- PRMT5 INHIBITORS AND USES THEREOF
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Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
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Paragraph 0298-0299
(2019/04/05)
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- PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
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Paragraph 00288
(2014/07/08)
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- A novel organic electron donor derived from N-methylisatin
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We report the reactivity of an electron donor derived from N-methylisatin on reduction by sodium amalgam. Transfer of a clear supernatant solution to iodoarenes affords the products of two-electron reduction. Reductions of sulfones, activated arenesulfonamides, and Weinreb amides are also reported.
- Sword, Ryan,O'Sullivan, Steven,Murphy, John A.
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p. 314 - 322
(2013/05/08)
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- NOVEL AMIDE AND AMIDINE DERIVATIVES AND USES THEREOF
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The present invention relates to inhibitors of 11-β-hydroxysteroid dehydrogenase type 1 enzyme and their use in treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, central nervous system disorders, and diseases and conditions that are related to excessive glucocorticoids.
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Page/Page column 35
(2010/11/03)
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- Stereospecific synthesis and bio-activity of novel β3-adrenoceptor agonists and inverse agonists
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Since it is widely distributed into the body, β3-adrenoceptor is becoming an attractive target for the treatment of several pathologies such as obesity, type 2 diabetes, metabolic syndrome, cachexia, overactive bladder, ulcero-inflammatory disorder of the gut, preterm labour, anxiety and depressive disorders, and heart failure. New compounds belonging to the class of arylethanolamines bearing one or two stereogenic centres were prepared in good yields as racemates and optically active forms. They were, then, evaluated for their intrinsic activity towards β3-adrenoceptor and their affinity for β1- and β2-adrenergic receptors. Stereochemical features were found to play a crucial role in determining the behaviour of such compounds. In particular, α-racemic, (αR)- and (αS)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}-2- methylpropanoic acid, (α-rac, β-rac)-, (αR, βS)- and (αR, βR)- 2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid were found to be endowed with β3-adrenoceptor agonistic activity. Whereas, (αS, βS)- and (αS, βR)-2-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenoxy}propanoic acid behaved as β3-adrenoceptor inverse agonists. Such compounds showed no affinity for β1- and β2-adrenergic receptor, respectively. Thus, resulting highly selective β3-adrenoceptor ligands.
- Perrone, Maria Grazia,Santandrea, Ernesto,Bleve, Laura,Vitale, Paola,Colabufo, Nicola Antonio,Jockers, Ralf,Milazzo, Ferdinando Maria,Sciarroni, Anna Floriana,Scilimati, Antonio
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p. 2473 - 2488
(2008/09/21)
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- One-pot reduction of aryl iodides using 4-DMAP methiodide salt
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An efficient one-pot procedure is described for the reduction of aryl iodides to aryl anions using a structurally simple bis-pyridinylidene electron donor, prepared in situ by treating 4-DMAP methiodide salt with base. The results show (i) that pyridinylidene carbenes can be easily used for intermolecular C-C bond formation, (ii) that bis-pyridinylidenes demonstrate superior robustness compared to electron-donor systems based on bis-imidazolylidenes, and (iii) that electron-donor strength is enhanced in the simplified DMAP-based donor. Deuterated analogues of this donor also provide mechanistic information on the source of protons when the aryl anions are quenched in situ. Georg Thieme Verlag Stuttgart.
- Garnier, Jean,Murphy, John A.,Zhou, Sheng-Ze,Turner, Andrew T.
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scheme or table
p. 2127 - 2131
(2009/05/07)
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- Super-electron donors: Bis-pyridinylidene formation by base treatment of pyridinium salts
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Deprotonation of bispyridinium salt 7b affords bispyridinylidene 10, a very powerful neutral organic two-electron donor [E1/2 (DMF) = -1.13 V vs Ag/AgCI/KCI (sat)], presumably via the pyridinylidene 8. Donor 10 reduces aryl iodides and bromides to aryl anions in excellent yield and also reductively cleaves selected phenylalkylsulfones very efficiently.
- Murphy, John A.,Gamier, Jean,Park, Stuart R.,Schoenebeck, Franziska,Zhou, Sheng-Ze,Turner, Andrew T.
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supporting information; experimental part
p. 1227 - 1230
(2009/04/06)
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- The generation of aryl anions by double electron transfer to aryl iodides from a neutral ground-state organic super-electron donor
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(Chemical Equation Presented) It takes two to cyclize: Aryl halides are reduced to aryl anions by double electron transfer from the neutral ground-state electron donor 1 (see scheme), as shown by the formation of a cyclic ketone (2). The reduced compound (3) is also formed. Calculations show that the loss of two electrons from 1 is both thermodynamically and kinetically viable and generates a more planar resonance-stabilized structure.
- Murphy, John A.,Zhou, Sheng-Ze,Thomson, Douglas W.,Schoenebeck, Franziska,Mahesh, Mohan,Park, Stuart R.,Tuttle, Tell,Berlouis, Leonard E. A.
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p. 5178 - 5183
(2008/03/27)
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- Amido compounds and their use as pharmaceuticals
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The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1, antagonists of the mineralocorticoid receptor (MR), and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1 and/or diseases associated with aldosterone excess.
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Page/Page column 43
(2010/02/15)
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- Copper(II)-catalyzed O-phenylation of tertiary alcohols with organobismuth(V) reagents
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A new method for the Cu(OAc)2-catalyzed phenylation of tertiary alcohols under mild basic conditions is described. Triphenylbismuth(V) diacetate and tetraphenylbismuth reagents undergo cross-coupling reactions with α-hydroxycarbonyl compouds efficiently. For non-chelating tertiary alcohols, tetraphenylbismuth fluoride is found suitable as a phenyl donor. Copyright
- Ikegai, Kazuhiro,Fukumoto, Kentarou,Mukaiyama, Teruaki
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p. 612 - 613
(2007/10/03)
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- Pd/C-Et3N-mediated catalytic hydrodechlorination of aromatic chlorides under mild conditions
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A mild and efficient one-pot procedure for the hydrodechlorination of aromatic chlorides using a Pd/C-Et3N system was developed. A variety of aromatic chlorides could be dechlorinated at room temperature and under ambient hydrogen pressure. Et3N activates the catalysis and is likely to work as a single electron donor in this system.
- Monguchi, Yasunari,Kume, Akira,Hattori, Kazuyuki,Maegawa, Tomohiro,Sajiki, Hironao
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p. 7926 - 7933
(2007/10/03)
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- PARA-SULFONYL SUBSTITUTED PHENYL COMPOUNDS AS MODULATORS OF PPARS
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Compounds as modulators of peroxisome proliferator activated receptors, pharmaceutical compositions comprising the same, and methods of treating disease using the same are disclosed.
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- Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors
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The present invention provides a compound of formula (1) wherein R1-R5, R25, R26, Y and X2 are defined as in claim 1. The compounds activate human peroxisome proliferator activated receptors (hPPARs) and arc useful for the treatment of associated disorders such as cardiovascular disease and hypercholesteremia.
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- Mild and general procedure for Pd/C-catalyzed hydrodechlorination of aromatic chlorides
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A mild and efficient one-pot hydrodechlorination using a Pd/C-Et3N system proceeds at room temperature, which is general for the dechlorination of a variety of aromatic chlorides.
- Sajiki, Hironao,Kume, Akira,Hattori, Kazuyuki,Hirota, Kosaku
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p. 7247 - 7250
(2007/10/03)
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- Beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acid.
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In a search for novel analogues of beta(3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective beta(3)-AR agonist in functional assays using the ferret detrusor (beta(3)-AR), rat uterus (beta(2)-AR), and rat atrium (beta(1)-AR); beta(3): EC(50)=7.8 nM, beta(2): IC(50)=7,300 nM, beta(1): EC(20)=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved beta(3)-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED(50)=31 microg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b-e), possess beta(3)-AR agonistic activity in the absence of undesirable beta(1)- or beta(2)-AR mediated actions, and may be useful for clinical treatment and pharmacological studies.
- Tanaka,Tamai,Mukaiyama,Hirabayashi,Muranaka,Ishikawa,Akahane,Akahane
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p. 3265 - 3271
(2007/10/03)
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- Treatment of skin conditions by use of PPAR alpha activators
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Disorders of the skin and mucous membrane that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor alpha , and oxysterol activators of the LXR alpha receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.
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