- CHROMAN-SUBSTITUTED, TETRAHYDROQUINOLINE-SUBSTITUTED AND THIOCHROMAN-SUBSTITUTED HETEROAROTINOIDS AS ANTI-CANCER AGENTS
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Chemical compounds that inhibit cancer cell growth are provided. The compounds are heteroarotinoids and derivatives thereof with oxygen, nitrogen or sulfur in chroman systems, tetrahydroquinoline systems, and tetrahydrothiochroman systems.
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- Activity of oxygen-versus sulfur-containing analogs of the Flex-Het anticancer agent SHetA2
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Five series of chromans with urea and thiourea linkers connecting a chroman unit (ring A) and a 4-substituted benzene unit (ring B) have been prepared and evaluated relative to SHetA2 (NSC 721689) for activity against the human A2780 ovarian cancer cell l
- Watts, Field M.,Pouland, Tim,Bunce, Richard A.,Berlin, K. Darrell,Benbrook, Doris M.,Mashayekhi, Maryam,Bhandari, Dipendra,Zhou, Donghua
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p. 720 - 732
(2018/09/29)
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- Co-Catalyzed Hydroarylation of Unactivated Olefins
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A mild, general, scalable, and functional group tolerant intramolecular hydroarylation of unactivated olefins using a Co(salen) complex, a N-fluoropyridinium salt, and a disiloxane reagent was reported. This method, which was carried out at room temperature, afforded six-membered benzocyclic compounds from mono-, 1,1- or trans-1,2-di, and trisubstituted olefins.
- Shigehisa, Hiroki,Ano, Takuya,Honma, Hiroshi,Ebisawa, Kousuke,Hiroya, Kou
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p. 3622 - 3625
(2016/08/16)
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- Friedel-Crafts cyclization of tertiary alcohols using bismuth(III) triflate
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Bismuth(III) triflate [Bi(OTf)3] has been developed as an efficient and mild catalyst for intramolecular Friedel-Crafts cyclizations of tertiary alcohols to prepare disubstituted tetrahydronapthalenes, chromans, thiochromans, tetrahydroquinolin
- Nammalwar, Baskar,Bunce, Richard A.
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supporting information
p. 4330 - 4332
(2013/07/26)
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- HETEROCYCLIC GPR40 MODULATORS
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The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.
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Page/Page column 158
(2008/06/13)
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- Synthesis of heterocycles via ligand-free palladium catalyzed reductive Heck cyclization
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Synthesis of five and six membered heterocycles, indolines, 2,3-dihydrobenzofurans, chromans, isochromans, 1,2,3,4-tetrahydroquinolines, and 1,2,3,4-tetrahydroisoquinolines, in 70-99% yield by a ligand-free palladium catalyzed reductive Heck cyclization of phenyl bromides and chlorides, under mild conditions, is reported. Water was found to be essential for these reactions.
- Liu, Pingli,Huang, Liang,Lu, Yuelie,Dilmeghani, Mina,Baum, Jean,Xiang, Tingjian,Adams, Jeff,Tasker, Andrew,Larsen, Rob,Faul, Margaret M.
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p. 2307 - 2310
(2007/10/03)
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- Biaromatic compounds and pharmaceutical and cosmetic compositions comprising them
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Biaromatic compounds connected by a propynylene or ailenylene bond, corresponding to the formula (I).
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Page column 10
(2010/02/04)
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- Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
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Retinoid-like activity is exhibited by compounds of the formula STR1 where X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; and B is H, --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH2 OH or an ether or ester derivative, or --CHO or an acetal derivative, or --COR1 or a ketal derivative where R1 is --(CH2)m CH3 where m is 0-4, or a pharmaceutically acceptable salt thereof.
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- Process for preparing 4,4-dialkyl-6-halo-chromans or thiochromans useful as pharmaceutical intermediates
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A process of preparing intermediates useful in making compounds with retinoic acid-like activity is disclosed. The intermediates are halogenated chromans and thiochromans of the formula shown below and are prepared by the alkylation of a phenol or thiophe
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- Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
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Retinoid-like activity is exhibited by compounds of the formula STR1 where X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-2; and B is H, --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH2 OH or an ether or ester derivative, or --CHO or an acetal derivative, or --COR1 or a ketal derivative where R1 is --(CH2)m CH3 where m is 0-4, or a pharmaceutically acceptable salt thereof.
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- Chroman esters of phenols and benzoic acids having retinoid-like activity
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Retinoid like activity is exhibited by compounds of the formula STR1 wherein the R 1 -R 7 groups are independently H or straight chain or branched chain lower alkyl or cycloalkyl of 1 to 6 carbons; X symbolizes an ester or thioester linkage, Y is cycloalk
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- Heteroarotinoids as anticancer agents
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Novel heteroarotinoid compositions characterized by the formulae: STR1 where: X is S or O; OAc is the acetate group STR2 and R is --H, --OH, --OCH3, or --OC2 H5 and includes STR3 for formulae (1) and (2). Such compositions exhibit activity as anticancer agents.
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- Acetylenes disubstituted with a phenyl group and a heterobicyclic group having retinoid-like activity
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Retinoid-like activity is exhibited by compounds of the formula STR1 where X is S, O or NR 1 where R 1 is hydrogen or lower alkyl; n is 0-5; R is H or lower alkyl and A is H, --COOH or a pharmaceutically acceptable salt, ester or amide thereof, --CH 2 OH or an ether or ester derivative thereof, or --CHO or an acetal derivative thereof, or --COR 2 or a ketal derivative thereof where R 2 is --(CH 2) m CH 3 where m is 0-4; or a pharmaceutically acceptable salt.
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- Heteroarotinoid compounds as anticancer agents
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Novel heteroarotinoid compositions characterized by the formulae: STR1 where R is H, CH3 or C2 H5 and X is S, S O, O, NCH3, Si(CH3)2, N+ (H)CH3 [Cl- ], N+ (H)CH3 [Br- ] or N+ (alkyl) CH3 [Cl- or Br-) where alkyl is CH3, C2 H5, CH2 =CHCH2 or C6 H5 CH2. Such compositions exhibit activity as anticancer agents.
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- Heteroarotinoids as anticancer agents
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Novel heteroarotinoid compositions characterized by the formulae: STR1 where: X is S or O; OAc is the acetate group STR2 and R is --H, --OH, --OCH3, or --OC2 H5 and includes STR3 for formulae (1) and (2). Such compositions exhibit activity as anticancer agents.
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- Method for inhibiting the degradation of cartilage
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Certain carboxylic acids of the formula STR1 and the pharmaceutically-acceptable salts thereof, and certain esters and amides thereof, are useful for inhibiting the degradation of articular cartilage when administered to a mammalian subject afflicted with
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- Prenylation of isopentenyl derivatives with 2-methyl-3-buten-2-ol
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The synthesis of the regular terpene skeleton from the title compounds has been investigated, a variety of isopentenylethers proved very reactive.Similar prenylation of 3,3-dimethylallyl derivatives led to the irregular terpene skeleton.
- Julia, M.,Schmitz, C.
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p. 630 - 636
(2007/10/02)
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- Synthesis and Characterization of Selected Heteroarotinoids. Pharmacological Activity as Assessed in Vitamin A Deficient Hamster Tracheal Organ Cultures. Single-Crystal X-ray Diffraction Analysis of 4,4-Dimethylthiochroman-6-yl Methyl Ketone 1,1-Dioxide and Ethyl (E)-p-<2-(4,4-Dimeth...
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There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-benzoate (1b), ethyl (E)-p-benzoate (1c), ethyl (E)-p-benzoate (1d), and (E)-p-benzoic acid (1e).IR, 1H NMR and 13C NMR data have been recorded for each compound and support the structural assignments.To provide a firm basis for comparison purposes of future analogues, an X-ray analysis was performed on asingle crystal of ethyl (E)-p-benzoate (1b) and a precursor 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide (18).These data for the heteroarotinoid 1b revealed that the two aryl ring systems were nearly perpendicular in each of the two molecules present in the unit cell (86.37 deg and 84.17 deg, respectively).The space group for both molecules was P1 in triclinic systems.Unit cell dimensions (at 15 deg C) are as follows: for 1b, a = 20.568 (6) Angstroem, b = 14.760 (3) Angstroem, c = 7.679 (2) Angstroem, α = 113.33 (2) deg, β = 79.45 (2) deg, γ = 79.98 (2) deg, Z = 4; for 18, a = 9.292 (5) Angstroem, b = 9.291 (5) Angstroem, c = 7.951 (3) Angstroem, α = 102.16 (3) deg, β = 77.49 (3) deg, γ = 79.60 (4) deg, Z = 2.The sulfur containing ring is in a distorted half-chair in 1b and the methyl carbon C(12) is shown to be trans to H(13) at the C(11)-C(13) bond.The biological activity of these arotinoids was determined in the tracheal organ culture asssay and compared with trans-retinoic acid for ability to reverse keratinization in vitamin A deficient hamsters.The ester 1b displayed activity about one-half log unit less than of the ref erence while 1c and 1e had activity nearly one log until less than trans-retinoic acid.The sulfoxide was the least active of the heteroretinoids.
- Waugh, Kristy M.,Berlin, K. Darrell,Ford, Warren T.,Holt, Elizabeth M.,Carrol, John P.,et al.
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p. 116 - 124
(2007/10/02)
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- Conformationally Restricted Retinoids
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A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter.These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring.The meta-substituted analogue 3 of 4-benzoic acid (2) was far less active than 2 in both assays.In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2.Analogues of 4-benzoic acid (7) were also screened.Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10).Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity.Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity.Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19).Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1.Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice.Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.
- Dawson, Marcia I.,Hobbs, Peter D.,Derdzinski, Krzysztof,Chan, Rebecca L.-S.,Gruber, John,et al.
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p. 1516 - 1531
(2007/10/02)
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- Methylase Models: Intramolecular Alkylation of a Phenol by an Adenosyl Sulphonium Salt
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The newly synthesized adenosylsulphonium ion, (2), undergoes a facile ring closure reaction in aqueous oxyanion buffers; in contrast, amine buffers effect an intermolecular dealkylation in competition with the lyate reaction.
- Vasquez, Peter J.,Coward, James K.
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p. 698 - 699
(2007/10/02)
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- Methylase Models: Studies on General-Base vs. Nucleophilic Catalysis in the Intramolecular Alkylation of Phenols
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The ortho substituted phenols, 1 and 3, have been synthesized as models for the O-methylation of catecholamines, as catalyzed by catechol O-methyltransferase.The decomposition of 1 and 3 was studied at 40 deg C over a wide range of pH in both oxyanion and
- Knipe, Jay O.,Vasquez, Peter J.,Coward, James K.
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p. 3202 - 3209
(2007/10/02)
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