- SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
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The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 581
(2018/01/20)
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- PHENYL AMINO PYRIMIDINE BICYCLIC COMPOUNDS AND USES THEREOF
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The present invention relates to phenyl amino pyrimidine bicyclic compounds formula (I) which are inhibitors of protein kinases including JAK kinases. In particular the compounds are active against JAK1, JAK2, JAK3 and TYK2 kinases. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.
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Page/Page column 51; 52
(2014/01/17)
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- BRUTON'S TYROSINE KINASE INHIBITORS
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Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)
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Page/Page column 82
(2014/05/24)
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- 5-HYDROXYMETHYL-OXAZOLIDIN-2-ONE-DERIVATIVES AND THEIR USES AS ANTIBACTERIALS
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The invention relates to novel chimeric antibiotics of formula I wherein R1 represents OH, OPO3H2 or OCOR5; R2 represents H, OH or OPO3H2; A represents N or CR6; Rsup
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Page/Page column 14
(2009/10/06)
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- 5-HYDROXYMETHYL-OXAZOLIDIN-2-ONE DERIVATIVES
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The invention relates to novel chimeric antibiotics of formula (I) wherein R1 represents OH, OPO3H2 or OCOR5; R2 represents H, OH or OPO3H2; A represents N or CR6; Rs
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Page/Page column 34
(2008/12/05)
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- Synthesis and in-vitro activity of new 1β-methylcarbapenem derivatives as antibacterial agents
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The synthesis of a new series of 1β-methylcarbapenems having pyrrolidine and piperidine moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. A particular compound III b having an oxime-pyrrolidine moiety showed the most potent antibacterial activity.
- Jung, Myung-Ho,Joon, Hee Hong,Cho, Jung-Hyuck,Oh, Chang-Hyun
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scheme or table
p. 780 - 786
(2009/04/07)
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- Poly(vinyl alcohol)-graft-poly(ethylene glycol) resins and their use in solid-phase synthesis and supported TEMPO catalysis
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New poly(vinyl alcohol)-graft-poly(ethylene glycol) (PVA-g-PEG) resins with various PEG chain lengths, which have high loadings and good swelling both in water and organic solvents, have been prepared via an anionic polymerization of ethylene oxide onto PVA beads and applied in solid-phase synthesis, supported TEMPO catalysis and in HR-MAS 1H NMR spectral analysis. The Royal Society of Chemistry.
- Luo, Juntao,Pardin, Christophe,Lubell, William D.,Zhu
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p. 2136 - 2138
(2008/02/09)
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- HETEROCYCLIC CETP INHIBITORS
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Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.
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Page/Page column 126
(2010/11/27)
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- Synthesis and biological studies of novel 2-aminoalkylethers as potential antiarrhythmic agents for the conversion of atrial fibrillation
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A series of 2-aminoalkylethers prepared as potential antiarrhythmic agents is described. The present compounds are mixed sodium and potassium ion channel blockers and exhibit antiarrhythmic activity in a rat model of ischemia-induced arrhythmias. Structure-activity studies led to the identification of three compounds 5, 18, and 26, which were selected based on their particular in vivo electrophysiological properties, for studies in two canine atrial fibrillation (AF) models. The three compounds converted AF in both models, but only compound 26 was shown to be orally bioavailable. Resolution of the racemate 26 into its corresponding enantiomers 40 and 41 and subsequent biological testing of these enantiomers led to the selection of (1S,2S)-1-(1-naphthalenethoxy)-2-(3- ketopyrrolidinyl)cyclohexane monohydrochloride (41) as a potential atrial selective antiarrhythmic candidate for further development.
- Plouvier, Bertrand,Beatch, Gregory N.,Jung, Grace L.,Zolotoy, Alexander,Sheng, Tao,Clohs, Lilian,Barrett, Terrance D.,Fedida, David,Wang, Wei Q.,Zhu, Jeff J.,Liu, Yuzhong,Abraham, Shlomo,Lynn, Leah,Dong, Ying,Wall, Richard A.,Walker, Michael J. A.
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p. 2818 - 2841
(2008/02/09)
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- SUBSTITUTED AZACYCLOALKANES USEFUL FOR TREATING CNS CONDITIONS
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The invention relates to substituted azacycloalkaπe compounds useful in treating conditions of the Central Nervous System (CNS); a pharmaceutical composition comprising same; a method of treating such conditions and of treating conditions in which inhibition of beta-secretase is indicated.
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Page/Page column 71
(2008/06/13)
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- FUSED BENZENE DERIVATIVE AND USE
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The present invention provides a compound represented by the general formula: [wherein Ring A represents an optionally substituted 5- to 8-membered ring, Ring B represents a further optionally substituted 4- to 10-membered ring, Ring C represents a further optionally substituted benzene ring, X1 represents carbon atom, X2 represents a carbon atom, an oxygen atom, etc., W represents a nitrogen atom, etc., Y11 represents a group represented by the formula CR2R3' (wherein R2 represents a hydrogen atom, a cyano group, a nitro group, etc., and R3' represents a hydrogen atom, a cyano group, a nitro group, etc., respectively), Y21 represents a group represented by the formula CR4R5' (wherein R4 represents a hydrogen atom, a cyano group, a nitro group, etc., and R5' represents a hydrogen atom, a cyano group, a nitro group, etc., respectively), etc., and R1 represents an electron-withdrawing group, respectively. The formula represents a single bond or a double bond] or a salt thereof, which is useful as an androgen receptor modulator.
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Page/Page column 51
(2010/02/12)
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- CYCLOHEXYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel cyclohexylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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- 1,2,4-OXADIAZOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel 1,2,4-oxadiazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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- FUSED PHENYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to fused phenylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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- AMINOCYCLOHEXYL ETHER COMPOUNDS AND USES THEREOF
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Aminocyclohexyl ether compounds of formula (I), or a solvate or pharmaceutically acceptable salt thereof: are disclosed. In said formula, A, X and R, -R5 have the meanings given in the description. The compounds of the present invention may be inco
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- PHENYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to phenylalanine derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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- Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors
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Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.
- Caldwell, Charles G.,Chen, Ping,He, Jiafang,Parmee, Emma R.,Leiting, Barbara,Marsilio, Frank,Patel, Reshma A.,Wu, Joseph K.,Eiermann, George J.,Petrov, Aleksandr,He, Huaibing,Lyons, Kathryn A.,Thornberry, Nancy A.,Weber, Ann E.
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p. 1265 - 1268
(2007/10/03)
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- Compounds useful as reversible inhibitors of cysteine proteases
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Disclosed are novel cathepsin S, K, F, L and B reversible inhibitory compounds of the formulas (I), (II), (Ia) and (Ib) further defined herein. The compounds are useful for treating autoimmune diseases. Also disclosed are processes for making such novel compounds.
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- Heterocyclic spiro-derivative
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The present invention provides an antibacterial compound useful as medicines, animal drugs, fisheries drugs or antibacterial preservatives and to an antibacterial agent or preparation which contains the same, more particularly a compound which possesses h
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- Heterocycyclic piperidines as modulators of chemokine receptor activity
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The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
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- Intramolecular N-H insertion of α-diazocarbonyls catalyzed by Cu(acac)2: An efficient route to derivatives of 3-oxoazetidines, 3-oxopyrrolidines and 3-oxopiperidines
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Cu(acac)2 was found to be an efficient catalyst for the intramolecular N-H insertion by carbenoids. The competitive intramolecular C-H insertion by carbenoids is not a problem in the diazo decomposition reaction with Cu(acac)2 as catalyst. The reaction provided derivatives of 3-oxoazetidine, 3-oxopyrrolidine and 3-oxopiperidine in moderate to good yields.
- Wang, Jianbo,Hou, Yihua,Wu, Peng
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p. 2277 - 2280
(2007/10/03)
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- TRIAZOLO-1,4-DIAZEPINE DERIVATIVES AND THEIR USE IN PHARMACEUTICALS
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A triazolo-1,4-di-azepine compound of the below given formulas and a pharmacologically acceptable salt thereof are disclosed and useful in the pharmaceutical field, especially to allergic diseases. STR1 in which R1 and R2 are hydrogen or an alkyl, R3 is hydrogen or a halogen, R4 is hydrogen or an alkyl, X is--OCO--,--NHCO--,--CO--or others and Y is a cycloalkyl, a cycloalkylalkyl, an alkynyl or others.
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- Preparation and in Vitro and in Vivo Evaluation of Quinolones with Selective Activity against Gram-Positive Organisms
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A series of quinolones were prepared which contained oximes or substituted oximes as replacements for the amine substituents normally found on the pyrrolidine or piperidine fragments of quinolone antibacterial agents.These substituents led to compounds that had selective activity against Gram-positive organisms.These compounds showed in vivo activity Staphylococcus aureus.Only compound 29 had in vivo activity against Streptococcus pneumoniae.
- Cooper, Curt S.,Klock, Pamela L.,Chu, Daniel T. W.,Hardy, Dwight J.,Swanson, Robert N.,Plattner, Jacob J.
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p. 1393 - 1398
(2007/10/02)
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