Substituted purine derivative
The present invention relates to a substituted purine derivative of formula (1) wherein R 1 is alkoxy or the like, R 2 is alkyl or the like, Ring Q 1 is aryl or the like, W 1 is alkylene or the like, Ring Q 2 is aromatic carbocyclyl or the like, n is 1-4, R 3 is hydrogen atom or the like, X 1 is single bond or the like, W 2 is alkylene or the like, and R 4 is hydrogen atom or the like, or a pharmaceutically acceptable salt thereof, which has a potent inhibitory effect against TLR7, and thereby is useful for treating autoimmune disease.
1. A compound of formula (1):
or a pharmaceutically acceptable salt thereof
wherein
R 1 is optionally-substituted C 1-6 alkoxy, optionally-substituted C 3-7 cycloalkoxy, optionally-substituted 4- to 10-membered saturated heterocyclyloxy, optionally-substituted C 1-6 alkyl, optionally-substituted C 3-7 cycloalkyl, optionally-substituted C 1-6 alkylthio, optionally-substituted 4- to 10-membered saturated heterocyclyl, optionally-substituted amino, halogen atom, or hydroxy;
R 2 is optionally-substituted C 1-6 alkyl, optionally-substituted C 3-7 cycloalkyl, or optionally-substituted amino;
W 1 is single bond, or optionally-substituted C 1-4 alkylene;
Ring Q 1 is
(1) pyridyl which may be substituted with 1-5 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) cyano,
(c) C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms, and
(d) C 1-6 alkoxy which may be substituted with 1-3 the same or different halogen atoms, or
(2) pyrimidinyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of (a)-(d) in the above (1),
Ring Q 2 is C 6-10 aromatic carbocyclyl, or 5- to 10-membered aromatic heterocyclyl;
n is 1, 2, 3, or 4;
R 3 is, independently if there are plural R 3 , hydrogen atom, halogen atom, cyano, hydroxy, optionally-substituted C 1-6 alkyl, optionally-substituted C 1-6 alkoxy, optionally-substituted C 3-7 cycloalkyl, optionally-substituted C 3-7 cycloalkoxy, or optionally-substituted amino;
Q 2 -X 1 — is Q 2 -(single bond)-, Q 2 -(CH 2 ) m —O—, Q 2 -(CH 2 ) m —S—, Q 2 -(CH 2 ) m —S(O) 2 —, Q 2 -(CH 2 ) m —NR a S(O) 2 —, Q 2 -(CH 2 ) m —S(O) 2 NR a —, Q 2 -(CH 2 ) m —C(O)—, Q 2 -(CH 2 ) m —NR a —, Q 2 -(CH 2 ) m —NR a C(O)—, or Q 2 -(CH 2 ) m —C(O)NR a —, wherein R a is hydrogen atom or C 1-6 alkyl; m is 0, 1, or 2;
W 2 is single bond, or optionally-substituted C 1-8 alkylene; and
R 4 is hydrogen atom, —OR b (wherein R b is hydrogen atom, optionally-substituted C 1-6 alkyl, optionally-substituted C 1-6 alkylcarbonyl, optionally-substituted aminocarbonyl, or optionally-substituted C 1-6 alkylsulfonyl), —NR c R d (wherein R c is hydrogen atom or optionally-substituted C 1-6 alkyl; and R d is hydrogen atom, optionally-substituted C 1-6 alkyl, optionally-substituted C 1-6 alkylcarbonyl, optionally-substituted C 1-6 alkoxycarbonyl, or optionally-substituted C 1-6 alkylsulfonyl), optionally-substituted 4- to 10-membered saturated heterocyclyl, or optionally-substituted 5- to 10-membered heteroaryl.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 is
(1) C 1-6 alkoxy which may be substituted with 1-3 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) hydroxy,
(c) C 1-6 alkoxy which may be substituted with 1-3 the same or different halogen atoms,
(d) C 3-7 cycloalkyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(e) C 3-7 cycloalkoxy which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(f) phenyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(g) 5- or 6-membered heteroaryl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy, and
(h) 4- to 7-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(2) C 3-7 cycloalkoxy which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(3) 4- to 10-membered saturated heterocyclyloxy which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(4) C 1-6 alkyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(5) C 3-7 cycloalkyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(6) C 1-6 alkylthio which may be substituted with 1-3 the same or different halogen atoms,
(7) 4- to 10-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(8) amino which may be substituted with 1-2 the same or different C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms,
(9) halogen atom, or
(10) hydroxy;
R 2 is C 1-6 alkyl (which may be substituted with 1-3 the same or different halogen atoms), C 3-7 cycloalkyl, or amino (which may be substituted with 1-2 the same or different C 1-6 alkyl);
Ring Q 1 is
(1) pyridyl which may be substituted with 1-5 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) cyano,
(c) C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atom, and
(d) C 1-6 alkoxy which may be substituted with 1-3 the same or different halogen atoms, or
(2) pyrimidinyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of (a)-(d) in the above (1);
W 1 is single bond, or C 1-4 alkylene which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
Ring Q 2 is C 6-10 aromatic carbocyclyl, or 5- to 10-membered aromatic heterocyclyl;
n is 1, 2, 3, or 4;
R 3 is, independently if there are plural R 3 ,
(1) hydrogen atom,
(2) halogen atom,
(3) cyano,
(4) hydroxy,
(5) C 1-6 alkyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(6) C 1-6 alkoxy which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(7) C 3-7 cycloalkyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(8) C 3-7 cycloalkoxy which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy, or
(9) amino which may be substituted with 1-2 the same or different C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms;
Q 2 -X 1 — is Q 2 -(single bond)-, Q 2 -(CH 2 ) m —O—, Q 2 -(CH 2 ) m —S—, Q 2 -(CH 2 ) m —S(O) 2 —, Q 2 -(CH 2 ) m —NR a S(O) 2 —, Q 2 -(CH 2 ) m —S(O) 2 NR a —, Q 2 -(CH 2 ) m —C(O)—, Q 2 -(CH 2 ) m —NR a —, Q 2 -(CH 2 ) m —NR a C(O)—, or Q 2 -(CH 2 ) m —C(O)NR a —, wherein R a is hydrogen atom or C 1-6 alkyl; m is 0, 1, or 2;
W 2 is single bond, or C 1-8 alkylene which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy; and
R 4 is
(1) hydrogen atom,
(2) —OR b wherein R b is hydrogen atom, C 1-6 alkyl, C 1-6 alkylcarbonyl, mono- or di-C 1-6 alkyl-aminocarbonyl, or C 1-6 alkylsulfonyl,
(3) —NR c R d wherein R c is hydrogen atom or C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms; and R d is hydrogen atom, C 1-6 alkyl (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), and C 1-6 alkoxy), C 1-6 alkylcarbonyl (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), and C 1-6 alkoxy), C 1-6 alkoxycarbonyl, or C 1-6 alkylsulfonyl,
(4) 4- to 10-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) hydroxy,
(c) cyano,
(d) C 1-6 alkyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(e) C 1-6 alkoxy which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(f) C 3-7 cycloalkyl,
(g) C 1-6 alkylcarbonyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), and C 1-6 alkoxy,
(h) C 1-6 alkoxycarbonyl,
(i) 4- to 7-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(j) phenyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(k) 5- or 6-membered heteroaryl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy, and
(1) oxo, or
(5) 5- to 10-membered heteroaryl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy.
3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1-6 alkoxy (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, C 1-6 alkoxy, C 3-7 cycloalkyl and 4- to 7-membered saturated heterocyclyl), 4- to 10-membered saturated heterocyclyloxy (which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, and C 1-6 alkyl), C 1-6 alkyl (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy), 4- to 10-membered saturated heterocyclyl (which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy), amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), halogen atom, or hydroxy.
4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1-6 alkoxy (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy), or halogen atom.
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 is C 1-6 alkyl or amino.
6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein W 1 is methylene.
7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Ring Q 2 is benzene ring group, or 5- or 6-membered aromatic heterocyclyl.
8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Ring Q 2 is pyridine ring group, pyrazole ring group, isoxazole ring group, or benzene ring group.
9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3 is hydrogen atom, halogen atom, cyano, hydroxy, C 1-6 alkyl (which may be substituted with 1-3 the same or different halogen atoms), or C 1-6 alkoxy (which may be substituted with 1-3 the same or different halogen atoms).
10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
Q 2 -X 1 — is Q 2 -(single bond)-, Q 2 -(CH 2 ) m —O—, Q 2 -(CH 2 ) m —C(O)—, Q 2 -(CH 2 ) m —NR a —, or Q 2 -(CH 2 ) m —C(O)NR a —, wherein R a is hydrogen atom or C 1-6 alkyl; m is 0, 1, or 2.
11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein X 1 is single bond or —O—.
12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein W 2 is single bond or C 1-3 alkylene.
13. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein W 2 is single bond or methylene.
14. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 4 is
(1) hydrogen atom,
(2) —OR b wherein R b is hydrogen atom, C 1-6 alkyl, or C 1-6 alkylsulfonyl,
(3) —NR c R d wherein R c and R d are independently hydrogen atom or C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms,
(4) 4- to 10-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) hydroxy,
(c) cyano,
(d) C 1-6 alkyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(e) C 1-6 alkoxy which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(f) C 3-7 cycloalkyl,
(g) C 1-6 alkylcarbonyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), and C 1-6 alkoxy,
(h) C 1-6 alkoxycarbonyl,
(i) 4- to 7-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy, and
(j) oxo, or
(5) 5- to 10-membered heteroaryl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy.
15. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 4 is
(1) —NR c R d wherein R c and R d are independently hydrogen atom or C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms, or
(2) 4- to 10-membered saturated nitrogen-containing heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) hydroxy,
(c) cyano,
(d) C 1-6 alkyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(e) C 1-6 alkoxy which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(f) C 3-7 cycloalkyl,
(g) C 1-6 alkylcarbonyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), and C 1-6 alkoxy, and
(h) 4- to 7-membered saturated heterocyclyl.
16. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is represented as formula (1a):
wherein
R 11 is C 1-6 alkoxy (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, C 1-6 alkoxy, C 3-7 cycloalkyl and 4- to 7-membered saturated heterocyclyl), 4- to 10-membered saturated heterocyclyloxy (which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, and C 1-6 alkyl), C 1-6 alkyl (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy), 4- to 10-membered saturated heterocyclyl (which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy), amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), halogen atom, or hydroxy;
R 12 is C 1-6 alkyl or amino;
Ring Q 11 is
(1) pyridyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) cyano,
(c) C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms, and
(d) C 1-6 alkoxy which may be substituted with 1-3 the same or different halogen atoms, or
(2) pyrimidinyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of (a)-(d) in the above (1);
Ring Q 12 is benzene ring group, or 5- or 6-membered aromatic heterocyclyl;
R 13 is hydrogen atom, halogen atom, hydroxy, C 1-6 alkyl (which may be substituted with 1-3 the same or different halogen atoms), or C 1-6 alkoxy (which may be substituted with 1-3 the same or different halogen atoms);
Q 2 -X 11 — is Q 12 -(single bond)-, Q 12 -(CH 2 ) m —O—, Q 12 -(CH 2 ) m —C(O)—, Q 12 -(CH 2 ) m —NR a —, or Q 12 -(CH 2 ) m —C(O)NR a —, wherein R a is hydrogen atom or C 1-6 alkyl; m is 0, 1, or 2;
W 12 is single bond or C 1-3 alkylene; and
R 14 is
(1) hydrogen atom,
(2) —OR b wherein R b is hydrogen atom, C 1-6 alkyl, or C 1-6 alkylsulfonyl,
(3) —NR c R d wherein R c and R d are independently hydrogen atom, or C 1-6 alkyl which may be substituted with 1-3 the same or different halogen atoms,
(4) 4- to 10-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of
(a) halogen atom,
(b) hydroxy,
(d) C 1-6 alkyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(e) C 1-6 alkoxy which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(f) C 3-7 cycloalkyl,
(g) C 1-6 alkylcarbonyl which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, amino (which may be substituted with 1-2 the same or different C 1-6 alkyl), and C 1-6 alkoxy,
(h) C 1-6 alkoxycarbonyl,
(i) 4- to 7-membered saturated heterocyclyl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy, and
(j) oxo, or
(5) 5- to 10-membered heteroaryl which may be substituted with 1-4 the same or different substituents selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy.
17. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein R 12 is C 1-4 alkyl.
18. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein R 13 is hydrogen atom or halogen atom.
19. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein Ring Q 11 is 5-fluoropyridin-3-yl, 5-cyanopyridin-3-yl, pyridin-3-yl, or pyrimidinyl.
20. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein Ring Q 12 is pyridine ring group, pyrazole ring group, isoxazole ring group, or benzene ring group.
21. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein
R 14 is the following formula (2), (3), (4), (5), (6), (8), (9), (10), (11), (12), (13), (14), (15), or (16):
wherein
R 15 is halogen, hydroxy, C 1-6 alkyl (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy), C 3-7 cycloalkyl, C 1-6 alkylcarbonyl (which may be substituted with one amino which may be substituted with 1-2 the same or different C 1-6 alkyl), or 4- to 7-membered saturated heterocyclyl.
22. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein
R 14 is the following formula (2), (3), (4), (5), (6), (8), (9), or (10):
wherein
R 15 is halogen, hydroxy, C 1-6 alkyl (which may be substituted with 1-3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy), C 3-7 cycloalkyl, C 1-6 alkylcarbonyl (which may be substituted with one amino which may be substituted with 1-2 the same or different C 1-6 alkyl), or 4- to 7-membered saturated heterocyclyl.
23. The compound of claim 1 which is selected from the following compounds, or a pharmaceutically acceptable salt thereof:
9-({6-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]pyridin-3-yl}methyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-({6-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]pyridin-3-yl}methyl)-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9-(4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-9H-purine,
2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9-(4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-9H-purine,
2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9-(4-{[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-9H-purine,
2-ethoxy-9-(4-{[(1 S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
9-(4-{[(1 S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9-(4-{[(1 S,4S)-5-propyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-9H-purine,
9-{4-[(5R)-1,4-diazabicyclo[3.2.1]oct-4-ylmethyl]benzyl}-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]benzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9-{4-[(4-methylpiperazine-1-yl)methyl]benzyl}-9H-purin,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-methoxybenzyl]-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
2-(1-azabicyclo[2.2.2]oct-3-yl)-5-{[2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purin-9-yl]methyl}benzonitrile,
9-{[1-(1-azabicyclo[2.2.2]oct-3-ylmethyl)-1H-pyrazol-4-yl]methyl}-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
2-(1-azabicyclo[2.2.2]oct-3-yl)-5-{[8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purin-9-yl]methyl}benzonitrile,
9-[2-fluoro-4-[(1-methylpiperidin-4-yl)methyl]benzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[2-fluoro-4-[(1-methylazetidin-3-yl)methoxy]benzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
5-f 9-[4-(1-ethylpiperidin-4-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-9H-purin-8-yl)pyridine-3-carbonitrile,
9-[2-fluoro-4-(1-methylpyrrolidin-3-yl)benzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[4-(1-ethylpyrrolidin-3-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[2-fluoro-4-(1-methylpiperidin-4-yl)benzyl]-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
9-[4-(1-ethylpiperidin-4-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-2-methoxy-6-methyl-8-(pyrimidin-5-yl)-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-3-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[3-(1-azabicyclo[2.2.2]oct-3-yl)benzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-{[6-(1-azabicyclo[2.2.2]oct-3-yl)-2-methylpyridin-3-yl]methyl}-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
9-{2-fluoro-4-[(1-methylpiperidin-4-yl)oxy]benzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3S)-1-methylpyrrolidin-3-yl]oxy}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3R)-1-methylpyrrolidin-3-yl]oxy}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-{2-fluoro-4-[(1-methylazetidin-3-yl)oxy]benzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
1-(3-fluoro-4-{[8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purin-9-yl]methyl}phenyl)-N,N-dimethylmethanamine,
9-[4-(azetidin-1-ylmethyl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[2-fluoro-4-(1-methylpiperidin-4-yl)benzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[4-(1-ethylpiperidin-4-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-2-methoxy-6-methyl-8-(pyrimidin-5-yl)-9H-purine,
5-[9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl}-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
5-[9-(4-{[(3-endo)-8-ethyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}-2-fluorobenzyl)-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(4-methylpyridin-3-yl)-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(5-methylpyridin-3-yl)-9H-purine,
5-[9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
5-[9-(4-{[(1 S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}-2-fluorobenzyl)-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
5-[2-ethoxy-9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
2-ethoxy-9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-6-methyl-8-(pyrimidin-5-yl)-9H-purine,
2-ethoxy-9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
5-(9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-2-methoxy-6-methyl-9H-purin-8-yl)pyridine-3-carbonitrile,
9-{[6-(1-azabicyclo[2.2.2]oct-3-yl)pyridin-3-yl]methyl}-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
5-{9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-9H-purin-8-yl}pyridine-3-carbonitrile,
9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-{4-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine, and
9-[5-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine.
24. The compound of claim 1 which is selected from the following compounds, or a pharmaceutically acceptable salt thereof:
1-(3-fluoro-4-{[8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purin-9-yl]methyl}phenyl)-N,N-dimethylmethanamine,
9-[4-(azetidin-1-ylmethyl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[2-fluoro-4-(1-methylpiperidin-4-yl)benzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-[4-(1-ethylpiperidin-4-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-2-methoxy-6-methyl-8-(pyrimidin-5-yl)-9H-purine,
5-[9-(2-fluoro-4-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl}-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
5-[9-(4-{[(3-endo)-8-ethyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}-2-fluorobenzyl)-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(4-methylpyridin-3-yl)-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-8-(5-methylpyridin-3-yl)-9H-purine,
5-[9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl}-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
5-({[(1 S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}-2-fluorobenzyl)-2-methoxy-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-2-methoxy-6-methyl-8-(pyridin-3-yl)-9H-purine,
5-[2-ethoxy-9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-6-methyl-9H-purin-8-yl]pyridine-3-carbonitrile,
2-ethoxy-9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl)-6-methyl-8-(pyrimidin-5-yl)-9H-purine,
2-ethoxy-9-(2-fluoro-4-{[(1 S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}benzyl}-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
5-(9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-2-methoxy-6-methyl-9H-purin-8-yl)pyridine-3-carbonitrile,
9-{[6-(1-azabicyclo[2.2.2]oct-3-yl)pyridin-3-yl]methyl}-2-ethoxy-8-(5-fluoropyridin-3-yl)-6-methyl-9H-purine,
9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
5-f 9-[4-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-2-methoxy-6-methyl-9H-purin-8-yl)pyridine-3-carbonitrile,
9-{4-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-f 4-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]-2-fluorobenzyl}-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine,
9-(2-fluoro-4-1f[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}benzyl)-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purin, and
9-[5-(1-azabicyclo[2.2.2]oct-3-yl)-2-fluorobenzyl]-8-(5-fluoropyridin-3-yl)-2-methoxy-6-methyl-9H-purine.
25. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient, and a carrier.
26. A method for treating autoimmune disease, comprising administering a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a mammal.
27. A method for treating systemic lupus erythematosus, lupus nephritis, Sjogren's syndrome, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, polymyositis, dermatomyositis, Behcet's disease, multiple sclerosis, or pemphigus, comprising administering a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a mammal.