- Formal synthesis of (±)-sedamine through gold(I)-catalyzed intramolecular dehydrative amination of sulfamate esters tethered to allylic alcohols
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A concise formal synthesis of (±)-sedamine has been accomplished. The synthesis is straightforward and demonstrates high efficiency. Key steps involve gold(I)-catalyzed cyclization of sulfamate esters tethered to allylic alcohols, sulfamate N-alkylation, and ring-closing metathesis.
- Park, Yunjeong,Ryu, Jae-Sang
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Read Online
- A general method for making bicyclic compounds with nitrogen at a bridgehead-application to the halichlorine spiro subunit
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N-Protected β-amino aldehydes having the nitrogen in a ring are easily converted into Morita-Baylis-Hillman adducts; O-acetylation and N-deprotection result in spontaneous cyclization to bicyclic structures having nitrogen at a bridgehead. The Royal Socie
- Clive, Derrick L. J.,Yu, Maolin,Li, Zhiyong
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Read Online
- Synthesis of Azocanes from Piperidines via an Azetidinium Intermediate
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α-Trifluoromethyl azocanes are accessible from 2-(trifluoropropan-2-ol) piperidines by metal-free ring-expansion involving a bicyclic azetidinium intermediate. The opening of the azetidinium intermediate was achieved by various nucleophiles (amines, alcoholates, carboxylates, phosphonates, halides and pseudo-halides) with an excellent regio- diastereo- and enantioselectivity and in good yields. The relative configuration of the piperidines and azocanes were assigned and the deprotected azocanes offer opportunities for further derivatization.
- Leverenz, Malte,Masson, Guillaume,Pardo, Domingo Gomez,Cossy, Janine
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supporting information
p. 16325 - 16328
(2021/10/25)
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- The phenothiazine compound and its preparation method and application
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The invention relates to a phenothiazine compound and a preparation method thereof. The invention further relates the application of the phenothiazine compound in anti-cancer drug preparation and anti-cancer drugs using the compound as the effective component. The phenothiazine compound has the advantages that the compound with broad-spectrum anti-cancer effect is obtained by modifying phenothiazine ternary interlink parent nucleuses, synthesizing method is simple, and high yield is achieved; the phenothiazine compound has certain restraining effect on human breast cancer cells line MCF-7 and human hepatoma cell line Hep-G2, and a new thought is provided to new drugs satisfying clinic requirements.
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Paragraph 0055-0058
(2018/07/30)
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- Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
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The neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the replacement of the piperidine and phenothiazine moieties, with the aim to improve the anti-tubercular activity and to reduce the cytotoxic effects. Among the resulting compounds, the indole derivative 12e showed an antimycobacterial activity significantly better than thioridazine and a cytotoxicity 15-fold lower.
- Scalacci, Nicolò,Brown, Alistair K.,Pavan, Fernando R.,Ribeiro, Camila M.,Manetti, Fabrizio,Bhakta, Sanjib,Maitra, Arundhati,Smith, Darren L.,Petricci, Elena,Castagnolo, Daniele
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p. 147 - 158
(2016/12/30)
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- Catalytic Oxygenative Allylic Transposition of Alkenes into Enones with an Azaadamantane-Type Oxoammonium Salt Catalyst
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The first catalytic oxygenative allylic transposition of unactivated alkenes into enones has been developed using an oxoammonium salt as the catalyst. This reaction converts various tri- and trans-disubstituted alkenes into their corresponding enones with transposition of their double bonds at ambient temperature in good yields. The use of a less-hindered azaadamantane-type oxoammonium salt as the catalyst and a combination of two distinct stoichiometric oxidants, namely, iodobenzene diacetate and magnesium monoperoxyphthalate hexahydrate (MMPP?6 H2O) are essential to facilitate the enone formation efficiently.
- Nagasawa, Shota,Sasano, Yusuke,Iwabuchi, Yoshiharu
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supporting information
p. 10276 - 10279
(2017/08/07)
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- Compounds and methods for treating tumors
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The present invention relates to pharmaceutical compositions and methods for controlling tumor growth in cancer patients. These compounds and pharmaceutical compositions modulate the P-glycoprotein multidrug transporter system and inhibit the activated PI3K/Akt/mTOR/p70S6K signaling pathway. The compounds and pharmaceutical compounds of the present invention are particularly useful for treating metastatic and drug-resistant tumors.
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Page/Page column 12
(2015/12/17)
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- USE OF AMINOINDANE COMPOUNDS IN TREATING OVERACTIVE BLADDER AND INTERSTITIAL CYSTITIS
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The present application provides methods of using the aminoindane compounds of formula (I) or (II) in treating an overactive bladder or interstitial cystitis by administering one or more of the compounds to a patient.
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Page/Page column 126-127
(2014/03/22)
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- Aminoindane Compounds and Use Thereof in Treating Pain
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The present application provides novel aminoindane compounds and methods for preparing and using these compounds. These compounds are useful in treating pain and/or itch in patients by administering one or more of the compounds to a patient. The methods include administering a compound of formula (I) or (II) and a TRPV 1 receptor activator. In one embodiment, the TRPV 1 receptor activator is lidocaine.
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Page/Page column 72
(2012/09/05)
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- Novel N-substituted benzimidazole CXCR4 antagonists as potential anti-HIV agents
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The lead optimization of a series of N-substituted benzimidazole CXCR4 antagonists is described. Side chain modifications and stereochemical optimization led to substantial improvements in potency and protein shift to afford compounds with low nanomolar a
- Miller, John F.,Turner, Elizabeth M.,Gudmundsson, Kristjan S.,Jenkinson, Stephen,Spaltenstein, Andrew,Thomson, Michael,Wheelan, Pat
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scheme or table
p. 2125 - 2128
(2010/06/13)
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- Substituted Spiroamine Compounds
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Substituted spiroamine compounds corresponding to the formula (I) In which m, n, o, p, Q, r, s, t, R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7, R8, R9, R10 and R11 have defined meanings; a process for the preparation of such compounds, pharmaceutical compositions containing such compounds and the use of substituted spiroamines for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin 1 receptor.
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Page/Page column 51
(2010/05/13)
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- Regioselective synthesis of azetidines or pyrrolidines by selenium-induced cyclization of secondary homoallylic amines
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Azetidines or pyrrolidines can be regioselectively obtained by selenocyclization of homoallylic amines, according to the double bond substitution.
- Franck, Xavier,Leleu, Stéphane,Outurquin, Francis
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scheme or table
p. 4437 - 4440
(2010/09/20)
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- Stereocontrol in N-directed hydroboration: Synthesis of amino alcohols related to the piperidine alkaloids
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Treatment of 2-(2'-alkenyl)-piperidine boranes with iodine or triflic acid induces internal hydroboration with high regiocontrol, even with a terminal alkene (R H). Good stereocontrol is possible for the N-benzyl substrates. Comparisons with acyclic model
- Wang, Guoqiang,Vedejs, Edwin
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scheme or table
p. 1059 - 1061
(2009/08/15)
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- SUBSTITUTED SULFONAMIDE DERIVATIVES
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The invention relates to substituted sulfonamide derivatives of the general formula (I'); processes for their preparation, medicaments containing these compounds, and the use of substituted sulfonamide derivatives for the preparation of medicaments
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Page/Page column 93; 94
(2009/08/16)
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- CHEMICAL COMPOUNDS
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The present invention provides novel compounds that demonstrate protective effects on target cells from HIV infection in a manner as to bind specifically to the chemokine receptor, and which affect the binding of the natural ligand or chemokine to a receptor such as CXCR4 and/or CCR5 of a target cell.
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Page/Page column 89
(2010/10/20)
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- Aryl-substituted benzimidazole and imidazopyridine ethers
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Aryl substituted benzimidazole and imidazo[4,5]pyridine ethers are described as inhibitors of Cds1 and useful as adjuvants to chemotherapy or radiation therapy in the treatment of cancer.
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(2010/02/15)
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- CHK-1 INHIBITORS
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Disclosed are novel inhibitors of Chk-1 and methods of using the same for therapy.
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Page/Page column 210
(2010/02/11)
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- QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES INHIBITING AUTOPHOSPHORYLATION OF Flt3 AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
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An objective of the present invention is to provide compounds and pharmaceticals useful for the treatment of disease where the inhibition of autophosphorylation of FMS-like tyrosine kinase 3(Flt3) is therapeutically effective. The present invention relates to a pharmaceutical composition for use in the treatment or prevention of diseases where the inhibition of autophosphorylation of Flt3 therapeutically or prophylactically effective, which comprises a compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; Z represents O or S; R1, R2, and R3 represent H, OH, or optionally substituted alkoxy; R4 represents H; R5, R6, R7, and R8 represent H, Hal, alkyl or the like; and R9 represents, e.g., alkyl substituted by t-butyl or the like.
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Page/Page column 24-25
(2010/02/13)
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- TRICYCLIC COMPOUND, PROCESS FOR PRODUCING THE SAME, AND USE
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A compound of the formula: wherein R1 is a 5- or 6-membered ring; ???Z1 is a 5- or 6-membered aromatic ring; ???Z2 is a group of -Z2a-W2-Z2b-, wherein Z2a and Z2b are each O, S(O)q (wherein q is 0, 1 or 2), an imino group, or a bond; and W2 is an alkylene chain; ???W is a group represented by wherein R3 and R3' are each a hydrogen atom, a lower alkyl group, or a lower alkoxy group; X is CH or N; n and n' are each an integer of 0 or 1 to 4; m and m' are each 1 or 2; Y is O, S(O)p (wherein p is 0, 1 or 2), CH2 or NR4 (wherein R4 is a hydrogen atom, a lower alkyl group, or a lower acyl group); and ???R2 is (1) an amino group, in which the nitrogen atom may be converted to a quaternary ammonium or an oxide, or (2) a nitrogen-containing heterocyclic group which may contain a sulfur atom or an oxygen atom as the ring-constituting atom, in which the nitrogen atommay be converted to a quaternary ammonium or an oxide; or a salt thereof. The compound exhibits excellent CCR antagonist activity against CCR5, and is useful as a prophylactic and/or therapeutic agent for HIV infection in human peripheral blood mononuclear cells, especially for AIDS.
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Page/Page column 47
(2010/02/14)
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- HISTAMINE H3 RECEPTOR LIGANDS
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Compounds of formula (I) (and pharmaceutically acceptable salts thereof) are histamine H3 receptor ligands. A in the formula represents (CH2)m, m being from 1 to 3; B is (CH2)n, n being from 1 to 3; x is from 0 to 2; Ris C1 to C10 hydrocarbyl, in which up to 2 carbon atoms may be replaced by O, S or N; and up to 2 hydrogen atoms may be replaced by halogen; Ris H or C1 to C15 hydrocarbyl, in which up to 3 carbon atoms may be replaced by O, S or N, and up to 3 hydrogen atoms may be replaced by halogen; Ris absent when -Y-Z-R2 is attached to W, or is H or C1 to C7 hydrocarbyl when -Y-Z-Ris not attached to W; W is nitrogen; X is -CH2-, -O- or -NR-, Rbeing H or C1 to C3 alkyl; Y replaces a hydrogen atom on any of A, B, W and X, and is C2 to C10 alkylene, in which one non-terminal carbon atom may be replaced by O; and Z is (II), (III), (IV), (V), (VI), or (VII) wherein R, Rand Rare independently H or C1 to C15 hydrocarbyl, in which up to 3 carbon atoms may be replaced by O or N, and up to 3 hydrogen atoms may be replaced by halogen, and Q is H or methyl, or Q is linked to Ror Rto form a five-membered ring or Q is linked to Rto form a six-membered ring
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- Studies toward labeling cytisine with [11C]phosgene: Rapid synthesis of a δ-lactam involving a new chemoselective lithiation-annulation method
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With the aim of the radiolabeling of cytisine, a potent agonist of nicotinic receptors, with [11C]-phosgene, the rapid synthesis of a lactam model of our target has been studied. The key step of the δ-lactam formation is a new chemoselective lithiation-annulation method, under high dilution, of a suitable piperidinylcarbamoyl chloride. This precursor was obtained from (2-hydroxyethyl)-piperidine in a linear synthetic sequence involving a Corey-Fuchs olefination of the corresponding aldehyde, followed by a selective reduction, using a diimide equivalent, of an iodoalkyne into a (Z)-iodopropene piperidine. This alkene served as main precursor to study the cyclization according to several procedures using phosgene as the required carbonylating reagent.
- Rouden, Jacques,Seitz, Thomas,Lemoucheux, Laurent,Lasne, Marie-Claire
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p. 3787 - 3793
(2007/10/03)
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- Novel photoresist monomer, polymer thereof and photoresist composition containing it
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The present invention provides novel bicyclic photoresist monomers, and photoresist copolymer derived from the same. The bicyclic photoresist monomers of the present invention comprise both amine functional group and acid labile protecting group, and are represented by the formula: where m, n, R, V and B are those defined herein. The photoresist composition comprising the photoresist copolymer of the present invention has excellent etching resistance and heat resistance, and remarkably enhanced PED stability (post exposure delay stability).
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- Farnesyl protein transferase inhibitors
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Disclosed are compounds of the formula: wherein R8represents a cyclic moiety to which is bound an imodazolylalkyl group; R9represents a carbamate, urea, amide or sulfonamide group; and the remaining substituents are as defined herein. Also disclosed is a method of treating cancer and a method of inhibiting farnesyl protein transferase using the disclosed compounds.
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- Concise total synthesis of (±)-aloperine and 6-epi-aloperine
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(figure presented) Total synthesis of aloperine and 6-epj-aloperine is reported. The crucial steps of the synthetic strategy are an aza-annulation reaction and an intermolecular Diels-Alder reaction. The synthetic plan proceeds from commercially available
- Passarella, Daniele,Angoli, Marco,Giardini, Alessandra,Lesma, Giordano,Silvani, Alessandra,Danieli, Bruno
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p. 2925 - 2928
(2007/10/03)
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- Design of selective thrombin inhibitors based on the (R)-Phe-Pro-Arg sequence
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Potent and selective inhibitors of thrombin were sought based on the (R)-Phe-Pro-Arg sequence. The objective was to generate similar binding interactions to those achieved by potent competitive inhibitors of the argatroban type, so eliminating the need for covalent interaction with the catalytic serine function, as utilized by aldehyde and boronic acid type inhibitors. Improving the S1 subsite interaction by substitution of arginine with a 4-alkoxybenzamidine residue provided potent lead 2 (Ki = 0.37 nM). Though an amide bond, which H-bonds to the active site, is lost, modeling indicated that a new H-bond is generated between the alkoxy oxygen atom and the catalytic Ser-195 hydroxyl group. Substitution of the benzamidine system by 1-amidinopiperidine then gave compound 4, which provided a further gain in selectivity over trypsin. However, previous work had shown that these compounds were likely to be too lipophilic (Log D +0.4 and +0.2, respectively) and to suffer rapid hepatic extraction, presumably via biliary elimination. Accordingly, both proved short-acting when administered intravenously to rats and showed poor activity when given intraduodenally. The aim was then to reduce lipophilicity below a log D of - 1.2, which in a previously reported series had been effective in preventing rapid clearance. It was anticipated that compounds of this type would rely on the cation selective paracellular route of absorption from the gastrointestinal tract. Potent polar analogues with selectivity >1000 over trypsin were obtained. The best in vivo activity was shown by compound 12. However, in the final analysis, its oral bioavilability proved poor, relative to analogues with similar physicochemical properties derived from argatroban, consistent with the hypothesis that molecular shape is an additional important determinant of paracellular absorption.
- Danilewicz, John C.,Abel, Stuart M.,Brown, Alan D.,Fish, Paul V.,Hawkeswood, Edward,Holland, Stephen J.,James, Keith,McElroy, Andrew B.,Overington, John,Powling, Michael J.,Rance, David J.
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p. 2432 - 2453
(2007/10/03)
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- Complex-induced proximity effects: The effect of varying directing-group orientation on carbamate-directed lithiation reactions
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A series of selected bicyclic carbamates in which the range of accessible angles and distances between the carbonyl group and the proton removed in an α-lithiation reaction are structurally defined have been investigated. Oxazolidinones 7-10 undergo stereoselective lithiation-substitution reactions to provide cis-18-27 and cis-31-35 as the major diastereomers. Two series of competition experiments show that the conformationally restricted carbamates 7, 10, 11, and 15 undergo lithiation via complexes more efficiently than Boc amines 4-6. These results along with semiempirical calculations suggest that a small dihedral angle and a calculated distance of 2.78 A between the carbamate carbonyl oxygen and the proton to be removed are favorable for a carbamate-directed lithiation. A series of tin-lithium exchange experiments on cis- and trans-18 and (S)-39 indicate that the configurational stability of a carbamate-stabilized organolithium species may be enhanced by restrictive geometry.
- Bertini Gross,Beak
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p. 315 - 321
(2007/10/03)
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- Antagonists of gonadotropin releasing hormone
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PCT No. PCT/US97/08428 Sec. 371 Date Nov. 12, 1998 Sec. 102(e) Date Nov. 12, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44037 PCT Pub. Date Nov. 27, 1997There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related conditions in both men and women.
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- Antagonists of gonadotropin releasing hormone
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PCT No. PCT/US97/08782 Sec. 371 Date Nov. 12, 1998 Sec. 102(e) Date Nov. 12, 1998 PCT Filed May 16, 1997 PCT Pub. No. WO97/44041 PCT Pub. Date Nov. 27, 1997There are disclosed compounds of formula (I) and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related conditions in both men and women.
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- Quinolones as gonadotropin releasing hormone (GnRH) antagonists: Simultaneous optimization of the C(3)-aryl and C(6)-substituents
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A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Young, Jonathan R.,Huang, Song X.,Chen, Irene,Walsh, Thomas F.,DeVita, Robert J.,Wyvratt Jr., Matthew J.,Goulet, Mark T.,Ren, Ning,Lo, Jane,Yang, Yi Tien,Yudkovitz, Joel B.,Cheng, Kang,Smith, Roy G.
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p. 1723 - 1727
(2007/10/03)
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- Synthesis of bridged azabicyclic compounds using radical translocation reactions of 1-(o-halogenobenzoyl)-2-(prop-2-enyl)-and -(prop-2-ynyl)-piperidines
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Methyl 1-(o-bromobenzoyl)-2-(prop-2-enyl)piperidine-2-carboxylate 8a, upon treatment with tributyltin hydride in the presence of azoisobutyronitrile in boiling toluene gave regioselectively the 8-azabicyclo[3.2.1]octane 14a (a 5-exo cyclisation product) in quantitative yield as a diastereomeric mixture (66:34). 1-(o-Bromobenzoyl)-2-(prop-2-enyl)piperidine 13 also gave the 8-azabicyclo-[3.2.1]octane 16 (75% as a diastereomeric mixture), along with the pyrido[2,1-a]isoindolone 17 (10%) and the simple reduction product 18 (5%). 1-(o-Iodobenzoyl)-2-[3-(trimethylsilyl)prop-2-ynyl]piperidine 23 afforded, in addition to the pyrido[2,1-a]isoindolone 25 (18%), the 8-azabicyclo-[3.2.1]octane 24 (75%) which was converted into the 6-oxo derivative 27. For comparison, the behaviour of the azetidine congener 31 was also examined.
- Ikeda, Masazumi,Kugo, Yasuhiro,Sato, Tatsunori
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p. 1819 - 1824
(2007/10/03)
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- Substituted amine derivatives, their production and use
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Substituted amino derivatives represented by the formula: STR1 wherein R1 and R2 each stand for an acyclic hydrocarbon residue or an alicyclic hydrocarbon residue; R3 and R4 each stand for hydrogen or a hydrocarbon residue optionally containing hetero-atom(s); A stands for a carbon chain having two or more carbon atoms optionally containing ether linkage or sulfide linkage, which may be substituted and which may per se form a ring; X1 and X2 each stand for oxygen atom or sulfur atom; and Y stands for amino group or an organic residue bonded through nitrogen atom, which may form a ring by combining with a carbon atom constituting A; and their salts have anti-arrhythmic activity and are useful for prevention and treatment of a variety of arrhythmias.
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