- ARYL AND HETEROARYL-CARBOXAMIDE SUBSTITUTED HETEROARYL COMPOUNDS AS TYK2 INHIBITORS
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Novel carboxamide substituted compounds of Formula (I) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Tyrosine Kinase 2 (Tyk2).
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Page/Page column 168-169
(2021/10/15)
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- Regioselective Biomimetic Synthesis of Dimeric Oxyresveratrol Derivatives
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Oxyresveratrol and its methylated derivative as coupling precursors were efficiently prepared in four steps, with Wittig reactions and subsequent isomerization reactions as the key steps. The coupling reactions of oxyresveratrol under various oxidative conditions gave a complex and inseparable mixture of coupling products. The oxidative dimerizations of methylated oxyresveratrols catalyzed by horseradish peroxidase-H 2O 2or FeCl 3·6H 2O in an acetone system predominantly produced the 8-5-coupled and 8-10-coupled dihydrobenzofuran-type dimers, respectively. This regioselective biomimetic strategy might be useful in synthesizing other dimeric oxyresveratrol derivatives.
- Ran, Lu,Li, Hongpeng,Chao, Ge,Kang, Xiaodong,Lei, Tian,Li, Wenling
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supporting information
p. 1809 - 1812
(2020/09/18)
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- SMALL MOLECULES FOR TREATING CANCER, INHIBITING CHEMOKINE ACTIVITY AND/OR INDUCING CELL DEATH
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Compounds capable of, or usable in, inducing death of cancer cells and/or modulating a biological activity of a chemokine e.g., cell migration, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migrati
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Page/Page column 8; 61-62
(2020/11/30)
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- Synthesis of p-O-Alkyl Salicylanilide Derivatives as Novel EGFR Inhibitors
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(Table Presented) Epidermal growth factor receptor (EGFR), a validated target for anticancer drugs, plays a critical role in tumorigenesis and tumor development. A series of p-O-alkyl salicylanilide derivatives were designed and synthesized as novel EGFR inhibitors using a salicylic acid scaffold. A simulated six-membered ring strategy formed through intramolecular hydrogen bonds was employed to mimic the planar quinazoline of the EGFR antagonist, gefitinib. The derived compounds with hydroxyl at the ortho position were more potent than ones with methoxyl group. In particular, compounds 5d and 5b displayed significant EGFR inhibitory (IC50 values = 0.30 and 0.45 μM, respectively) activity as well as potent antiproliferative activity in A431 and HCT-116 tumor cells. These salicylanilides could be considered as promising lead compounds for developing novel EGFR inhibitors.
- Zhang, Li,Hou, Lin,Sun, Wenyan,Yu, Zidong,Wang, Jibo,Gao, Hua,Yang, Guiming
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- Concise synthesis of broussonone A
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A concise and expeditious approach to the total synthesis of broussonone A, a p-quinol natural compound, has been developed. The key features of the synthesis include the Grubbs II catalyst mediated cross metathesis of two aromatic subunits, and a chemoselective oxidative dearomatizationin the presence of two phenol moieties. Especially, optimization associated with the CM reaction of ortho-alkoxystyrenes was also studied, which are known to be ineffective for Ru-catalyzed metathesis reactions under conventional reaction conditions because ortho-alkoxy group could coordinate to the ruthenium center, resulting in the potential complication of catalyst inhibition.
- Jo, Hyeju,Choi, Minho,Viji, Mayavan,Lee, Young Hee,Kwak, Young-Shin,Lee, Kiho,Choi, Nam Song,Lee, Yeon-Ju,Lee, Heesoon,Hong, Jin Tae,Lee, Mi Kyeong,Jung, Jae-Kyung
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p. 15966 - 15975
(2015/12/01)
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- INDANYLOXYPHENYLCYCLOPROPANECARBOXYLIC ACIDS
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The present invention relates to compounds of general formula I, wherein the groups R1, R2, R3, m and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.
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Paragraph 0362
(2014/01/07)
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- NEW INDANYLOXYPHENYLCYCLOPROPANECARB OXYLIC ACIDS
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The present invention relates to compounds of general formula I, (I) wherein the groups R1, R2, R3, m and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.
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Page/Page column 58
(2014/01/07)
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- AGONISTS OF GPR40
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The present invention relates to compounds that have the ability to modulate the activity of GPR40 and are there-fore useful in the treatment of GPR40 related disorders. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders related to GPR40 activity.
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Page/Page column 145-146
(2012/02/05)
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- N-SUBSTITUTED PIPERIDINE DERIVATIVES AS SEROTONIN RECEPTOR AGENTS
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Disclosed herein are substantially pure forms of the compounds of Formula (I), (II), (III), (IV) and (V), or a pharmaceutically acceptable salt, prodrug, hydrate, solvate, polymorph, stereoisomer or ester thereof. Also disclosed are methods of inhibiting an activity of a serotonin receptor, methods inhibiting an activation of a serotonin receptor, and methods of alleviating or treating various disease conditions and side effects.
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Page/Page column 58
(2010/11/04)
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- Enantioselective total synthesis of hydramicromelin B
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The first total synthesis of hydramicromelin B is described. An AuCl3/AgOTf-catalyzed intramolecular reaction was used as key step for the construction the coumarin ring.
- Huo, Xing,Ren, Xingfeng,Xu, Yanfen,Li, Xinyun,She, Xuegong,Pan, Xinfu
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p. 343 - 347
(2008/09/19)
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- QUINOLINE DERIVATIVES
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The invention concerns quinoline derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 111
(2008/06/13)
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- NAPHTHYRIDINE DERIVATIVES
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The invention concerns naphthyridine derivatives of Formula (Ia) or (Ib) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, G1, G2, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders or disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 135
(2010/11/28)
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- NAPHTHYRIDINE DERIVATIVES AS ANTI-CANCER AGENTS
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The invention concerns naphthyridine derivatives of Formula (I): or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, G1, G2, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders or disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 91
(2010/11/28)
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- Design, synthesis, and conformational dynamics of a gated molecular basket
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We have developed a synthesis and examined the conformational behavior and recognition properties of dynamic molecular containers 1-3. As follows from the 1H NMR dilution, diffusion NMR, and vapor pressure osmometry measurements, compound 1 has a low affinity for intermolecular aggregation and is mostly present in monomeric form in dilute chloroform solutions. Inspecting the O-H chemical shift resonances of 1, 3, and model compound 4 as a function of temperature afforded the Δδ/ΔT coefficients of 17.0, 17.3, and 4.7 ppb K-1, respectively. In combination with the results from variable temperature 1H NMR and IR measurements, the existence of conformers of 1 and 3 in equilibrium, each having a different extent of hydrogen bonding, was confirmed. Molecular mechanics calculations suggested 1 a as the most favorable conformation, with three additional conformers, 1b, 1C, and 1d, populating local energy minima. Further optimization of each of the four conformers using semiempirical PM3 and ab initio (HF/6-31G*) methods allowed a determination of their relative free energies and the corresponding Boltzmann population distributions which were heavily weighted toward 1a. A computed composite IR spectrum of a fraction-weighted mixture of the conformers of 1 reproduced the experimentally observed IR spectrum in its structural features, leading to a conclusion that conformer 1a indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 A3) is complementary in size, shape, and electrostatic potential to chloroform (74.9 A3). A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand along its C3, axis.
- Maslak, Veselin,Yan, Zhiqing,Xia, Shijing,Gallucci, Judith,Hadad, Christopher M.,Badjic, Jovica D.
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p. 5887 - 5894
(2007/10/03)
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- Mechanism-based molecular design of highly selective fluorescence probes for nitrative stress
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Nitrative stress is implicated in various pathogenic processes, including neurodegenerative disorders, but there is no practical fluorescence probe which can monitor the generation of nitrative stress with high selectivity. To design a suitable fluorescence probe, we have first focused on the fluorescence quenching mechanism of the nitro group, which has been believed to be a unique quencher of fluorescent dyes. We found that nitro group-based fluorescence quenching could be explained in terms of an electron transfer process, from the excited fluorophore to the electron-deficient aromatic nitro moiety. By utilizing this result, we succeeded in developing novel fluorogenic probes, NiSPYs, which can selectively monitor the generation of nitrative stress based on aromatic nitration. NiSPYs showed strong fluorescence enhancement upon the reaction with nitrating agents, including peroxynitrite, but showed little or no fluorescence augmentation in the presence of other reactive oxygen species. NiSPYs should be potentially useful as tools to study the role of nitrative stress in various biological applications. Copyright
- Ueno, Tasuku,Urano, Yasuteru,Kojima, Hirotatsu,Nagano, Tetsuo
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p. 10640 - 10641
(2007/10/03)
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- QUINAZOLINE DERIVATIVES
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The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 103
(2008/06/13)
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- Complementary diastereoselectivity in the intermolecular addition of titanium and magnesium naphtholates to asymmetric lactaldehydes
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Addition of 7-benzyloxy-4,5-dimethoxy-1-naphthol 3 as its triisopropoxytitanium naphtholate to (2R, 1′R or S)-2-(1′-ethoxyethoxy)propanal 4 afforded solely (15, 2R, 1″R or S)-1-(7′-benzyloxy-4′,5′-dimethoxy-1′-hydroxy-2′- naphthyl)-2-(1″-ethoxyethoxy)propan-l-ol 5, being the erythro product arising from anti addition. Complementary reaction of the naphthol 3 as its bromomagnesium naphtholate with aldehyde 4 gave rise solely to the alternative (1R, 2R, 1″R or S) diastereomer 6. The naphthol 3 was prepared through the completely regioselective addition of 2-methoxyfuran 9 to 5-benzyloxy-3-methoxydehydrobenzene 8. This differentially protected bisalkoxybenzyne was conveniently prepared from vanillin. The Royal Society of Chemistry 1999.
- Giles, Robin G. F.,Joll, Cynthia A.,Sargent, Melvyn V.,Tilbrook, D. Matthew G.
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p. 3029 - 3038
(2007/10/03)
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- 2-Azetidinone cholesterol absorption inhibitors: Increased potency by substitution of the C-4 phenyl ring
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SAR studies directed towards the optimization of 2-azetidinone cholesterol absorption inhibitors led to the discovery of 11a, the most potent cholesterol absorption inhibitor yet identified. Copyright (C) 1998 Elsevier Science Ltd.
- Vaccaro, Wayne D.,Sher, Rosy,Davis Jr., Harry R.
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p. 1429 - 1437
(2007/10/03)
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- Oligomeric Isoflavonoids. Part 1. Structure and Synthesis of the First (2,3')-Isoflavone-Isoflavan Dimer
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The structure and stereochemistry of a novel -isoflavone-isoflavan oligomer, 2',7-dihydroxy-2--4'-methoxyisoflavone (1; R=H), from Dalbergia nitidula are established by synthesis.The strategy of condens
- Bezuidenhoudt, Barend C. B.,Brandt, E. Vincent,Steenkamp, Jacobus A.,Roux, David G.,Ferreira, Daneel
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p. 1227 - 1236
(2007/10/02)
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