- Synthesis and biological evaluation of p-carborane bisphenols and their derivatives: Structure-activity relationship for estrogenic activity
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p-Carborane bisphenols and their derivatives were prepared and evaluated for binding affinity to estrogen receptor α. Their estrogenic activity was evaluated by means of transcriptional assay and cell proliferation assay using MCF-7 cell lines. 1,12-Bis(4
- Ogawa, Takumi,Ohta, Kiminori,Iijima, Toru,Suzuki, Tomoharu,Ohta, Shigeru,Endo, Yasuyuki
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- Design and synthesis of an activity-based protein profiling probe derived from cinnamic hydroxamic acid
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In our continued effort to discover new anti-hepatitis C virus (HCV) agents, we validated the anti-replicon activity of compound 1, a potent and selective anti-HCV hydroxamic acid recently reported by us. Generally favorable physicochemical and in vitro absorption, distribution, metabolism, and excretion (ADME) properties exhibited by 1 made it an ideal parent compound from which activity-based protein profiling (ABPP) probe 3 was designed and synthesized. Evaluation of probe 3 revealed that it possessed necessary anti-HCV activity and selectivity. Therefore, we have successfully obtained compound 3 as a suitable ABPP probe to identify potential molecular targets of compound 1. Probe 3 and its improved analogs are expected to join a growing list of ABPP probes that have made important contributions to not only the studies of biochemical and cellular functions but also discovery of selective inhibitors of protein targets.
- Ai, Teng,Qiu, Li,Xie, Jiashu,Geraghty, Robert J.,Chen, Liqiang
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Read Online
- CELL SURFACE RECEPTOR BINDING COMPOUNDS AND CONJUGATES
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The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface receptor, such as a mannose-6-phosphate receptor (M6PR) or a cell surface asialoglycoprotein receptor (ASGPR). The cell surface M6PR or ASGPR binding compounds can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor, e.g., M6PR or ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided are methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.
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Paragraph 00915-00916
(2021/07/17)
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- Total Synthesis of Asparenydiol by Two Sonogashira Cross-Coupling Reactions Promoted by Supported Pd and Cu Catalysts
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Asparenydiol, which is an important natural compound with potential pharmacological activities, was synthesized through two Sonogashira cross-coupling reactions catalyzed by supported Pd and Cu catalysts and by a Mitsunobu etherification. The optimization
- Angelici, Gaetano,Carpita, Adriano,Casotti, Gianluca,Evangelisti, Claudio,Ferreri, Matteo,Fusini, Graziano,Pardini, Luca Fidia
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p. 1795 - 1803
(2020/06/08)
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- ANDROGEN RECEPTOR MODULATORS AND METHODS FOR THEIR USE
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The present invention relates to compounds of formula (I)-(VI) and/or (A)-(H-I), or any subgenera thereof, or a pharmaceutically acceptable salt, tautomer or stereoisomer. The compounds of the present disclosure are useful in modulating androgen receptor activity and for treating cancer including prostate cancer.
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Paragraph 0996; 0997
(2020/05/06)
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- NOVEL MACROCYCLIC DERIVATIVES, PROCESS FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
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Compound of formula (I): wherein A1, A2, Ra, Rb, Rc, Rd, R3, R4, X, Y and G are as defined in the description, and their use in the manufacture of medicaments.
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Paragraph 0394-0396
(2020/08/25)
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- Efficient synthesis of 3-benzoyl Benzo[b]thiophenes and raloxifene via Mercury(II)-Catalyzed cyclization of 2-alkynylphenyl alkyl sulfoxides
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The unique selective estrogen receptor modulator, Raloxifene (1), and antitubulin agent 2 were synthesized through the key intermediate, 4-methoxybenzyl 2-bromo-4-methoxyphenyl sulfoxide (6), respectively. It was found that compared with the o-sulfanyl aryl bromides, the sulfinyl group at ortho position accelerated the Sonogashira coupling reaction of aryl bromides. Thus, compound 6 was coupled with 3,4,5-trimethoxyphenyl acetylene, followed by mercury-catalyzed cyclization reaction afford compound 2 in 79% overall yield. Raloxifene (1) was prepared from compound 6 in four steps and 33% overall yield via coupling reaction with 1-trimethylsily-2-(4-tert-butyldimethylsiloxy)phenylethyne, mercury-catalyzed cyclization reaction, alkylation and demethylation.
- Wen, Shi-Ming,Lin, Cheng-Han,Chen, Chin-Chau,Wu, Ming-Jung
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p. 2493 - 2499
(2018/04/16)
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- AN ISOXAZOLE DERIVATIVES AS NUCLEAR RECEPTOR AGONISTS AND USED THEREOF
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The present invention relates to isoxazole derivatives, including pharmaceutical compositions and for the preparation of isoxazole derivatives. And more particularly the present invention provided a pharmaceutical composition of isoxazole derivatives for activation of Farnesoid X receptor(FXR, NR1H4).
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Paragraph 608-611
(2018/11/10)
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- Sulfoxide compound and method of producing benzothiophene derivatives using the same
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A sulfoxide compound and method of producing benzothiophene derivatives using the same are provided. The sulfoxide compound is represented by formula (I), wherein R1 and R2 are individually and independently benzoyl group; alkyl, acyl or silyl group of C1-C6 straight chain or branched chain; or alkenyl group of C3-C6 straight chain or branched chain; and X is halogen atom. The sulfoxide compound reacts with alkynyl compound, and then the synthesis efficiency of benzothiophene derivatives can be effectively increased.
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Page/Page column 11; 12
(2017/09/26)
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- Synthesis and evaluation of (E)-2-(5-phenylpent-2-en-4-ynamido)cyclohex-1-ene-1-carboxylate derivatives as HCA2 receptor agonists
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Novel series of compounds consisting of 2-amidocyclohex-1-ene carboxylate and phenyl parts which are connected by enyne (compounds 2a–f), but-1-yne (compounds 4a–j), and phenylethylene (compounds 5a–f) linkers as HCA2 full agonists were designed and their
- Bobileva, Olga,Ikaunieks, Martins,Duburs, Gunars,Mandrika, Ilona,Petrovska, Ramona,Klovins, Janis,Loza, Einars
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p. 4314 - 4329
(2017/07/22)
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- OXIME DERIVATIVE, METHOD OF PRODUCING THE SAME AND INSECTICIDE COMPRISING THE SAME AS ACTIVE INGREDIENT
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PROBLEM TO BE SOLVED: To provide a compound having excellent insecticidal effect and useful as an active ingredient of an insecticide. SOLUTION: This invention provides an oxime derivative represented by general formula (1) (where Ra, X and n represent definitions described in the specifications) and an insecticide that comprises the same as an active ingredient. COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0254-0256
(2018/10/03)
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- Design and diastereoselective synthesis of C-2,C-20-diaryl steroidal derivatives
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A novel and efficient synthetic strategy to access unique C-2 substituted steroid analogues 3 and 4 is described. The unusual C-2 aryl ether analogues 3 were shown to act as virtual antagonists of LRH-1 and were prepared as single diastereoisomers, employing a fifteen-step sequence from pregnenolone (9). The key steps include the stereoconvergent nucleophilic displacement of an epimeric mixture of 3-keto 2-bromo steroids, chemoselective carbonylation of an enol triflate and conversion of a thiopyridyl ester into an aryl ketone. The related C-2 benzyl analogues 4 were prepared in a similar manner. Starting from pregnenolone, a diastereoselective fifteen-step synthesis was developed to access novel C-2-substituted steroid analogues. A range of C-2 benzyl and aryl ether analogues were prepared to probe their efficacy as antagonists of the nuclear receptor LRH-1. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Rey, Jullien,O'Riordan, Timothy J. C.,Hu, Haipeng,Snyder, James P.,White, Andrew J. P.,Barrett, Anthony G. M.
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supporting information; experimental part
p. 3781 - 3794
(2012/10/08)
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- MODULATORS OF THE PROSTACYCLIN (PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
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The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to metho
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Page/Page column 173
(2009/10/22)
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- Biphenyl compounds and use thereof as oestrogenic agents
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A compound having the formula wherein R5 is an [A]—CH3, —[A]—C(OH)ZZ′ or —[A]—C(O)Z″ grouping where —[A]— is an alkylene, alkenylene or alkynylene radical or a single bond, and Z, Z′ and Z″ are a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl or aryl radical; and R1, R2, R3, R4, R6, R7 and R8 are as defined in the description; the use thereof as a drug, pharmaceutical compositions containing same, a preparation method therefor, and intermediates of said method, are disclosed.
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- Highly efficient and selective procedures for the synthesis of γ-alkylidenebutenolides via palladium-catalyzed ene-yne coupling and palladium- or silver-catalyzed lactonization of (Z)-2-en-4-ynoic acids. Synthesis of rubrolides A, C, D, and E
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The diacetates of rubrolides A, C, D, and E (1 a-d) were prepared in modest yields by the Pd-catalyzed cross coupling-lactonization tandem reaction of 5a or 5b with 6a or 6b using Cl2Pd(PPh3)2 and CuI as catalysts. The feasibility of converting the diacetates into rubrolides was demonstrated by the synthesis of rubrolide C by treatment of 1b with methanolic K2CO3 in THF. A detailed investigation of various parameters and conditions has indicated that formation of the corresponding six-membered lactones 7 and/or the cross coupling-lactonization-Heck substitution products 11 can be serious side reactions under non-optimized conditions and that the use of Pd(PPh3)4 rather than phosphine-free complexes, e.g., CI2Pd(PhCN)2, or complexes of low phosphine content, e.g., Cl2Pd(PPh3)2, along with CuI and NEt3 in MeCN provides satisfactory conditions for the cross coupling-lactonization tandem reaction. Thus, the diacetate of rubrolide A (1a) was prepared in 70% isolated yield. The optimized conditions reported herein appear to be generally applicable to the stereoselective and regioselective synthesis of γ-alkylidenebutenolides in a highly efficient manner.
- Kotora, Matin,Negishi, Ei-Ichi
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p. 121 - 128
(2007/10/03)
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- Quinclidine derivatives as squalene synthase inhibitors
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Quinuclidine derivatives of formula, and their pharmaceutically acceptable salts, in which: R1 is hydrogen or hydroxy; R2 is hydrogen; pr R1 and R2 are joined together so that CR1 -CR2 is a
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- Arocalciferols: Synthesis and biological evaluation of aromatic side-chain analogues of 1α,25-dihydroxyvitamin D31a
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Aromatic side-chain analogues (arocalciferols 6-9) of the steroid hormone 1α,25-dihydroxyvitamin D3 (1) were synthesized and biologically evaluated. The analogues were prepared by coupling the vitamin D A-ring enyne 14 with the appropriate enol
- Figadere,Norman,Henry,Koeffler,Zhou,Okamura
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p. 2452 - 2463
(2007/10/02)
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