- ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model
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Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biological functions, including smooth muscle contraction, cell motility, proliferation, and morphological change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma. Herein, we report our medicinal chemistry effort to identify a novel and highly potent ATX inhibitor, ONO-8430506 (20), with good oral availability. To enhance the enzymatic ATX inhibitory activity, we designed several compounds by structurally comparing our hit compound with the endogenous ligand LPC. Further optimization to improve the pharmacokinetic profile and enhance the ATX inhibitory activity in human plasma resulted in the identification of ONO-8430506 (20), which enhanced the antitumor effect of paclitaxel in a breast cancer model.
- Hiramatsu, Atsushi,Hirooka, Yasuo,Hisaichi, Katsuya,Imagawa, Akira,Iwaki, Yuzo,Katoh, Makoto,Kobayashi, Juta,Komichi, Yuka,Maeda, Tatsuo,Matsumura, Naoya,Moriguchi, Hideki,Nakatani, Shingo,Nishiyama, Taihei,Ohhata, Akira,Okabe, Yasuyuki,Okada, Masahiro,Ota, Hiroto,Saga, Hiroshi,Sugiyama, Tetsuya,Watanabe, Toshihide,Yamamoto, Shingo
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supporting information
p. 1335 - 1341
(2020/07/06)
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- TETRAHYDRO-IMIDAZO QUINOLINE COMPOSITIONS AS CBP/P300 INHIBITORS
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The present disclosure is directed to inhibitors of the CBP/p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP/p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP/p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP/p300 family of bromodomains, and methods of synthesis of these compounds.
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Paragraph 0087
(2019/04/11)
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- SUBSTITUTED BICYCLIC PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I: and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Paragraph 0228; 0231
(2018/11/21)
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- As a substituted bicyclic pyrazole compound and use ROR γ T inhibitor
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The present invention relates to compounds according to Formula I: and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Paragraph 0182; 0184
(2019/01/10)
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- SUBSTITUTED INDAZOLE COMPOUNDS AS RORGAMMAT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula (I) and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Paragraph 00196
(2017/05/17)
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- Hydroxypurine compound and use thereof
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The invention discloses a hydroxypurine compound and a use of the hydroxypurine compound as a PDE2 or TNFa inhibitor and concretely discloses a compound shown in the formula (I) and its tautomer or pharmaceutically acceptable salt.
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Paragraph 0337; 0341; 0342; 0343
(2016/10/08)
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- SUBSTITUTED AMINOPURINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are Aminopurine Compounds having the following structures: wherein R1, R2, and R3 are as defined herein, compositions comprising an effective amount of an Aminopurine Compound, and methods for treating or preventing a cancer, for example, melanoma.
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Paragraph 0333
(2016/05/02)
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- 3-CYCLOHEXENYL AND CYCLOHEXYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Paragraph 0261
(2015/07/15)
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- PYRAZOLE AMIDE DERIVATIVE
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The present invention relates to a novel compound having a function of inhibiting RORγ activity. The present invention also relates to pharmaceutical composition comprising the compound, a use of the compound in treating or preventing autoimmune diseases, inflammatory diseases, metabolic diseases, or cancer diseases.
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Page/Page column 186
(2015/09/28)
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- 3-CYCLOHEXENYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORGAMMAT INHIBITORS AND USES THEREOF
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Disclosed are compounds of Formula (I) or a pharmaceutically acceptable salt or solvate thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 37
(2014/03/22)
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- 3-CYCLOHEXENYL AND CYCLOHEXYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 43
(2014/03/22)
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- TETRAHYDROCARBOLINE DERIVATIVE
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An object of the present invention is to provide a drug having the inhibitory activity on ENPP2 which is a different target from that of the existing drug, as a medicament useful in a urinary excretion disorder patient for whom the existing drug has the insufficient effect. The present invention provides a compound represented by the general formula (I): (wherein definition of each group is as defined in the description) having the ENPP2 inhibitory activity, a salt thereof or a solvate thereof or a prodrug thereof, and an agent for preventing or treating urinary excretion disorder and/or improving symptoms thereof, containing them as an active ingredient.
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Paragraph 2011-2014
(2013/05/09)
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- COMPOUNDS AS DGAT-1 INHIBITORS
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Described herein are compounds of formula I. The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.
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Page/Page column 51; 52
(2013/07/05)
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- NOVEL PYRAZOLO[1,5-a]PYRROLO[3,2-e]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
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The present invention relates to certain pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidine compounds of Formula (I) as inhibitors of mammalian Target of Rapamycin (mTOR) kinase, which is also known as FRAP, RAFT, RAPT or SEP. The compounds may be used in the treatm
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Page/Page column 50
(2012/03/26)
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- NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
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The present invention relates to certain pyrazolo[1,5-a]pyrimidine compounds of Formula (I) as inhibitors of mammalian Target Of Rapamycin (mTOR) kinase, which is also known as FRAP, RAFT, RAPT or SEP. The compounds may be used in the treatment of cancer and other disorders where mTOR is deregulated. The present invention further provides pharmaceutical compositions comprising the pyrazolo[1,5-a]pyrimidine compounds.
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Page/Page column 59
(2012/03/26)
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- IMIDAZOLE DERIVATIVES
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Described herein are compounds of formula (I), The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.
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Page/Page column 64
(2013/02/27)
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- FUSED TRICYCLIC COMPOUNDS AS NOVEL mTOR INHIBITORS
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The present invention provides Fused Tricyclic Compounds of the Formula (I) wherein Q, R1, R2, R3, and R4 are as defined herein, and pharmaceutically acceptable salts of such Fused Tricyclic Compounds. The Fused Tricyclic Compounds are useful in the treatment of cancer and other proliferative disorders.
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Page/Page column 70-71
(2011/02/24)
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- Synthesis of "Trioxaquantel" derivatives as potential new antischistosomal drugs
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Over the past 20 years, praziquantel, a pyrazinoisoquinoline derivative, has become the mainstay for morbidity control of human and animal schistosomiasis. From early in their lives in vertebrate hosts, schistosomes ingest hemoglobin and aggregate the released heme as a dark pigment very similar to the hemozoin produced by Plasmodium in malaria infection. The antimalarial artemisinin derivatives have real, though low, schistosomicide activity. Because of the complementarity of the two drug classes - praziquantel and artemisinin derivatives - we designed new molecules, named trioxaquantels, that combine the 1,2,4-trioxane unit responsible for the activity of artemisinin, and the pyrazinoisoquinoline moiety of praziquantel within a single drug. The synthesis of these new drugs and their preliminary evaluation in mice infected with Schistosoma mansoni is reported here. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Laurent, Sophie A.-L.,Boissier, Jerome,Cosledan, Frederic,Gornitzka, Heinz,Robert, Anne,Meunier, Bernard
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experimental part
p. 895 - 913
(2009/04/08)
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- A new efficient deprotection of azines, hydrazones and oximes. An excellent route for exchanging oxygen isotopes in carbonyls
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Carbonyls, protected as azines or other C=N derivatives can be deprotected by HOF·CH3CN in seconds to the corresponding ketone or aldehyde in very good yields. This reaction also offers a very efficient route for replacing the oxygen atom of most carbonyls with any other oxygen isotope, for example, [18]O.
- Carmeli, Mira,Rozen, Shlomo
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p. 763 - 766
(2007/10/03)
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- Synthesis of bridgehead-substituted bicyclo[2.2.1]heptanes. Radical cyclization of an oxime ether and an α,β-unsaturated ester
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The synthesis of bicyclo[2.2.1]heptanes with useful functionality at each bridgehead is achieved by radical cyclization of appropriately substituted 4-methylene- and 4-benzyloxyiminocyclohexylmethyl radicals. The latter process, for example, leads to a br
- Della,Knill
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p. 1833 - 1841
(2007/10/02)
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- Compound and use of the same as medicine
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Disclosed herein is a specific cinnamic acid derivative such as methyl 4-(4-acetoxy-3-methoxycinnamanide)-1-cyclohexanecarboxylate, or a pharmaceutically acceptable salt thereof. These compounds are useful as IV-type allergic reaction-suppressive drugs.
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