- SUBSTITUTED SULFONYL HYDRAZIDES AS INHIBITORS OF LYSINE BIOSYNTHESIS VIA THE DIAMINOPIMELATE PATHWAY
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The present invention relates to substituted sulfonyl hydrazides that have the ability to inhibit lysine biosynthesis via the diaminopimelate pathway in certain organisms. As a result of this activity these compounds can be used in applications where inhibition of lysine biosynthesis is useful applications of this type include the use of the compound as herbicides and/or anti- bacterial agents.
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Paragraph 0213
(2020/01/24)
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- 5-LIPOXYGENASE INHIBITORS
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The present invention relates to pyrazole derivatives of formula 1 and to process as for their synthesis as 5-lipoxygenase (5-LO) inhibitors. The present invention also relates to pharmacological compositions containing these pyrazole derivatives, as well as, methods of treating bronchial asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple sclerosis, Type I diabetes, psoriasis, allograft rejection, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, cancer, pruritis, allergic rhinitis and other inflammatory and/or autoimmune disorders.
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Page/Page column 58
(2012/01/13)
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- SEPIAPTERIN REDUCTASE INHIBITORS FOR THE TREATMENT OF PAIN
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Disclosed herein are small molecule heterocyclic inhibitors of sepiapterin reductase (SPR), and pro-drugs and pharmaceutically acceptable salts thereof. The Also featured are pharmaceutical compositions of the compounds and uses of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, and neuropathic pain)
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Page/Page column 77
(2011/05/05)
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- Discovery of (3 S,3a R)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5- tetrahydro-2 H -benzo[ g ]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy
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We have discovered a novel class of nonsteroidal pyrazoline antagonists of the mineralocorticoid receptor (MR) that show excellent potency and selectivity against other nuclear receptors. Early analogues were poorly soluble and had a propensity to inhibit the hERG channel. Remarkably, both of these challenges were overcome by incorporation of a single carboxylate moiety. Structural modification of carboxylate-containing lead R-4g with a wide range of substituents at each position of the pyrazoline ring resulted in R-12o, which shows excellent activity against MR and reasonable pharmacokinetic profile. Introduction of conformational restriction led to a novel series characterized by exquisite potency and favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection. As a result of these findings, 3S,3aR-27d was advanced to clinical studies.
- Meyers, Marvin J.,Arhancet, Graciela B.,Hockerman, Susan L.,Chen, Xiangyang,Long, Scott A.,Mahoney, Matthew W.,Rico, Joseph R.,Garland, Danny J.,Blinn, James. R.,Collins, Joe T.,Yang, Shengtian,Huang, Horng-Chih,McGee, Kevin F.,Wendling, Jay M.,Dietz, Jessica D.,Payne, Maria A.,Homer, Bruce L.,Heron, Marcia I.,Reitz, David B.,Hu, Xiao
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experimental part
p. 5979 - 6002
(2010/11/02)
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- Methods and Compositions for Modulating P300/CBP Activity
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The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.
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Page/Page column 19
(2010/09/05)
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- Pyridoindolone derivatives substituted in the 3-position by a phenyl, their preparation and their application in therapeutics
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The present invention relates to pyridoindolone derivatives substituted in the 3-position by a phenyl of general formula (I): to processes for preparing the same and to their use in therapeutics.
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Page/Page column 7
(2010/02/15)
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- PYRAZOLIDINEDIONE DERIVATIVES AND THEIR USE AS PLATELET AGGREGATION INHIBITORS
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Pyrazolidinedione derivatives of the general formula (I), wherein R1 is hydrogen, optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; and R2 is aryl or heteroaryl; tautomers thereof; geometric is
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- Synthesis of [3-[2-(dimethylamino)ethyl]-2-[[3-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-1H-indol-5-yl]-N-methylmethanesulfonamide - The main sumatriptane impurity
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Alkylation of sumatriptane in position 2 by 3-[2-(dimethylamino)ethyl]-5-indolemethanol has been described. Alternative multistep synthesis of 3-[2-(dimethylamino)ethyl]-5-indolemethanol has been presented.
- Skwierawska,Paluszkiewicz
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p. 329 - 332
(2007/10/03)
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- Process for producing 3-anilino-5-pyrazolones
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A process for producing a 3-anilino-5-pyrazolone which comprises reacting a β-anilino-β-alkoxy-acrylate with a hydrazine in the presence of a compound having a pKa of about 8 up to about 14.
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