- Substitution effect, absorption, and fluorescence behaviors of 11,12-benzo-1,7,10,13-tetraoxa-4-azacyclopentadec-11-ene (Benzoaza-15-crown-5) derivatives upon cation complexation in solvent extraction
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Substitution effect, absorption, and fluorescence behaviors of some benzoaza-15-crown-5 derivatives upon cation complexation in solvent extraction were studied. The introduction of a substituent on the nitrogen atom in benzoaza-15-crown-5 enhanced extractabilities in the solvent extraction of aqueous alkali metal picrates. The nondonating substituents raised the cation selectivity for Na+ over K+, but the donating substituents reduced the cation selectivity. The absorption and fluorescence spectral behavior was different with the alkali metal cations.
- Nakamura, Mitsunobu,Yokono, Hideaki,Tomita, Ken-Ichi,Ouchi, Mikio,Miki, Masamichi,Dohno, Reizo
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Read Online
- Complex Formation between Boric Acid and Triethanolamine in Aqueous Solutions
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The complex formation behavior between boric acid and triethanolamine (TEA, H3L) in aqueous solutions was thoroughly examined by 11BNMR spectroscopy. In chloroform, one 11BNMR signal appeared due to triethanolamine borate (TEA-B, L-B) at -4.6 ppm, whereas in aqueous solutions two signals appeared due to TEA-B and a new boron complex at -5.8 and -9.5 ppm, respectively, in addition to a signal ascribed to boric acid and borate ion. The area ratios between the signals at -5.8 and -9.5 ppm were almost constant regardless of the molar ratios between boric acid and TEA, suggesting that the new complex is a 1: 1 complex between boric acid and TEA. Both complexes were stable in aqueous solutions over the pH range of 6.7 to 10.9. Their chemical shift values were constant and independent of the pH value. This also implies that the new complex has a tetrahedral structure around the boron atom, similar to TEA-B. Based on 1H and 13C NMR spectroscopy and a preliminary examination of complexation between boric acid and aminoalkanols, we have concluded that the new complex (NB, HL-B(OH)) is a 1 : 1 boron to TEA complex with a bicyclo[3,3,0]structure having a boron-nitrogen bond.
- Sonoda, Akinari,Takagi, Norio,Ooi, Kenta,Hirotsu, Takahiro
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Read Online
- Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056)
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Four optical isomers of SIPI5056 were synthesized and evaluated for their antidepressant activities and acute toxicities as novel multiple reuptake inhibitors of monoamine transmitters. Chiral alanines were used as educts to prepare their respective target compounds in nine steps. Pharmacological results showed that the (1R,2S)-SIPI5056 isomer has higher inhibitory activity and lower toxicity than other three isomers and is worthy of further development.
- Weng, Zhijie,Li, Jianqi
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Read Online
- A mild and efficient cyanosilylation of ketones using in situ generated n-oxides-ti(iPrO)4 complexes as catalysts
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The addition of TMSCN to ketones catalyzed by complex of racemic N-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide (rac-1) or N-benzyl-N,N-dihydroxyethylamine N-oxide and Ti(iPrO)4 affords the racemic O-TMS cyanohydrins in good to excellent isolated yields (up to 97%) under mild reaction conditions.
- Shen, Yongcun,Feng, Xiaoming,Li, Yan,Zhang, Guolin,Jiang, Yaozhong
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Read Online
- Aza-crown ether complex cation ionic liquids: Preparation and applications in organic reactions
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Aza-crown ether complex cation ionic liquids (aCECILs) were devised, fabricated, and characterized by using NMR spectroscopy, MS, thermogravimetric differential thermal analysis (TG-DTA), elemental analysis and physical properties. These new and room-temperature ILs were utilized as catalysts in various organic reactions, such as the cycloaddition reaction of CO2 to epoxides, esterification of acetic acid and alcohols, the condensation reaction of aniline and propylene carbonate, and Friedel-Crafts alkylation of indole with aldehydes were investigated carefully. In these reactions, the ionic liquid exhibited cooperative catalytic activity between the anion and cation. In addition, the aza-[18-C-6HK][HSO4]2 was the best acidic catalyst in the reactions of esterification and Friedel-Crafts alkylation under mild reaction conditions. Jewel in the crown: Nine new and room-temperature aza-crown ether complex ionic liquids (aCECILs) composed of multiple cations and anions were fabricated through a convenient procedure (see scheme). Some of them were used as catalysts in various organic reactions, such as the cycloaddition reaction of CO2 to propylene oxide, esterification of acetic acid and alcohols, the condensation of aniline and propylene carbonate, and Friedel-Crafts alkylation of indole with aldehydes.
- Song, Yingying,Cheng, Chen,Jing, Huanwang
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Read Online
- Steroidal Lariat Ethers: A New Class of Macrocycles and the Crystal Structure of N-(Cholesteryloxycarbonyl)aza-15-crown-5
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Several examples of a new class of lariat ethers, those having steroidal side arms, are reported.These include the following carbon-pivot and nitrogen-pivot structures: 2-(3-dihydrocholesteryloxymethyl)-15-crown-5, mp 61-63 deg C; N-(3-cholesteryloxycarbonylmethyl)aza-15-crown-5, mp 85-86 deg C; N-(3-cholesteryloxycarbonylmethyl)aza-18-crown-6, mp 66-67 deg C; N-(3-dihydrocholesteryloxycarbonylmethyl)aza-15-crown-5, mp 60-61 deg C; N-(3-dihydrocholesteryloxycarbonylmethyl)aza-18-crown-6, mp 55-56 deg C; N-(3-cholesteryloxycarbonyl)aza-15-crown-5, mp 96-98 dec C; and N-(3-cholesteryloxycarbonyl)aza-18-crown-6, mp 82-84 deg C.Alkali-metal cation binding by these structures is generally weak, since the macroring binding is not augmented by side arm donor group participation.The high lipophilicity of the side arm does not enhance the caion binding strength.The X-ray crystal structure of one of these novel lariat ethers, N-(cholesteryloxycarbonyl)aza-15-crown-5 has been determined.This is the first example of an uncomplexed, 15-membered crown ether compound containing only nitrogen and oxygen heteroatoms.The macroring structure has one N-C-C-O torsion angle anti; thus one methylene group is turned inward
- Gokel, George W.,Hernandez, Jeanette C.,Viscariello, Anthony M.,Arnold, Kristin A.,Campana, Charles F.,et. al.
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Read Online
- Compound serving as SHP2 inhibitor and application thereof
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The invention belongs to the field of medical chemistry, relates to a compound serving as an SHP2 inhibitor and an application of the compound, and particularly provides a compound shown in a formula (I) or an isomer, pharmaceutically acceptable salt, solvate, crystal or prodrug of the compound, processes for the preparation, pharmaceutical compositions containing these compounds and the use of these compounds or compositions for the treatment of SHP2 mediated diseases.
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Paragraph 0238; 0240-0242
(2021/05/12)
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- SHP2 INHIBITORS, COMPOSITIONS AND USES THEREOF
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Provided herein are compounds of Formula (I), methods of using the compounds as SHP2 inhibitors, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating SHP2-mediated diseases.
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Page/Page column 46
(2021/11/06)
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- Preparation method of 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride
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The invention relates to the technical field of organic synthesis, in particular to a preparation method of 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride. The preparation method disclosed by the invention comprises the following steps of: (1) preparing benzyl diethanolamine by taking benzyl chloride and diethanolamine as raw materials; (2) preparing benzyl dichloroethylamine hydrochloride by taking benzyl diethanolamine and thionyl chloride as raw materials; and (3) preparing the 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride by taking the benzyl dichloroethylamine hydrochloride and the benzyl cyanide as raw materials. The preparation method disclosed by the invention is simple in process and suitable for industrial production, the HPLC content of the finally obtained 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride is greater than or equal to 98.0%, the total yield (based on diethanolamine) is greater than or equal to 89%, and the 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride has a very good market prospect.
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Paragraph 0007; 0023-0030; 0049-0055; 0074-0080
(2021/05/29)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS
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Compositions and methods for the treatment of viral infections include conjugates containing inhibitors of viral neuraminidase (e.g., zanamivir, peramivir, or analogs thereof) linked to an Fc monomer, an Fc domain, and Fc-binding peptide, an albumin protein, or albumin-binding peptide. In particular, conjugates can be used in the treatment of viral infections (e.g., influenza viral infections).
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Page/Page column 461
(2020/03/29)
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- Pyrazinothiazole compound and application thereof, and pharmaceutical composition containing pyrazinothiazole compound
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The invention discloses a pyrazinothiazole compound, an application of the pyrazinothiazole compound, and a pharmaceutical composition containing the pyrazinothiazole compound, and provides a pyrazinothiazole compound represented by a formula A or a pharmaceutically acceptable salt of the pyrazinothiazole compound. The pyrazinothiazole compound provided by the invention has relatively good SHP2 inhibitory activity.
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Paragraph 0151-0154; 0155-0157
(2020/11/09)
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- NOVEL HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS
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Provided is a compound of formula I, their synthesis and their use for treating a SHP2 mediated disorder. More particularly, provided is a pharmaceutical composition comprising the said compound.
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Page/Page column 86
(2020/05/12)
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- IMIDAZOPYRIMIDINE DERIVATIVES
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The present disclosure provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating cancers.
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Paragraph 0852-0853
(2020/04/29)
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- Secondary amine containing ether bond, amido podand ligand, as well as preparation method and application thereof
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The invention discloses an secondary amine containing ether bond, an amido podand ligand, as well as a preparation method and application thereof, wherein the secondary amine containing ether bond hasa structural general formula as shown in the specification, contains ether bonds, has higher flexibility than pure carbon chain secondary amine, and is easy to prolong the number of atoms; Therefore,candidate secondary amines with excellent performance are provided for the fields of organic synthetic chemistry and medicinal chemistry. The amido podand ligand prepared by taking secondary amine asa raw material is used as an extraction agent of a lanthanide/actinide co-extraction system in spent fuel post-treatment, and can effectively inhibit the formation of three phases under higher metalion concentration or nitric acid concentration, so that a good separation effect is achieved in an acidity range of industrial application; therefore, the amido podand not only has strong practicability, but also has a good application prospect in the field of advanced nuclear fuel circulation.
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Paragraph 0076-0080; 0087-0091; 0098-0102; 0109-0113; 0138
(2020/11/23)
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- Barium complexes with crown-ether-functionalised amidinate and iminoanilide ligands for the hydrophosphination of vinylarenes
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The detailed multistep syntheses of two nitrogen-based sterically congested iminoanilidine and amidine proligands bearing a tethered 15-member aza-ether-crown macrocycle, namely {I^Acrown}H and {Amcrown}H, are reported. These proligands react with [Ba{N(SiMe2H)2}2·(thf)n] to generate the heteroleptic barium complexes [{I^Acrown}BaN(SiMe2H)2] (5) and [{Amcrown}BaN(SiMe2H)2] (6) in high yields. These complexes exhibit high coordination numbers (resp. eight and seven) and are in addition stabilised by mild Ba?H-Si interactions. Unusually for oxophilic elements such as barium, the amidinate ligand in 6 is only η1-coordinated. Complexes 5 and 6 mediate the intermolecular hydrophosphination of styrene with primary (PhPH2) and secondary (HPPh2) phosphines. Their catalytic performance compares favourably with those of other barium precatalysts for these reactions. During the course of the hydrophosphination of styrene with HPPh2 catalysed by 5, the phosphide complex [{I^Acrown}BaPPh2] (7) could be intercepted and crystallographically characterised.
- Le Coz, Erwann,Roueindeji, Hanieh,Roisnel, Thierry,Dorcet, Vincent,Carpentier, Jean-Francois,Sarazin, Yann
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supporting information
p. 9173 - 9180
(2019/07/04)
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- Novel heterocyclic derivative capable of being used as SHP2 inhibitor
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The invention relates to a novel heterocyclic derivative capable of being used as an SHP2 inhibitor, specifically relates to a compound shown by a formula I or pharmaceutically acceptable salts thereof, further relates to a use of the compound shown by the formula I or the pharmaceutically acceptable salts thereof and a pharmaceutical composition thereof in drug preparation, and particularly relates to a use in preparation of drugs for treatment, inhibition or prevention of diseases or discomforts mediated by SHP2 activity.
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Paragraph 0211; 0212
(2019/08/30)
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- METHODS USING HDAC11 INHIBITORS
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The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases.
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Paragraph 0770-0771
(2018/05/16)
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- NOVEL HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS
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This invention relates to certain novel pyrazine derivatives (Formula I) as SHP2 inhibitors which is shown as formula I, their synthesis and their use for treating a SHP2 mediated disorder. More particularly, this invention is directed to fused heterocyclic group derivatives useful as inhibitors of SHP2, methods for producing such compounds and methods for treating a SHP2-mediated disorder.
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Page/Page column 53
(2018/10/19)
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- Anti-tumor compound of targeting Neddylation path
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The invention discloses an anti-tumor compound of a targeting Neddylation path. The compound can be represented by a structural formula shown as a general formula I, a general formula II, a general formula III, a general formula IV, a general formula V, a general formula VI or a general formula VII. The compound provided by the invention has good anti-tumor activity; a plurality of compounds are close to a positive control drug MLN4924 and can be used as the good anti-tumor compound. The compound and a composition, provided by the invention, can be used with other drugs to provide combined therapy, and the other drugs can form a part of the same composition or can be used as different components for drug administration at the same time or at different time.
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Paragraph 0046; 0050; 0051
(2019/01/07)
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- SUBSTITUTED AMIDE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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The present invention relates to substituted amide derivatives of formula (I) having dual pharmacological activity towards both the sigma (σ) receptor, and the p-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
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Page/Page column 201
(2017/02/24)
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- USE OF DIETHANOLAMMONIUM DERIVATIVES AS SKIN MOISTURIZER
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The present invention relates to the cosmetic use as moisturizer for keratin materials, preferably the skin, of one or more diethanolammonium derivatives corresponding to formula (I) below, and also the optical isomers and/or geometrical isomers thereof: (I)
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Page/Page column 33
(2017/03/14)
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- Alkynyl quaternary ammonium salt multifunctional surfactants and preparation method thereof
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The invention discloses a series of alkynyl quaternary ammonium salt multifunctional surfactants and a preparation method thereof. A structural formula of quaternary ammonium salt is shown in the description, wherein R represents a C4-C22 linear, branched or cycloalkyl, aryl or alkenyl group. The preparation method comprises the following steps: (1) carrying out alkylation on ethanol amine under alkaline and acetonitrile reflux conditions by virtue of bromo-hydrocarbon; and (2) carrying out further alkylation on tertiary amine under an ethanol reflux condition by virtue of propargyl bromide, so as to obtain alkynyl quaternary ammonium salt, namely reddish brown semitransparent viscous liquid or solid. The alkynyl quaternary ammonium salt multifunctional surfactants have very high surface activity, good corrosion resistance and excellent viscoelasticity, the preparation method is simple and feasible, the raw material cost is low, the operation is easy, the yield is high, and the surfactants are environmentally friendly.
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Paragraph 0038-0043
(2017/05/02)
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- DERIVATIVES OF 6-(2,3-DICHLOROPHENYL)-1,2,4-TRIAZIN-5- AMINE
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The instant disclosure relates to (among other things) compounds that are derivatives of 6-(2,3-dichlorophenyl)-1,2,4-triazin-5-amine. The compounds provided possess unique effects and differences over other phenyltriazines known in the art.
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Paragraph 0432
(2015/07/07)
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- SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
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Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
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Paragraph 0554-0555
(2015/11/09)
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- Ring-closing metathesis reaction-based synthesis of new classes of polyether macrocyclic systems
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Ring closing metathesis (RCM) reactions of suitable substrates having terminal olefins, which are assembled from various linkers and hydroxy benzaldehydes and syntheses of a wide range of 16-30 membered, new crown ether-type polyether, aza-polyether, bis aza-polyether macrocycles and dilactone moiety embedded polyether macrocycles (macrolides) are reported. After the ring-closure reaction, installation of different functional groups and functional group modification on the periphery of the synthesized polyether/crown ether macrocycles obtained in the RCM reactions are accomplished using the epoxidation, oxidation and catalytic hydrogenation-based synthetic transformations. Along this line, the syntheses of a variety of polyether macrocycles possessing epoxide or α-hydroxy ketone or 1,2-diol functionalities at the periphery have been shown. Furthermore, the synthesized α-hydroxy ketone functionality installed polyether macrocycles were subjected to the allylation and Reformatsky type reactions to obtain homoallyl alcohol moiety-based and lactone ring-appended polyether macrocycles.
- Naveen,Babu, Srinivasarao Arulananda
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p. 7758 - 7781
(2015/09/08)
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- Integrating docking scores, interaction profiles and molecular descriptors to improve the accuracy of molecular docking: Toward the discovery of novel Akt1 inhibitors
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A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (Rtrain2 = 0.948, R test2 = 0.907 and Qcv2 = 0.794). The established MD-SVR model based structural modification of new 4-amino-pyrimidine derivatives was further performed, and six compounds 56a,b and 60a-d with good prediction activities were synthesized and biologically evaluated. All of these compounds exhibited promising Akt1 inhibitory and antiproliferative activities, suggesting the reliability and good application value of the established MD-SVR model in the development of Akt1 inhibitors.
- Zhan, Wenhu,Li, Daqiang,Che, Jinxin,Zhang, Liangren,Yang, Bo,Hu, Yongzhou,Liu, Tao,Dong, Xiaowu
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- Organocatalytic ring-opening polymerization of morpholinones: New strategies to functionalized polyesters
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The oxidative lactonization of N-substituted diethanolamines with the Pd catalyst [LPd(OAc)]22+[OTf-]2 generates N-substituted morpholin-2-ones. The organocatalytic ring-opening polymerization of N-acyl morpholin-2-ones occurs readily to generate functionalized poly(aminoesters) with N-acylated amines in the polyester backbone. The thermodynamics of the ring-opening polymerization depends sensitively on the hybridization of the nitrogen of the heterocyclic lactone. N-Acyl morpholin-2-ones polymerize readily to generate polymorpholinones, but the N-aryl or N-alkyl substituted morpholin-2-ones do not polymerize. Experimental and theoretical studies reveal that the thermodynamics of ring opening correlates to the degree of pyramidalization of the endocyclic N-atom. Deprotection of the poly(N-Boc-morpholin-2-one) yields a water-soluble, cationic polymorpholinone.
- Blake, Timothy R.,Waymouth, Robert M.
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supporting information
p. 9252 - 9255
(2014/07/21)
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- CATIONIC LIPID
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The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R1 and R2 are, the same or different, alkenyl, etc, and X1 and X2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L3 is a single bond, etc, R3 is alkyl, etc, L1 and L2 are -0-, -CO-O- or -O-CO-), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like.
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Paragraph 0161
(2013/03/26)
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- CATIONIC LIPID
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The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R1 and R2 are, the same or different, alkenyl, etc, andX1 and X2 are hydrogen atoms, or are combined together to form a single bond or alkylene, andX3 is absent or is alkyl, etc,Y is absent or anion,a and b are, the same or different, 0 to 3, andL3 is a single bond, etc,R3 is alkyl, etc,L1 and L2 are —O—, —CO—O— or —O—CO—),a composition comprising the cationic lipid and a nucleic acid, anda method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like.
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Paragraph 0306; 0307
(2013/11/05)
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- A highly selective pyrene based "off-on" fluorescent chemosensor for cyanide
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A novel pyrene (compound 1) based "off-on" fluorescent chemosensor for cyanide has been designed and synthesized. A prominent fluorescence enhancement of 1·Cu(ii) only for cyanide was found in aqueous acetonitrile solution with a detection limit as low as 1.2 × 10-6 M.
- Wang, Mian,Xu, Jinlei,Liu, Xiaomei,Wang, Hongmei
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p. 3869 - 3872
(2013/12/04)
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- Dual coordination modes of ethylene-linked NP2 ligands in cobalt(II) and nickel(II) iodides
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Here we report the syntheses and crystal structures of a series of cobalt(II) and nickel(II) complexes derived from RNP2 ligands (where R = OMeBz, HBz, BrBz, Ph) bearing ethylene linkers between a single N and two P donors. The CoII complexes generally adopt a tetrahedral configuration of general formula [(NP2)Co(I) 2], wherein the two phosphorus donors are bound to the metal center but the central N-donor remains unbound. We have found one case of structural isomerism within a single crystal structure. The CoII complex derived from BzNP2 displays dual coordination modes: one in the tetrahedral complex [(BzNP2)Co(I)2]; and the other in a square pyramidal variant, [(BzNP2)Co(I)2]. In contrast, the NiII complexes adopt a square planar geometry in which the P(Et)N(Et)P donors in the ligand backbone are coordinated to the metal center, resulting in cationic species of formula [(RNP2)Ni(I)]+ with iodide as counterion. All NiII complexes exhibit sharp 1H and 31P spectra in the diamagnetic region. The Co II complexes are high-spin (S = 3/2) in the solid state as determined by SQUID measurements from 4 to 300 K. Solution electron paramagnetic resonance (EPR) experiments reveal a high-spin/low-spin CoII equilibrium that is dependent on solvent and ligand substituent.
- Dong, Qingchen,Rose, Michael J.,Wong, Wai-Yeung,Gray, Harry B.
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experimental part
p. 10213 - 10224
(2011/12/01)
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- BISPHOSPHONATE COMPOUNDS
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Novel bisphosphonate cyclic acetal compounds are disclosed, as well as methods of preparing the compounds, pharmaceutical compositions including the compounds, and administration of the compounds in methods of treating bone metabolism disorders, such as abnormal calcium and phosphate metabolism.
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Page/Page column 69
(2011/05/05)
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- DIARYL-CYCLYLALKYL DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
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Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type and/or T-type calcium channel activity are disclosed. Specifically, a series of compounds of substituted or unsubstituted N-cyclylalkyl-diphenylpropanamide derivatives as shown in formula (1).
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- SUBSTITUTED BENZIMIDAZOLONE DERIVATIVES, MEDICAMENTS COMPRISING THEM AND THEIR USE
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The present invention relates to novel benzimidazolone derivatives of the general formula (I) in which the substituents R1, R2, R3, A1, A2, and B are as defined in claim 1, medicaments comprising these, and the use thereof for the prophylaxis and/or treatment of vasopressin-dependent diseases.
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(2008/06/13)
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- Unique spirocyclopiperazinium salt III: Further investigation of monospirocyclopiperazinium (MSPZ) salts as potential analgesics
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Two novel classes of monospirocyclopiperazinium salts were designed, synthesized, and evaluated for their in vivo analgesic activities. Some interesting structure-activity relationships are revealed: (1) Spirocyclopiperazinium moiety is favorable to improve the analgesic activity; (2) The size and conformation of spirocyclopiperazinium moiety significantly affects the analgesic activity; (3) Phenylethyl group of 3d is a crucial pharmacophore. Among the compounds synthesized, 3d exhibited the most potent activity with low toxicity. Further antinociceptive mechanism studies of 3d showed that these compounds will be a new kind of analgesics.
- Sun, Qi,Yue, Cai-Qin,Ye, Jia,Li, Chang-Ling,Cheng, Tie-Ming,Li, Run-Tao
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p. 6245 - 6249
(2008/04/07)
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- Synthesis and evaluation of carbamate prodrugs of a phenolic compound
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A series of carbamates of the phenolic compound 1 were prepared and evaluated in vivo as its prodrug. Each carbamate was orally administered to rats, and plasma concentrations of the parent compound 1 were measured with the passage of time. We judged which carbamate was suitable for the prodrug of 1 from both the AUC value of 1 and absence of the carbamate in plasma. The AUC value of 1 after oral administration of 2b was approximately 40-fold higher than that for an administration of 1, and the bioconversion from 2b to 1 was excellent. As a whole, di-substituted carbamates resulted in higher plasma concentrations of 1 than did mono-substituted ones. However di-substituted carbamates were almost always detected in plasma. As a result, we found that the ethycarbamoyl derivative 2b demonstrates the best prodrug property in this series.
- Igarashi, Yasushi,Yanagisawa, Erika,Ohshima, Toshihiro,Takeda, Shuichi,Aburada, Masaki,Miyamoto, Ken-Ichi
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p. 328 - 333
(2007/10/03)
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- Enantioselective preparation of N-chirogenic tertiary amine oxides
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We found that PLE can be used as an efficient catalyst for desymmetrization of prochiral tertiary amine N-oxides and demonstrated that they were hydrolyzed by PLE efficiently to afford N-chirogenic tertiary amine oxides up to 99% ee in moderate to good yields.
- Suzuki, Ichiro,Kerakawauchi, Ran,Hirokawa, Takako,Takeda, Kei
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p. 6873 - 6876
(2008/02/12)
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- CHEMICAL COMPOUNDS
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The present invention relates to cyclic amine derivatives of formula(I) (I)whereinR represents halogen, C1-4 alkyl, cyano, C1-4 alkoxy, trifluoromethyl or trifluoromethoxy;R1 represents hydrogen, halogen, C3-7cycloalkyl, hydroxy, nitro, cyano or C1-4 alkyl optionally substituted by halogen, cyano or C1-4 alkoxy;R2 represents hydrogen or C1-4 alkyl;R3 and R4 independently represent hydrogen, cyano, C1-4 alkyl or R3 together with R4 represents C3-7 cycloalkyl;R5 represents trifluoromethyl, S(O)t C 1-4 alkyl, C1-4 alkyl, C1-4 alkoxy, trifluoromethoxy, halogen or cyano;R6 represents hydrogen or (CH2)rR7;R7 represents hydrogen, C3-7 cycloalkyl, NH(C1-4alkylOC1-4alkoxy), NH(C1-4alkyl), N(C1-4alkyl)2, OC(O)NR9R8, NR8C(O)R9 or C(O)NR9R8;R9 and R8 independently represent hydrogen, C1-4 alkyl or C3-7 cycloalkyl; m represents zero or an integer from 1 to 4;n represents 1 or 2;p is zero or an integer from 1 to 3;q is an integer from 1 to 3;r is an integer from 1 to 4;t is 0, 1 or 2;provided that when m is 0, p is 2, q, r and n represent 1, R1, R2,R3, R4, R5 and R7 are hydrogen and R is chlorine, R5 is not iodine; and pharmaceutically acceptable salts and solvates thereof; process for their preparation and their use in the treatment of conditions mediated by tackykinins and/or by selective inhibition of serotonin reuptake transporter protein.
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- CANNABINOID RECEPTOR LIGANDS
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There are disclosed compounds of the formula I: or a pharmaceutically acceptable salt of the compound, which exhibit anti-inflammatory and immunomodulatory activity. Also disclosed are pharmaceutical compositions containing said compounds.
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Page/Page column 52-53
(2010/02/05)
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- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
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- Synthesis and structure - Activity relationship of N-substituted 4-arylsulfonylpiperidine-4-hydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis
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The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-α-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues). To circumvent these two problems, a series of novel and orally active N-substituted 4-benzenesulfonylpiperidine-4-carboxylic acid hydroxyamide derivatives have been synthesized. The present paper deals with the synthesis and SAR of these compounds. Among the several compounds synthesized, derivative 55 turned out to be a potent, selective, and an orally active MMP inhibitor in the clinically relevant advanced rabbit osteoarthritis model. Detailed pharmacokinetics and metabolism data are described.
- Aranapakam, Venkatesan,Davis, Jamie M.,Grosu, George T.,Baker, Jannie,Ellingboe, John,Zask, Arie,Levin, Jeremy I.,Sandanayaka, Vincent P.,Du, Mila,Skotnicki, Jerauld S.,DiJoseph, John F.,Sung, Amy,Sharr, Michele A.,Killar, Loran M.,Walter, Thomas,Jin, Guixian,Cowling, Rebecca,Tillett, Jeff,Zhao, Weiguang,McDevitt, Joseph,Xu, Zhang Bao
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p. 2376 - 2396
(2007/10/03)
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- N-HYDROXY-2-(ALKYL, ARYL, OR HETEROARYL SULFANYL, SULFINYL OR SULFONYL)-3-SUBSTITUTED ALKYL, ARYL OR HETEROARYLAMIDES AS MATRIX METALLOPROTEINASE INHIBITORS
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Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF- alpha converting enzymes (TACE), a pro-inflammatory cytokine, catalyze the formation of TNF- alpha from membrane-bound TNF- alpha precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF- alpha converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by formula (I), where R, R, R and R are described herein.
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- Phenoxyalkylamine derivatives useful as opioid receptor agonists
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A medicament useful for preventive and/or therapeutic treatment of nerve system diseases which comprises, as an active ingredient, a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof: wherein, X represents a group represented by the following general formula (II), (III), (IV), (V), or (VI), “A” represents a saturated or unsaturated 3- to 6-membered carbocyclic group and the like, “B” represents CH2 and the like, “n” represents 0 to 2, R1 represents a hydrogen atom, a halogen atom and the like, R2, R3, and R7 to R14 represent a hydrogen atom, a lower alkyl group which may be substituted and the like, R4 represents a hydrogen atom, a lower alkyl group which may be substituted and the like, R5 represents a hydrogen atom, a halogen atom and the like, R6 represents a saturated or unsaturated monocyclic or bicyclic carbocyclic group and the like, and R5 and R6, R7 and R8, R9 and R10, or R11 and R12 may bind to each other to form a cyclic structure.
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- Diphenylalkylamine derivatives useful as opioid receptor agonists
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A substance having affinity for an opioid δ receptor, which is represented by the following general formula (I): 1 wherein, X represents a group of the general formula: —CO—N(R5)(R6) (II) and the like, n represents 1 to 3, R1 and R2 represent a hydrogen atom, a halogen atom, a lower alkyl group and the like, R3 represents a hydrogen atom, a halogen atom, a lower alkyl group and the like, R4 represents a saturated or unsaturated monocyclic or bicyclic carbocyclic group and the like, R5 to R12 represent a hydrogen atom, a lower alkyl group and the like, and R3 and R4, R5 and R6, R7 or R8 and R9 and R10 may bind to each other to form a cyclic structure, and a medicament useful for preventive and/or therapeutic treatment of central nervous system diseases and peripheral nervous system diseases comprising the substance as an active ingredient.
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- A mild and efficient cyanosilylation of ketones catalyzed by a Lewis acid-Lewis base bifunctional catalyst
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A new family of bifunctional catalysts (N-oxides-Ti(OiPr)4 (2:1)) containing a Lewis acid and a Lewis base was developed and applied to the catalytic cyanosilylation of ketones. Utilizing rac((1R,2S) and (1S,2R))-1-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide-titanium (2:1) complex and N-benzyl-diethanolamine N-oxide-titanium (2:1) complex as catalysts, the cyanosilylation products were obtained in 42-97% yield. Based on experimental phenomena and kinetic studies, a catalytic cycle was proposed to explain the remarkable activities of these catalysts. Investigations indicated that rac((1R,2S) and (1S,2R))-1-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide-titanium (2:1) complex and N-benzyl-diethanolamine N-oxide-titanium (2:1) complex should promote the reaction via a dual activation of the ketone by the titanium and TMSCN by the N-oxide.
- Shen, Yongcun,Feng, Xiaoming,Li, Yan,Zhang, Guolin,Jiang, Yaozhong
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p. 5667 - 5675
(2007/10/03)
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- Glucagon antagonists/inverse agonists
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Non-peptide compounds comprising a central hydrazide motif and methods for the synthesis thereof are disclosed. The compounds act to antagonize the action of the glucagon peptide hormone.
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- Photoactive chemosensors 3: A unique case of fluorescence enhancement with Cu(II)
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Chemosensor (4a) shows fluorescence enhancement with Cu(II) and can estimate 1-300 μM Cu(II) by using fluorescence (1-20 μM) and UV-Vis (10-300 μM) spectroscopic techniques. Ni(II), Cd(II), Zn(II), Ag(I) and Hg(II) do not interfere in fluorescence studies and only Ag(I) and Hg(II) interfere in UV-Vis studies.
- Kaur, Sukhdeep,Kumar, Subodh
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p. 2840 - 2841
(2007/10/03)
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- N-hydroxy-2-(Alkyl,Aryl or Heteroaryl sulfanyl, sulfinyl or sulfonyl) 3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors
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Matrix metalloproteinases (MMps) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-α converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-α from membrane bound TNF-α precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-α converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by the formula where R1, R2, R3and R4are described herein.
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Page column 58-59
(2010/02/04)
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- REMEDIES FOR PAIN
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The present invention provides a pain control agent, which contains, as an active ingredient, a compound having both μ opioid receptor agonist activity and dopamine D2 receptor antagonist activity. The compound having both of these activities exerts a potent morphine-like analgetic effect and causes no psychological dependence, and even regulates side effects. In particular, a novel compound represented by general formula (I) or a pharmacologically acceptable salt thereof has both μ opioid receptor agonist activity and dopamine D2 receptor antagonist activity, and is useful as pain control agent with regulated side effects.
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- Process for preparing N,N-bis(2-hydroxyethyl)benzylamine and N,N-bis(2-chloroethyl)benzylamine
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Improvements are shown in the successive preparations of N,N-bis(2-hydroxyethyl)benzylamine starting with benzyl chloride, its conversion to the corresponding N,N-bis(2-chloroethyl)benzylamine in substantially quantitative yield in toluene solution and using the latter by reaction with phenylacetonitrile in the presence of aqueous sodium hydroxide solution and a tetra-n-butylammonium salt, preferably the hydrogen sulfate, to produce improved over-all yields of up to over 75% (based on benzyl chloride) of 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride, an intermediate for preparing meperidine.
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