- Development of a scaleable synthesis of NDT 9533750, a key intermediate to a series of novel subtype preferring GABAA partial agonists
-
A scaleable route to 6-chloro-4-[2-(3-fluoropyridin-2-yl)-imidazol-1- ylmethyl]-5-propyl-pyrimidine (NDT 9S33750), a key intermediate to a series of novel subtype preferring GABAA partial agonists, is described in which various scaleup issues were addressed to provide an efficient and robust route for the preparation of kilogram quantities of the compound.
- Xu, Yuelian,Han, Bingsong,Wang, Zhe-Qing,Shaw, Kenneth R.,Chenard, Bertrand L.,Maynard, George,Xie, Linghong
-
-
Read Online
- METHODS OF USING RAD51 INHIBITORS FOR TREATMENT OF PANCREATIC CANCER
-
This application is directed to inhibitors of RAD51 represented by the following structural formula, and methods for their use, such as to treat pancreatic cancer.
- -
-
Paragraph 1155-1157
(2021/01/22)
-
- RAD51 Inhibitors
-
This application is directed to inhibitors of RAD51 represented by the following structural formula, and methods for their use, such as to treat cancer, autoimmune diseases, immune deficiencies, or neurodegenerative diseases.
- -
-
Paragraph 0454-0455
(2019/03/30)
-
- A Bifunctional Reagent Designed for the Mild, Nucleophilic Functionalization of Pyridines
-
Herein is reported the design and application of a reagent for the direct functionalization of pyridines. These reactions occur under mild conditions and exhibit broad functional group tolerance, enabling the late-stage functionalization of drug-like molecules. The reagent can be easily prepared on large scale from inexpensive reagents, and reacts in the title reaction with acetonitrile, sodium chloride, and sodium methanesulfonate as the sole byproducts. Although this Communication focuses primarily on reactions with cyanide as nucleophile, preliminary experiments with other nucleophiles foreshadow the broad reaching synthetic utility of this approach.
- Fier, Patrick S.
-
supporting information
p. 9499 - 9502
(2017/07/24)
-
- CYANOPYRROLIDINES AS DUB INHIBITORS FOR THE TREATMENT OF CANCER
-
The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C- terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of cancer and conditions involving mitochondrial dysfunction. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1,R2,R3,R4,R5,R6,R7,R8 and R9 are as defined herein.
- -
-
Page/Page column 85
(2017/02/09)
-
- Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy
-
Nrf2 activators represent a good drug target for designing agents to treat diseases associated with oxidative stress. Building upon previous work, we designed and prepared a series of heterocyclic chalcone-based Nrf2 activators with reduced lipophilicity
- Lounsbury, Nicole,Mateo, George,Jones, Brielle,Papaiahgari, Srinivas,Thimmulappa, Rajash K.,Teijaro, Christiana,Gordon, John,Korzekwa, Kenneth,Ye, Min,Allaway, Graham,Abou-Gharbia, Magid,Biswal, Shyam,Childers, Wayne
-
supporting information
p. 5352 - 5359
(2015/11/11)
-
- FUNCTIONALIZED HETROARYL ENONES EXHIBITING NRF2 ACTIVATION AND THEIR METHOD OF USE
-
Pharmaceutical compositions are disclosed, which include functionalized hetroaryl enones and are useful for treating or preventing a disease, disorder or condition associated with an NRF2-regulated pathway and/or which involves oxidative stress.
- -
-
Paragraph 0205
(2016/01/22)
-
- Copper-catalyzed cyanation of heterocycle carbon-hydrogen bonds
-
A method for regioselective cyanation of heterocycles has been developed. A number of aromatic heterocycles as well as azulene can be cyanated in reasonable to good yields by using a copper cyanide catalyst and an iodine oxidant.
- Do, Hien-Quang,Daugulis, Olafs
-
supporting information; experimental part
p. 2517 - 2519
(2010/08/07)
-
- Tetrabutylammonium salt induced denitration of nitropyridines: Synthesis of fluoro-, hydroxy-, and methoxypyridines
-
(Chemical Equation Presented) An efficient method for the synthesis of fluoropyridines via the fluorodenitration reaction is reported. The reaction is mediated by tetrabutylammonium fluoride (TBAF) under mild conditions without undue regard to the presence of water. The fluorodenitration is general for 2- or 4-nitro-substituted pyridines, while 3-nitropyridines require attendant electron-withdrawing groups for the reaction to proceed efficiently. Nitropyridines also undergo hydroxy- and methoxydenitration under mild conditions in the presence of the corresponding tetrabutylammonium species.
- Kuduk, Scott D.,DiPardo, Robert M.,Bock, Mark G.
-
p. 577 - 579
(2007/10/03)
-
- Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function
-
Fused cyclic compounds, methods of using such compounds in the treatment of nuclear hormone receptor-associated conditions such as cancer and immune disorders, and pharmaceutical compositions containing such compounds.
- -
-
-
- Calcilytic compounds
-
Novel calcilytic compounds and methods of using them are provided.
- -
-
-
- Site-Selectivity in the Cyanation of 3-Substituted Pyridine 1-Oxides with Trimethylsilanecarbonitrile
-
The cyanation of 3-halo-, 3-methoxy-, and 3-dimethylaminopyridine 1-oxide with trimethylsilanecarbonitrile gave predominantly the corresponding 3-substituted 2-pyridinecarbonitriles.The deoxygenation of nitropyridine 1-oxides to nitropyridines with the same reagent is also described.Keywords - site-selective reaction; trimethylsilanecarbonitrile; pyridine 1-oxide; 2-pyridine-carbonitrile; nitropyridine 1-oxide; deoxygenation; aromatic amine N-oxide; cyanation
- Sakamoto, Takao,Kaneda, Soh-ichi,Nishimura, Sumiko,Yamanaka, Hiroshi
-
p. 565 - 571
(2007/10/02)
-
- REGIOSELECTIVE CYANATION OF 3-SUBSTITUTED PYRIDINE 1-OXIDES
-
Cyanation of 3-X-pyridine 1-oxides with trimethylsilanecarbonitrile and dimethylcarbamoyl chloride occurs quantitatively to give 3-X-pyridinecarbonitriles in > 90percent isolated yields when X = -CH3, -OCH3, -OH and -Cl, and approximately equal amounts of the 3- and 5-X derivatives when X = -CN and -COOCH3.
- Fife, Wilmer K.
-
-