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US 8,008,501 B2Granted
Quinoline compounds and their uses
AssigneeRigel Pharmaceuticals, Inc.
InventorsRajinder Singh, Hui Li
Life of this patent
Estimating the term…
Abstract
The present invention provides quinoline compounds that inhibit the IgE receptor signaling cascade that leads to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE receptor signaling cascade.
Claims23
A compound according to structural formula (I):
- and a salt, hydrate, solvate or N-oxide thereof, wherein:
- R1 is an alkyl group optionally substituted with one or more of the same or different Rl0 groups;
- R2, R3, R5, R6, R7 and R8 are each, independently of one another, seleted from the group consisting of a hydrogen atom, —ORd, —SRd, (C1-C3) haloalkyloxy, (C1-C3) perhaloalkyloxy, —NRc-aryl, —NRc-heteroaryl, halogen, (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, —CF3, —CH2CF3, —CF2CF3, (C1-C6) alkyl optionally substituted with one or more of the same or different R10 groups, (C5-C10) aryl optionally substituted with one or more of the same or different R10 groups, phenyl optionally substituted with one or more of the same or different R10 groups, and 5-10 membered heteroaryl optionally substituted with one or more of the same or different R10 groups;
- R9 is selected from the group consisting of (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, —CF3, —CH2CF3, —CF2CF3, (C1-C6) alkyl optionally substituted with one or more of the same or different R10 groups, (C5-C10) aryl optionally substituted with one or more of the same or different R10 groups, phenyl optionally substituted with one or more of the same or different R10 groups;
- R10 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, —ORa substituted with one or more of the same or different Ra or Rb, —(CH2)m—Rb, —(CHRa)m—Rb, —O—(CH2)m—Rb,—S—(CH2)m—Rb, and-O—(CHRa)m—Rb;
- each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl;
- each Rb is a suitable group independently selected from the group consisting of —ORd, (C1-C3) haloalkyloxy, halogen, and —CF3,
- each Rc is independently a protecting group, Ra or Ra optionally substituted with one or more of the same or different Ra or suitable Rb groups;
- each Rd is independently a protecting group, Ra or Ra optionally substituted with one or more of the same or different Ra or suitable Rb groups;
- each m is independently an integer from 1 to 3;
- A is NH or CO;
- and
- B is CO, NH or O, provided that one of A or B is C(O).
10 more elements
A compound according to structural formula (I):
- and a salt, hydrat;
- solvate or N-oxide thereof, wherein:
- R1 is an alkyl group optionally substituted with one or more of the same or different R10 groups;
- R2, R3, R5, R6, R7 and R8 are each, independently of one another, selected from the group consisting of hydrogen, —ORd, —SRd, (C1-C3) haloalkyloxy, (C1-C3) perhaloalkyloxy, —NRc-aryl, —NR-heteroaryl, halogen, (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, —CF3, —CH2CF3, —CF2CF3, (C1-C6) alkyl optionally substituted with one or more of the same or different R10 groups, (C5-C10) aryl optionally substituted with one or more of the same or different R10 groups, phenyl optionally substituted with one or more of the same or different R10 groups, and 5-10 membered heteroaryl optionally substituted with one or more of the same or different R10 groups;
- R9 is selected from the group consisting of (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, —CF3, —CH2CF3, —CF2CF3, (C1-C6) alkyl optionally substituted with one or more of the same or different R10 groups, and phenyl optionally substituted with one or more of the same or different R10 groups;
- R10 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, —ORasubstituted with one or more of the same or different Ra or Rb, —(CH2)m—Rb, —(CHRa)m—Rb, —O—(CH2)m—Rb, —S—(CH2)m—Rb, and-O—(CHRa)m—Rb;
- each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, and benzyl;
- each Rb is a suitable group independently selected from the group consisting of —ORd, (C1-C3) haloalkyloxy, halogen, and —CF3,
- each Rc is independently a protecting group, Ra or Ra optionally substituted with one or more of the same or different Ra or suitable Rb groups;
- each Rd is independently a protecting group, Ra or Ra optionally substituted with one or more of the same or different Ra or suitable Rb groups;
- each m is independently an integer from 1 to 3;
- A is NH or CO;
- and
- B is CO, NH or O, provided that one of A or B is CO.
11 more elements
A compound according to structural formula (I):
- and a salt, hydrate, solvate or N-oxide thereof, in which A, B, R1, R2, R3, R5. R6, R7, R8 and R9 are selected from the group of substituent combinations delineated below:
- No.
- A
- B
- R1
- R2
- R3
- R5
- R6
- R7
- R8
- R9
- 1
- CO
- NH
- Me
- Ph
- H
- H
- H
- H
- H
- Me
- 3
- NH
- CO
- Me
- Me
- H
- H
- H
- H
- H
- Ph
- 5
- O
- CO
- Me
- H
- H
- H
- H
- H
- H
- Ph
- 7
- O
- CO
- Me
- H
- H
- H
- H
- Cl
- H
- Ph
- 9
- O
- CO
- Me
- Me
- H
- H
- H
- H
- H
- Ph
- 13
- O
- CO
- Me
- H
- H
- H
- H
- Cf3
- H
- Ph
- 15
- O
- CO
- Me
- H
- H
- H
- H
- H
- CF3
- Ph
- 17
- O
- CO
- Me
- H
- COOEt
- H
- H
- CF3
- H
- Ph
- 19
- O
- CO
- Me
- COOEt
- H
- H
- H
- H
- H
- Ph
- 21
- O
- CO
- Me
- Me
- H
- H
- F
- H
- H
- Me
- 23
- O
- CO
- Me
- Me
- H
- H
- F
- H
- H
- 25
- O
- CO
- Me
- Me
- H
- H
- F
- H
- H
- 27
- O
- CO
- Me
- CF3
- H
- H
- OCF3
- H
- H
- Ph
- 29
- O
- CO
- Me
- CF3
- H
- H
- OCF3
- H
- H
- Me
- 31
- O
- CO
- Me
- CF3
- H
- H
- OCF3
- H
- H
- 33
- O
- CO
- Me
- CF3
- H
- H
- OCF3
- H
- H
- 35
- NH
- CO
- Me
- H
- H
- H
- H
- CF3
- H
- Ph
- 37
- NH
- CO
- Me
- H
- H
- H
- H
- CF3
- H
- Me
- 39
- NH
- CO
- Me
- H
- H
- H
- H
- CF3
- H
- 41
- NH
- CO
- Me
- H
- H
- H
- H
- CF3
- H
- 43
- CO
- NH
- Me
- Cl
- H
- H
- Br
- H
- H
- Ph
- 45
- CO
- NH
- Me
- Cl
- H
- H
- Br
- H
- H
- Me
- 47
- CO
- NH
- Me
- Me
- H
- H
- F
- H
- H
- Ph
- 49
- CO
- NH
- Me
- Me
- H
- H
- F
- H
- H
- Me
- 51
- O
- CO
- Me
- H
- H
- H
- OCF3
- H
- H
- Ph
- 53
- O
- CO
- Me
- H
- H
- H
- OCF3
- H
- H
- 57
- O
- CO
- Me
- H
- H
- H
- OCF3
- H
- H
- 61
- CO
- NH
- Me
- Ph
- H
- H
- H
- H
- H
- Ph
- 63
- CO
- NH
- Me
- H
- H
- H
- H
- H
- H
- Ph
- 65
- CO
- NH
- Me
- H
- H
- Br
- H
- H
- Ph
- 67
- CO
- NH
- Me
- —NHCH3
- H
- H
- Br
- H
- H
- Ph
- 69
- CO
- NH
- Me
- H
- H
- Br
- H
- H
- Ph
- 71
- CO
- NH
- Me
- H
- H
- Br
- H
- H
- Ph;
- and
- 73
- CO
- NH
- Me
- H
- H
- Br
- H
- H
- Ph.
372 more elements
A pharmaceutical composition comprising a quinoline compound and a pharmaceutically acceptable excipient, carrier or diluent, said quinoline compound being a compound according to structural formula (I):
- and a salt, hydrate, solvate or N-oxide thereof, wherein:
- R1 is an alkyl group optionally substituted with one or more of the same or different R10 groups;
- R2, R3, R5, R6, R7 and R8 are each, independently of one another, selected from the group consisting of a hydrogen atom, —ORd, —SRd, (C1-C3) haloalkyloxy, (C1-C3) perhaloalkyloxy, —NRc-aryl, —NRc-heteroaryl, halogen, (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, —CF3, —CH2CF3, —CF2CF3, (C1-C6) alkyl optionally substituted with one or more of the same or different R10 groups, (C5-C10) aryl optionally substituted with one or more of the same or different R10 groups, phenyl optionally substituted with one or more of the same or different R10 groups, (and 5-10 membered heteroaryl optionally substituted with one or more of the same or different R10 groups;
- R9 is selected from the group consisting of (C1-C3) haloalkyl, (C1-C3) perhaloalkyl, —CF3, —CH2CF3, —CF2CF3, (C1-C6) alkyl optionally substituted with one or more of the same or different R10 groups, (C5-C10) aryl optionally substituted with one or more of the same or different R10 groups, phenyl optionally substituted with one or more of the same or different R10 groups;
- R10 is selected from the group consisting of Ra, Rb, Ra substituted with one or more of the same or different Ra or Rb, —ORa substituted with one or more of the same or different Ra or Rb, —(CH2)m—Rb, —(CHRa)m—Rb, —O—(CH2)m—Rb, —S—(CH2)m—Rb, and —O—(CHRa)m—Rb;
- each Ra is independently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, and benzyl;
- each Rb is a suitable group independently selected from the group consisting of —ORd, (C1-C3) haloalkyloxy, halogen, and —CF3,
- each Rc is independently a protecting group, Ra or Ra optionally substituted with one or more of the same or different Ra or suitable Rb groups;
- each Rd is independently a protecting group, Ra or Ra optionally substituted with one or more of the same or different Ra or suitable Rb groups;
- each m is independently an integer from 1 to 3;
- A is O, NH or CO;
- and
- B is CO, NH or O, provided that one of A or B is CO.
10 more elements
Dependencies are inferred from the claim text.