- RETINOID COMPOUND, PREPARATION METHOD THEREFOR, INTERMEDIATES THEREOF AND APPLICATION THEREOF
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Disclosed are a retinoid compound, a preparation method therefor, intermediates thereof and an application thereof. The retinoid compound I of the present invention has a good tumor growth inhibition rate.
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Paragraph 0136; 0137
(2019/01/29)
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- Hypervalent-Iodine-Mediated Formation of Epoxides from Carbon(sp2)-Carbon(sp3) Single Bonds
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We have developed an efficient method for direct formation of epoxide groups from carbon(sp2)-carbon(sp3) single bonds of β-keto esters; the reaction is mediated by the water-soluble hypervalent iodine(V) reagent AIBX (5-trimethylammonio-1,3-dioxo-1,3-dihydro-1λ5-benzo[d][1,2]iodoxol-1-ol anion). On the basis of the results of density functional theory calculations and experimental studies, we propose that the reaction proceeds by a two-stage mechanism involving dehydrogenation of the β-keto ester substrates and epoxidation of the resulting enone intermediates. The rate-limiting step is abstraction of the β′-C-H (calculated free energy of activation, 24.5 kcal/mol).
- Jiang, Shan,Yan, Tai-Shan,Han, Yong-Chao,Cui, Li-Qian,Xue, Xiao-Song,Zhang, Chi
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p. 11691 - 11702
(2017/11/24)
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- Cu-Catalyzed cascades to carbocycles: Union of diaryliodonium salts with alkenes or alkynes exploiting remote carbocations
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Copper-catalyzed cascade reactions between alkenes or alkynes and diaryliodonium salts form carbocyclic products in a single step. Arylation of the unsaturated functional group is proposed to form a carbocation intermediate that facilitates hydride shift pathways to translocate the positive charge to a remote position and enables ring formation via a Friedel-Crafts-type reaction.
- Zhang, Fengzhi,Das, Shoubhik,Walkinshaw, Andrew J.,Casitas, Alicia,Taylor, Michael,Suero, Marcos G.,Gaunt, Matthew J.
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supporting information
p. 8851 - 8854
(2014/07/08)
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- Conformationally restricted novel pyrazole derivatives: Synthesis of 1,8-disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g]indazoles as a new class of PDE4 inhibitors
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A number of novel 1,8-disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g] indazoles based on a conformationally restricted pyrazole framework have been designed as potential inhibitors of PDE4. All these compounds were readily prepared by using simple chem
- Shyamsunder Reddy,Shiva Kumar,Meda, Chandana L.T.,Kandale, Ajit,Rambabu,Rama Krishna,Hariprasad,Venugopala Rao,Venkataiah,Malla Reddy,Naidu,Dubey,Parsa, Kishore V.L.,Pal, Manojit
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body text
p. 3248 - 3255
(2012/06/29)
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- O- or S- substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
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Compounds of the formula where the symbols have the meaning described in the application, have retinoid-like or retinoid antagonist-like biological activity.
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Page column 72
(2010/11/29)
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- Method for inhibiting gene expression promoted by AP1 protein with RAR beta selective retinoids and method for treatment of diseases and conditions with such retinoids
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Retinoid compounds which repress expression of the gene promoted by AP1 protein but which do not significantly activate expression of the genes having RA-responsive elements in their promoter region through RAR alpha and RAR GAMMA receptor subtypes, are u
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- Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities
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Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.
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- SYNTHESIS AND USE OF RETINOID COMPOUNDS HAVING NEGATIVE HORMONE AND/OR ANTAGONIST ACTIVITIES
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2,2-Dialkyl-4-aryl-substituted benzopyran and benzothiopyran derivatives of the formula STR1 where the symbols have the meaning described in the specification, have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists.
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- High affinity retinoic acid receptor antagonists: Analogs of AGN 193109
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A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para- position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the presence of polar functionality was also well tolerated.
- Johnson, Alan T.,Wang, Liming,Gillett, Samuel J.,Chandraratna, Roshantha A. S.
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p. 573 - 576
(2007/10/03)
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- Oxime substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity
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Compounds of the formula STR1 have retinoid-like or retinoid antagonist-like biological activity.
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- Clarification of the binding mode of teleocidin and benzolactams to the Cys2 domain of protein kinase Cδ by synthesis of hydrophobically modified, teleocidin-mimicking benzolactams and computational docking simulation
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Phorbol esters (12-O-tetradecanoylphorbol 13-acetate; TPA) and teleocidins are known to be potent tumor promoters and to activate protein kinase C (PKC) by binding competitively to the enzyme. The relationship between the chemical structures and the activities of these compounds has attracted much attention because of the marked structural dissimilarities. The benzolactam 5, with an eight-membered lactam ring and benzene ring instead of the nine-membered lactam ring and indole ring of teleocidins, reproduces the active ring conformation and biological activities of teleocidins. Herein we describe the synthesis of benzolactams with hydrophobic substituents at various positions. Structure-activity data indicate that the existence of a hydrophobic region between C-2 and C-9 and the steric factor at C-8 play critical roles in the appearance of biological activities. We also computationally simulated the docking of teleocidin and the modified benzolactam molecules to the Cys2 domain structure observed in the crystalline complex of PKCδ with phorbol 13-acetate. Teleocidin and benzolactams fitted well into the same cavity as phorbol 13-acetate. Of the three functional groups hydrogenbonding to the protein, two hydrogen-bonded with protein atoms in common with phorbol 13-acetate, but the third one hydrogen-bonded with a different protein atom from that in the case of phorbol 13-acetate. The model explains well the remarkable difference in activity between 5 and its analogue having a bulky substituent at C-8.
- Endo, Yasuyuki,Takehana, Shunji,Ohno, Michihiro,Driedger, Paul E.,Stabel, Silvia,Mizutani, Miho Y.,Tomioka, Nobuo,Itai, Akiko,Shudo, Koichi
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p. 1476 - 1496
(2007/10/03)
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- Retinoid-like compounds
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The present invention relates to a compound of formula I STR1 or a nontoxic pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof, in whichX is --O--CO--, --NH--CO--, --CS--NH--, --CO--O--, --CO--NH--, --COS--, --SCO--, --SCH 2 --, --CH 2 --CH 2 --, --C C--, --CH 2 --NH--, --COCH 2 --, --NHCS--, --CH 2 S--, --CH 2 O--, --OCH 2 --, --NHCH 2 -- or --CR 5 CR 6 --;R m and R k are independently hydrogen, halogen, C 1-6 alkyl, hydroxy, C 1-6 alkyloxy or nitro;n is zero or one;R 4 is --(CH 2) t --Y, C 1-6 alkyl, or C 3-6 cycloalkyl;R 1 is --CO 2 Z, C 1-6 alkyl, CH 2 OH, --CONHR y, or CHO;R 2 and R 3 are independently hydrogen or C 1-6 alkyl;R a and R b are independently hydrogen or C 1-6 alkyl; but when n is one, R a and R b together can form a radical of the formula STR2 Y is naphthyl or phenyl, both radicals can be optionally substituted with one to three same or different C 1-6 alkyl or halogen;Z is hydrogen or C 1-6 alkyl;R 5, R 6 and R y are independently hydrogen or C 1-6 alkyl; andt is zero to six.
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- Retinoid-like compounds
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The present invention relates to a compound of formula STR1 or a nontoxic pharmaceutically acceptable salt, physiologically hydrolyzable ester or solvate thereof, in which X is --O--CO--, --NH--CO--, --CS--NH--, --CO--O--, --CO--NH--, --COS--, --SCO--, --SCH2 --, --CH2 --CH2 --, --C C--, --CH2 --NH--, --COCH2 --, --NHCS--, --CH2 S--, --CH2 O--, --OCH2 --, --NHCH2 -- or --CR5 =CR6 --; Rm and Rk are independently hydrogen, halogen, C1-6 alkyl, hydroxy, C1-6 alkyloxy or nitro; n is zero or one; R4 is --(CH2)t --Y, C1-6 alkyl, or C3-6 cycloalkyl; R1 is --CO2 Z, C1-6 alkyl, CH2 OH, --CONHRy, or CHO; R2 and R3 are independently hydrogen or C1-6 alkyl; Ra and Rb are independently hydrogen or C1-6 alkyl; but when n is one, Ra and Rb together can form a radical of the formula STR2 Y is naphthyl or phenyl, both radicals can be optionally substituted with one to three same or different C1-6 alkyl or halogen; Z is hydrogen or C1-6 alkyl; R5, R6 and Ry are independently hydrogen or C1-6 alkyl; and t is zero to six.
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- Acetylenes disubstituted with a 5-amino or substituted 5-amino substituted tetrahydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity
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Compounds of the formula STR1 having retinoid like biological activity.
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