| 摘要 |
The present invention is concerned with deuterium-enriched pyrimidine compounds of formula I, their derivatives and pharmaceutically acceptable salts and methods of use thereof,;
The compounds of formula I are useful for the prevention and treatment of liver fibrosis and cirrhosis, hepatocellular carcinoma, neuroendrcrine neoplasia including metastasis and fibrosis fibrotic processes associated with neuroendocrine cell dysregulation for example Crohn's disease, pulmonary arterial hypertension, pulmonary hypertension associated with chronic obstructive pulmonary disease (COPD), right ventricular hypertrophy, pulmonary vascular remodeling, asthma, cystic fibrosis, hypertension, ischemic stroke, angina pectoris, congestive heart failure, arrhythmia, arterial fibrillation, gastrointestinal disorders, anxiety, depression, stress disorders, post-traumatic stress disorder, obsessive compulsive disorders, demyelinating diseases, acute or chronic cerebrovascular damage, cerebral infarction, subarachanoid hemorrhage, and cerebral edema, neuropathological diseases and cardiovascular system regulation. |
| 主权项 |
1. A method of treating liver cirrhosis, liver fibrosis, hepatocellular carcinoma, carcinoid syndrome, neuroendocrine neoplasia tumor progression, neuroendocrine neoplasia tumor fibrosis and neuroendocrine neoplasia tumor metastasis, comprising administering a pharmaceutically effective dose of a deuterium-enriched compound of formula I and the enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof to a patient in need of such treatment, wherein R1 is D (Deuterium), F, Cl, CD3, CN, CF3, CD(CD3)2, i-Bu(d1-9), O(CD2CD2CD3), Phenyl-d5, 4-F-Ph-d4, deuterated-thiophenyl-d3, deuterated furanyl-d3, deuterated thiazolyl-d3, deuterated-pyridyl (C5D4), deuterated-imidazolyl -d3 or deuterated-pyrrolyl-d4; R2 is D, F, Cl, CD3, CF3, CN, OCF3, OCD3, CD(CD3)2, C6D5, 4-F—C6D4, 3-F—C6D4, 2-F—C6D4; deuterated-thiophenyl-d3, deuterated furanyl-d3, deuterated thiazolyl -d3, deuterated-pyridyl (C5D4), deuterated-imidazolyl-d3 and deuterated-pyrrolyl-d4; R3 is H, D, CD3, NHCD3, NHCD2CD3, NHCD2CD2CD3, NHCD2CD2CD2CD3, NHCD2CD2CD2CD2CD3; CN, F, Cl, OCD3, C6D5 or pyridyl-d4; R4 and R5 independently are D or H, CD3 or CH3; R6, R7, R8, R9 and R10 independently are D, H, F, Cl, CN, CD3, CF3, OCD3, OCF3, OCD2CD2CD3, CONDCD3, CON(CD3)2 or SO2CD3; R11, R12, R13, R14, R15, R16, R17, R18, and R19 independently are D, F or H; and R20 is D or H; and at least one of R2, R5, R9, R11, R17, and R18 is D. |
