- Dual Inhibition of TAF1 and BET Bromodomains from the BI-2536 Kinase Inhibitor Scaffold
-
Recent reports have highlighted the dual bromodomains of TAF1 (TAF1(1,2)) as synergistic with BET inhibition in cellular cancer models, engendering interest in TAF/BET polypharmacology. Here, we examine structure activity relationships within the BI-2536 PLK1 kinase inhibitor scaffold, previously reported to bind BRD4. We examine binding by this ligand to TAF1(2) and apply structure guided design strategies to discriminate binding to both the PLK1 kinase and BRD4(1) bromodomain while retaining activity on TAF1(2). Through this effort we discover potent dual inhibitors of TAF1(2)/BRD4(1), as well as biased derivatives showing marked TAF1 selectivity. We resolve X-ray crystallographic data sets to examine the mechanisms of the observed TAF1 selectivity and to provide a resource for further development of this scaffold.
- Remillard, David,Buckley, Dennis L.,Seo, Hyuk-Soo,Ferguson, Fleur M.,Dhe-Paganon, Sirano,Bradner, James E.,Gray, Nathanael S.
-
supporting information
p. 1443 - 1449
(2019/10/11)
-
- BRD4-KINASE INHIBITORS AS CANCER THERAPEUTICS
-
Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I through IV.
- -
-
Page/Page column 232-233; 234
(2017/05/02)
-
- Visible-light-mediated, nitrogen-centered radical amination of tertiary alkyl halides under metal-free conditions to form α-tertiary amines
-
A mild and operationally convenient amino-functionalization of a range of tertiary alkyl halides by reaction with iminoiodinanes (PhINNs) and I2 has been developed. According to the mechanistic experiments described within, the reaction is spec
- Brueckner, Alexander C.,Hancock, Erin N.,Anders, Evan J.,Tierney, Matthew M.,Morgan, Heather R.,Scott, Kristina A.,Lamar, Angus A.
-
supporting information
p. 4387 - 4392
(2016/06/06)
-
- POTENT DUAL BRD4-KINASE INHIBITORS AS CANCER THERAPEUTICS
-
Disclosed herein are compounds that are inhibitors of BRD4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BRD4 are also disclosed. In certain aspects, disclosed are compounds of Formula I-IV.
- -
-
Page/Page column 122; 123
(2016/04/26)
-
- SNAAP sulfonimidate alkylating agent for acids, alcohols, and phenols 1
-
Stable, crystalline ethyl N-tert-butyl-4-nitrobenzenesulfonimidate has been prepared in high yield by direct O-ethylation of N-tert-butyl-4- nitrobenzenesulfonamide with iodoethane and silver(I) oxide in dichloromethane. This sulfonimidate directly ethylates various acids to esters; the stronger the acid, the faster it alkylates and in higher yield. It readily ethylates alcohols and phenols to ethers at room temperature in the presence of tetrafluoroboric acid catalyst without molecular rearrangements or racemization. We have defined these reactions as SNAAP alkylations: [substitution, nucleophilic of acids, alcohols and phenols]. The hard sulfonimidate alkylating agent is chemoselective, preferring oxygen > nitrogen > sulfur. The sulfonamide byproduct of alkylation is readily recycled to the sulfonimidate. Georg Thieme Verlag Stuttgart . New York.
- Maricich, Tom J.,Allan, Matthew J.,Kislin, Brett S.,Chen, Andrea I-T.,Meng, Fan-Chun,Bradford, Christine,Kuan, Nai-Chia,Wood, Jeremy,Aisagbonhi, Omonigho,Poste, Alethea,Wride, Dustin,Kim, Sylvia,Santos, Therese,Fimbres, Michael,Choi, Dianne,Elia, Haydi,Kaladjian, Joseph,Abou-Zahr, Ali,Mejia, Arturo
-
p. 3361 - 3368
(2014/01/06)
-
- Hepatitis C Virus Inhibitors
-
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
- -
-
Page/Page column 103-105
(2008/12/05)
-
- METHOD OF PREPARING 4-(IMIDAZOLE-1-IL)BENZENESULPHONAMIDE DERIVATIVES
-
Process for the preparation of 4-(imidazol-1-yl)benzenesulfonamide derivatives of formula I, wherein R1 represents optionally substituted aryl or heteroaryl, which comprises treating a compound of formula II, wherein R1 has the same
- -
-
-
- Phosphonamidic-Sulfonic Mixed Anhydrides: Possible Initial Products in the Base-induced Rearrangement Reactions of N-Phosphinoyl-O-sulfonylhydroxylamines
-
In PriNH2-ButNH2 competition experiments the behaviour of the two phosphonamidic-sulfonic mixed anhydrides 2 and 7 resembles that of the corresponding hydroxylamine derivatives 1 and 6.
- Harger, Martin J. P.
-
p. 110 - 111
(2007/10/03)
-