- PYRAZOLYL PYRIMIDINONE COMPOUNDS AS PDE2 INHIBITORS
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The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Page/Page column 44
(2016/10/11)
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- Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes
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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.
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scheme or table
p. 5721 - 5726
(2012/09/22)
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- Novel Compounds
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The present invention relates to the new compounds of general formula I wherein A, U, V, X, Y, R1, R2 and R3 are defined as stated hereinafter, the tautomers, the isomers thereof, the diastereomers, the enantiomers, the hydrates, the mixtures and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, their use and processes for preparing them.
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Page/Page column 67-68
(2012/04/18)
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- SUBSTITUTED TRIAZOLOPYRIMIDINES AS PDE8 INHIBITORS
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Compounds of Formula (I): wherein R1 , R2, R3, R4, and R5 are as defined herein, are disclosed.
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Page/Page column 30-31
(2011/06/16)
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- Discovery of a potent nicotinic acid receptor agonist for the treatment of dyslipidemia
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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
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scheme or table
p. 171 - 176
(2011/03/23)
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- 4-AMINO-PYRIMIDINE DERIVATIVES
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4-Amino-pyrimidine derivatives of Formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 75
(2009/07/25)
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- First dual M3 antagonists-PDE4 inhibitors: Synthesis and SAR of 4,6-diaminopyrimidine derivatives
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SAR around 4,6-diaminopyrimidine derivatives allowed the discovery of the first potent dual M3 antagonists and PDE4 inhibitors. Various chemical modulations around that scaffold led to the discovery of ucb-101333-3 which is characterized by the
- Provins, Laurent,Christophe, Bernard,Danhaive, Pierre,Dulieu, Jacques,Durieu, Véronique,Gillard, Michel,Lebon, Florence,Lengelé, Sébastien,Quéré, Luc,Van Keulen, Berendjan
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p. 1834 - 1839
(2007/10/03)
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- CHEMICAL COMPOUNDS WITH DUAL ACTIVITY, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS
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The present invention concerns chemical compounds combining affinity and antagonism against the human m3 muscarinic receptor with activity as selective phosphodiesterase IV (PDE IV) inhibitors, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals.
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Page/Page column 31
(2008/06/13)
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- Substituted aminopyrimidines
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The present invention is directed to certain aminopyrimidines of the general formula STR1 wherein R1, R2, and R3 are hydrogen, halogen, alkoxy, alkylthio, or alkyl having 1 to 4 carbon atoms, or cycloalkyl having 3 to 5 carbon atoms and R4 is hydrogen or an aliphatic or aromatic acyl group, as well as physiologically compatible acid addition salts thereof. Compounds of the present invention are useful as blood pressure lowering agents and in the treatment of glaucoma.
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