- Preparation method of 4-chloro-2-trifluoromethyl pyrimidine
-
The invention discloses a preparation method of 4-chloro-2-trifluoromethyl pyrimidine (formula I). According to the preparation method, cheap and easily purchased methyl trifluoroacetate and malonamide are taken as the raw materials. The preparation method has the advantages that no pricy material is used, the reaction conditions are mild, the used equipment is simple, the EHS risk is little, the cost is low, and the preparation method is suitable for massive production.
- -
-
Paragraph 0017
(2017/07/20)
-
- Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes
-
PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and lipophilic ligand efficiency (LLE). These triazolopyrimidines were optimized for potency, selectivity and ADME properties ultimately leading to compound 42. This compound was highly potent and selective with good bioavailability and advanced into pre-clinical development.
- Deninno, Michael P.,Wright, Stephen W.,Etienne, John B.,Olson, Thanh V.,Rocke, Benjamin N.,Corbett, Jeffrey W.,Kung, Daniel W.,Dirico, Kenneth J.,Andrews, Kim M.,Millham, Michele L.,Parker, Janice C.,Esler, William,Van Volkenburg, Maria,Boyer, David D.,Houseknecht, Karen L.,Doran, Shawn D.
-
scheme or table
p. 5721 - 5726
(2012/09/22)
-
- Discovery of a potent nicotinic acid receptor agonist for the treatment of dyslipidemia
-
Nicotinic acid has been used clinically for decades to control serum lipoproteins. Nicotinic acid lowers very low-density lipoprotein (VLDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and lipoprotein-a (LPa), and it is also effective in raising high-density lipoprotein (HDL)-cholesterol. However, nicotinic acid has several side effects in clinical use. The most notable is intense cutaneous vasodilation "flushing"+ on the upper body and face. We discovered a pyranopyrimidinedione series to be nicotinic acid receptor agonists. A potent nicotinic acid receptor agonist from this series {5-(3-cyclopropylpropyl)-2-(difluoromethyl)-3H-pyrano[2,3-d] pyrimidine-4,7-dione}with reduced flushing side effect in dogs was identified.
- Qin, Jun,Rao, Ashwin,Chen, Xiao,Zhu, Xiaohong,Liu, Zhidan,Huang, Xianhai,Degrado, Sylvia,Huang, Ying,Xiao, Dong,Aslanian, Robert,Cheewatrakoolpong, Boonlert,Zhang, Hongtao,Greenfeder, Scott,Farley, Constance,Cook, John,Kurowski, Stan,Li, Qiu,Van Heek, Margaret,Chintala, Madhu,Wang, Ganfeng,Hsieh, Yunsheng,Li, Fangbiao,Palani, Anandan
-
scheme or table
p. 171 - 176
(2011/03/23)
-
- SUBSTITUTED TRIAZOLOPYRIMIDINES AS PDE8 INHIBITORS
-
Compounds of Formula (I): wherein R1 , R2, R3, R4, and R5 are as defined herein, are disclosed.
- -
-
Page/Page column 35
(2011/06/16)
-
- PYRIMIDINE DERIVATIVES FOR THE TREATMENT OP GABA B MEDIATED NERVOUS SYSTEM DISORDERS
-
The invention relates to novel heterocyclic compounds of the formula (I) in free base form or in acid addition salt form, in which R1, R2, R3, R4 and A are as defined in the specification, to their preparation, to their use as medicaments for the treatment of certain nervous system disorders and to medicaments comprising them.
- -
-
Page/Page column 25-26
(2010/11/25)
-
- PYRIMIDINE DERIVATIVES AND METHODS OF TREATMENT RELATED TO THE USE THEREOF
-
The present invention encompasses novel substituted pyrimidine compounds of Formula (I): which act as MCH receptor antagonists. These compounds are useful in pharmaceutical compositions whose use includes prophylaxis or treatment of improving memory function, sleeping and arousal, anxiety, depression, mood disorders, seizure, obesity, diabetes, appetite and eating disorders, cardiovascular disease, hypertension, dyslipidemia, myocardial infarction, binge eating disorders including bulimia, anorexia, mental disorders including manic depression, schizophrenia, delirium, dementia, stress, cognitive disorders, attention deficit disorder, substance abuse disorders and dyskinesias including Parkinson’s disease, epilepsy, and addiction.
- -
-
Page/Page column 140
(2008/06/13)
-
- Process for large-scale production of BMY 21502
-
An improved process, suitable for adaption to large-scale manufacture for synthesis of the cerebral function enhancing agent BMY 21502.
- -
-
-