- CYCLIC CYANOENONE DERIVATIVES AS MODULATORS OF KEAP1
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The present invention relates to cyclic cyanoenone derivatives of Formula (I) or pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, R3, R4 and m are as defined herein. The present invention also relates to pharmaceutical compositions comprising the cyclic cyanoenone derivatives of Formula (I) and to their use in therapy.
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- EMULSION WITH IMPROVED BIOABSORPTION COMPOSITION COMPRISING CATIONIC POLYESTER COPOLYMER AND HYDROPHOBIC DRUG AND METHOD FOR PREPARING THE SAME
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The present invention relates to an emulsion composition with an improved bioabsorption rate containing a cationic polyester-based copolymer, and a poorly soluble drug. The emulsion composition comprises: a cationic polyester-based copolymer including a c
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Paragraph 0122; 0126
(2019/01/12)
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- Hydrogen Borrowing Catalysis with Secondary Alcohols: A New Route for the Generation of β-Branched Carbonyl Compounds
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A hydrogen borrowing reaction employing secondary alcohols and Ph? (Me5C6) ketones to give β-branched carbonyl products is described (21 examples). This new C-C bond forming process requires low loadings of [Cp?IrCl2]2, relatively low temperatures, and up to 2.0 equiv of the secondary alcohol. Substrate-induced diastereoselectivity was observed, and this represents the first example of a diastereoselective enolate hydrogen borrowing alkylation. By utilizing the Ph? group, the β-branched products could be straightforwardly cleaved to the corresponding esters or amides using a retro-Friedel-Crafts reaction. Finally, this protocol was applied to the synthesis of fragrance compound (±)-3-methyl-5-phenylpentanol.
- Akhtar, Wasim M.,Cheong, Choon Boon,Frost, James R.,Christensen, Kirsten E.,Stevenson, Neil G.,Donohoe, Timothy J.
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supporting information
p. 2577 - 2580
(2017/03/01)
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- FeCl3·6H2O/acetaldehyde, a versatile system for the deprotection of ketals and acetals via a transacetalization process
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Mild and efficient catalytic deprotection of ketals/acetals mediated by FeCl3·6H2O/acetaldehyde has been described in this paper. The versatility and high chemoselectivity of the iron(iii)/aldehyde system are demonstrated by a large scope of examples. Deprotected ketones/aldehydes are nearly quantitatively isolated after filtration over a pad of silica gel followed by evaporation of volatile by-products.
- Schiavo, Lucie,Jeanmart, Lo?c,Lanners, Steve,Choppin, Sabine,Hanquet, Gilles
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p. 1421 - 1424
(2017/02/23)
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- AMINOACYLINDAZOLE IMMUNOMODULATORS FOR TREATMENT OF AUTOIMMUNE DISEASES
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2-Acylindazole compounds of formula I or formula II are disclosed. These compounds inhibit Coagulation Factor XIIa. They are useful to treat autoimmune diseases.
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Paragraph 532
(2017/12/29)
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- Development of Phenyl Cyclohexylcarboxamides as a Novel Class of Hsp90 C-terminal Inhibitors
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Inhibition of the heat shock protein 90 (Hsp90) C-terminus represents a promising therapeutic strategy for the treatment of cancer. Novobiocin, a coumarin antibiotic, was the first Hsp90 C-terminal inhibitor identified, however, it manifested poor anti-proliferative activity (SKBr3, IC50≈700 μm). Subsequent structure–activity relationship (SAR) studies on novobiocin led to development of several analogues that exhibited improved anti-proliferative activity against several cancer cell lines. Recent studies demonstrate that the biphenyl core could be used in lieu of the coumarin ring system, which resulted in more efficacious analogues. In continuation of previous efforts, the work described herein has identified the phenyl cyclohexyl core as a novel scaffold for Hsp90 C-terminal inhibition. Structure–activity relationship (SAR) studies on this scaffold led to the development of compounds that manifest mid-nanomolar activity against SKBr3 and MCF-7 breast cancer cell lines through Hsp90 inhibition.
- Garg, Gaurav,Forsberg, Leah K.,Zhao, Huiping,Blagg, Brian S. J.
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supporting information
p. 16574 - 16585
(2017/11/13)
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- COMPOUNDS USEFUL AS KINASE INHIBITORS
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This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK).The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.
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Paragraph 00226; 00287; 00288
(2017/07/14)
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- Stereoelectronic Model to Explain Highly Stereoselective Reactions of Seven-Membered-Ring Oxocarbenium-Ion Intermediates
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Nucleophilic attack on seven-membered-ring oxocarbenium ions is generally highly stereoselective. The preferred mode of nucleophilic attack forms the product in a conformation that minimizes transannular interactions, thus leading to different stereoselectivity as compared to that of reactions involving six-membered-ring oxocarbenium ions.
- Beaver, Matthew G.,Buscagan, Trixia M.,Lavinda, Olga,Woerpel
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supporting information
p. 1816 - 1819
(2016/02/03)
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- A 5-hydrocarbyloxy-2-oxo-cyclohexyl amide compound and its preparation method and application
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The invention belongs to the technical field of agricultural chemistry, and particularly relates to a 5-oxyl-2-oxocyclohexylsulfonamide compound as well as a preparation method and application thereof. The preparation method comprises the following steps:
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Paragraph 0026; 0029; 0030; 0032
(2016/10/31)
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- PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS
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The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
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Page/Page column 78
(2015/10/05)
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- Discovery of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as potent NOP and opioid receptor agonists
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We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors.
- Schunk, Stefan,Linz, Klaus,Frormann, Sven,Hinze, Claudia,Oberb?rsch, Stefan,Sundermann, Bernd,Zemolka, Saskia,Englberger, Werner,Germann, Tieno,Christoph, Thomas,K?gel, Babette-Y.,Schr?der, Wolfgang,Harlfinger, Stephanie,Saunders, Derek,Kless, Achim,Schick, Hans,Sonnenschein, Helmut
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supporting information
p. 851 - 856
(2014/09/17)
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- A combined experimental and computational study of the substituent effect on micellar behavior of γ-substituted thermoresponsive amphiphilic poly(ε-caprolactone)s
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The effect of the core substituent structure on the micellar behavior of thermoresponsive amphiphilic poly(ε-caprolactone) diblock copolymer micelles was investigated through a combination of experimental and computational methods. The polycaprolactone (P
- Hao, Jing,Cheng, Yixing,Ranatunga, R. J. K. Udayana,Senevirathne, Suchithra,Biewer, Michael C.,Nielsen, Steven O.,Wang, Qian,Stefan, Mihaela C.
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p. 4829 - 4838
(2013/07/26)
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- PENTYLENETETRAZOLE DERIVATIVES
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Provided are compounds having formula I: ( l ) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as disclosed herein, or a pharmaceutically
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Page/Page column 36
(2012/11/14)
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- CYCLOHEXANE ANALOGUES AS GPR119 AGONISTS
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This invention relates to a series of substituted cyclohexane containing analogues which are agonists of GPR119 intended to treat metabolic diseases mediated by GPR119 including Type I & II diabetes mellitus. Diabetes mellitus is an ever-increasing threat to human health causing various complications (blindness, kidney failure, neuropathy, heart attack, stroke, etc.). Recently it was found that activation of GPR119 which is highly expressed in pancreatic beta cells causes glucose dependent insulin secretion and GLP-1 release. Many pharmaceuticals are currently developing GPR119 agonists and herein we disclose alternative GPR119 agonists. Our invention describes GPR119 agonists having structural Formula (I), pharmaceutically acceptable salt or solvate of Formula (I), isomer or prodrug of Formula (I), and combination therapy of Formula (I) with other anti-diabetic drugs like DPP-IV inhibitors and/or insulin sensitizers.
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Page/Page column 23
(2012/03/12)
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- Spectroscopic and X-ray crystallographic evidence for electrostatic effects in 4-substituted cyclohexanone-derived hydrazones, imines, and corresponding salts
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The axial conformer of several 4-substituted cyclo-hexanone hydrazone salts was found to predominate in solution. Changes in the charge of the molecule and the polarity of the solvent led to changes in the conformational preference of each molecule that were consistent with electrostatic stabilization of the axial conformer. H NMR spectroscopic analysis was utilized to determine the structure of cyclohexanone-derived substrates by comparison to conformationally restricted trans-decalone derivatives and computational models. X-ray crystallography demonstrated that the axial configuration of a pendant benzyloxy group is the preferred conformation of an iminium ion in the solid state. The structure of a neutral hydrazone was also determined to favor the axial configuration for a pendant benzyloxy group in the solid state.
- Dibble, David J.,Ziller, Joseph W.,Woerpef
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supporting information; experimental part
p. 7706 - 7719
(2011/12/02)
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- HERBICIDALLY ACTIVE 2-(SUBSTITUTED-PHENYL)-CYCLOPENTANE-1,3-DIONE DERIVATIVES
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Compounds of formula (I) are suitable for use as herbicides: wherein R is methyl, ethyl, vinyl, ethynyl or cyclopropyl, R1 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C7cycloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, vinyl, propenyl, ethynyl, propynyl, halogen, or optionally substituted phenyl, R2 is methyl, ethyl, vinyl, ethynyl or methoxy, R3 and R4 are hydrogen or together form a double bond, A is C3-C7cycloalkyl which is unsubstituted or substituted once or twice by C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6alkylcarbonyloxy, C2-C6alkenyl, =0 or =N-R10, or A is cyclohexyl substituted once, at the 4-position, by one (C3-C6cycloalkyl)methoxy, C3-C6cycloalkyloxy, C2-C5alkenyl-CH2-oxy, or benzyloxy substituent, or A is decahydro-1-naphthyl or decahydro-2-naphthyl, or A is optionally substituted phenyl, and G is hydrogen or an agriculturally acceptable metal, sulfonium, ammonium or a latentiating group.
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Page/Page column 61
(2011/02/24)
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- 2-iodoxybenzenesulfonic acid as an extremely active catalyst for the selective oxidation of alcohols to aldehydes, ketones, carboxylic acids, and enones with oxone
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Electron-donating group-substituted 2-iodoxybenzoic acids (IBXs) such as5-Me-IBX (1g), 5-MeO-IBX (1h), and 4,5-Me2-IBX were superior to IBX 1a as catalysts for the oxidation of alcohols with Oxone (a trad emark of DuPont) under nonaqueous conditions, although Oxone was almost insoluble in most organic solvents. The catalytic oxidation proceeded more rapidly and cleanly in nitromethane. Furthermore, 2-iodoxybenzenesulfonic acid (IBS, 6a) was much more active than modified IBXs. Thus, we established a highly efficient and selective method for the oxidation of primary and secondary alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones with Oxone in nonaqueous nitromethane, acetonitrile, or ethyl acetate in the presence of 0.05-5molpercentof 6a, which was generated in situ from 2-iodobenzenesulfonic acid (7a) or its sodium salt. Cycloalkanones could be further oxidized to α,β- cycloalkenones or lactones by controlling the amounts of Oxone under the same conditions as above. When Oxone was used under nonaqueous conditions, Oxone wastes could be removed by simple filtration. Based on theoretical calculations, we considered that the relatively ionic character of the intramolecular hypervalent iodine-OSO2 bond of IBS might lower the twisting barrier of the alkoxyperiodinane intermediate 16.
- Uyanik, Muhammet,Akakura, Matsujiro,Ishihara, Kazuaki
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supporting information; experimental part
p. 251 - 262
(2009/06/28)
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- Stereoselective Synthesis of Amino Acid Analogs for Tumor Imaging
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The radiolabeled non-natural amino acid 1-amino-3-cyclobutane-1-carboxylic acid (ACBC) and its analogs are candidate tumor imaging agents useful for positron emission tomography and single photon emission computed tomography due to their selective affinity for tumor cells. The present invention provides methods for stereo-selective synthesis of syn-ACBC analogs. The disclosed synthetic strategy is reliable and efficient and can be used to synthesize a gram quantity of various syn-isomers of the ACBC analogs, particularly, syn-[18F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC) and syn-[123I]-1-amino-3-iodocyclobutane-1-carboxylic (IACBC) acid analogs.
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Page/Page column 12
(2010/11/25)
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- Electrostatic effects on the reactions of cyclohexanone oxocarbenium ions
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Nucleophilic substitution reactions of 4-substituted cyclohexanone acetals display different selectivities depending upon the electronic nature of the substituent. Alkyl groups favor equatorial positions in the oxocarbenium ions, but alkoxy groups prefer
- Baghdasarian, Glen,Woerpel
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p. 6851 - 6858
(2007/10/03)
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- Phosphoryl choline coating compositions
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A polymer comprising phospholipid moieties and a biocompatible polymer backbone, a composition comprising the polymer and optionally a bioactive agent, an implantable devices such as a DES comprising thereon a coating comprising the polymer and optionally a bioactive agent, and a method of using the device for the treatment of a disorder in a human being are provided.
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Page/Page column 8
(2010/02/14)
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- Mild and chemoselective catalytic deprotection of ketals and acetals using cerium(IV) ammonium nitrate
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Cerium(IV) ammonium nitrate (CAN) is a powerful, though mild, reagent for the efficient and selective removal of a range of ketals and acetals. This novel deprotection method requires only catalytic amounts of CAN and tolerates a variety of functional and protecting groups. Mechanistic insights suggest that the Ce(IV) salts act as unique Lewis acids and not as redox active species.
- Ates, Ali,Gautier, Arnaud,Leroy, Bernard,Plancher, Jean-Marc,Quesnel, Yannick,Vanherck, Jean-Christophe,Markó, István E.
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p. 8989 - 8999
(2007/10/03)
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- A diene-transmissive approach to the quassinoid skeleton
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Several tetracyclic molecules were prepared by diene-transmissive Diels-Alder cycloadditions. Control over the stereochemical outcome of the cycloaddition was achieved and the structural features of the precursors affecting the stereochemistry is discussed. Useful information was gathered concerning the factors governing this stereocontrol, which will be indispensable for the future of this strategy.
- Spino, Claude,Hill, Bryan,Dube, Pascal,Gingras, Stephane
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- Aminocyclohexane derivatives as 5-HT receptor agonists
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A class of substituted aminocyclohexane derivatives are selective agonists of 5-HT1-like receptors, being potent agonists of the human 5-HT1Dαreceptor subtype while possessing at least a 10-fold selective affinity for the
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- Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. Part 14: Regioselectivity of the opening reactions with MeOH of remote O-substituted 1,2-epoxycyclohexanes under gas-phase operating conditions
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The regiochemical behavior of cyclohexene oxides bearing a remote O-functionality was determined in the gas-phase in opening reactions with MeOH, using a gaseous acid (D3/+, C(n)H5/+, Me2F+
- Crotti, Paolo,Di Bussolo, Valeria,Favero, Lucilla,Pineschi, Mauro,Marianucci, Francesco,Renzi, Gabriele,Amici, Giuseppina,Roselli, Graziella
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p. 7513 - 7524
(2007/10/03)
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- Remarkably efficient deprotection of cyclic acetals and ketals
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A simple and mild procedure for the efficient deprotection of cyclic acetals and ketals, using cerium ammonium nitrate (CAN) is reported. The method tolerates a range of functional and protecting groups and is suitable for acid-labile substrates.
- Ates, Ali,Gautier, Arnaud,Leroy, Bernard,Plancher, Jean-Marc,Quesnel, Yannick,Marko, Istvan E.
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p. 1799 - 1802
(2007/10/03)
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- Amino acid analogs for tumor imaging
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The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ?18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid.
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- Amino acid analogs for tumor imaging
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The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ?18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid.
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- Homogeneous oxidation of alcohols by copper permanganate
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An improved protocol for the oxidation of sec. alcohols by copper permanganate is described by carrying out the reaction in a homogeneous medium (acetic acid), affording rapid and complete conversion to the ketones.
- Ansari, M. Aslam,Craig, J. Cymerman
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p. 1789 - 1792
(2007/10/03)
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- Intramolecular allylstannane-aldehyde cyclizations: Stereochemical results with flexible tethers for reactions forming vinylcyclohexanols
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Intramolecular Lewis acid-promoted cyclization reactions of both (Z)- and (E)-3-phenyl-8-(tri-n-butylstannyl)oct-6-enal and (Z)- and (E)-3-(benzyloxy)-8-(tri-n-butylstannyl)oct-6-enal have been examined using a variety of Lewis acids, specifically BF
- Keck, Gary E.,Dougherty, Shawn M.,Savin, Kenneth A.
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p. 6210 - 6217
(2007/10/02)
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- Enantioselective deprotonation of protected 4-hydroxycyclohexanones
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A series of derivatives of 4-hydroxycyclohexanone (1a-g) with the hydroxy group protected as a silyl ether (1a,b), ether (1d,g), an acetal (1c), or an ester (1e,f) were deprotonated with chiral, optically pure, lithium amides 3-9. The resulting non-racemic enolates were trapped as enol acetates. The enantioselectivity of deprotonation was up to 74percent ee.
- Majewski, Marek,Mackinnon, John
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p. 1699 - 1704
(2007/10/02)
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- An Oxidatively Removable Protecting Group for Aldehydes and Ketones
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Aldehydes and ketones can be converted to the corresponding p-methoxyphenylethylene acetals and ketals in good to excellent yield.Deprotection can be accomplished under mild conditions to produce uniformly excellent yields of the original carbonyl compound.
- McDonald, Chriss E.,Nice, Lois E.,Kennedy, Kenneth E.
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- Aryl-cycloalkyl[b]pyrrole derivatives
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Aryl-cyclopenta- and arylcyclohexa[b]pyrrole derivatives are provided having the structure STR1 wherein n is 1 or 2; X is --OR1 or --NR2 R3 wherein R1 is H, lower alkyl, cycloalkyl, aryl, aralkyl or cycloalkylalkyl, and R2 and R3 may be the same or different and are H, lower alkyl, cycloalkyl, aryl, aralkyl or cycloalkylalkyl; Y is --OR4 or --NR5 R6 wherein R4 is H or lower alkyl, and R5 and R6 are the same or different and are H or lower alkyl; and Z is aryl. These compounds are useful in inhibiting the 5-lipoxygenation of arachadonic acid in RBL-1 cells and preventing leukotriene formation in macrophages and as such are useful as antiallergy agents and in treating inflammation and psoriasis.
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- Synthesis of (+/-)-Mesembranol and (+/-)-O-Methyljoubertiamine. Aza-Ring Expansion of cis-Bicyclooctanones
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The Syntheses of (+/-)-mesembranol (1) and (+/-)-O-methyljoubertiamine (2) are described.Each synthesis is developed from a regio- and stereospecific heteroannelation sequence of the respective 1-arylcyclohexanes 4 and 10 to provide the 3a-aryl-cis-octahy
- Jeffs, Peter W.,Cortese, Nicholas A.,Wolfram, Joachim
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p. 3881 - 3886
(2007/10/02)
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