- IMMUNOPROTEASOME INHIBITORS
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Provided herein are compounds, such as a compound of Formula (I), or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Paragraph 0420; 0441
(2019/06/13)
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- IMMUNOPROTEASOME INHIBITORS
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Provided herein are compounds, such as a compound of Formula (I), as described herein, or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Paragraph 0213
(2018/08/20)
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- TYROSINE KINASE INHIBITORS
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The present disclosure provides compounds of formula (I) that are tyrosine kinase inhibitors, in particular Bruton tyrosine kinase ("BTK") inhibitors, and are therefore useful for the treatment of diseases treatable by inhibition of BTK such as cancer, au
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Page/Page column 75
(2017/04/19)
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- SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
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Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.
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Paragraph 0250; 0251
(2014/09/30)
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- PYRAZOLOPYRIMIDINE COMPOUNDS AS KINASE INHIBITORS
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The present disclosure provides compounds of Formula (LA) and/ or pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BTK, and are potentially useful for the treatment of diseases treatable by inhibition of ty r-osine kinases such as cancer, inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and/or pharmaceutically acceptable salts thereof and processes for preparing such compounds and p h ar-maceutically acceptable salts thereof
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Page/Page column 59; 64; 65-66; 67-68; 77; 78
(2014/03/26)
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- Stereocontrolled 1,3-phosphatyloxy and 1,3-halogen migration relay toward highly functionalized 1,3-dienes
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A double migratory cascade reaction of α-halogen-substituted propargylic phosphates to produce highly functionalized 1,3-dienes has been developed. This transformation features 1,3-phosphatyloxy group migration followed by 1,3-shifts of bromine and chlorine as well as the unprecedented 1,3-migration of iodine. The reaction is stereodivergent: (Z)-1,3-dienes are formed in the presence of a copper catalyst, whereas gold-catalyzed reactions exhibit inverted stereoselectivity, producing the corresponding E products.
- Kazem Shiroodi, Roohollah,Dudnik, Alexander S.,Gevorgyan, Vladimir
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supporting information; experimental part
p. 6928 - 6931
(2012/06/15)
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- Unsymmetrical bidentate ligands of α-aminoaldimines leading to sterically controlled selectivity of geometrical isomerism in square planar coordination
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New α-aminoaldimines with the formula of Et2NCMe 2CHNR (R = iPr, tBu, Ph) and their dichloro or diacetato complexes of Ni, Pd, Pt are prepared and structurally characterized. A nickel complex is in a distorted tetrahedral configuration, and the Pd and Pt complexes (4-6) are of square planar form. The α-aminoaldimines can chelate to the metal in a C2-unsymmetric bidentate motif through the hetero functionalities of amine and imine, which show comparable trans influence. Square planar organometallic palladium derivatives bearing α-aminoaldimines, including Pd-methyl, Pd-acetyl, and Pd- (η2-acetylnorboryl) (7-10), are also synthesized. The latter two species are a result of CO-insertion into Pd-methyl complexes and ensuing norbornene-insertion, respectively. The geometrical isomerism is found in the trans configuration in most studied cases. Such a stereoselectivity results from the thermodynamic stability governed predominantly by steric control. The stereoselectivity is also supported by DFT calculations.
- Lee, Jen-Jeh,Yang, Feng-Zhao,Lin, Ya-Fan,Chang, Ya-Chun,Yu, Kuo-Hsuan,Chang, Mu-Chieh,Lee, Gene-Hsiang,Liu, Yi-Hung,Wang, Yu,Liu, Shiuh-Tzung,Chen, Jwu-Ting
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experimental part
p. 5945 - 5956
(2009/02/07)
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- Pharmaceutical compounds
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Compounds of Formulae Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 89-90
(2008/06/13)
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- ALPHA-UNSUBSTITUTED ARYLMETHYL PIPERAZINE PYRAZOLO[1,5-A] PYRIMIDINE AMIDE DERIVATIVES
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Methods of preventing, treating or delaying the onset of HIV in a subject by administering to the subject novel pharmaceutically active arylmethyl pyrazolo[1,5-α ]pyrimidine amide derivatives, or pharmaceutical compositions containing the same are described. Additionally, compounds of novel pharmaceutically active arylmethyl piperazine pyrazolo[l,5-α]pyrimidine amide derivatives and their use for the manufacture of specific medicaments are described.
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Page/Page column 185-186
(2008/12/08)
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- Total synthesis of seco-lateriflorone
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A convergent strategy toward the synthesis of lateriflorone (5) is described. Our approach is based on biosynthetic considerations and draws on a sequence of prenylation, oxygenation and Claisen reactions for the construction of chromenequinone 6, and a tandem Claisen/Diels-Alder reaction cascade for the synthesis of caged tricycle 7. Union of fragments 6 and 7 led to the synthesis of seco-lateriflorone (49).
- Tisdale, Eric J.,Vong, Binh G.,Li, Hongmei,Kim, Sun Hee,Chowdhury, Chinmay,Theodorakis, Emmanuel A.
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p. 6873 - 6887
(2007/10/03)
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- Enhanced D1 Affinity in a Series of Piperazine Ring Substituted 1-Piperazino-3-Arylindans with Potential Atypical Antipsychotic Activity
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A study of the effect of aromatic substitution on D1 and D2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro-or 6-fluoro-substituted derivatives show preference for D1 receptors.D1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives.Potent D1 and D2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl, 2,2-dimethyl, 2-spirocyclobutyl or 2-spiro-cyclopentyl).Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans.All these compounds except the 4-, 5-, 7- and 4'-chloro-substituted derivatives have potent D1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SKF 38393-induced circling in 6-OHDA-lesioned rats with ED50 values about 1μmol/kg.In vitro all compounds show preference for D1 receptors, but in vivo they are equally effective as D1 and D2 antagonists.The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for α1 adrenoceptors.Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats.These compounds have the potential of being "atypical" antipsychotics and have consequently been selected for further studies.The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazinering.Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10nM.Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D2 and 5-HT2 receptors.It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D1 receptor site.
- Boegesoe, Klaus P.,Arnt, Joern,Frederiksen, Kristen,Hansen, Hans Otto,Hyttel, John,Pedersen, Henrik
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p. 4380 - 4392
(2007/10/02)
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- Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors: Synthesis and Biological Properties of alkenoic Acids
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The design, synthesis, and pharmacology of a new class of compounds possessing bith thromboxane receptor antagonist and thromboxane synthase inhibitory properties are described.Replacement of the phenol group of the known thromboxane antagonist series 4(Z)-6-hex-4-enoic acid by a 3-pyridyl group led to a series of compounds, 5, which were potent thromboxane synthase inhibitors and weak thromboxane antagonists.Further modifications at the dioxane C2 position led to compounds, 7, which were potent dual-acting agents.In the case of compound 7w, the dual activity was shown to reside almost exclusively in the (-)-enantiomer, 7x.Following oral dosing to rats and dogs, 7x (3 mg/kg) displayed significant dual activity over a period of at least 8 h.
- Faull, Alan W.,Brewster, Andrew G.,Brown, George R.,Smithers, Michael J.,Jackson, Ruth
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p. 686 - 694
(2007/10/02)
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- THE MUKAIYAMA REACTION OF KETENE BIS(TRIMETHYLSILYL)ACETALS WITH α-HALO ACETALS - A CONVENIENT BUTENOLIDE SYNTHESIS
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Ketene bis(trimethylsilyl) acetals were reacted with α-halo acetals giving β-alkoxy-γ-halo acids which were converted to butenolides by reaction with equivalents of base.This constitutes a novel and short butenolide synthesis.
- Demnitz, F. W. J.
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p. 6109 - 6112
(2007/10/02)
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- 5,5-Dibromobarbituric Acid, a Convenient New Reagent for the Bromination of Saturated and α,β-Unsaturated Carbonyl Compounds
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5,5-Dibromobarbituric acid (1) was used for the bromination of saturated and α,β-unsaturated aldehydes and keto compounds.
- Grundke, Guenter,Keese, Wolfgang,Rimpler, Manfred
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p. 4288 - 4291
(2007/10/02)
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- Hydroxyalkyl pyrid-2-yl dithiocarbamates, their preparation and their use
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New dithiocarbamates of the formula: STR1 in which R1 is hydrogen or halogen in the 4-, 5- or 6-position, n is equal to 0 or 1, R2 represents hydrogen or various aliphatic or aromatic radicals which may be substituted, R3 represents hydrogen or various aliphatic radicals, and R4 represents a hydrogen atom or an alkyl radical, their optically active forms, and their salts, when such salts exist, are valuable anthelmintic agents. They may be made inter alia by reduction of the corresponding ketones.
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- REACTION OF α-NITRO EPOXIDES WITH HYDROHALIC ACIDS AND THEIR SALTS
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The reaction of α-nitro epoxides of the aliphatic series with hydrohalic acids and their salts leads to the formation of the corresponding α-halogencarbonyl compounds.
- Sokolov, N. A.,Tishchenko, I. G.,Kovganko, N. V.
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p. 248 - 250
(2007/10/02)
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