- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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- A Dual Modulator of Farnesoid X Receptor and Soluble Epoxide Hydrolase to Counter Nonalcoholic Steatohepatitis
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Nonalcoholic steatohepatitis arising from Western diet and lifestyle is characterized by accumulation of fat in liver causing inflammation and fibrosis. It evolves as serious health burden with alarming incidence, but there is no satisfying pharmacological therapy to date. Considering the disease's multifactorial nature, modulation of multiple targets might provide superior therapeutic efficacy. In particular, farnesoid X receptor (FXR) activation that revealed antisteatotic and antifibrotic effects in clinical trials combined with inhibition of soluble epoxide hydrolase (sEH) as anti-inflammatory strategy promises synergies. To exploit this dual concept, we developed agents exerting partial FXR agonism and sEH inhibitory activity. Merging known pharmacophores and systematic exploration of the structure-activity relationship on both targets produced dual modulators with low nanomolar potency. Extensive in vitro characterization confirmed high dual efficacy in cellular context combined with low toxicity, and pilot in vivo data revealed favorable pharmacokinetics as well as engagement on both targets in vivo.
- Schmidt, Jurema,Rotter, Marco,Weiser, Tim,Wittmann, Sandra,Weizel, Lilia,Kaiser, Astrid,Heering, Jan,Goebel, Tamara,Angioni, Carlo,Wurglics, Mario,Paulke, Alexander,Geisslinger, Gerd,Kahnt, Astrid,Steinhilber, Dieter,Proschak, Ewgenij,Merk, Daniel
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supporting information
p. 7703 - 7724
(2017/10/06)
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- HETEROCYCLIC AMIDE DERIVATIVE AND MEDICINE CONTAINING SAME
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Compound represented by formula (I): wherein each symbol is as defined herein, exhibit TRPA1 antagonist activity, and are useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.
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Paragraph 0309
(2015/10/28)
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- Mild Benzylic Monobromination of Methyl Toluates in Aqueous CTAB
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A strategy has been developed for the regioselective monobromination of methyl toluates by using tert-butylhydrogen peroxide and potassium bromide (TBHP/KBr) in a cetyltrimethylammonium bromide (CTAB) micellar medium. Ultrasonic and microwave-assisted protocols recorded increased rates and product yields under mild reaction conditions, coupled with a straightforward isolation procedure.
- Reddy, Kancharla Rajendar,Rajanna, Kamatala C.,Venkateswarlu, Marri,Saiprakash
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p. 2485 - 2487
(2015/07/27)
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- Histone Deacetylase Inhibitors
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This invention relates to generally inhibiting histone deacetylase (“HDAC”) enzymes (e.g., HDAC1, HDAC2, and HDAC3).
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Paragraph 0468
(2013/12/04)
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- HISTONE DEACETYLASE INHIBITORS
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This invention relates to generally inhibiting histone deacetylase (HDAC) enzymes (e.g., HDAC1, HDAC2, and HDAC3).
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Page/Page column 97-98
(2012/09/21)
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- SMALL MOLECULE BRADYKININ B1 RECEPTOR ANTAGONISTS
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Disclosed are compounds of formula (I) which are bradykinin B1 receptor (B1R) antagonists. These compounds are useful to treat diseases or relieve adverse symptoms associated with inflammation and pain. The invention encompasses novel compounds and acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases involving inflammation and pain.
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Page/Page column 97-98
(2009/04/25)
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- Heterobiaryl human immunodeficiency virus entry inhibitors
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Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC50 values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design. 2009 American Chemical Society.
- Lu, Rong-Jian,Tucker, John A.,Pickens, Jason,Ma, You-An,Zinevitch, Tatiana,Kirichenko, Olga,Konoplev, Vitalii,Kuznetsova, Svetlana,Sviridov, Sergey,Brahmachary, Enugurthi,Khasanov, Alisher,Mikel, Charles,Yang, Yang,Liu, Changhui,Wang, Jian,Freel, Stephanie,Fisher, Shelly,Sullivan, Alana,Zhou, Jiying,Stanfield-Oakley, Sherry,Baker, Brian,Sailstad, Jeff,Greenberg, Michael,Bolognesi, Dani,Bray, Brian,Koszalka, Barney,Jeffs, Peter,Jeffries, Cynthia,Chucholowski, Alexander,Sexton, Connie
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supporting information; experimental part
p. 4481 - 4487
(2010/03/01)
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- Non-nucleoside reverse transcriptase inhibitors
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The present invention provides for compounds useful for treating an HIV infection, or preventing an HIV infection, or treating AIDS or ARC. The compounds of the invention are of formula I wherein R1, R2, R3, R4, R5a, R5b, R6a, R6b and X are as herein defined. Also disclosed in the present invention are methods of treating an HIV infection with compounds defined herein and pharmaceutical compositions containing said compounds.
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Page/Page column 39; 40
(2008/12/06)
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- Optimization of sulfonamide derivatives as highly selective EP1 receptor antagonists
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A series of 4-[(2-{isobutyl[(5-methyl-2-furyl)sulfonyl]amino}phenoxy)methyl]benzoic acids and 4-({2-[isobutyl(1,3-thiazol-2-ylsulfonyl)amino]phenoxy}methyl)benzoic acids were synthesized and evaluated for their EP receptor affinities and EP1 receptor anta
- Naganawa, Atsushi,Matsui, Toshiaki,Ima, Masaki,Yoshida, Koji,Tsuruta, Hiroshi,Yamamoto, Shingo,Yamamoto, Hiroshi,Okada, Hiroki,Maruyama, Takayuki,Nakai, Hisao,Kondo, Kigen,Toda, Masaaki
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p. 7774 - 7789
(2007/10/03)
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- HETEROCYCLIC CONDENSED COMPOUNDS USEFUL AS ANTIDIURETIC AGENTS
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The invention concerns compounds according to general formulae 1, wherein G1 is an amine. Compounds according to the invention are vasopressin V2 receptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents.
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Page/Page column 19
(2010/10/20)
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- Non-peptide oxytocin agonists
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The first non-peptide, low molecular weight agonists of the hormone oxytocin (OT) are reported. The most potent compound, 39, showed an EC 50 = 33 nM and was selective for the OT receptor. A library of compounds targeted to the vasopressin/oxytocin family of receptors was screened for activity at a cloned human oxytocin receptor using a reporter gene assay. Potency and selectivity were optimised to afford compound 39, EC50 = 33 nM. This series of compounds represents the first disclosed, non-peptide, low molecular weight agonists of the hormone oxytocin (OT).
- Pitt, Gary,Batt, Andrzej,Haigh, Robert,Penson, Andrew,Robson, Peter,Rooker, David,Tartar, André,Trim, Julie,Yea, Christopher,Roe, Michael
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p. 4585 - 4589
(2007/10/03)
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- benzamide derivatives as oxytocin agonists and vasopressin antagonists
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Novel compounds according to general formula 1, wherein G1 is NR5R6 or a fused polycyclic group that are specific OT receptor agonists and/or Via receptor antagonists. Pharmaceutical compositions comprising such compounds are useful in the treatment of, inter alia, primary dysmenorrhoea.
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- Fused azepine derivatives and their use as antidiuretic agents
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Compounds according to general formulae (1 and 2), wherein G1 is an azepine derivative and G2 is a group according to general formulae (9-11) are new. Compounds according to the invention are vasopressin V2 receptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents.
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- Bicyclic vasopressin agonists
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Compounds according to general formula (1), and pharmaceutically acceptable salts thereof, wherein V is a covalent bond or NH, X is selected from CH2, O and N-alkyl, Z is either S or —CH═CH—, R1and R2are independently sele
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Page column 10
(2010/11/30)
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- Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: Discovery, initial SAR, and molecular modeling
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The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.
- Colarusso, Stefania,Koch, Uwe,Gerlach, Benjamin,Steinkühler, Christian,De Francesco, Raffaele,Altamura, Sergio,Matassa, Victor G.,Narjes, Frank
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p. 345 - 348
(2007/10/03)
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- Condensed azepines as vasopressin agonists
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This invention provides novel compounds according to general formula (1) wherein A is a bicyclic or tricyclic azepine derivative, V1 and V2 are both H, OMe or F, or one of V1 and V2 is Br, Cl, F, OH, OMe, OBn, O
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- CONDENSED PYRAZOLE DERIVATIVES, METHOD OF MANUFACTURING THE SAME, AND ANDROGEN INHIBITOR
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This invention provides a condensed pyrazole derivative of the Formula (1): STR1 (where A denotes CH or N, R 0 and R 3 denote same or different, a hydrogen atom or a lower alkyl group, R 1 and R 2 denote same or different, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a nitro group or a halogen atom, m denotes 1 or 2, and n denotes 1, 2 or 3, provided that, when n is 2, two R 2 may be connected to each other to form a lower alkylenedioxy group), or its pharmaceutically acceptable salt. This derivative or its salt is excellent in the effect of inhibiting the expression of action of androgen, thereby being excellent in therapeutical effect of benign prostatic hypertrophy, prostatic carcinoma, etc., and has a long lasting of efficacy and high oral absorption.
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