Uracil derivative and use thereof for medical purposes

A compound represented by formula (I) or physiologically acceptable salts thereof:

• [wherein
• R1 represents a hydrogen atom, a C1-10 alkyl group, a C2-6 alkene group or a three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S,
• said alkyl group and said alkene group for R1 may be optionally substituted at substitutable positions with one or multiple substituents selected from the group consisting of
• Substituent List 1:
• (1) hydroxy group,
• (2) halogen atom,
• (3) cyano group,
• (4) C1-6 alkoxy group (said alkoxy group may be optionally substituted at substitutable positions with
• hydroxy group,
• halogen atom,
• cyano group,
• —C(═O)ORb,
• —C(═O)NRcRd,
• five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group) or
• three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group),
• (5) C1-6 alkylthio group (said alkylthio group may be optionally substituted at substitutable positions with hydroxy group,
• halogen atom,
• cyano group,
• —C(═O)ORb,
• —C(═O)NRcRd,
• five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaC(═O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group) or
• three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NR C(═O)Rb group, —NRaC(O)NRcRd group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group),
• (6) five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be substituted at substitutable positions with
• C1-3 alkyl group optionally substituted with hydroxy or halogen,
• C1-3 alkoxy group optionally substituted with hydroxy or halogen,
• hydroxy group,
• halogen atom,
• cyano group,
• —NRaC(═O)Rb,
• —NRaC(═O)NRcRd,
• —NRaS(═O)mRb,
• —C(═O)ORb,
• —C(═O)NRcRd,
• —S(═O)mNRcRd,
• —S(═O)mRb or
• —NRcRd),
• (7) three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with
• C1-3 alkyl group (said alkyl group may be optionally substituted with hydroxy, halogen, cyano, —NRaC(═O)Rb, —NRaC(═O)NRcRd, —NRaS(═O)mRb, —C(═O)ORb, —C(═O)NRcRd or —NRcRd),
• C1-3 alkoxy group optionally substituted with hydroxy or halogen,
• hydroxy group,
• halogen atom,
• cyano group,
• —NRaC(═O)Rb,
• —NRaC(═O)NRcRd,
• —NRaS(═O)mRb,
• —C(═O)ORb,
• —C(═O)NRcRd,
• —C(═O)Rb,
• —S(═O)mNRcRd,
• —S(═O)mRb,
• —NRcRd or
• oxo group),
• (8) —NRaRe group,
• (9) —OC(═O)NRcRd group,
• (10) —C(═O)Rf group,
• (11) —S(═O)mRg group,
• (12) thiol group,
• (13) nitro group and
• (14) —ORe group,
• said three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group for R1 may be optionally substituted at substitutable positions with one or multiple substituents selected from the group consisting of
• Substituent List 2:
• (1) hydroxy group,
• (2) halogen atom,
• (3) cyano group,
• (4) C1-6 alkyl group (said alkyl group may be optionally substituted at substitutable positions with
• hydroxy group,
• halogen atom,
• cyano group,
• five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group) or
• three- to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group),
• (5) C1-6 alkoxy group (said alkoxy group may be optionally substituted at substitutable positions with
• hydroxy group,
• halogen atom,
• cyano group,
• five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or a —NRcRd group) or
• three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group),
• (6) C1-6 alkylthio group (said alkylthio group may be optionally substituted at substitutable positions with
• hydroxy group,
• halogen atom,
• cyano group,
• five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —S(═O)mNRcRd group, —S(═O)mRb group or —NRcRd group) or
• three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —NRaC(═O)Rb group, —NRaS(═O)mRb group, —C(═O)ORb group, —C(═O)NRcRd group, —NRcRd group or oxo group),
• (7) five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group may be optionally substituted at substitutable positions with
• C1-3 alkyl group optionally substituted with hydroxy or halogen,
• C1-3 alkoxy group optionally substituted with hydroxy or halogen,
• hydroxy group,
• halogen atom,
• cyano group,
• —NRaC(═O)Rb,
• —NRaS(═O)mRb,
• —C(═O)ORb,
• —C(═O)NRcRd,
• —S(═O)mNRcRd,
• —S(═O)mRb or
• —NRcRd),
• (8) three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with
• C1-3 alkyl group optionally substituted with hydroxy or halogen,
• C1-3 alkoxy group optionally substituted with hydroxy or halogen,
• hydroxy group,
• halogen atom,
• cyano group,
• —NRaC(═O)Rb,
• —NRaS(═O)mRb,
• —C(═O)ORb,
• —C(═O)NRcRd,
• —NRcRd or
• oxo group),
• (9) —NRaRe group,
• (10) —OC(═O)NRcRd group,
• (11) —C(═O)Rf group,
• (12) —S(═O)mRg group,
• (13) thiol group,
• (14) oxo group,
• (15) nitro group,
• (16) —NRaC(═O)Rb group,
• (17) —NRaC(═O)NRcRd group,
• (18) —NRaS(═O)mRb group,
• (19) —C(═O)ORb group and
• (20) —C(═O)NRcRd group,
• R2 represents a hydrogen atom, a halogen atom, a cyano group, a —NRcRd group, a —N═CHN(CH3)2 group or a C1-3 alkyl group (said alkyl group may be optionally substituted with hydroxy, halogen, —NRcRd, —ORa or —OC(═O)R),
• Ar1 represents a five to six-membered aromatic ring group optionally containing one to three heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group is substituted at substitutable positions with C1-6 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, phenyl group, —NRaC(═O)Rh group, —NRaS(═O)mRh group, —NRaC(═O)NRcRd group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)mNRcRd group, —S(═O)nRh group or —NRcRd group),
• L represents a six membered unsubstituted aromatic ring group optionally containing 1 to 2 nitrogen atoms, a Pyr-1 group of the following formula or a Tri-1 group of the following formula:
• (in each formula,
• the bond 1 represents a binding to uracil ring, the bond 2 represents a binding to Ar2, and the Z1 and Z2 represent independently of each other a cyano group, a halogen atom, a —C(═O)NRcRd group, a —C(═O)ORb2 group, a —CHO group, a nitro group, a hydroxy group, a —NRcRd group, a —NRaC(═O)Rh group, a hydrogen atom, a —S(═O)mNRc2Rd2 group, a —S(═O)mNRaC(═O)Rb3 group, a —S(═O)mNRaC(═O)ORb4 group, a —S(═O)mNRaC(═O)NRaRb3 group, a —S(═O)mRg2 group, a —S—Rg3 group, a three to six-membered saturated aliphatic ring group optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said saturated aliphatic ring group may be optionally substituted with hydroxy, halogen, C1-6 alkyl, C1-3 alkoxy, —C(═O)ORa, —C(═O)Ra or —NRaRb), a C1-6 alkyl group or an C2-6 alkene group (said alkyl group and said alkene group may independently of each other be optionally substituted with halogen, hydroxy, —NRcRd, —C(═O)NRcRd, —NRaS(O)mRh, —C(═O)NRcRd or —C(═O)ORa),
• Ar2 represents a five to six-membered aromatic ring group optionally containing one to three heteroatoms independently selected from the group consisting of N, O and S (said aromatic ring group is substituted at one or more substitutable positions with C1-6 alkyl group optionally substituted with hydroxy, cyano or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, nitro group, —NRaC(═O)Rh group, —NRaS(═O)mRh group, —NRaC(═O)NRcRd group, —C(═O)NRcRd group, —C(═O)ORa group, —C(═O)Ra group, —S(═O)mNRcRd group, —S(═O)nRh group or —NRcRd group),
• Ra represents a hydrogen atom or a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy or halogen),
• Rb represents a hydrogen atom, a C1-6 alkyl group optionally substituted with hydroxy or halogen, a benzyl group optionally substituted with methoxy or nitro, or a C3-6 cycloalkyl group optionally substituted with hydroxy or halogen,
• Rb2 represents a hydrogen atom, a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, —NRaRb or halogen), a benzyl group (said benzyl group may be optionally substituted with methoxy or nitro) or a C3-6 cycloalkyl group (said cycloalkyl group may be optionally substituted with hydroxy or halogen),
• Rb3 represents a hydrogen atom, a phenyl group (said phenyl group may be optionally substituted with halogen), a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy or halogen) or a C3-6 cycloalkyl group (said cycloalkyl group may be optionally substituted with hydroxy or halogen),
• Rb4 represents a hydrogen atom, a phenyl group (said phenyl group may be optionally substituted with halogen), a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy or halogen), a C3-6 cycloalkyl group (said cycloalkyl group may be optionally substituted with hydroxy or halogen) or an 2-isopropyl-5-methylcyclohexyl,
• Rc and Rd represent independently of each other a hydrogen atom or a C1-3 alkyl group optionally substituted with C1-3 alkoxy, cyano, hydroxy or halogen, or alternatively may combine each other together with N to which they are attached and optionally together with further one to two heteroatoms independently selected from the group consisting of N, O and S to represent a four to six-membered saturated or unsaturated aliphatic ring group (said aliphatic ring group may be optionally substituted at substitutable positions with C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, —NRaRb, —NRaC(═O)ORh or —NRaC(═O)Rh), C1-3 alkoxy group, —NRaRb group, —NRaC(═O)ORh group, —NRaC(═O)Rh group, —C(═O)ORa group, hydroxy group, halogen atom or oxo group),
• Rc2 and Rd2 represent independently of each other a hydrogen atom or a C1-3 alkyl group (said alkyl group may be optionally substituted with phenyl group optionally substituted with methoxy, —NRaRb group, —NRa(C═O)ORh group, —NRaC(═O)Rh group, C1-3 alkoxy group, cyano group, hydroxy group or halogen atom), or alternatively may combine each other together with N to which they are attached and optionally together with further one to two heteroatoms independently selected from the group consisting of N, O and S to represent a four to six-membered saturated or unsaturated aliphatic ring group (said aliphatic ring group may be optionally substituted at substitutable positions with C1-6 alkyl group, C1-3 alkoxy group, —NRaRb group, —NRaC(═O)ORh group, —NRaC(═O)Rh group, —C(═O)ORa group, hydroxy group, halogen atom or oxo group),
• Re represents
• a hydrogen atom,
• a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd),
• an -A group,
• a —C(═O)-A group,
• a C1-6 alkylcarbonyl group (the alkyl moiety of said alkylcarbonyl may be optionally substituted with hydroxy, halogen, cyano, C1-3 alkoxy or —NRcRd),
• a C1-6 alkoxycarbonyl group (the alkyl moiety of said alkoxycarbonyl group may be optionally substituted with hydroxy or halogen),
• a —C(═O)NRcRd group or
• a —S(═O)mRb group,
• Rf represents
• a hydrogen atom,
• a hydroxy group,
• a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd),
• a C1-3 alkoxy group (said alkoxy group may be optionally substituted with phenyl group optionally substituted with methoxy or nitro, hydroxy group, cyano group, halogen atom, C1-3 alkoxy group or —NRcRd group),
• an -A group or
• a —NRaRi group,
• Rg represents
• a hydroxy group,
• a chlorine atom,
• a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd),
• an -A group or
• a —NRaRi group,
• Rg2 represents
• a hydroxy group,
• a chlorine atom,
• a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or —NRcRd) or
• an -A group,
• Rg3 represents
• a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy or NRcRd) or
• an -A group,
• Rh represents a C1-6 alkyl optionally substituted with hydroxy or halogen,
• Ri represents
• a hydrogen atom,
• a C1-6 alkyl group (said alkyl group may be optionally substituted with hydroxy, cyano, halogen, C1-3 alkoxy, C3-6 cycloalkyl or —NRcRd),
• an -A group,
• a —C(═O)Rh group,
• a —C(═O)A group or
• a C1-6 alkylcarbonyl group (the alkyl moiety of said alkylcarbonyl group may be optionally substituted with hydroxy, halogen, cyano, C1-3 alkoxy or —NRcRd),
• A represents
• a five to six-membered aromatic ring group optionally containing one to four heteroatoms independently selected from the group consisting of N, O and S (said aromatic group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —C(═O)OH group or —NRcRd group),
• a three to six-membered saturated- or four to six-membered unsaturated-aliphatic ring group each optionally containing one to two heteroatoms independently selected from the group consisting of N, O and S (said aliphatic ring group may be optionally substituted at substitutable positions with C1-3 alkyl group optionally substituted with hydroxy or halogen, C1-3 alkoxy group optionally substituted with hydroxy or halogen, hydroxy group, halogen atom, cyano group, —C(═O)OH group, —NRcRd group or oxo group),
• m represents an integer of 1 or 2 and
• n represents an integer of 0 to 2].