USRE49128EActiveUtility
Hydroxyl purine compounds and applications thereof
Assignee: GUANGDONG RAYNOVENT BIOTECH CO LTDPriority: Oct 9, 2014Filed: Sep 22, 2015Granted: Jul 12, 2022
Est. expiryOct 9, 2034(~8.3 yrs left)· nominal 20-yr term from priority
A61K 31/522C07D 261/06A61K 31/52C07D 473/30C07D 241/10A61P 29/00A61P 9/10A61P 25/28A61P 11/00C07D 277/20A61P 9/00A61P 43/00A61P 25/00A61P 19/02C07D 473/14C07D 473/04
55
PatentIndex Score
0
Cited by
120
References
22
Claims
Abstract
Hydroxyl purine compounds represented by formula (I), tautomers or pharmaceutically acceptable salts thereof, and applications thereof as PDE2 or TNF-α inhibitors.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A compound having a structure of formula (I), a tautomer thereof or a pharmaceutically acceptable salt thereof,
wherein,
the structural unit
can be replaced with
L 11 is selected from absence, or C(R)(R′);
each of R and R′ is independently selected from H, a halogen, OH, NH 2 , CN, or an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
or, R and R′ to join together and form a 3- to 6-membered cycloalkyl or heterocycloalkyl including the carbon of L 11 by cyclization;
A is selected from
L 12 is selected from methylene,
R 1 is selected from an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
“hetero” represents N, O, S, C(═O), S(═O), or S(═O) 2 , the number of the heteroatom on each group is selected from 1, 2, 3 or 4.
2. The compound according to claim 1 , wherein the substituents in the R, R′, and R 1 are independently selected from a halogen, OH, NH 2 , CN, or an optionally substituted 1- to 6-membered alkyl and heteroalkyl, the number of the substituent on each group is independently selected from 1, 2 or 3.
3. The compound according to claim 1 , wherein the R and R′ are independently selected from H, Me, CF 3 , or Et.
4. The compound according to claim 1 , wherein the R 1 is selected from Me, CHF 2 , CF 3 , Et, CH 2 CF 3 , isopropyl,
cyclopropyl,
5. A compound selected from the group consisting of:
6. A compound selected from the group consisting of:
7. A method for inhibiting PDE2 and TNF-α in a subject in need thereof, comprising: administering to the subject an effective amount of a compound having a structure of formula (I), a tautomer thereof or a pharmaceutically acceptable salt thereof,
wherein,
the structural unit
can be replaced with
L 11 is selected from absence, or C(R)(R′),;
each of R and R′ is independently selected from H, a halogen, OH, NH 2 , CN, or an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
or, R and R′ to join together and form a 3- to 6-membered cycloalkyl or heterocycloalkyl including the carbon of L 11 by cyclization;
A is selected from cyclopropyl, cyclopentyl, cyclohexyl, epoxypentyl, phenyl, pyridyl, pyrazinyl, oxazolyl, isoxazolyl, thiazolyl, or bicyclor[1.1.11]pentane bicyclo[1.1.1]pentane, or a bicyclic group, a spiro group or a fused cyclic group consisting of any two of the above groups, each of which is optionally substituted;
L 12 is selected from an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
R 1 is selected from an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
“hetero” represents N, O, S, C(═O), S(═O), or S(═O) 2 , the number of the heteroatom on each group is selected from 1, 2, 3 or 4.
8. The compound according to claim 1 , wherein the structural unit
is replaced with
9. The compound according to claim 2 , wherein the substituents in the R, R′and R′ and R 1 are independently selected from the halogen, CF 3 , CN, OH, Me, Et, n-propyl, isopropyl, cyclopropyl,
10. The compound according to claim 3 , wherein the L 11 is selected from
11. The method according to claim 7 , wherein the substituents in the R, R′, A, L 12 and R 1 are independently selected from a halogen, OH, NH 2 , CN, or an optionally substituted 1- to 6-membered alkyl and heteroalkyl, the number of the substituent on each group is independently selected from 1, 2 or 3.
12. The method according to claim 7 , wherein the R and R′ are independently selected from H, Me, CF 3 , or Et.
13. The method according to claim 7 , wherein the L 12 is selected from methylene,
14. The method according to claim 7 , wherein the R 1 is selected from Me, CHF 2 , CF 3 , Et, CH 2 CF 3 , isopropyl,
cyclopropyl,
15. The method according to claim 7 , wherein the structural unit
is replaced with
16. The method according to claim 11 , wherein the substituents in the R, R′, A, L 12 and R 1 are independently selected from the halogen, CF 3 , CN, OH, Me, Et, n-propyl, isopropyl, cyclopropyl,
17. The method according to claim 12 , wherein the L 11 is selected from
18. The method according to claim 7 , wherein the A is selected from
each of which is optionally substituted.
19. The method according to claim 7 , wherein the A is selected from
20. A compound having a structure of formula (I), a tautomer thereof or a pharmaceutically acceptable salt thereof,
wherein,
the structural unit
can be replaced with
L 11 is selected from absence, or C(R)(R′);
each of R and R′ is independently selected from H, a halogen, OH, NH 2 , CN, or an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
or, R and R′ join together and form a 3- to 6-membered cycloalkyl or heterocycloalkyl including the carbon of L 11 by cyclization;
A is selected from cyclopropyl, cyclopentyl, cyclohexyl, epoxypentyl, pyridyl, pyrazinyl, oxazolyl, isoxazolyl, thiazolyl, or bicyclo[1.1.1]pentane, each of which is optionally substituted;
L 12 is selected from methylene,
R 1 is selected from an optionally substituted 1- to 6-membered alkyl or heteroalkyl;
“hetero” represents N, O, S, C(═O), S(═O), or S(═O) 2 , the number of the heteroatom on each group is selected from 1, 2, 3 or 4,
the substituents in the R, R′, A and R 1 are independently selected from a halogen, OH, NH 2 , CN, CF 3 ,
or 1- to 6-membered alkyl and heteroalkyl, the number of the substituent on each group is independently selected from 1, 2 or 3.
21. The compound according to claim 20, wherein the substituents in the R, R′ and R 1 are independently selected from the halogen, CF 3 , CN, OH, Me, Et, n-propyl, isopropyl, cyclopropyl,
22. The compound according to claim 20, wherein the R and R′ are independently selected from H, Me, CF 3 , or Et,
or, the R 1 is selected from Me, CHF 2 , CF 3 , Et, CH 2 CF 3 , isopropyl,
cyclopropyl,
or, the L 11 is selected from
or the structural unit
is replaced withCited by (0)
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