- SULFONYL-SUBSTITUTED BICYCLIC COMPOUND WHICH ACTS AS ROR INHIBITOR
-
Provided is a sulfonyl-substituted bicyclic compound (A) which acts as a RORγ inhibitor, said compound has good RORγ inhibitory activity and is expected to be used for treating diseases mediated by a RORγ receptor in mammals.
- -
-
Paragraph 0430; 0431
(2020/08/16)
-
- Iron-Catalyzed Synthesis of Sulfur-Containing Heterocycles
-
An iron-catalyzed synthesis of sulfur- and sulfone-containing heterocycles is reported. The method is based on the cyclization of readily available substrates and proceeded with high efficiency and diastereoselectivity. A variety of sulfur-containing heterocycles bearing moieties suitable for subsequent functionalization are prepared. Illustrative examples of such postcyclization modifications are also presented.
- Bosset, Cyril,Lefebvre, Gauthier,Angibaud, Patrick,Stansfield, Ian,Meerpoel, Lieven,Berthelot, Didier,Guérinot, Amandine,Cossy, Janine
-
p. 4020 - 4036
(2017/04/27)
-
- Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions
-
A high-yielding and practical method for the synthesis of phenols from electron-deficient haloarenes and heteroarenes has been developed. The products are formed from acetohydroxamic acid as the hydroxide source via a novel SNAr reaction/Lossen rearrangement sequence. Notably, these reactions employ inexpensive and air-stable reagents, require no special handling, occur under mildly basic conditions, and form products in high yields in the presence of electrophilic and protic functionality. The utility of this methodology is demonstrated by the high-yielding hydroxylation of two base-sensitive complex substrates.
- Fier, Patrick S.,Maloney, Kevin M.
-
supporting information
p. 2244 - 2247
(2016/06/01)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
-
The present invention relates to piperidine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 68
(2009/10/01)
-
- PYRROLIDINE-2-CARBONITRILE DERIVATIVES AND THEIR USE AS INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DPP-IV)
-
The present invention relates to compounds of formula (I), (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, b-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
- -
-
Page/Page column 122
(2008/06/13)
-
- Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
-
The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, β-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
- -
-
Page/Page column 54
(2010/02/12)
-
- CALCILYTIC COMPOUNDS
-
Novel calcilytic compounds and methods of using them are provided.
- -
-
Page/Page column 7; 15
(2008/06/13)
-
- Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators
-
All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
- Kalgutkar, Amit S.,Kozak, Kevin R.,Crews, Brenda C.,Hochgesang Jr., G. Phillip,Marnett, Lawrence J.
-
p. 4800 - 4818
(2007/10/03)
-
- Adrenergic agents. III. Synthesis and adrenergic activity of some catecholamine analogs bearing a substituted sulfonyl or sulfonylalkyl group in the meta position
-
The m phenolic group of catecholamine β adrenergic agonists may be replaced by various functionalities capable of undergoing H bonding. Considerable latitude in the nature of the OH simulating group is permissible with retention of activity; however, the most extensively studied analogs are ones in which a mobile proton is attached to an O or N atom. In a search for new selective bronchodilators a series of catecholamine analogs bearing a substituted sulfonyl or sulfonylalkyl group in the meta position (i.e., groups in which the mobile H is attached to a C atom) was examined. These compounds were studied for β adrenergic agonist activity in vitro by measuring their ability to relax tracheal smooth muscle and to increase the rate of spontaneously beating right atria of guinea pigs. Adrenergic activity was influenced by the nature of the aklylene bridge between the sulfonyl and aromatic groups, branching of the ethanolamine side chain, stereochemistry, and substitution of the sulfonyl and amino groups. β Adrenergic blockade was noted for some compounds having the sulfonyl attached directly to the ring. Greatest β adrenergic agonist potency and tissue selectivity was observed with a m MeSO2CH2 substituent. One of these compounds, α [[(1,1 dimethylethyl)amino]methyl] 4 hydroxy 3 [(methylsulfonyl)methyl]benzenemethanol hydrochloride (sulfonterol hydrochloride, USAN), was studied more extensively in animals and is presently being examined for bronchodilator activity in man.
- Kaiser,Schwartz,Colella,Wardell Jr.
-
p. 674 - 683
(2007/10/06)
-