ANTAGONISTS OF HUMAN INTEGRIN (ALPHA4)(BETA7)

• US 20190315692A1
• Filed: 04/12/2019
• Published: 10/17/2019
• Est. Priority Date: 04/12/2018
• Status: Active Grant

• Current Assignee: Morphic Therapeutic, Inc. (Morphic Holding, Inc.)
• Original Assignee: Morphic Therapeutic, Inc. (Morphic Holding, Inc.)
• Inventors: Bursavich, Matthew G., Troast, Dawn M., Harrison, Bryce A., Lippa, Blaise S., Rogers, Bruce N., Konze, Kyle D., Gerasyuto, Aleksey I., Day, Tyler, Lin, Fu-Yang, Hahn, Kristopher N., Svensson, Mats A., Kim, Byungchan, Zhong, Cheng, Lugovskoy, Alexey A., Sosa, Brian
• Granted Patent: US 10,759,756 B2
• Time in Patent Office: Days
• CPC Class Codes: C07D 205/08 with one oxygen atom directly attached in position 2, e.g. beta-lactams
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 237/32 with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
• CPC Class Codes: C07D 239/90 with acyclic radicals attached in position 2 or 3
• CPC Class Codes: C07D 241/18 Oxygen or sulfur atoms
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Disclosed are small molecule antagonists of α4β7 integrin, and methods of using them to treat a number of specific diseases or conditions.

Claims

1. A compound represented by formula (I):

2. The compound of claim 1, wherein R¹ is alkyl.

26. The compound of claim 1, wherein R² is selected from

27. The compound of claim 1, wherein R² is selected from

28. The compound of claim 1, wherein R³ is

29. The compound of claim 28, wherein R^a is methyl, cyclopropyl, CN, or —

OMe.

30. The compound of claim 28, wherein R^b is alkyl, aryl, heterocyclyl, heteroaryl, —

O-cycloalkyl, —

O-aryl, or —

O-heteroaryl.

38. The compound of claim 28, wherein R^b is selected from

42. The compound of claim 28, wherein R^b is selected from

43. The compound of claim 28, wherein R^b is selected from

48. The compound of claim 1, wherein R³ is

49. The compound of claim 48, wherein R^c is alkyl, cycloalkyl, (heterocyclyl)akyl, halogen, or CF₃.

52. The compound of claim 1, wherein R³ is

53. The compound of claim 52, wherein R^d is aryl, heteroaryl, or heterocyclyl.

57. The compound of claim 53, wherein R^d is selected from

62. The compound of claim 53, wherein R^d is

64. The compound of claim 53, wherein R^d is selected from

65. The compound of claim 1

70. The compound of claim 65, wherein R^e is or

74. The compound of claim 65, wherein R^e is

75. The compound of claim 1, wherein R⁴ is H.

76. The compound of claim 1, wherein R⁴ is (C₁-C₆)-alkyl.

78. The compound of claim 1, wherein the compound is selected from the group consisting of:

79. The compound of claim 1, wherein the compound is selected from the group consisting of:

80. The compound of claim 1, wherein the compound is selected from the group consisting of:

81. The compound of claim 1, wherein the compound is selected from the group consisting of:

82. The compound of claim 1, wherein the compound is selected from the group consisting of:

83. The compound of claim 1, wherein the compound is selected from the group consisting of:

84. The compound of claim 1, wherein the compound is selected from the group consisting of:

85. The compound of claim 1, wherein the compound is selected from the group consisting of:

86. The compound of claim 1, wherein the compound is selected from the group consisting of:

87. The compound of claim 1, wherein the compound is selected from the group consisting of:

88. The compound of claim 1, wherein the compound is selected from the group consisting of:

89. The compound of claim 1, wherein the compound is selected from group consisting of:

90. The compound of claim 1, wherein the compound is selected from group consisting of:

92. A method of treating a disease or condition selected from the group consisting of inflammatory bowel disease, ileoanal anastomosis, eosinophilic esophagitis, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, pericholangitis, chronic bronchitis, chronic sinusitis, asthma, graft versus host disease, a chronic inflammatory disease of the lung, HIV, and hematological tumor, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of aneasef claim 1.

3-25. -25. (canceled)

31-37. -37. (canceled)

39-41. -41. (canceled)

44-47. -47. (canceled)

50-51. -51. (canceled)

54-56. -56. (canceled)

58-61. -61. (canceled)

63. (canceled)

66-69. -69. (canceled)

71-73. -73. (canceled)

77. (canceled)

91. (canceled)

93-104. -104. (canceled)