11 and R12 are each independently a hydrogen atom or —(CH2)m5Q, or N, R11 and R12 mean, as a whole, a substituent of formula (II):
• or a substituent of formula (III):
• T is a hydroxy group, a C1-6 alkoxy group or a C1-6 alkyl group,
• Q is a hydroxy group, a C1-3 alkoxy group or —NR13R14,
• R13 and R14 are each independently a hydrogen atom or a C1-3 alkyl group,
• R15 is a hydrogen atom, a C1-3 alkyl group or an amino-protecting group,
• R16 and R17 are each independently a hydrogen atom, a C1-3 alkylcarbonyl group or a C1-3 alkylsulfonyl group,
• R18 is a hydrogen atom or a C1-3 alkyl group,
• R19 is a C2-9 heterocyclyl group or a C2-14 aryl group, and
• R20 is a hydrogen atom, a C1-10 alkyl group which may be substituted with a substituent independently represented by V4 or a C1-10 alkylcarbonyl group which may be substituted with a substituent independently represented by V4.