- Desymmetrization of Diarylmethylamido Bis(phenols) through Peptide-Catalyzed Bromination: Enantiodivergence as a Consequence of a 2 amu Alteration at an Achiral Residue within the Catalyst
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Diarylmethylamido bis(phenols) have been subjected to peptide-catalyzed, enantioselective bromination reactions. Desymmetrization of compounds in this class has been achieved such that enantioenriched products may be isolated with up to 97:3 er. Mechanist
- Hurtley, Anna E.,Stone, Elizabeth A.,Metrano, Anthony J.,Miller, Scott J.
-
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Read Online
- Exploring intermolecular contacts in multi-substituted benzaldehyde derivatives: X-ray, Hirshfeld surface and lattice energy analyses
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Crystal structures of six benzaldehyde derivatives (1-6) have been determined and their supramolecular networks were established by an X-ray crystallographic study. The study has shown that the compounds are linked by various intermolecular interactions s
- Hosten, Eric C.,Hulushe, Siya T.,Louzada, Marcel,Manyeruke, Meloddy H.,Rigin, Sergei,Watkins, Gareth M.
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Read Online
- Development of DHQ-based chemical biology probe to profile cellular targets for HBV
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Chronic hepatitis B virus (HBV) infection has been a serious public health burden worldwide. Current anti-HBV therapies could not eliminate HBV ultimately. Considering the characteristics of HBV, it is impossible to be entirely cured based on current therapies. Therefore, it is urgently needed to develop novel therapeutic agents with new mechanism of action. The dihydroquinolizinone (DHQ) derivatives exhibited potent anti-HBV activity by decreasing HBV DNA and HBsAg level in an obscure mechanism of action. In this study, we have optimized the DHQ scaffold, developed the photoaffinity probe, with which to identify potential binding proteins.
- Zhang, Qing,Huang, Jianzhou,Chow, Hoi Yee,Wang, Jinzheng,Zhang, Yingjun,Fung, Yi Man Eva,Ren, Qingyun,Li, Xuechen
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supporting information
(2020/10/29)
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- Choline Hydroxide as a Versatile Medium for Catalyst-Free O-Functionalization of Phenols
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A versatile synthetic protocol for benzyl phenyl ether preparation via O-alkylation of phenolic oxygen with readily available benzyl derivatives was demonstrated. The newly designed procedure was carried out using an eco-friendly medium, room-temperature ionic liquid (choline hydroxide), under metal- and base-catalyst-free aerobic conditions. The reaction platform was also successfully applied to phenol protection strategy.
- Joo, Seong-Ryu,Kim, Seung-Hoi,Kwon, Gyu-Tae,Park, Soo-Youl
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p. 1200 - 1205
(2020/11/30)
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- Structural Simplification of a Tetrahydroquinoline-Core Peptidomimetic μ-Opioid Receptor (MOR) Agonist/δ-Opioid Receptor (DOR) Antagonist Produces Improved Metabolic Stability
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We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in mice, and do not produce dependence. Although these attributes are promising, these analogues exhibit poor metabolic stability in mouse liver microsomes, likely due to the central tetrahydroquinoline scaffold in this series. As such, a structure-activity relationship (SAR) campaign was pursued to improve their metabolic stability. This resulted in a shift from our original bicyclic tetrahydroquinoline core to a monocyclic benzylic-core system. By eliminating one of the rings in this scaffold and exploring the SAR of this new core, two promising analogues were discovered. These analogues (5l and 5m) had potency and efficacy values at MOR better or comparable to morphine, retained their DOR-antagonist properties, and showed a 10-fold improvement in metabolic stability.
- Henry, Sean P.,Fernandez, Thomas J.,Anand, Jessica P.,Griggs, Nicholas W.,Traynor, John R.,Mosberg, Henry I.
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p. 4142 - 4157
(2019/05/06)
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- IMMUNE CHECKPOINT INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. For Formula (I) compounds R1, R2, X1, Y1 and n are as defined in the specification. The inventive Formula (I) compounds are inhibitors of the PD-1/PD-L1 protein/protein binding or functional interaction and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer and infectious diseases.
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Paragraph 0332
(2018/03/25)
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- FUSED TRICYCLIC COMPOUNDS AND USES THEREOF IN MEDICINE
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The present invention relates to a fused tricyclic compound and use thereof as a medicament, in particular as a medicament for the treatment and/or prevention of hepatitis B. Specifically, the invention relates to a compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, wherein each variate is as defined in specification. The invention also relates to the use of the compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof as a medicament, especially as a medicament for the treatment and/or prevention of hepatitis B.
- -
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Paragraph 00257
(2019/01/05)
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- COMPOSITIONS FOR THE TREATMENT OF PULMONARY FIBROSIS
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The present invention relates to compounds and their use in the prophylactic and/or therapeutic treatment of pulmonary fibrosis and/or related conditions.
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Paragraph 00144; 00145
(2018/02/28)
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- Design and synthesis of novel meta-linked phenylglycine macrocyclic FVIIa inhibitors
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Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/ FVIIa Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.
- Richter, Jeremy M.,Cheney, Daniel L.,Bates, J. Alex,Wei, Anzhi,Luettgen, Joseph M.,Rendina, Alan R.,Harper, Timothy M.,Narayanan, Rangaraj,Wong, Pancras C.,Seiffert, Dietmar,Wexler, Ruth R.,Priestley, E. Scott
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supporting information
p. 67 - 72
(2017/12/12)
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- Synthesis and evaluation of 3-hydroxy-3-phenylpropanoate ester-AZT conjugates as potential dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors
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Novel 3-hydroxy-3-phenylpropanoate ester-azidothymidine (AZT) conjugates have been prepared using Baylis-Hillman methodology, and their potential as dual-action HIV-1 Integrase and Reverse Transcriptase inhibitors has been explored using enzyme inhibition
- Manyeruke, Meloddy H.,Olomola, Temitope O.,Majumder, Swarup,Abrahams, Shaakira,Isaacs, Michelle,Mautsa, Nicodemus,Mosebi, Salerwe,Mnkandhla, Dumisani,Hewer, Raymond,Hoppe, Heinrich C.,Klein, Rosalyn,Kaye, Perry T.
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p. 7521 - 7528
(2015/12/18)
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- BILATERALLY-SUBSTITUTED TRICYCLIC COMPOUNDS FOR THE TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) INFECTION AND OTHER DISEASES
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The invention relates to bilaterally-substituted tricyclic compounds and pharmaceutical compositions containing them, for use as medicaments. Due to their ability to interact with an internal RNA loop and to mimic a protein a-helix these compounds are effective in the treatment and/or prevention of HIV-1 (Human Immunodeficiency Virus-1) infection and other diseases such as those caused by other RNA viruses and by gram-positive and gram-negative bacteria, or infectious or chronic diseases responsive to inhibition of DNA transcription, or infectious or chronic diseases where these compounds can be used to modulate the function of RNA internal loops, or infectious or chronic diseases where these compounds can be used as agonists or inhibitors of a-helical proteins in interaction with other biomolecules.
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Page/Page column 46-47
(2014/09/03)
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- MACROCYCLIC FACTOR VIIA INHIBITORS
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The present invention provides compounds of Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.
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Paragraph 00146; 00153
(2015/01/09)
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- Evaluation of Baylis-Hillman Routes to 3-(Aminomethyl)coumarin Derivatives
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The relative merits of two different Baylis-Hillman approaches toward the preparation of coumarin derivatives, containing peptide-like side chains, have been explored. In one approach, use of methyl acrylate as the activated alkene requires a protecting group strategy, an approach that is not necessary when using tert-butyl acrylate. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Olasupo, Idris,Rose, Nathan R.,Klein, Rosalyn,Adams, Luqman A.,Familoni, Oluwole B.,Kaye, Perry T.
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p. 251 - 258
(2013/12/04)
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- Synthesis of cinnamate ester-AZT conjugates as potential dual-action HIV-1 integrase and reverse transcriptase inhibitors
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Synthetic approaches to a series of novel cinnamate ester-AZT conjugates have been explored and a successful pathway has finally been developed. α-(Halomethyl)cinnamate esters, obtained in high yield by treating benzyl-protected salicylaldehde-derived Bay
- Olomola, Temitope O.,Klein, Rosalyn,Kaye, Perry T.
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p. 9449 - 9455
(2015/03/03)
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- AROMATIC RING COMPOUND
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Provided is an aromatic ring compound having a GPR40 agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a GPR40 agonist activity, and is useful as an agent for the prophylaxis or treatment of diabetes and the like.
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Paragraph 0353; 0354
(2015/01/18)
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- Structure-based design of an RNA-binding p-terphenylene scaffold that inhibits HIV-1 rev protein function
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Rev(ersing) RNA binding: RNA-binding inhibitors based on a bilaterally substituted p-terphenylene scaffold (green) project their substituents in a broad spatial angle and reproduce the interactions of a protein α-helix (red) embedded in its RNA receptor.
- Gonzalez-Bulnes, Luis,Ibanez, Ignacio,Bedoya, Luis M.,Beltran, Manuela,Catalan, Silvia,Alcami, Jose,Fustero, Santos,Gallego, Jose
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supporting information
p. 13405 - 13409
(2014/01/06)
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- Scalable synthesis of the desoxy-biphenomycin B core
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We describe the evolution of a kilogram-scale synthesis of the protected cyclic tripeptide desoxy-biphenomycin B, based on an early discovery route. The retrosynthetic concept included a macrolactamization strategy to build the core ring system of biphenomycin B in combination with a double catalytic asymmetric hydrogenation protocol for the construction of the ansa-tripeptide precursor. Eventually, the kilogram process comprised a 16-step sequence with an overall yield for the longest linear sequence of 19.5%.
- Berwe, Mathias,Joentgen, Winfried,Krueger, Jochen,Cancho-Grande, Yolanda,Lampe, Thomas,Michels, Martin,Paulsen, Holger,Raddatz, Siegfried,Weigand, Stefan
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experimental part
p. 1348 - 1357
(2012/01/12)
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- Synthesis of benzyloxycyanophenylboronic esters
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The synthesis of six new benzyloxycyanoboronic esters: 2-benzyloxy-6- cyanophenyl-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane (4a), 4-benzyloxy-2- cyanophenyl-4,4,5, 5-tetramethyl-[1,3,2]dioxaborolane (4b), 4-benzyloxy-3- cyanophenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (8a), 2-benzyloxy-5- cyanophenyl-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane (8b), 3-benzyloxy-4- cyanophenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (12a), and 2-benzyloxy-5-cyanophenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (12b) is reported. Copyright by Walter de Gruyter Berlin Boston.
- El Bialy, Serry A.A.,Abd El Kader, Kamelia F.,Boykin, David W.
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experimental part
p. 10 - 16
(2011/10/18)
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- PAI-1 INHIBITOR
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The compound represented by the following formula (I) and the like have PAI-1 inhibition activity; wherein: R1 represents a C6-10 aryl group which may be substituted or the like; T represents a single bond or the like; m represents 0
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Page/Page column 248
(2011/02/17)
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- Redox-active tripodal aminetris(aryloxide) complexes of titanium(IV)
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New sterically encumbered tripodal aminetris(aryloxide) ligands N(CH 2C6H2-3-tBu-5-X-2-OH)3 (tBu,XLH3) with relatively electron-rich phenols are prepared by Mannich condensation (X = OCH3) or by a reductive amination/Hartwig-Buchwald amination sequence on the benzyl-protected bromosalicylaldehyde (X = N[C6H4-p-OCH3] 2), followed by debenzylation using Pearlman's catalyst (Pd(OH) 2/C). The analogous dianisylamino-substituted compound lacking the tert-butyl group ortho to the phenol (H,An2NLH 3) is also readily prepared. The ligands are metalated by titanium(IV) tert-butoxide to form the five-coordinate alkoxides LTi(O tBu). Treatment of the tert-butoxides with aqueous HCl yields the five-coordinate chlorides LTiCl, and with acetylacetone gives the six-coordinate diketonates LTi(acac). The diketonate complexes tBu,XLTi(acac) show reversible ligand-based oxidations with first oxidation potentials of +0.57, +0.33, and -0.09 V (vs ferrocene/ferrocenium) for X = tBu, MeO, and An2N, respectively. Both dianisylamine-substituted complexes R,An2NLTi(acac) (R = tBu, H) show similar electrochemistry, with three one-electron oxidations closely spaced at ~0 V and three oxidations due to removal of a second electron from each diarylaminoaryloxide arm at ~ + 0.75 V. The new electron-rich tripodal ligands therefore have the capacity to release multiple electrons at unusually low potentials for aryloxide groups.
- Lionetti, Davide,Medvecz, Andrew J.,Ugrinova, Vesela,Quiroz-Guzman, Mauricio,Noll, Bruce C.,Brown, Seth N.
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experimental part
p. 4687 - 4697
(2010/08/13)
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- Thiazolidinedione derivatives as PTP1B inhibitors with antihyperglycemic and antiobesity effects
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Benzylidene-2,4-thiazolidinedione derivatives with substitutions on the phenyl ring at the ortho or para positions of the thiazolidinedione (TZD) group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 3e, the lowest, bore an IC50 of 5.0 μM. In vivo efficacy of 3e as an antiobesity and hypoglycemic agent was evaluated in a mouse model system. Significant improvement of glucose tolerance was observed. This compound also significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA. Compound 3e was also found to activate peroxisome proliferator-activated receptors (PPARs) indicating multiple mechanisms of action.
- Bhattarai, Bharat Raj,Kafle, Bhooshan,Hwang, Ji-Sun,Khadka, Deegendra,Lee, Sun-Myung,Kang, Jae-Seung,Ham, Seung Wook,Han, Inn-Oc,Park, Hwangseo,Cho, Hyeongjin
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supporting information; experimental part
p. 6161 - 6165
(2010/06/16)
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- PAI-1 INHIBITOR
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The compound represented by the following formula (I) and the like have PAI-1 inhibition activity; wherein: R1 represents a C6-10 aryl group which may be substituted or the like; T represents a single bond or the like; m represents 0
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Page/Page column 274
(2009/12/27)
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- Rhodanine Derivatives, a Process for the Preparation Thereof and Pharmaceutical Composition Containing the Same
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Disclosed herein are rhodanine derivatives, a method for the preparation thereof, and a pharmaceutical composition containing the same. The rhodanine derivatives have inhibitory activity against protein phosphatases (PPase) such as PTP1B, Prl-3, LAR, CD45
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Page/Page column 15
(2009/03/07)
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- Regio-Controlled Michaelis-Arbuzov reactions of 3-(halomethyl)-coumarins
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3-(Iodomethyl)coumarins and 3-(chloromethyl)coumarins, obtained chemoselectively via Baylis-Hillman reactions of salicylaldehyde derivatives with t-butyl acrylate, can be reacted with triethyl phosphite to afford regioisomeric Michaelis-Arbuzov products.
- Rashamuse, Thompo J.,Musa, Musiliyu A.,Klein, Rosalyn,Kaye, Perry T.
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scheme or table
p. 302 - 305
(2009/12/25)
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- Highly diastereoselective synthesis of orthoquinone monoketals through λ13-iodane-mediated oxidative dearomatization of phenols
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(Chemical Equation Presented) Versatile chiral substrates for asymmetric synthesis are formed through the spiroketalization of phenols with a chiral substituted ethanol unit O-tethered to the ortho position upon treatment with PhI-(OAc)2 (see example; TFE = 2,2,2-tri-fluoroethanol). Intermediates with a six-membered iodine(III)-containing ring (the natural localized molecular orbitals associated with the I-C6 bond are shown) undergo ligand coupling to give the spiroketals.
- Pouysegu, Laurent,Chassaing, Stefan,Dejugnac, Delphine,Lamidey, Anne-Marie,Miqueu, Karinne,Sotiropoulos, Jean-Marc,Quideau, Stephane
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supporting information; experimental part
p. 3552 - 3555
(2009/02/07)
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- Carboxilic acid derivatives
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A compound represented by the following general formula (I) or a salt thereof, or a hydrate thereof or a solvate thereof having an inhibitory action against plasminogen activator inhibitor-1 (PAI-1): wherein R1 represents a C6-10 ary
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Page/Page column 39; 40
(2008/12/08)
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- AMINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES
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A novel amine compound represented by the following formula (I), which is superior in immunosuppressive action, rejection suppressive action and the like, and shows reduced side effects such as bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or hydrates thereof, or solvate, as well as a pharmaceutical composition containing this compound and a pharmaceutically acceptable carrier. wherein R is a hydrogen atom or P(=O)(OH)2, X is an oxygen atom or a sulfur atom, Y is CH2CH2 or CH=CH, R1 is cyano or alkyl having a carbon number of 1 to 4 and substituted by a halogen atom(s), R2 is alkyl having a carbon number of 1 to 4 and optionally substituted by a hydroxyl group(s) or a halogen atom(s), R3 and R4 may be the same or different and each is a hydrogen atom or alkyl having a carbon number of 1 to 4, and n is 5 - 8.
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Page/Page column 57; 58
(2008/12/08)
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- CCR5 receptor antagonists: Discovery and SAR study of guanylhydrazone derivatives
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High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.
- Wei, Robert G.,Arnaiz, Damian O.,Chou, Yuo-Ling,Davey, Dave,Dunning, Laura,Lee, Wheeseong,Lu, Shou-Fu,Onuffer, James,Ye, Bin,Phillips, Gary
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p. 231 - 234
(2007/10/03)
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- Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of β-secretase
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Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme β-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 μM) and 6c (IC50 = 24 μM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM).
- Congreve, Miles,Aharony, David,Albert, Jeffrey,Callaghan, Owen,Campbell, James,Carr, Robin A. E.,Chessari, Gianni,Cowan, Suzanna,Edwards, Philip D.,Frederickson, Martyn,McMenamin, Rachel,Murray, Christopher W.,Patel, Sahil,Wallis, Nicola
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p. 1124 - 1132
(2007/10/03)
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- RHODANDSE DERIVARIVES, A PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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Disclosed herein are rhodanine derivatives, a method for the preparation thereof, and a pharmaceutical composition containing the same. The rhodanine derivatives have inhibitory activity against protein phosphatases (PPase) such as PTPlB, Prl-3, LAR, CD45
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Page/Page column 19
(2010/11/28)
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- Discovery of novel, non-acidic 1,5-biaryl pyrrole EP1 receptor antagonists
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Replacement of the carboxylic acid group in a series of previously described 1,5-biaryl pyrrole EP1 receptor antagonists led to the discovery of various novel non-acidic antagonists. Several analogues displayed high binding affinity and high bi
- Hall, Adrian,Atkinson, Stephen,Brown, Susan H.,Chessell, Iain P.,Chowdhury, Anita,Giblin, Gerard M.P.,Goldsmith, Paul,Healy, Mark P.,Jandu, Karamjit S.,Johnson, Matthew R.,Michel, Anton D.,Naylor, Alan,Sweeting, Jennifer A.
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p. 1200 - 1205
(2007/10/03)
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- NOVEL 2-OXO-1,2,3,4-TETRAHYDROPYRIMIDINES, BICYCLIC PYRIMIDINE DIONES AND IMIDAZOLIDINE-2,4-DIONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
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The present invention relates to novel 2-oxo-l,2,3,4-tetrahydropyrimidines, bicyclic pyrimidine diones and imidizolidine-2,4-diones and methods useful as inhibitors of nitric oxide synthase.
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Page/Page column 30
(2010/11/28)
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- Palladium catalyzed α-arylation of methyl isobutyrate and isobutyronitrile: an efficient synthesis of 2,5-disubstituted benzyl alcohol and amine intermediates
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Several 2,5-disubstituted benzyl alcohols containing a functionalized t-butyl moiety were synthesized via palladium catalyzed α-arylation of methyl isobutyrate and butyronitrile on synthetically useful scales. The resulting benzyl alcohols could then be further elaborated to benzyl amines or other desirable intermediates.
- Shetty, Rupa,Moffett, Kristofer K.
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p. 8021 - 8024
(2007/10/03)
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- Structure-activity relationships of 1,5-biaryl pyrroles as EP1 receptor antagonists
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The preliminary SAR of a series of novel 1,5-biaryl pyrrole EP1 receptor antagonists derived from compound 1 is described. Replacement of the benzyl group of 1 with isosteric groups was investigated. The most effective replacement was found to be the isobutyl group. The cyclopentylmethyl and cyclohexylmethyl groups were also effective benzyl replacements. The cyclohexylmethyl derivative 19 demonstrated the lowest metabolic clearance within this series. In addition, several high affinity substituted benzyl analogues were also identified. Compound 39 was found to have good bioavailability in rats and demonstrated efficacy in the established FCA preclinical model of inflammatory pain with a calculated ED50 of 9.2 mg/kg.
- Hall, Adrian,Atkinson, Stephen,Brown, Susan H.,Chessell, Iain P.,Chowdhury, Anita,Clayton, Nicholas M.,Coleman, Tanya,Giblin, Gerard M.P.,Gleave, Robert J.,Hammond, Beverley,Healy, Mark P.,Johnson, Matthew R.,Michel, Anton D.,Naylor, Alan,Novelli, Riccardo,Spalding, David J.,Tang, Sac P.
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p. 3657 - 3662
(2007/10/03)
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- Synthesis and biological evaluation of rhodanine derivatives as PRL-3 inhibitors
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A series of rhodanine derivatives was synthesized and evaluated for their ability to inhibit PRL-3. Benzylidene rhodanine derivative showed good biological activity, while compound 5e was the most active in this series exhibiting an IC50 value of 0.9 μM in vitro and showed a reduced invasion in cell-based assay.
- Ahn, Jin Hee,Kim, Seung Jun,Park, Woul Seong,Cho, Sung Yun,Ha, Jae Du,Kim, Sung Soo,Kang, Seung Kyu,Jeong, Dae Gwin,Jung, Suk-Kyeong,Lee, Sang-Hyeup,Kim, Hwan Mook,Park, Song Kyu,Lee, Ki Ho,Lee, Chang Woo,Ryu, Seong Eon,Choi, Joong-Kwon
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p. 2996 - 2999
(2008/09/20)
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- Compounds for the treatment of ischemia
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A3 agonists, methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists. The A3 agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia
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- NOVEL BICYCLIC AROMATIC COMPOUNDS, THE PRODUCTION AND USE THEREOF IN THE FORM OF DRUGS
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The invention relates to novel aromatic bicycle compounds of formula (I), wherein Ar, X, Y and R1-R3 are such as specified in a claim 1. Said invention also relates to the tautomers, enantiomers, diasteriomers, mixtures, pro-drugs an
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- Design, synthesis, and biological activity of potent and selective inhibitors of blood coagulation factor Xa
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Factor Xa (FXa) has materialized as a key enzyme for the intervention of the blood coagulation cascade and for the development of new antithrombotic agents. FXa is the lone enzyme responsible for the production of thrombin and therefore is an attractive t
- Willardsen, J. Adam,Dudley, Danette A.,Cody, Wayne L.,Chi, Liguo,McClanahan, Thomas B.,Mertz, Thomas E.,Potoczak, Ronald E.,Narasimhan, Lakshmi S.,Holland, Debra R.,Rapundalo, Stephen T.,Edmunds, Jeremy J.
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p. 4089 - 4099
(2007/10/03)
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- Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation
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A series of 2′-benzyloxy-5′-substituted-5-benzylidene- thiazolidine-2,4-thione and -dione derivatives was synthesized and evaluated as inhibitors of translation initiation. In an effort to generate novel translation initiation inhibitors for cancer therapy, a series of 2′-benzyloxy- 5′-substituted-5-benzylidene-thiazolidine-2,4-thione and dione derivatives was synthesized and evaluated for activity in translation initiation specific assays. Several candidates of the 5-benzylidene-thiazolidine-2,4-diones (3c, 3d, and 3f) and -thiones (2b, 2e, and 2j), inhibit cell growth with low μM GI50 mediated by inhibition of translation initiation, which involves partial depletion of intracellular Ca2+ stores and strong phosphorylation of eIF2Iα.
- Chen, Han,Fan, Yun-Hua,Natarajan, Amarnath,Guo, Yuhong,Iyasere, Julia,Harbinski, Fred,Luus, Lia,Christ, William,Aktas, Huseyin,Halperin, Jose A.
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p. 5401 - 5405
(2007/10/03)
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- Biaromatic compound activators of PPARy-type receptors
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The invention relates to novel biaromatic compounds which correspond to the general formula (I) below: and also to the method for preparing them and their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and also in the field of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism), or alternatively in cosmetic compositions.
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- PYRROLE COMPOUNDS FOR THE TREATMENT OF PROSTAGLANDIN MEDIATED DISEASES
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Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein A, R1, R2a, R2b, Rx, R8, and R9 are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine, in particular their use in the treatment of prostaglandin mediated diseases such as pain, inflammatory, immunological, bone, neurodegenerative or renal disorder.
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- Benzoxazinoes/benzothiazinones as serine protease inhibitors
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This invention discloses benzoxazinone and benzothiazinone compounds which display inhibitory effects on serine proteases such as factor Xa, thrombin, and/or factor VIIa. The invention also discloses pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnornal thrombosis.
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- A convenient and improved Baylis-Hillman synthesis of 3-substututed 2H-1-benzopyran-2-ones
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Halogen acid-catalysed deprotection and cyclisation of Baylis-Hillman products obtained using O-benzylated salicylaldehyde precursors has been shown to afford 3-(halomethyl)coumarins (3-halomethyl-2H-1-benzopyran-2-ones) chemoselectively and in good yield.
- Kaye, Perry T.,Musa, Musiliyu A.
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p. 2701 - 2706
(2007/10/03)
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- Synthesis of the indole alkaloids meridianins from the tunicate Aplidium meridianum
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The marine natural products meridianins A and C-E have been synthesized for the first time starting from the appropriate N-tosyl-3-acetylindole. A facile two-step conversion of N-tosyl-3-acetylindoles to the corresponding meridianins by treatment with dimethylformamide dimethylacetal and further cyclization of the resulting enaminone with aminoguanidine is described. This method has also been applied for the preparation of the 3-[(2-amino)pyrimidin-4-yl]-7-azaindole.
- Fresneda, Pilar M,Molina, Pedro,Bleda, Juan A
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p. 2355 - 2363
(2007/10/03)
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- Aromatic amine compounds that antagonize the pain enhancing effects of prostaglandins
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PCT No. PCT/GB96/01443 Sec. 371 Date Dec. 16, 1997 Sec. 102(e) Date Dec. 16, 1997 PCT Filed Jun. 17, 1996 PCT Pub. No. WO97/00864 PCT Pub. Date Jan. 9, 1997Compounds antagonistic of the pain enhancing effects of prostaglandins are disclosed. The compounds
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- Synthetic studies towards the 2-aminopyrimidine alkaloids variolins and meridianins from marine origin
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A nine-step synthesis of 9-amino-4-methoxypyrido[3',2':4,5]pyrrolo[1,2- c]pyrimidine, a tricyclic ring system present in the marine alkaloids variolins is described. The natural marine products meridianins C-E have been synthesized for the first time starting from N-protected 3-acylindoles. (C) 2000 Elsevier Science Ltd.
- Fresneda, Pilar M.,Molina, Pedro,Delgado, Santiago,Bleda, Juan A.
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p. 4777 - 4780
(2007/10/03)
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- Aromatic compounds and pharmaceutical compositions containing them
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The invention relates to compounds of formula I and pharmaceutically acceptable salts and in vivo hydrolysable esters and amides thereof and processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them.
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- Aromatic amino ethers as pain relieving agents
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The present invention relates to compounds of formula (I), STR1 wherein A is an optionally substituted phenyl naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, thienyl, thiazolyl, oxazolyl, thiadiazolyl having at least two adjacent ring carbon atoms or a bicyclic ring system, provided that the --CH(R3)N(R2)B--R1 and --OCH(R4 --)--D linking groups arm positioned in a 1,2 relationship to one another on ring carbon atoms and the ring atom positioned ortho to the --OCHR4 -- linking group (and therefore in the 3-position relative to the --CHR3 NR2 -- linking group) is not substituted; B is an optionally substituted ring system; D is an optionally substituted ring system; R1 is a variety of group as defined in the description; R2 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenylC1-3 alkyl or 5- or 6-membered heteroarylC1-3 alkyl; R3 is hydrogen or C1-4 alkyl; R4 is hydrogen or C1-4 alkyl; and N-oxides of NR2 where chemically possible; and S-oxides of sulphur containing rings were chemically possible; and pharmaceutically acceptable salts and in vivo hydrolysable esters and amides thereof. Process for their preparation, intermediates in theirpreparation, their use as therapeutic agents and pharmaceutical compositions containing them.
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- ORTHO SUBSTITUTED AROMATIC COMPOUNDS USEFUL AS ANTAGONISTS OF THE PAIN ENHANCING EFFECTS OF E-TYPE PROSTAGLANDINS
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The invention relates to compounds of the formula (I): STR1 wherein A, B and D are various ring systems such as phenyl, R. sup.1 includes carboxy, R 3 is hydrogen or C 1-4 alkyl and Z is a linking group such as--(CH(R 5)) m--wherein m is 2, 3 or 4, and R 5 includes hydrogen and methyl; and pharmaceutically acceptable salts and in vivo hydrolysable esters or amides thereof, processes for preparing these compounds, pharmaceutical compositions comprising them, and their use in the treatment of pain.
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