Claims for Patent: 8,987,441

Summary for Patent: 8,987,441

Title:	Substituted polycyclic carbamoyl pyridone derivative prodrug
Abstract:	The present invention provides a compound having antiviral effects, particularly having growth inhibitory activity on influenza viruses, a preferred example of the compound being a substituted 3-hydroxy-4-pyridone derivative prodrug having cap-dependent endonuclease inhibitory activity.
Inventor(s):	Chika Takahashi, Hidenori Mikamiyama, Toshiyuki Akiyama, Kenji Tomita, Yoshiyuki Taoda, Makoto Kawai, Kosuke Anan, Masayoshi Miyagawa, Naoyuki Suzuki
Assignee:	Shionogi and Co Ltd
Application Number:	US13/824,723
Patent Claims:	1. A compound represented by formula (I): a pharmaceutically acceptable salt, or a solvate thereof: wherein: —C(═O)—PR0, a) —C(═O)—PR1, b) —C(═O)-L-PR1, c) —C(═O)-L-O—PR1, d) —C(═O)-L-O-L-O—PR1, e) —C(═O)-L-O—C(═O)—PR1, f) —C(═O)—O—PR2, g) —C(═O)—N(PR2)2, h) —C(═O)—O-L-O—PR2, i) —CH2—O—PR3, j) —CH2—O-L-O—PR3, k) —CH2—O—C(═O)—PR3, l) —CH2—O—C(═O)—O—PR3, m) —CH(—CH3)—O—C(═O)—O—PR3, n) —CH2—O—C(═O)—N(—K)—PR3, o) —CH2—O—C(═O)—O-L-O—PR3, p) —CH2—O—C(═O)—O-L-N(PR3)2, q) —CH2—O—C(═O)—N(—K)-L-O—PR3, r) —CH2—O—C(═O)—N(—K)-L-N(PR3)2, s) —CH2—O—C(═O)—O-L-O-L-O—PR3, t) —CH2—O—C(═O)—O-L-N(—K)—C(═O)—PR3, u) —CH2-O—P(═O)(—OH)2, v) —CH2—O—P(═O)(—OBn)2, w) —CH2—PR4(except for a benzyl group), x) —C(═N+PR5 2)(—NPR5 2) y); (wherein L is straight or branched lower alkylene, or straight or branched lower alkenylene, K is hydrogen, or straight or branched lower alkylene, PR0 is lower alkyl optionally substituted by substituent group F, or lower alkenyl optionally substituted by substituent group F, PR1 is carbocyclic group optionally substituted by substituent group F, heterocyclic group optionally substituted by substituent group F, lower alkyl amino optionally substituted by substituent group F, or lower alkylthio optionally substituted by substituent group F, PR2 is lower alkyl optionally substituted by substituent group F, carbocyclic group optionally substituted by substituent group F, or heterocyclic group optionally substituted by substituent group F, PR3 is lower alkyl optionally substituted by substituent group F, carbocyclic group optionally substituted by substituent group F, heterocyclic group optionally substituted by substituent group F, lower alkyl amino optionally substituted by substituent group F, carbocycle lower alkyl optionally substituted by substituent group F, heterocycle lower alkyl optionally substituted by substituent group F, or lower alkylsilyl, and PR5 is lower alkyl optionally substituted by substituent group F; wherein Substituent group F is chosen from oxo, lower alkyl, hydroxy lower alkyl, amino, lower alkylamino, carbocycle lower alkyl, lower alkylcarbonyl, halogen, hydroxy, carboxy, lower alkylcarbonylamino, lower alkylcarbonyloxy, lower alkvloxycarbonyl, lower alkyloxy, cyano, and nitro); R1a is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkenyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocycleoxy optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C, —Z—N(RA1)(RA2), —Z—N(RA3)—SO2—(RA4), —Z—C(═O)—N(RA5)—SO2—(RA6), —Z—N(RA7)—C(═O)—RA8, —Z—S—RA9, —Z—SO2—RA10, —Z—S(═O)—RA11, —Z—N(RA12)—C(═O)—O—RA13, —Z—N(RA14)—C(═O)—N(RA15)(RA16), —Z—C(═O)—N(RA17)—C(═O)—N(RA18)(RA19), —Z—N(RA20)—C(═O)—C(═O)—RA21, or —Z—B(—ORA22)(—ORA23); (wherein RA1, RA2, RA3, RA5, RA7, RA8, RA9, RA12, RA13, RA14, RA15, RA16, RA17, RA18, RA19, RA20, and RA21 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RA4, RA6, RA10, and RA11 are each independently selected from a substituent group consisting of lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RA1 and RA2, RA15 and RA16, and RA18 and RA19, each may be taken together with an adjacent atom to form heterocycle, RA22 and RA23 are each independently an hydrogen atom, lower alkyl optionally substituted by substituent group C, or RA22 and RA23 may be taken together with an adjacent atom to form heterocycle, and Z is a single bond or straight or branched lower alkylene); R2a is hydrogen, halogen, carboxy, cyano, formyl, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkenyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocyclecarbonyl optionally substituted by substituent group C, carbocycleoxy optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocyclecarbonyl optionally substituted by substituent group C, heterocycleoxy optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C, —Z—N(RB1)—SO2—RB2, —Z—N(RB3)—C(═O)—RB4, —Z—N(RB5)—C(═O)—O—RB6, —Z—C(═O)—N(RB7)(RB8), —Z—N(RB9)(RB10), or —Z—SO2—RB11 (wherein RB1, RB3, RB4, RB5, RB6, RB7, RB8, RB9, and RB10 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RB2 and RB11 are each independently selected from a substituent group consisting of lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RB7 and RB8, and RB9 and RB10 may be taken together with an adjacent atom to form heterocycle and Z is a single bond or straight or branched lower alkylene); R3a is hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, —Z—N(RC1)—SO2—RC2, —Z—N(RC3)—C(═O)—RC4, —Z—N(RC5)—C(═O)—O—RC6, —Z—C(═O)—N(RC7)(RC8), or —Z—N(RC9)(RC10), (wherein RC1, RC3, RC4, RC5, RC6, RC7, RC8, RC9, and RC10 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RC2 is independently selected from a substituent group consisting of lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RC7 and RC8, and RC9 and RC10 each may be taken together with an adjacent atom to form heterocycle, and Z is a single bond or straight or branched lower alkylene) and; B1 is NR7a and B2 is CR5aR6a; R5a, R6a, and R7a are each independently selected from a substituent group consisting of hydrogen, carboxy, cyano, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyl carbonyl optionally substituted by substituent group C, lower alkyl oxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, carbocyclecarbonyl optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocycleoxy lower alkyl optionally substituted by substituent group C, heterocyclecarbonyl optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C, —Y—S—RD1, —Z—S(═O)—RD2, —Z—SO2—RD3, —C(═O)—C(═O)—RD4, —C(═O)—N(RD5)(RD6), —Z—C(RD7)(RD8)(RD9), —Z—CH2—RD10, —Z—N(RD11)—C(═O)—O—RD12, or —Z—N(RD13)—C(═O)—RD14, or R5a and R6a may be taken together to form heterocyclic group optionally substituted by substituent group C, (wherein RD1, RD4, RD5, RD6, RD9, RD11, RD12, RD13, and RD14 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RD2 and RD3 are each independently selected from a substituent group consisting of lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C, RD7, RD8, and RD10 are each independently carbocyclic group optionally substituted by substituent group C, or heterocyclic group optionally substituted by substituent group C, RD5 and RD6 may be taken together with an adjacent atom to form heterocycle, Y is straight or branched lower alkylene, and Z is a single bond or straight or branched lower alkylene), and RD5 and RD6 may be taken together with an adjacent atom to form carbocycle; R3a and R6a may be taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D, with a proviso that the following c) is excluded c) R5a, R6a, and R7a are all hydrogens; wherein the substituent group C is chosen from halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, lower alkenyl, lower alkynyl, halogeno lower alkyl, lower alkyloxy, lower alkynyloxy, lower alkylthio, hydroxy lower alkyl, carbocyclic group, heterocyclic group, heterocyclic group substituted by oxo, carbocycle lower alkyloxy, carbocycleoxy lower alkyl, carbocycle lower alkyloxy lower alkyl, heterocycle lower alkyloxy, heterocycleoxy lower alkyl, heterocycle lower alkyloxy lower alkyl, halogeno lower alkyloxy, lower alkyloxy lower alkyl, lower alkyloxy lower alkyloxy, lower alkylcarbonyl, lower alkylcarbonyloxy, lower alkyloxycarbonyl, lower alkylamino, lower alkylcarbonylamino, halogeno lower alkyl carbonylamino, lower alkylaminocarbonyl, lower alkylsulfonyl, lower alkylsulfinyl, and lower alkylsulfonylamino; and wherein the substituent is chosen from halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, halogeno lower alkyl, lower alkyloxy, carbocycle lower alkyloxy, heterocycle lower alkyloxy, halogeno lower alkyloxy, lower alkyloxy lower alkyl, lower alkyloxy lower alkyloxy, lower alkylcarbonyl, lower alkyloxycarbonyl, lower alkylamino, lower alkylcarbonylamino, lower alkylaminocarbonyl, lower alkylsulfonyl, lower alkylsulfonylamino, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C. 2. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R1a is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkenyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocycleoxy optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C, —Z—N(RA1)(RA2), —Z—N(RA3)—SO2—(RA4), —Z—N(RA7)—C(═O)—RA8, —Z—S—RA9, —Z—SO2—RA10, —Z—N(RA12)—C(═O)—O—RA13, —Z—N(RA20)—C(═O)—C(═O)—RA21, or —Z—B(—ORA22)(—ORA23) 3. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R1a is hydrogen, halogen, hydroxy, carboxy, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, —Z—N(RA1)(RA2), —Z—N(RA7)—C(═O)—RA8, —Z—N(RA12)—C(═O)—O—RA13, or —Z—B(—ORA22)(—ORA23) 4. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R1a is hydrogen, halogen, hydroxy, carboxy, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, or —Z—N(RA1)(RA2) 5. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R1a is hydrogen, or carboxy. 6. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R2a is hydrogen, lower alkyl optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, or) —Z—N(RB9)(RB10) 7. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R2a is hydrogen or lower alkyl optionally substituted by substituent group C 8. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R3a is hydrogen, lower alkyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C. 9. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R5a, R6a and R7a are each independently hydrogen, carboxy, cyano, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyl carbonyl optionally substituted by substituent group C, lower alkyl oxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, carbocyclecarbonyl optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocycleoxy lower alkyl optionally substituted by substituent group C, heterocyclecarbonyl optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C, —Y—S—RD1, —Z—S(═O)—RD2, —Z—SO2—RD3, —C(═O)—C(═O)—RD4, —C(═O)—N(RD5)(RD6), —Z—C(RD7)(RD8)(RD9), —Z—N(RD11)—C(═O)—O—RD12, or —Z—N(RD13)—C(═O)—RD14 10. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R5a is hydrogen, R6a is hydrogen, or lower alkyl optionally substituted by substituent group C, and R7a is lower alkyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, or —Z—C(RD7)(RD8)(RD9) 11. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R7a is a group shown below: 12. The compound according to claim 1, or the pharmaceutically acceptable salt thereof or the solvate thereof, wherein R1a is hydrogen, or carboxy, R2a is hydrogen, R3a is lower alkyl optionally substituted by substituent group C, B1 is NR7a, and B2 is CH2, and R7a is a group shown below: 13. The compound according to claim 1, or a pharmaceutically acceptable salt, or a solvate thereof: wherein, R1a is hydrogen, halogen, hydroxy, carboxy, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, or —Z—N(RA1)(RA2), R2a is hydrogen, lower alkyl optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, or —Z—N(RB9)(RB10), R3a is hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, —Z—N(RC1)—SO2—RC2, —Z—N(RC3)—C(═O)—RC4, —Z—N(RC5)—C(═O)—O—RC6, —Z—C(═O)—N(RC7)(RC8), or —Z—N(RC9)(RC10), R3a and R6a may be taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D, with a proviso that the following c) is excluded c) R5a, R6a, and R7a are all hydrogens. 14. The compound according to claim 1 or a pharmaceutically acceptable salt, or a solvate thereof: wherein, R1a is hydrogen or carboxy; R2a is hydrogen or lower alkyl optionally substituted by substituent group C; R3a is hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, —Z—N(RC1)—SO2—RC2, —Z—N(RC3)—C(═O)—RC4, —Z—N(RC5)—C(═O)—O—RC6, —Z—C(═O)—N(RC7)(RC8), or —Z—N(RC9)(RC10), R3a and R6a may be taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D, with a proviso that the following c) is excluded c) R5a, R6a, and R7a are all hydrogens. 15. The compound according to claim 1, or a pharmaceutically acceptable salt, or a solvate thereof; wherein, R1a is hydrogen or carboxy; R2a is hydrogen or lower alkyl optionally substituted by substituent group C; R3a is hydrogen or lower alkyl optionally substituted by substituent group C; R3a and R6a may be taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D; with a proviso that the following c) is excluded c) R5a, R6a, and R7a are all hydrogens. 16. The compound according to claim 1, or a pharmaceutically acceptable salt, or a solvate thereof: wherein, R1a is hydrogen or carboxy; R2a is hydrogen or lower alkyl optionally substituted by substituent group C; R3a is hydrogen or lower alkyl optionally substituted by substituent group C; B1 is NR7a and B2 is CHR6a (wherein, R7a is carbocyclic group optionally substituted by substituent group C or heterocyclic group optionally substituted by substituent group C) R3a and R6a may be taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D. 17. The compound according to claim 1, or a pharmaceutically acceptable salt, or a solvate thereof: wherein, R1a is hydrogen or carboxy; R2a is hydrogen; R3a is hydrogen or lower alkyl optionally substituted by halogen; B1 is NR7a and B2 is CHR6a; wherein, R7a is carbocyclic group optionally substituted by substituent group C or heterocyclic group optionally substituted by substituent group C; and Substituent group C: halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, lower alkynyl, halogeno lower alkyl, lower alkyloxy, lower alkyamino, halogeno lower alkyloxy, carbocyclic group; and R3a and R6a may be taken together with an adjacent atom to form heterocycle. 18. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof, wherein R7a is a tricyclic heterocyclic group optionally substituted by substituent group C; and Substituent group C; halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, lower alkynyl, halogeno lower alkyl, lower alkyloxy, lower alkyamino, halogeno lower alkyloxy, carbocyclic group. 19. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof wherein R7a is a tricyclic heterocyclic group optionally substituted by substituent group C; and Substituent group C: halogen, lower alkyl, halogeno lower alkyl, lower alkyloxy. 20. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof wherein R7a is the following group: wherein RE6 is independently halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, lower alkynyl, halogeno lower alkyl, lower alkyloxy, lower alkyl amino, halogeno lower alkyloxy, carbocyclic group; and m is an integer from 0 to 6. 21. The compound according to claim 20, or a pharmaceutically acceptable salt, or a solvate thereof wherein RE6 is independently halogen or lower alkyloxy; and m is an integer from 0 to 2. 22. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof, wherein, R6a is hydrogen. 23. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof, wherein, R3a and R6a are taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D. 24. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof, wherein, R3a and R6a are taken together with an adjacent atom to form 5- to 7-membered heterocycle optionally substituted by substituent group D. 25. The compound according to claim 23, or a pharmaceutically acceptable salt, or a solvate thereof: wherein PR is a group selected from the following: —C(═O)—PR0, a) —C(═O)—PR1, b) —C(═O)—O—PR2, g) —C(═O)—O-L-O—PR2, i) —CH2—O—PR3, j) —CH2—O-L-O—PR3, k) —CH2—O—C(═O)—PR3, l) —CH2—O—C(═O)—O—PR3, m) —CH(—CH3)—O—C(═O)—O—PR3, n) —CH2—O—C(═O)—N(—K)—PR3, o) 26. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof: wherein PR is a group selected from the following: —C(═O)—PR0, a) —C(═O)—PR1, b) —CH2—O—C(═O)—PR3, l) —CH2—O—C(═O)—O—PR3. m) 27. The compound according to claim 13, or a pharmaceutically acceptable salt, or a solvate thereof: wherein PR is a group selected from the following: —C(═O)—PR0, a) —C(═O)—PR1, b) —CH2—O—C(═O)—PR3, l) —CH2—O—C(═O)—O—PR3, m) wherein: PR0 is lower alkyl; PR1 is carbocyclic group or heterocyclic group; and PR3 is lower alkyl, carbocyclic group or heterocyclic group. 28. The compound according to claim 1, or a pharmaceutically acceptable salt, or a solvate thereof: wherein: PR is a group selected from the following: —C(═O)—PR0, a) —C(═O)—PR1, b) —CH2—O—C(═O)—PR3, l) —CH2—O—C(═O)—O—PR3, m) wherein: PR0 is lower alkyl; PR1 is carbocyclic group or heterocyclic group; PR3 is lower alkyl, carbocyclic group or heterocyclic group; R1a is hydrogen or carboxy; R2a is hydrogen or lower alkyl optionally substituted by substituent group C; R3a is hydrogen or lower alkyl optionally substituted by substituent group C; B1 is NR7a and B2 is CHR6a wherein, R7a is carbocyclic group optionally substituted by substituent group C or heterocyclic group optionally substituted by substituent group C; wherein substituent group C is chosen from halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, lower alkynyl, halogeno lower alkyl, lower alkyloxy, lower alkyamino, halogeno lower alkyloxy, carbocyclic group; wherein R3a and R6a may be taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D; and 29. The compound according to claim 28, or a pharmaceutically acceptable salt, or a solvate thereof: wherein R7a is the following group: wherein, RE6 is independently halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, lower alkyl, lower alkynyl, halogeno lower alkyl, lower alkyloxy, lower alkyl amino, halogeno lower alkyloxy, carbocyclic group; and m is an integer from 0 to 6. 30. A pharmaceutical composition containing a compound according to any one of claims 1-8, 10, 11, 12 and 16-29, or a pharmaceutically acceptable salt thereof or a solvate thereof. 31. The pharmaceutical composition according to claim 30 which exhibits anti influenza activity. 32. The pharmaceutical composition according to claim 30 which exhibits cap-dependent endonuclease inhibitory activity.