Diaminopyrazolo[1,5-a]pyrimidine-6-carbonitrile compounds as adenosine 2A receptor and adenosine 2B receptor antagonists

Abstract

The present disclosure provides a compound of formula I or its pharma- ceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, stereoisomers, racemates, and pharma- ceutically active derivatives thereof. The compound of formula I acts as an antagonist to adenosine receptors. The present disclosure also provides processes for the preparation of the compound of formula I and its pharmaceutical compositions. TIFF2024507022000440.tif50163

Claims

1. Equation I 【Chemistry 1】 Compounds thereof, or pharmaceutically acceptable salts, hydrates, solvates, tautomers, stereoisomers, and racemates thereof. (In the formula, A is, 【Chemistry 2】 (* indicates an attachment point) Selected from, In the equation, Q is N, R 2 is hydrogen or C 1～6 It is alkyl; R 3 is hydrogen or C 1～6 It is alkyl; R 4 and R 5 are each independently selected from halogen, C 1～6 alkyl, C 3～6 cycloalkyl or C 1～6 haloalkyl, where C 1～6 alkyl is optionally substituted with C 3～6 cycloalkyl; R 6 is hydrogen, C 1～6 Alkyl, C 1～6 Haloalkyl, C3-6 cycloalkyl, C 1～6 Alkoxy, C 1～6 Alkylhydroxy, C 1～6 Aminoalkyl, -Y-CO-NH-R 13 , -YZ or C 1～10 Selected from heterocyclines, where C 1～6 Alkyl, C 1～6 Alkoxy, C 3～6 Cycloalkyl, C 1～6 Haloalkyl, C 1～6 Aminoalkyl, C 1～6 Alkylhydroxy or C 1～10 Heterocyclines are halogens, hydroxyls, amines, and C 1～6 Alkoxy, C 3～6 Cycloalkyl, C 1～6 Alkylhydroxy, C 1～6 Aminoalkyl or C 1～10 It is optionally substituted with one or more groups selected from heterocyclines, where C 3～6 Cycloalkyl, or C 1～6 Aminoalkyls are halogens, hydroxyls, and C 1～6 Alkylhydroxy, -C(O)C 1～6 Alkyl, -C(O)NH 2 or -C(O)-C 1～6 It is further optionally substituted with one or more groups independently selected from alkylhydroxy; Y is C 1～6 Alkyl or C 3～6 It is a cycloalkyl; Z is -SOCH 3 ,-SCH 3 CH 2 -NH-(C 1～6 Alkyl)-SOCH 3 or -NHCO(C 1～6 Selected from alkyl; R 13 is hydrogen, C 1～6 Alkyl or C 3～6 Selected from cycloalkyl groups; R 7 , R 8 , and R9 are hydrogen, halogen, cyano, C 1～6 Alkyl or C 1～6 Selected independently of alkoxy; n is either 0 or 1.

2. A compound according to claim 1, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer, or racemate thereof, selected from the group consisting of the following:

1. 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridine-2-yl)ethyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 2. 7-amino-2,3-dimethyl-5-{[(1S)-1-(6-methylpyridine-2-yl)ethyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 3. (R)-7-amino-3-ethyl-2-methyl-5-((1-(pyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 4. (S)-7-amino-3-ethyl-2-methyl-5-((1-(pyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 5. (S)-7-amino-3-ethyl-2-methyl-5-((1-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 6. 7-amino-2,3-dimethyl-5-{[(6-methylpyridine-2-yl)methyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 7. 7-amino-5-{[(6-ethylpyridine-2-yl)methyl]amino}-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 8. 7-amino-2,3-dimethyl-5-{methyl[(6-methylpyridine-2-yl)methyl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 9. 7-amino-5-({[6-(2-hydroxypropan-2-yl)pyridine-2-yl]methyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 10. 7-amino-2,3-dimethyl-5-((2-(5-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 11. 7-amino-5-((2-(5-fluoropyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 12. 7-amino-5-((2-(6-methoxypyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 13. 7-amino-5-((2-(6-methylpyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 14. Chiral 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridine-2-yl)propane-2-yl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile (isomer 1) 【Transformation 3】 (In the formula, 'a' indicates that the absolute configuration is unknown); 15. Chiral 7-amino-2,3-dimethyl-5-{[1-(6-methylpyridine-2-yl)propane-2-yl]amino}pyrazolo[1,5-a]pyrimidine-6-carbonitrile (isomer 2) 【Chemistry 4】 (In the formula, 'a' indicates that the absolute configuration is unknown); 16. 7-amino-5-({2-[6-(2-hydroxypropan-2-yl)pyridine-2-yl]ethyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 17. 7-amino-3-ethyl-2-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 18. 7-amino-3-ethyl-2-methyl-5-((2-(5-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 19. 7-amino-3-ethyl-5-((2-(5-methoxypyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 20. 7-amino-3-ethyl-5-((2-(6-methoxypyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 21. 7-amino-3-ethyl-5-((2-(5-fluoropyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 22. Chiral 7-amino-3-ethyl-2-methyl-5-((1-(pyridine-2-yl)propan-2-yl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (isomer 1) 【Transformation 5】 (In the formula, 'a' indicates that the absolute configuration is unknown); 23. Chiral 7-amino-3-ethyl-2-methyl-5-((1-(pyridine-2-yl)propan-2-yl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (isomer 2) 【Transformation 6】 (In the formula, 'a' indicates that the absolute configuration is unknown.) 24. 7-amino-3-ethyl-2-methyl-5-((1-(6-methylpyridine-2-yl)propan-2-yl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 25. 7-amino-3-ethyl-5-({2-[6-(2-hydroxypropan-2-yl)pyridine-2-yl]ethyl}amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 26. 7-amino-3-(cyclopropylmethyl)-2-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 27. 7-amino-3-(isopropylmethyl)-2-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 28. 7-amino-3-(isopropyl)-2-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 29. 7-amino-5-{[2-(1-ethyl-1H-pyrazole-3-yl)ethyl]amino}-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 30. 7-amino-3-ethyl-5-{[2-(1-ethyl-1H-pyrazole-3-yl)ethyl]amino}-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 31. 7-amino-5-({2-[1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazole-3-yl]ethyl}amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 32. 7-amino-3-ethyl-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 33. 7-amino-3-chloro-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 34. 7-amino-3-chloro-5-((2-(6-(1-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 35. 7-amino-3-chloro-5-((2-(1-(2-hydroxyethyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 36. 7-amino-3-chloro-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 37. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 38. 7-amino-3-chloro-5-((2-(6-(2-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 39. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 40. Amino-5-((2-(6-ethylpyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 41. 7-amino-5-((2-(3-fluoro-6-methylpyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 42. 7-amino-2-ethyl-3-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 43. 7-amino-2-ethyl-5-((2-(6-(2-hydroxypropan-2-yl)pyridine-2-yl)ethyl)amino)-3-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 44. 7-amino-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 45. 7-amino-3-ethyl-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 46. ​​7-amino-3-(cyclopropylmethyl)-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 47. 7-amino-2-cyclopropyl-5-((2-(6-(2-hydroxypropan-2-yl)pyridine-2-yl)ethyl)amino)-3-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 48. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 49. 7-amino-5-((2-(6-(1-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 50. 7-amino-3-ethyl-5-((2-(6-(1-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 51. 7-amino-5-((2-(6-(2-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 52. 7-amino-3-ethyl-5-((2-(6-(1-hydroxy-2-methylpropan-2-yl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 53. 7-amino-5-((2-(6-(1-hydroxy-2-methylpropane-2-yl)pyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 54. 7-amino-3-ethyl-5-((2-(1-(2-hydroxyethyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 55. 7-amino-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 56. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 57. 7-amino-5-(((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazole-3-yl)methyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 58. 7-Amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 59. 7-Amino-2-(difluoromethyl)-3-ethyl-5-((2-(6-(2-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitriel; 60. 7-amino-3-ethyl-5-((2-(6-(2-(hydroxymethyl)cyclopropyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 61. 7-amino-3-chloro-5-((2-(4-(1-(hydroxymethyl)cyclopropyl)thiazole-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 62. 7-amino-3-ethyl-5-((2-(4-fluoro-1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 63. 7-amino-3-ethyl-5-((2-(1-((1-(hydroxymethyl)cyclopropyl)methyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 64. 7-amino-3-chloro-5-((2-(6-(1,1-difluoro-2-hydroxyethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 65. 7-amino-3-chloro-5-((2-(6-(1-hydroxy-2-methylpropane-2-yl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 66. 7-amino-3-ethyl-5-((2-(4-(1-(hydroxymethyl)cyclopropyl)thiazole-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 67. 7-amino-3-chloro-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 68. 7-amino-5-((2-(1-(1-(aminomethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-3-chloro-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 69. 7-amino-3-bromo-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 70. 7-amino-3-chloro-5-((2-(1-ethyl-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 71. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 72. 7-amino-3-bromo-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 73. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-4-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 74. 7-amino-3-(cyclopropylmethyl)-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 75. 7-amino-3-chloro-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 76. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 77. N-((1-(3-(2-((7-amino-3-chloro-6-cyano-2-methylpyrazolo[1,5-a]pyrimidine-5-yl)amino)ethyl)-1H-pyrazole-1-yl)cyclopropyl)methyl)acetamide; 78. (+)-7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 79. (-)-7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 80. 7-amino-3-ethyl-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 81. 7-amino-3-ethyl-5-((2-(1-(1-hydroxypropan-2-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 82. (+-)-7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl)methyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 83. (+)-7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl)methyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 84. (-)-7-amino-3-chloro-5-((2-(1-((3-hydroxycyclobutyl)methyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(83b); 85. 7-amino-3-ethyl-5-((2-(1-((3-hydroxycyclobutyl)methyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 86. 7-amino-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 87. 7-amino-3-chloro-2-methyl-5-((2-(1-methyl-2-oxo-1,2-dihydropyridine3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 88. 7-amino-3-ethyl-2-methyl-5-((2-(1-methyl-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitriel; 89. 7-amino-3-bromo-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 90. 7-amino-3-chloro-5-((2-(6-(((2-hydroxyethyl)amino)methyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 91. 7-amino-3-ethyl-5-((2-(5-fluoro-6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 92. 7-amino-3-chloro-5-((2-(1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 93. 7-amino-3-chloro-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 94. 7-amino-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methyl-3-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 95. 7-amino-5-((2-(1-(2-(aminomethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-3-chloro-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 96. 7-amino-3-ethyl-5-((2-(6-(((2-methoxyethyl)amino)methyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 97. 7-amino-3-ethyl-5-((2-(6-(((2-hydroxyethyl)amino)methyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 98. 7-amino-3-chloro-5-((2-(1-(1-(((2-hydroxyethyl)amino)methyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 99. N-((1-(3-(2-((7-amino-3-chloro-6-cyano-2-methylpyrazolo[1,5-a]pyrimidine-5-yl)amino)ethyl)-1H-pyrazole-1-yl)cyclopropyl)methyl)-3-hydroxypropanamide; 100. 7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 101. 7-amino-3-cyclopropyl-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 102. 7-amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 103. (+-)-7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 104. (+)-7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(104a); 104b. (-)-7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(104b); 105. 7-amino-5-((2-(6-(((2-hydroxyethyl)amino)methyl)pyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 106. 7-amino-3-ethyl-5-((2-(1-(1-(((2-hydroxyethyl)amino)methyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 107. 7-amino-3-ethyl-5-((2-(1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 108. 7-amino-3-ethyl-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 109. 7-amino-5-((2-(1-(2-(aminomethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 110. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-1H-pyrazole-5-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 111. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 112. 7-amino-3-chloro-5-((2-(1-(1-(2-hydroxyethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 113. 7-amino-3-ethyl-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 114. 7-amino-3-chloro-5-((2-(1-(2-(hydroxymethyl)cyclopentyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 115. 7-amino-3-ethyl-5-((2-(1-(2-(hydroxymethyl)cyclopentyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 116. 7-amino-3-(cyclopropylmethyl)-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 117. 7-amino-3-chloro-5-((2-(1-(2-(((2-hydroxyethyl)amino)methyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 118. 7-amino-5-((2-(1-(2-(aminomethyl)cyclopentyl)-1H-pyrazole-3-yl)ethyl)amino)-3-chloro-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 119. 7-amino-3-chloro-2-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 120. 7-amino-3-chloro-5-((2-(6-ethylpyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 121. (+-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 122a. (+)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(122a); 122b. (-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 123. 7-amino-3-ethyl-5-((2-(1-(3-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 124. 7-amino-3-ethyl-5-((2-(1-(1-(2-hydroxyethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 125. 7-amino-5-((2-(1-(2-aminoethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-3-chloro-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 126. 7-amino-5-((2-(1-(2-aminoethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 127. 7-amino-3-chloro-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 128. 7-amino-3-ethyl-5-((2-(1-((3-hydroxycyclobutyl)methyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; 129. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-3-chloro-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 130. 7-amino-3-bromo-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 131. 7-Amino-2-(difluoromethyl)-3-ethyl-5-((2-(1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 132. (+-)-7-amino-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 133a. (+)-7-amino-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(133a); 133b. (-)-7-amino-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 134. 2-(((2-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-5-yl)amino)ethyl)-1H-pyrazole-1-yl)cyclobutyl)methyl)amino)acetamide; 135. 7-amino-3-ethyl-2-methyl-5-((2-(6-(2,2,2-trifluoro-1-hydroxyethyl)pyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6 ​​carbonitrine; 136. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 137. 7-amino-3-(cyclobutylmethyl)-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 138. 7-amino-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 139. 7-amino-3-ethyl-5-((2-(6-(2-hydroxyethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 140. 7-amino-2,3-dimethyl-5-((2-(6-methylpyrazine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 141. 7-amino-5-((2-(1-(3-aminopropyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 142. 7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methylthio)ethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 143. (+-)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methylsulfinyl)ethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 144a. (+)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methylsulfinyl)ethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitriel; 144b. (-)7-amino-3-ethyl-2-methyl-5-((2-(1-(2-(methylsulfinyl)ethyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 145. N-(3-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-5-yl)amino)ethyl)-2-oxopyridine-1(2H)-yl)propyl)acetamide; 146. 7-amino-5-((2-(1-(1-(aminomethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 147. N-((1-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-5-yl)amino)ethyl)-1H-pyrazole-1-yl)cyclopropyl)methyl)acetamide; 148. 7-amino-5-((2-(1-(1-(2-aminoethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 149. N-(2-(1-(3-(2-((7-amino-6-cyano-3-ethyl-2-methylpyrazolo[1,5-a]pyrimidine-5-yl)amino)ethyl)-1H-pyrazole-1-yl)cyclopropyl)ethyl)acetamide; 150. 7-amino-3-ethyl-5-((2-(6-(2-hydroxyethoxy)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 151. 7-Amino-5-((2-(1-(1-(2-aminoethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-3-chloro-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 152. 7-amino-5-((2-(6-(2-hydroxyethyl)pyridine-2-yl)ethyl)amino)-2,3-dimethylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 153. 7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylthio)propyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 154a. (-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylsulfinyl)propyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile(154a); 154b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylsulfinyl)propyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 155. 7-amino-3-ethyl-5-((2-(6-(3-hydroxypropyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 156. 7-amino-5-((2-(1-(3-hydroxypropyl)-2-oxo-1,2-dihydropyridine-3-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 157. 7-amino-5-((2-(6-(hydroxymethyl)pyridine-2-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 158. 7-amino-5-((2-(1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 159a. (+)-7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(159a); 159b. (-)-7-amino-3-ethyl-5-((2-(6-(1-hydroxyethyl)pyridine-2-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 160a. (+)7-amino-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitrile (160a); 160b. (-)7-amino-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-1H-pyrazole-3-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 161. 7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylthio)propyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 162a. (-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylsulfinyl)propyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile(162a); 162b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(3-(methylsulfinyl)propyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 163a. ​​(-)-7-amino-3-ethyl-2-methyl-5-((2-(1-(1-(((2-(methylsulfinyl)ethyl)amino)methyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (163a); 163b. (+)-7-amino-3-ethyl-2-methyl-5-((2-(1-(1-(((2-(methylsulfinyl)ethyl)amino)methyl)cyclopropyl)-1H-pyrazole-3-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitride; 164. 7-amino-2-methyl-5-((2-(6-methylpyridine-2-yl)ethyl)amino)-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitrile; 165a. (+)-7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitrile(165a); 165b. (-)-7-amino-5-((2-(1-(2-(hydroxymethyl)cyclobutyl)-1H-pyrazole-3-yl)ethyl)amino)-2-methyl-3-propylpyrazolo[1,5-a]pyrimidine-6-carbonitride; 166. (R)-7-amino-3-ethyl-2-methyl-5-((2-(6-(((tetrahydrofuran-3-yl)oxy)methyl)pyridine-2-yl)ethyl)amino)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 167. (-)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitriel; and 168. (+)-7-amino-3-ethyl-5-((2-(1-(4-(hydroxymethyl)tetrahydrofuran-3-yl)-5-methyl-1H-pyrazole-3-yl)ethyl)amino)-2-methylpyrazolo[1,5-a]pyrimidine-6-carbonitride.

3. A pharmaceutical product comprising the compound described in claim 1 or 2, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer, or racemate thereof.

4. Adenosine 2a receptor (A 2a R) or adenosine 2b receptor (A 2b R) or adenosine 2a receptor (A 2a R) and adenosine 2b receptor (A 2b A compound according to claim 1 or 2, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer, or racemate thereof, which acts as an antagonist to the combination of R).

5. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer, or racemic mixture thereof, comprising an adenosine 2a receptor (A 2a R) or adenosine 2b receptor (A 2b R) or A 2a R and A 2b A pharmaceutical composition for use in the treatment of a disease, disorder, or condition selected from cancer, Parkinson's disease, asthma, diabetes, and immune response-related disorders, which is at least partially mediated by a combination of R.

6. A method for preparing a compound of formula I according to claim 1 or 2, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer, or racemate thereof, comprising the step of reacting formulas (A) and (B) in the presence of a base and a solvent to obtain a compound of formula I. 【Transformation 7】 (In the formula, R is C 1～6 Alkyl, C 3～6 Cycloalkyl, C 5～10 Ariel, C 2～10 Heteroaryl or C 1～10 (Selected from heterocyclines).

7. The method according to claim 6, wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium tertoxide, sodium hydride, lithium bis(trimethylsilyl)amide (LiHMDS), N-diisopropylethylamine, or a combination thereof.

8. The method according to claim 6, wherein the solvent is selected from isopropanol, methanol, n-butanol, dichloromethane, tetrahydrofuran, dimethylformamide, n-methylpyrrolidone, dimethyl sulfoxide, water, dioxane, acetonitrile, or a combination thereof.

9. A pharmaceutical composition comprising a compound of formula I as described in claim 1 or 2 and one or more additional therapeutic agents.

10. One or more additional therapeutic agents are chemotherapeutic agents or immune checkpoint inhibitors; chemotherapeutic agents are selected from phosphoinositide 3-kinase inhibitors (PI3K) inhibitors, tyrosine kinase inhibitors, Stat-3 (T3) inhibitor signal transducers and activators, topoisomerase inhibitors, protein kinase B (AKT) inhibitors, c-Jun N-terminal kinase (JNK1 / K2) inhibitors, hypoxia-inducing factor 1 alpha (HIF-1a) inhibitors, extracellular signal-regulated kinase (ERK) inhibitors, poly-ADP-ribose polymerase-1 (PARP-1) inhibitors, cisplatin, or oxaliplatin; immune checkpoint inhibitors are selected from programmed death-1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, anti-PD1 antibodies, anti-PD-L1 antibodies, or cytotoxic T-lymphocyte-associated protein 4 The composition according to claim 9, selected from a (CTLA4) inhibitor, an anti-CTLA4 antibody, a T cell immunoglobulin and an ITIM domain (TIGIT) inhibitor, an ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase, CD39) inhibitor, or an ecto-5'-nucleotidase (ecto-5'NTase, CD79) inhibitor.

11. The pharmaceutical composition according to claim 5, wherein the disease, disorder, or condition is cancer or an immune response-related disease, disorder, or condition.

12. The pharmaceutical composition according to claim 11, wherein the cancer is a cancer of the adrenal gland, brain, bladder, breast, bone, colon, endometrium, esophagus, head, stomach, kidney, liver, lung, mouth, muscle, neck, pancreas, prostate, retina, skin, thyroid, or leukocyte, and the immune response-related disease, disorder, or condition is selected from the group consisting of allergy, Alzheimer's disease, asthma, Crohn's disease, colitis, chronic obstructive pulmonary disease, diabetic nephropathy, glaucoma, lupus, rheumatoid arthritis, multiple sclerosis, pain, panic disorder, pancreatitis, Parkinson's disease, psoriasis, systemic sclerosis, and ulcerative colitis.

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