- BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
- -
-
Paragraph 1550-1551
(2019/10/23)
-
- Stereoselective amination of racemic sec-alcohols through sequential application of laccases and transaminases
-
A one-pot/two-step bienzymatic asymmetric amination of secondary alcohols is disclosed. The approach is based on a sequential strategy involving the use of a laccase/TEMPO catalytic system for the oxidation of alcohols into ketone intermediates, and their following transformation into optically enriched amines by using transaminases. Individual optimizations of the oxidation and biotransamination reactions have been carried out, studying later their applicability in a concurrent process. Therefore, 17 racemic (hetero) aromatic sec-alcohols with different substitutions in the aromatic ring have been converted into enantioenriched amines with good to excellent selectivities (90-99% ee) and conversion values (67-99%). The scalability of the process was also demonstrated when two different amine donors were used in the transamination step, such as isopropylamine and cis-2-buten-1,4-diamine. Satisfyingly, both sacrificial amine donors can shift the equilibrium toward the amine formation, leading to the corresponding isolated enantioenriched amines with good to excellent results.
- Martínez-Montero, Lía,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
-
p. 474 - 480
(2017/06/23)
-
- Trading N and O. Part 3: Synthesis of 1,2,3,4-tetrahydroisoquinolines from α-hydroxy-β-amino esters
-
A range of enantiopure 1,2,3,4-tetrahydroisoquinolines have been prepared directly from α-hydroxy-β-amino esters. Activation of the α-hydroxy group upon treatment with Tf2O and 2,6-di-tert-butyl-4-methylpyridine promotes aziridinium formation,
- Davies, Stephen G.,Fletcher, Ai M.,Frost, Aileen B.,Kennedy, Matthew S.,Roberts, Paul M.,Thomson, James E.
-
p. 2139 - 2163
(2016/04/09)
-
- N-BIPHENYLMETHYLINDOLE MODULATORS OF PPARG
-
The invention provides molecular entities that bind with high affinity to PPARG (PPAR3), inhibit kinase-mediated, e.g., cdk5-mediated, phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. In methods of treatment of these conditions using a compound of the invention, the compound can avoid producing side effects of significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, in the patient receiving the compound. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.
- -
-
Page/Page column 185
(2012/12/14)
-
- α-Methylation at benzylic fragment of N-aryl-N′-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model
-
SAR studies for N-aryl-N′-benzyl urea class of TRPV1 antagonists have been extended to cover α-benzyl alkylation. Alkylated compounds showed weaker in vitro potencies in blocking capsaicin activation of TRPV1 receptor, but possessed improved pharmacokinetic properties. Further structural manipulations that included replacement of isoquinoline core with indazole and isolation of single enantiomer led to TRPV1 antagonists like (R)-16a with superior pharmacokinetic properties and greater potency in animal model of inflammatory pain.
- Gomtsyan, Arthur,Bayburt, Erol K.,Keddy, Ryan,Turner, Sean C.,Jinkerson, Tammie K.,Didomenico, Stanley,Perner, Richard J.,Koenig, John R.,Drizin, Irene,McDonald, Heath A.,Surowy, Carol S.,Honore, Prisca,Mikusa, Joe,Marsh, Kennan C.,Wetter, Jill M.,Faltynek, Connie R.,Lee, Chih-Hung
-
p. 3894 - 3899
(2008/02/09)
-
- Process for producing optically active 1-(fluoro- or trifluoromethyl-substituted phenyl) ethylamine and process for purifying same
-
An optically active 1-(fluoro- or trifluoromethyl-substituted phenyl)ethylamine is produced with high optical purity and in an industrially simple and efficient manner by asymmetrically reducing an optically active imine, obtained by dehydration and conde
- -
-
Page column 25
(2008/06/13)
-
- Highly regioselective hydrogenolysis of bis(α-methylbenzyl)amine derivatives affected by the trifluoromethyl substituent on the aromatic ring
-
(Matrix presented) The highly regioselective hydrogenolysis of bis(α-methylbenzyl)amine derivatives proceeded with influence not from the electronic effect but from the steric effect of the trifluoromethyl substituent on the aromatic ring to provide a practical asymmetric synthesis of trifluoromethyl-substituted α-phenylethylamines.
- Kanai, Masatomi,Yasumoto, Manabu,Kuriyama, Yokusu,Inomiya, Kenjin,Katsuhara, Yutaka,Higashiyama, Kimio,Ishii, Akihiro
-
p. 1007 - 1010
(2007/10/03)
-
- Optically Active Amines. 31. Spectral Observations on the Substituted Benzene Chromophore
-
Examination of the isotropic absorption and circular dichroism spectra of para-substituted and 3,5-disubstituted α-phenyl- and α-benzylethylamines and their hydrochlorides indicates that the sign of 1Lb Cotton effects (CEs) of the be
- Smith, Howard E.,Neergaard, Jon R.,Paulis, Tomas de,Chen, Fu-Ming
-
p. 1578 - 1584
(2007/10/02)
-
