- COMPOUNDS FOR TARGETED DEGRADATION OF BRD9
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BRD9 protein degradation compounds or pharmaceutically acceptable salts thereof are provided for the treatment of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation.
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Page/Page column 590-591; 618-619
(2021/09/11)
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- Crystal (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
-
The present invention provides a crystal of (6S,9aS)-N-benzyl-8-({6-[3-4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl} methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide.
- -
-
Paragraph 0109; 0110; 0111
(2018/06/04)
-
- MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00480
(2018/08/20)
-
- List fluoro Radicamine compounds and their use and preparation method
-
The invention discloses a mono-fluorinated Radicamine compound which has a structure as shown in a formula (1), and further provides a preparation method for the mono-fluorinated Radicamine compound with the structure as shown in the formula (1) and an application of the mono-fluorinated Radicamine compound or the mono-fluorinated Radicamine compound prepared with the method to preparation of drugs for preventing and/or treating diabetes, drugs for preventing and/or treating Gaucher's diseases, drugs for preventing and/or treating tumors or antiviral drugs. The mono-fluorinated Radicamine compound provided by the invention is good in glycosidase inhibition activity.
- -
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Paragraph 0078-0081
(2017/12/02)
-
- Fluorinated Radicamine A and B: Synthesis and Glycosidase Inhibition
-
Fluorinated derivatives of radicamine A and radicamine B have been synthesized from D-arabinose-derived cyclic nitrone. Structure-activity relationship studies showed that glycosidase inhibition of these fluorinated derivatives was significantly influenced by the position of the fluorine atom. C-7 or C-11 fluorination of the aromatic ring decreased α-glucosidase inhibition of the derivatives, whereas C-8 or C-10 fluorination preserved glycosidase inhibitory activities. Fluorinated derivatives of radicamine A and B have been synthesized from D-arabinose-derived cyclic nitrone. Structure-activity relationship studies revealed that glycosidase inhibition of these fluorinated derivatives was significantly influenced by the position of the fluorine atom.
- Li, Yi-Xian,Iwaki, Ren,Kato, Atsushi,Jia, Yue-Mei,Fleet, George W. J.,Zhao, Xuan,Xiao, Min,Yu, Chu-Yi
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p. 1429 - 1438
(2016/03/16)
-
- TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE
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Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
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Page/Page column 73
(2016/12/22)
-
- Design, synthesis and evaluation of potent G-protein coupled receptor 40 agonists
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GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22g and 23e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.
- Huang, Jing,Guo, Bin,Chu, Wen-Jing,Xie, Xin,Yang, Yu-She,Zhou, Xian-Li
-
supporting information
p. 159 - 162
(2016/01/26)
-
- (6S,9aS)-N-Benzyl-6-[(4-hydroxyphenyl)methyl]-4,7-dioxo-8-(methyl)-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide compound
-
A compound represented by formula (1) or pharmaceutically acceptable salt thereof: wherein R1 is a C1-6 alkyl group; R2 and R3 are the same or different from each other and each is a hydrogen atom or a C1-6 alkyl group; X2, X3 and X4 are the same or different from each other and each is a hydrogen atom or a halogen atom; and X5 is a hydrogen atom or —P(═O)(OH)2 has a Wnt Pathway modulating activity.
- -
-
Paragraph 0258 - 0260
(2015/07/02)
-
- SUBSTITUTED ALKYL CARBOXYLIC ACID DERIVATIVES AS GPR AGONISTS
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The present invention relates to substituted alkyl carboxylic acid derivatives (the compounds of Formula (I)), processes for their preparation, pharmaceutical compositions containing said compounds, their use as GPR (G-protein coupled receptor) agonists,
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Page/Page column 225
(2014/11/11)
-
- P-Hydroxyphenacyl photoremovable protecting groups Robust photochemistry despite substituent diversity
-
A broadly based investigation of the effects of a diverse array of substituents on the photochemical rearrangement of p-hydroxyphenacyl esters has demonstrated that common substituents such as F, MeO, CN, CO2R, CONH2, and CH3 have little effect on the rate and quantum efficiencies for the photo-Favorskii rearrangement and the release of the acid leaving group or on the lifetimes of the reactive triplet state. A decrease in the quantum yields across all substituents was observed for the release and rearrangement when the photolyses were carried out in buffered aqueous media at pHs that exceeded the ground-state pKa of the chromophore where the conjugate base is the predominant form. Otherwise, substituents have only a very modest effect on the photoreaction of these robust chromophores.
- Givens, Richard S.,Stensrud, Kenneth,Conrad, Peter G.,Yousef, Abraham L.,Perera, Chamani,Senadheera, Sanjeewa N.,Heger, Dominik,Wirz, Jakob
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scheme or table
p. 364 - 384
(2011/06/22)
-
- Regioselective SNAr reactions of substituted difluorobenzene derivatives: practical synthesis of fluoroaryl ethers and substituted resorcinols
-
In this Letter, we describe a practical and highly selective method for the preparation of fluoroaryl ethers and differentially substituted resorcinol derivatives. This synthetic strategy relies on a selective SNAr of substituted difluorobenzen
- Ouellet, Stéphane G.,Bernardi, Anna,Angelaud, Remy,O'Shea, Paul D.
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supporting information; experimental part
p. 3776 - 3779
(2009/10/11)
-
- Regioselectivity of fluorine substitution by alkoxides on unsymmetrical difluoroarenes
-
An efficient approach to unsymmetrical halogenated resorcinol diethers has been developed. This synthesis consists of two subsequent nucleophilic aromatic substitutions (SNAr) of unsymmetrical difluoroarenes by alkoxides. The novelty of this ap
- Dirr, Ronan,Anthaume, Cyril,Désaubry, Laurent
-
p. 4588 - 4590
(2008/09/21)
-
- 2-Heteroaryl-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists
-
Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is R1-isoxazolyl, R1-oxadiazolyl, R1-dihydrofuranyl, R1-pyrazolyl, R1-imidazolyl, R1-pyrazinyl or R1-pyrimidinyl; R1 is 1, 2 or 3 substituents selected from H, alkyl, alkoxy and halo; Z is optionally substituted-aryl, or optionally substituted-heteroaryl; are disclosed, as well as their use in the treatment of central nervous system diseases, in particular Parkinson's disease and Extra Pyramidal Syndrome, pharmaceutical compositions comprising them, and combinations with other agents.
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-
Page/Page column 10-11
(2008/06/13)
-
- BICYCLIC DERIVATIVES AS PPAR MODULATORS
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The present invention is directed to compounds represented by the following structural formula, Formula (I), and stereoisomers, pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R2 is selected from the group consisting of C0-C8 alkyl and C1-4- heteroalkyl; (b) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (c) U is an aliphatic linker wherein one carbon atom of the aliphatic linker is optionally replaced with O, NH or S, and wherein such aliphatic linker is optionally substituted with from one to four substituents each independently selected from R30; (d) Y is selected from the group consisting of C, O, S, NH and a single bond; and (e) E is C(R3)(R4)A or A.
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Page/Page column 69
(2008/06/13)
-
- 2-Alkynyl-and 2-alkenyl-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists
-
Compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is R1, R2, R3, R4 and R5 are H, alkyl or alkoxyalkyl; R6 is H, alkyl, hydroxyalkyl or —CH2F; R7, R8 and R9 are H, alkyl, alkoxy, alkylthio, alkoxyalkyl, halo or —CF3; and Z is optionally substituted aryl, heteroaryl or heteroaryl-alkyl are disclosed. Also disclosed is the use of compounds of formula I in the treatment of central nervous system diseases, in particular Parkinson's disease, alone or in combination with other agents for treating Parkinson's disease, and pharmaceutical compositions comprising them.
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-
-
- CHIRALE OXAZOLE-ARYLPROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
-
The present invention relates to compounds of Formula (I), wherein R1 to R6 and n are as defined in the description and claims, and pharmaceutically acceptable salts and esters thereof. The compounds are useful for the treatment and/
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-
-
- NOVEL 2-ARYLTHIAZOLE COMPOUNDS AS PPARALPHA AND PPARGAMA AGONISTS
-
The present invention relates to compounds of formula (I) wherein Rl to R10, X, Y and n are as defined in the description and claims, and pharmaceutically acceptable salts and esters thereof. The compounds are useful for the treatment of diseases such as diabetes.
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Page 118-119
(2010/02/06)
-
- Side-chain liquid crystal polymers derived from oxetane monomers containing 2- or 3-fluorophenyl moieties in the core of the mesogen
-
Two series of side-chain liquid crystalline polymers were prepared by cationic ring-opening of oxetane substituted mesogens. Each of the terminally appended side chain polymers prepared had a flexible spacer length of six methylene units separating a meso
- Cowling,Toyne,Goodby
-
p. 1590 - 1599
(2007/10/03)
-
- The synthesis and mesomorphic properties of some novel antiferroelectric liquid crystals
-
Several esters have been synthesised that exhibit the antiferroelectric smectic C phase. The core structures, like virtually all antiferroelectric materials, are very similar to that of MHPOBC. Lateral fluoro substituents have been used to reduce melting points and to investigate their effect on mesomorphic properties, spontaneous polarisation and tilt angle. A new device format reported by Lagerwall requires antiferroelectric liquid crystals with a 45° tilt angle. Novel antiferroelectric materials were prepared with fluoro substituents in lateral positions and in a terminal chain to provide low melting points, high antiferroelectric phase stability, high spontaneous polarisation and tilt angles of up to 45°. The synthetic routes to the novel materials are discussed, and the transition temperatures, tilt angles and spontaneous polarisations are compared to those of known materials.
- Hird, Michael,Goodby, John W.,Toyne, Kenneth J.,Gleeson, Helen F.,Peter Buxton,Seed, Alexander J.,Herbert, Mark R.
-
p. 213 - 220
(2007/10/03)
-
- Liquid crystal compound and liquid crystal composition containing the same
-
A liquid crystal compound represented by formula (I) and a liquid crystal composition containing the same. The compound exhibits an antiferroelectric liquid crystal phase and has good compatibility with known liquid crystal compounds. STR1 wherein R1 represents a straight-chain or branched alkyl, alkoxy, alkoxycarbonyl, alkanoyloxy or alkoxycarbonyloxy group having 4 to 16 carbon atoms; R2 represents a straight-chain alkyl group having 4 to 10 carbon atoms or a branched alkyl group containing 1 to 3 carbon atoms in its branch and 4 to 12 carbon atoms in total; X represents an oxygen or sulfur atom; rings A and B each represent an F-substituted or unsubstituted phenylene group, a cyclohexylene group or a divalent nitrogen-containing heterocyclic group, provided that either one of rings A and B is the nitrogen-containing heterocyclic group; ring C represents an F-substituted or unsubstituted phenylene group; and C* represents an asymmetric carbon atom.
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