- Benzylideneacetone Derivatives Inhibit Osteoclastogenesis and Activate Osteoblastogenesis Independently Based on Specific Structure-Activity Relationship
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(E)-3,4-Dihydroxybenzylideneacetone (compound 1) inhibited receptor activator of NF-κB ligand-induced osteoclastogenesis of C57BL/6 bone marrow monocyte/macrophages with IC50 of 7.8 μM (IC50 of alendronate, 3.7 μM) while stimulating the differentiation of MC3T3-E1 osteoblastic cells, accompanied by the induction of Runt-related transcription factor 2, alkaline phosphatase, and osteocalcin. (E)-4-(3-Hydroxy-4-methoxyphenyl)-3-buten-2-one (compound 2c) showed a dramatically increased osteoclast-inhibitory potency with IC50 of 0.11 μM while sustaining osteoblast-stimulatory activity. (E)-4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one (compound 2g) stimulated alkaline phosphatase production 2-fold at 50 μM without changing osteoclast-inhibitory activity, compared with compound 1. Oral administration of compounds 1, 2c, and 2g prevented ovariectomy-induced osteoporosis in ddY mice to a degree proportional to their osteoclastogenesis-inhibitory potencies. The administration of 1 (mg/kg)/d compound 2c ameliorated histomorphometry of osteoporotic bone to a degree comparable with 10 (mg/kg)/d alendronate. Conclusively, the in vitro capacity of a few benzylideneacetone derivatives to inhibit osteoclastogenesis supported by independent osteoblastogenesis activation was convincingly reflected in in vivo management of osteoporosis, suggesting a potential novel therapeutics for osteopenic diseases.
- Pativada, Triveni,Kim, Myung Hwan,Lee, Jung-Hun,Hong, Seong Su,Choi, Chun Whan,Choi, Yun-Hyeok,Kim, Woo Jung,Song, Da-Woon,Park, Serk In,Lee, Eun Jung,Seo, Bo-Yeon,Kim, Hankyeom,Kim, Hong Kyu,Lee, Kee Ho,Ahn, Sung K.,Ku, Jin-Mo,Park, Gil Hong
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- NOVEL BENZYLIDENEACETONE DERIVATIVE AND USE THEREOF
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The present invention relates to novel benzylideneacetone derivatives or uses thereof, more specifically, the present invention relates to a pharmaceutical composition for preventing or treating, or food composition for ameliorating a cancer or a bone disease comprising a compound defined by Formula 1 or pharmaceutically acceptable salt thereof as an active ingredient. Since compounds according to the present invention exhibit strong inhibitory activity on proliferation and differentiation of osteoclast, and activity on proliferation and differentiation of osteoblast, it can be usefully used to develop safe and effective anti-cancer agents, and therapeutic agents for preventing and treating or foods for ameliorating bone diseases including osteoporosis, and the like.
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Paragraph 0113-0114
(2020/06/23)
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- NOVEL COMPOUNDS, USES AND METHODS FOR THEIR PREPARATION
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The present disclosure relates to novel compounds HIF-2α inhibitors and pharmaceutical compositions thereof which may be useful in the treatment and/or prevention of various conditions. The present disclosure also provides methods of preparing such HIF-2α inhibitors and compositions, and methods of using the same.
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Paragraph 00341
(2018/03/06)
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- Macrocyclic compounds and methods for their production
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There is provided inter alia compounds of formula (I): for use in treatment of viral infection or as an immunosuppressant.
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Page/Page column 38
(2015/11/10)
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- Sanglifehrin Derivatives and Methods for Their Production
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There are provided inter alia compounds of formula (I) and (II) and their use in therapy, particularly for the treatment of viral infection.
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Paragraph 0150; 0151
(2014/04/03)
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- Novel Dosage Form
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There is provided inter alia a pharmaceutical dosage form for oral administration comprising a sanglifehrin as active ingredient in which the sanglifehrin active ingredient is protected from acid degradation in the stomach environment following oral admin
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Paragraph 0255; 0256
(2014/09/03)
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- TRICYCLIC BORON COMPOUNDS FOR ANTIMICROBIAL THERAPY
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Provided herein are antimicrobial tricyclic boron compounds of the following formula I: or pharmaceutically acceptable salts, complexes, or tautomers thereof that are antibacterial agents, pharmaceutical compositions containing them, methods for their use
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Paragraph 0167
(2013/07/05)
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- NOVEL DOSAGE FORM
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There is provided inter alia apharmaceutical dosage form fororal administration comprising a sanglifehrin as active ingredient in which the sanglifehrin active ingredient is protected from acid degradation in the stomach environment following oral adminis
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Page/Page column 62
(2013/05/21)
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- Novel Compounds
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The present invention provides compounds of formula (I): wherein Ra, Rb, Rc, R1, R2, R3, X1, Y1, Z1, A, n and m are as defined in the specification, and pharmaceutically acceptable salts thereof, as well as processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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Page/Page column 64
(2011/06/24)
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- NOVEL GLUCOCORTICOID RECEPTOR AGONISTS
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This invention relates to novel glucocorticoid receptor agonists of formula (I) and to processes and intermediates for their preparation. The present invention also relates to pharmaceutical compositions containing these compounds, to their combination with one or more other therapeutic agents, as well as to their use for the treatment of a number of inflammatory and allergic diseases, disorders and conditions.
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Page/Page column 39
(2010/12/26)
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- Novel Compounds Active as Muscarinic Receptor Antagonists
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The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical compositions containing them.
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Page/Page column 13
(2009/04/24)
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- Identification of a PPARδ agonist with partial agonistic activity on PPARγ
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The discovery and optimization of a series of potent PPARδ full agonists with partial agonistic activity against PPARγ is described.
- Connors, Richard V.,Wang, Zhulun,Harrison, Martin,Zhang, Alex,Wanska, Malgorzata,Hiscock, Steve,Fox, Brian,Dore, Michael,Labelle, Marc,Sudom, Athena,Johnstone, Sheree,Liu, Jinsong,Walker, Nigel P.C.,Chai, Anne,Siegler, Karen,Li, Yang,Coward, Peter
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body text
p. 3550 - 3554
(2010/04/05)
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- HETEROARYL COMPOUNDS, COMPOSITIONS THEREOF, AND USE THEREOF AS PROTEIN KINASE INHIBITORS
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Provided herein are Heteroaryl Compounds having the following structure: (I) wherein R1, R2, L, X, Y, Z, Q, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.
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Page/Page column 114
(2008/12/05)
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- ARYLUREA DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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A compound of formula (I), wherein substituents are as given above, useful in the treatment of a disease mediated by the action of CCR3, in particular inflammatory or obstructive airway diseases.
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Page/Page column 60-61
(2008/06/13)
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- Cinnamide compound
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The present invention relates to a compound represented by Formula (I): (wherein Ar1 represents an imidazolyl group which may be substituted with 1 to 3 substituents; Ar2 represents a pyridinyl group, a pyrimidinyl group, or a phenyl group which may be substituted with 1 to 3 substituents; X1 represents (1) —C≡C— or (2) a double bond etc. which may be substituted; R1 and R2 represent, for example, a C1-6 alkyl group or C3-8 cycloalkyl group which may be substituted) or a pharmacologically acceptable salt thereof and to the use thereof as pharmaceutical agents. The object of the present invention is to find a therapeutic or preventive agent for diseases caused by Aβ. According to the present invention, a therapeutic or preventive agents for diseases caused by Aβ can be provided.
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Page/Page column 51
(2008/06/13)
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- IMIDAZOPYRAZINE TYROSINE KINASE INHIBITORS
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Compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein Q1 and R1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.
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Page/Page column 184
(2008/06/13)
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- Synthesis of high-specific-radioactivity 4- and 6-[18F]fluorometaraminol- PET tracers for the adrenergic nervous system of the heart
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Fluorine-18 (t12:109.8min)-labeled analogues of metaraminol, 4-[18F]FMR ((1R,2S)-2-amino-1-(4-[18F]fluoro-3-hydroxy phenyl)-1-propanol) and 6-[18F]FMR ((1R,2S)-2-amino-1-(2-[18F]fluoro-5-hydroxyphenyl)-1-propanol), were synthesized as new positron-emission-tomography (PET) tracers for mapping cardiac adrenergic nerve terminals. Copyright
- Langer, Oliver,Dollé, Frédéric,Valette, Héric,Halldin, Christer,Vaufrey, Fran?oise,Fuseau, Chantal,Coulon, Christine,Ottaviani, Michéle,N?gren, Kjell,Bottlaender, Michel,Maziére, Bernard,Crouzel, Christian
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p. 677 - 694
(2007/10/03)
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- Synthesis and Adrenergic Activity of Ring-Fluorinated Phenylephrines
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2-Fluoro-, 4-fluoro-, and 6-fluorophenylephrine (6-FPE) were synthesized from the corresponding fluorinated 3-hydroxybenzaldehydes.New routes to 2-fluoro- and 6-fluoro-3-hydroxybenzaldehydes were developed based on regioselective lithiation of 2- and 4-fluorobenzene ortho to fluorine.As with norepinephrine and isoproterenol analogues, the adrenergic properties of phenylephrine were markedly altered by ring fluorination.The order of potency of the fluoro analogues as α1-adrenergic agonists in the stimulation of contraction of aorticstrips and of phosphatidylinositol turnover and potentiation of cyclic AMP accumulation in guinea pig synaptoneurosomes was 6-FPE > PE > 4-FPE > 2-FPE.The same pattern was observed for the displacement of radioligands specific for α1- and α2-adrenergic receptors on brain membranes.The order of potency for the displacement of 3H>dihydroalprenolol, a β-specific adrenergic ligand from brain membranes, was 2-FPE > 4-FPE = PE >> 6-FPE. 6-FPE was much more selective for α-adrenergic receptors compared to β-receptors than was phenylephrine.A rationale for the observed fluorine-induced alterations in potency and selectivity of the FPEs for α- and β-adrenergic systems is presented based on fluorine-induced conformations due to electrostatic repulsion of fluorine and the benzyl hydroxyl group.
- Kirk, Kenneth L.,Olubajo, Olarangbe,Buchhold, Konstantin,Lewandowski, Gail A.,Gusovsky, Fabian,et al.
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p. 1982 - 1988
(2007/10/02)
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