- TYK2 INHIBITORS AND USES THEREOF
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Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.
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Paragraph 00639
(2020/09/27)
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- Asymmetric Total Synthesis and Evaluation of Antitumor Activity of Ophiorrhisine A and Its Derivatives
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The first asymmetric total synthesis of ophiorrhisine A (1), a new cyclic tetrapeptide isolated from Ophiorrhiza nutans, was accomplished via an intramolecular aromatic nucleophilic substitution reaction (IMSNAr) of a linear tripeptide to construct a 14-membered paracyclophane ring, resulting in confirmation of its structure and absolute configuration. The structure-activity relationship study of 1 and its derivatives demonstrated that some derivatives possessed cytotoxicity toward human cancer cell lines A549, HT29, and HCT116.
- Onozawa, Tadayoshi,Kitajima, Mariko,Kogure, Noriyuki,Takayama, Hiromitsu
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p. 15312 - 15322
(2019/01/03)
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- Heterocycle type derivative and preparing method and pharmaceutical application thereof
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The invention relates to a novel heterocycle type derivative, a preparing method thereof, a medicine composition containing the derivative and application of the heterocycle type derivative as therapeutic agent, particularly an FGFR4 inhibitor. The preferable compound has a good inhibiting effect on FGFR4.
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Paragraph 0280; 0283-0286
(2018/07/30)
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- Pyrimidine derivatives as well as preparation method and medical applications thereof
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The invention relates to pyrimidine derivatives as well as a preparation method and medical applications thereof, in particular to pyrimidine derivatives shown as a general formula (I) in the description, a preparation method and medicinal salts thereof and applications of the pyrimidine derivatives and the medicinal salts as therapeutic agents, especially as FGFR4 (fibroblast growth factor receptor 4) kinase inhibitors. Definitions of substituent groups in the general formula (I) are the same as those in the description.
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Paragraph 0293; 0295-0298
(2017/12/27)
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- IMINOTETRAHYDROPYRIMIDINONE DERIVATIVES AS PLASMEPSIN V INHIBITORS
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A series of 2-imino-6-methyltetrahydropyrimidin-4(lH)-one derivatives, substituted in the 6-position by a phenyl moiety which in turn is meta-substituted by an optionally substituted unsaturated fused bicyclic ring system containing at least one nitrogen atom, being selective inhibitors of plasmepsin V activity, are beneficial as pharmaceutical agents, especially in the treatment of malaria.
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Page/Page column 54
(2017/07/05)
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formula (I): wherein, A, C, D, X, and Y have any of the values defined in the specification, and salts thereof. The compounds are SIRT2 inhibitors and are useful for treating SIRT2 associated conditions.
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Paragraph 0395; 0396; 0400
(2017/01/23)
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- Asymmetric synthesis of 3-azide-4-fluoro-L-phenylalanine
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The asymmetric synthesis of N-Fmoc-protected 3-azide-4-fluoro-L-phenylalanine as a photoactive phenylalanine analog has been achieved by Sch?llkopf's alkylation.
- Adachi, Masaatsu,Nakajima, Mado,Isobe, Minoru
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p. 707 - 709
(2015/10/05)
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- p27 PROTEIN INDUCER
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The present invention provides a p27 protein inducing agent comprising a compound represented by general formula (11) below or pharmaceutically acceptable salt thereof as an active ingredient: wherein G 1 , G 2 , G 3 and G 8 are each independently selected from -N= etc., Ring G 6 is selected from divalent aryl etc., A is selected from amino etc., G 4 is selected from oxygen etc., G 5 is selected from oxygen etc., G 7 is selected from -CH 2 - etc., and R 2 is selected from C 1-6 alkyl etc.
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Paragraph 2903-2907
(2016/10/08)
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- Discovery of potent, selective, and orally bioavailable inhibitors of interleukin-1 receptor-associate kinase-4
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In this Letter, we report the continued optimization of the N-acyl-2-aminobenzimidazole series, focusing in particular on the N-alkyl substituent and 5-position of the benzimidazole based on the binding mode and the early SAR. These efforts led to the discovery of 16, a highly potent, selective, and orally bioavailable inhibitor of IRAK-4.
- Wang, Zhulun,Sun, Daqing,Johnstone, Sheree,Cao, Zhaodan,Gao, Xiong,Jaen, Juan C.,Liu, Jingqian,Lively, Sarah,Miao, Shichang,Sudom, Athena,Tomooka, Craig,Walker, Nigel P.C.,Wright, Matthew,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
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p. 5546 - 5550
(2015/11/17)
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- Microwave-assisted solid-phase synthesis of a 1,2-disubstituted benzimidazole library by using a phosphonium linker
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An efficient and rapid microwave-assisted solid-phase method for the synthesis of 5-methyl-1,2-disubstituted benzimidazoles derivatives has been developed. The phosphonium linker, obtained by reaction between polymer-supported triphenylphosphine and 4-fluoro-3-nitrobenzyl iodide, underwent aromatic substitution with primary amines, followed by one-pot reaction with aldehydes in the presence of SnCl2·2H 2O, yielded the benzimidazole system under microwave irradiation. The final products were released from the resin with NaOH under microwave irradiation and were obtained in high purity and good overall yield.
- Rios, Natalia,Chavarria, Cecilia,Gil, Carmen,Porcal, Williams
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p. 720 - 726
(2013/06/27)
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- COUMARIN DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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The present invention relates to a coumarin derivative of formula (I): wherein X, Y1, Y2, Y3, R1, R2, R3 and R4 are as defined herein, or a pharmaceutically acceptable salt or so
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Page/Page column 22-23
(2013/02/28)
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- Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl] phenylamino}acetate (ON 01910.Na): Synthesis, structure-activity relationship, and biological activity
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Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene in the mammary tissues protects mice from breast cancer. Accordingly, there is an increasing awareness of this novel nonenzymatic target for cancer therapeutics. We have developed novel, nonalkylating styrylbenzylsulfones that induce cell death in wide variety of cancer cells without affecting the proliferation and survival of normal cells. The development of derivatized styrylbenzylsulfones followed logically from a tumor cell cytotoxicity screen performed in our laboratory that did not have an a priori target profile. Modifications of some of the precursor molecules led to lead optimization with regard to tumor cell cytotoxicity. In this report we describe the synthesis and structure-activity relationships of novel, nonalkylating (E)-styrylbenzylsulfones and the development of the novel anticancer agent sodium (E)-2-{2-methoxy-5-[(2′,4′,6′- trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na), which is in phase III trials for myelodysplastic syndromes (MDS) associated with aberrant expression of cyclin D proteins.
- Reddy, M. V. Ramana,Venkatapuram, Padmavathi,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Cosenza, Stephen C.,Robell, Kimberly A.,Akula, Balaiah,Hoffman, Benjamin S.,Reddy, E. Premkumar
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experimental part
p. 6254 - 6276
(2011/11/01)
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- p27 PROTEIN INDUCER
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The present invention provides a p27 protein inducing agent comprising a compound represented by general formula (11) below or pharmaceutically acceptable salt thereof as an active ingredient: wherein G1, G2, G3 and G8 are each independently selected from -N= etc., Ring G6 is selected from divalent aryl etc., A is selected from amino etc., G4 is selected from oxygen etc., G5 is selected from oxygen etc., G7 is selected from -CH2- etc., and R2 is selected from C1-6 alkyl etc.
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- NOVEL COUMARIN DERIVATIVE HAVING ANTITUMOR ACTIVITY
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The present invention provides a compound represented by general formula (1) below or a pharmaceutically acceptable salt thereof: wherein: X is selected from heteroaryl etc., Y1 and Y2 are selected from -N= etc., Y3 and Y4 are selected from -CH= etc., A is selected from sulfamide etc., R1 is selected from hydrogen etc., and R2 is selected from C1-6 alkyl etc. The compound or salt has sufficiently high antitumor activity, and is useful in the treatment of cell proliferative disorders, particularly cancers. The present invention also provides a pharmaceutical composition containing the compound or salt as an active ingredient.
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Page/Page column 198
(2008/12/04)
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- Benzylbenzimidazolyl derivatives
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Novel benzyl-benzimidazolyl derivatives as inhibitors of tyrosine kinases, particularly TIE-2, VEGFR, PDGFR, FGFR and/or FLT/KDR, for the treatment of tumors, according to formula (I), wherein the radicals R1, R2, r and s are defined according to Claim (1).
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- BENZYL-BENZIMIDAZOLYL DERIVATIVES
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Novel benzyl-benzimidazolyl derivatives as inhibitors of tyrosine kinases, particularly TIE-2, VEGFR, PDGFR, FGFR and/or FLT/KDR, for the treatment of tumors, according to formula (I), wherein the radicals R1, R2, r and s are defined according to Claim (1).
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Page/Page column 52
(2010/02/11)
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- Synthesis and evaluation of fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives for dopamine D4 receptor imaging
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Seven fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives were synthesized based on a lead ligand, 3-[[4-(4-iodophenyl)piperazin-1-yl]-methyl]- 1H-pyrrolo[2,3-b]pyridine (L-750,667) and evaluated as potential dopamine D 4 receptor imagin
- Oh, Seung-Jun,Lee, Kyo Chul,Lee, Sang-Yoon,Ryu, Eun Kyoung,Saji, Hideo,Choe, Yearn Seong,Chi, Dae Yoon,Kim, Sang Eun,Lee, Jeewoo,Kim, Byung-Tae
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p. 5505 - 5513
(2007/10/03)
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- Solid phase synthesis of vancomycin mimics
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A solid phase synthesis of a model system of the DE ring system of vancomycin is described. The synthesis involved biocatalytic resolutions of unnatural amino acids, is compatible with conventional solid phase peptide synthesis and contains as the key step: an on-be.ad SNAr cyclization. Binding of a cyclic peptide to the carboxylate of N-Ac-D-Ala was demonstrated. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Arnusch, Christopher J.,Pieters, Roland J.
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p. 3131 - 3138
(2007/10/03)
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- Benzimidazole derivatives
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Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of inflammatory and immune-related conditions or disorders. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, immune response regulation and cell proliferation. The subject compounds are 2-amino-imidazole derivatives.
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- Benzoxazepinones and their use as squalene synthase inhibitors
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There is disclosed a compound represented by the formula [I]: wherein R1 is optionally substituted 1-carboxyethyl group, optionally substituted alkyl-sulfonyl group, optionally substituted (carboxy-cycloalkyl)-alkyl group, -X1-X2-Ar-X3-X4-COOH (wherein X1 and X4 are a bond or alkylene group, X2 and X3 are a bond, -O-, -S-, Ar is divalent aromatic group etc.), R2 is alkyl group optionally substituted with alkanoyloxy group and/or hydroxy group, R3 is alkyl group, and W is halogen atom, etc., or a salt thereof. The compound has the cholesterol lowering activity and the triglyceride lowering activity and is useful for preventing and/or treating hyperlipidemia.
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- A rapid access to biaryl ether containing macrocycles by pairwise use of Ugi 4CR and intramolecular S(N)Ar-based cycloetherification.
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[reaction: see text] From readily accessible starting materials, macrocycles with an endo aryl-aryl ether bond are synthesized in only two operations by combination of the Ugi four-component reaction and an intramolecular S(N)Ar reaction. The nitro group serves as an activator for the macrocyclization and provides a handle for the introduction of functional group diversity. A Ugi reaction promoted by ammonium chloride in aprotic solvent is documented for the first time.
- Cristau,Vors,Zhu
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p. 4079 - 4082
(2007/10/03)
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- Synthetic studies towards the synthesis of western and eastern chloropeptin I, II subunits
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The western subunit (16-membered ring) was synthesized by the intramolecular SNAr reaction while the first 16-membered ring compound was obtained as a model of the eastern subunit via an intramolecular Ni0 mediated coupling reaction.
- Roussi, Georges,Gonzalez Zamora, Eduardo,Carbonnelle, Annie-Claude,Beugelmans, Rene
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p. 2041 - 2063
(2007/10/03)
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- Synthetic studies towards glycopeptide antibiotics: Synthesis of the 16-membered cyclic tripeptide (DOEG ring) system of teicoplanin
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The synthesis of the 16-membered cyclic DOEG ring system of teicoplanin, which forms the binding pocked for the carboxylate region of terminal D-Ala-D-Ala of the bacterial cell wall via macroetherification of linear tripeptide 20 is described.
- Rama Rao,Laxma Reddy,Srinivasa Rao,Vittal,Reddy,Pathi
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p. 3023 - 3026
(2007/10/03)
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- The first examples of S(N)Ar-based macrocyclisation: Synthesis of model carboxylate-binding pockets of vancomycin
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Model carboxylate-binding pocket C-O-D rings of vancomycin and related glycopeptides were efficiently synthesized by intramolecular S(N)Ar reaction.
- Beugelmans,Zhu,Husson,Bois-Choussy,Singh
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p. 439 - 440
(2007/10/02)
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- SNAr-Based Macrocyclization: An Application to the Synthesis of Vancomycin Family Models
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The first examples of macrocyclization using the intramolecular SNAr reaction are reported.The method has allowed the efficient preparation of the elusive 16-membered macrocyclic COD and DOE rings related to vancomycin.The mild conditions used allow the incorporation of very racemization-prone amino acids, such as p-methoxyphenylglycine, into the peptide chain.After serving as an activator, the nitro group ortho to the diaryl ether linkage is converted either into a chlorine or a hydrogen atom, thus achieving the substitution pattern found in the vancomycin family of glycopeptides.When compound 20 was submitted to the same macrocyclization conditions, two atropisomers 21 and 22 were isolated and characterized.
- Beugelmans, Rene,Singh, Girij Pal,Bois-Choussy, Michele,Chastanet, Jacqueline,Zhu, Jieping
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p. 5535 - 5542
(2007/10/02)
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