- Intramolecular electron transfer reactions in meso-(4-nitrophenyl)-substituted subporphyrins
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A2B-type meso-(4-nitrophenyl)-substituted subporphyrins have been synthesized and shown to undergo very fast photoinduced intramolecular charge separation (CS) and charge recombination (CR) between the subporphyrin core and the meso-4-nitrophenyl group in CH2Cl2 as probed by femtosecond time-resolved transient absorption spectroscopy. Red-shifted emissions were detected from charge-separated states as a rare case for porphyrinoids.
- Copley, Graeme,Oh, Juwon,Yoshida, Kota,Shimizu, Daiki,Kim, Dongho,Osuka, Atsuhiro
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Read Online
- Augmenting the Activity of Macrolide Adjuvants against Acinetobacter baumannii
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Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 μg/mL at a concentration of 10 μM. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 μM, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 μM. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 μM, the parent compound reduced the CLR MIC from 512 to 2 μg/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.
- Hubble, Veronica B.,Bartholomew, Kyle R.,Weig, Alexander W.,Brackett, Sara M.,Barlock, Samantha L.,Mattingly, Anne E.,Nemeth, Ansley M.,Melander, Roberta J.,Melander, Christian
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Read Online
- Spiro-bis-benzoxazole diamine and preparation method and application thereof, polyimide and preparation method and application thereof
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The invention belongs to the technical field of macromolecules, and particularly relates to spirobibenzoxazole diamine, a preparation method and application thereof, polyimide and a preparation method and application thereof. According to the present invention, the spiro-bis-benzoxazole diamine is adopted as the monomer to prepare the polyimide, and the spiro structure is introduced into the diamine structure, such that the obtained polyimide has excellent solubility and excellent processability; meanwhile, the polyimide forms a microporous structure, so that the gas permeability of the polyimide is improved.
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Paragraph 0065-0066; 0195-0197
(2021/09/04)
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- HETEROCYCLIC COMPOUNDS AS AHR MODULATORS
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The present invention relates compounds of the general formula (I) or (III) which are ARH inhibitors, methods for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds and pharmaceutical compositions for the treatment or prevention of diseases, in particular cancer or conditions with dysregulated immune functions, or other conditions associated with aberrant AHR signalling, as a sole agent of in combination with other active ingredients. Such compounds may also be of utility in the expansion of hematopoietic stem cells (HSCs) and the use of HSCs in autologous or allogenic transplantation for the treatment of patients with inherited immunological and autoimmune diseases and diverse hematopoietic disorders.
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Page/Page column 15
(2020/03/24)
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- A method of preparing intermediates the request cuts down the Pu Tanzania
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The invention relates to a method for preparing a tolvaptan intermediate, namely 7-chlorine-5-oxo-1-(2-methyl-4-nitrobenzene formyl)-1,2,3,4-tetrahydro-benzo-azepine. The tolvaptan intermediate which is a compound as shown in the formula (1) is obtained by 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo-azepine (2) reacting with 4-nitryl-2-methylbenzene formyl chloride (3). The tolvaptan intermediate prepared by the method has the advantages of high purity, high yield and short reaction time, thereby being suitable for large-scale industrialized production.
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Paragraph 0015
(2017/03/08)
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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 00129
(2015/01/09)
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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; 00147
(2014/01/08)
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- Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)- 3,5-difluorobenzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A phosphonooxymethylene prodrug of a potent and selective hA2A receptor antagonist
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The discovery and structure-activity relationship of a series of hA 2A receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptableADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.
- Sams, Anette G.,Mikkelsen, Gitte K.,Larsen, Mogens,Langg?rd, Morten,Howell?, Mark E.,Schr?der, Tenna J.,Brennum, Lise T.,Torup, Lars,J?rgensen, Erling B.,Bundgaard, Christoffer,Kreilg?rd, Mads,Bang-Andersen, Benny
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supporting information; experimental part
p. 751 - 764
(2011/04/18)
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- NMR evaluation of interactions between substituted-indole and PDZ1 domain of PSD-95
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We synthesized small organic molecules designed as PDZ ligands. These indole-based compounds were evaluated for their interaction with the PDZ1 domain of the post-synaptic density 95 (PSD-95) protein. Three molecules were found to interact with the targeted PDZ protein by NMR. One of them showed chemical shift perturbations closely related to the natural ligands.
- Vogrig, Alexandre,Boucherle, Benjamin,Deokar, Hemantkumar,Thomas, Isabelle,Ripoche, Isabelle,Lian, Lu-Yun,Ducki, Sylvie
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scheme or table
p. 3349 - 3353
(2011/07/07)
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- BETA- AND GAMMA-AMINO-ISOQUINOLINE AMIDE COMPOUNDS AND SUBSTITUTED BENZAMIDE COMPOUNDS
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Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.
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Page/Page column 20
(2010/02/17)
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- 2-Amino-aryl-7-aryl-benzoxazoles as potent, selective and orally available JAK2 inhibitors
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A series of novel benzoxazole derivatives has been designed and shown to exhibit attractive JAK2 inhibitory profiles in biochemical and cellular assays, capable of delivering compounds with favorable PK properties in rats. Synthesis and structure-activity relationship data are also provided.
- Gerspacher, Marc,Furet, Pascal,Pissot-Soldermann, Carole,Gaul, Christoph,Holzer, Philipp,Vangrevelinghe, Eric,Lang, Marc,Erdmann, Dirk,Radimerski, Thomas,Regnier, Catherine H.,Chene, Patrick,Pover, Alain De,Hofmann, Francesco,Baffert, Fabienne,Buhl, Thomas,Aichholz, Reiner,Blasco, Francesca,Endres, Ralf,Trappe, J?rg,Drueckes, Peter
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scheme or table
p. 1724 - 1727
(2010/07/03)
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- Fibrinogen receptor antagonists and their use
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This invention relates to novel fused bicyclic compounds of the general formula (I): wherein the symbols are defined herein, to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and to methods of using the compounds, alone or in combination with other therapeutic agents. The compounds are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, and are therefore useful for the inhibition of platelet aggregation, and for the treatment of thrombotic diseases and other diseases.
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Page/Page column 47
(2010/08/04)
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- HETEROARYL DERIVATIVES AS PROTEIN KINASE INHIBITORS
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Objects of the present invention are the compounds of formula I their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.
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Page/Page column 56
(2010/11/30)
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- PROCESS FOR THE PREPARATION OF SUBSTITUTED HETEROCYCLES
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The present disclosure generally relates to a process for the preparation of hydroxy-substituted heterocycles such as isoquinolines, naphthyridines, pyridopyridazines, and pyridopyrimidines.
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Page/Page column 4
(2010/11/27)
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- FIBRINOGEN RECEPTOR ANTAGONISTS AND THEIR USE
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This invention relates to novel fused bicyclic compounds of the general formula (I): wherein the symbols are defined herein, to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and to methods of using the compounds, alone or in combination with other therapeutic agents. The compounds are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, and are therefore useful for the inhibition of platelet aggregation, and for the treatment of thrombotic diseases and other diseases.
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Page/Page column 60-61
(2010/02/11)
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- 7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5- tetrahydro-1H-1-benzazepine (OPC-41061): A potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist
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We previously reported a series of benzazepine derivatives as orally active nonpeptide arginine vasopressin (AVP) V2 receptor antagonists. After the lead structure OPC-31260 was structurally evaluated and optimized, the introduction of the 7-Cl moiety on the benzazepine and 2-CH3 on the aminobenzoyl moiety enhanced its oral activity. The new AVP-V2 selective antagonist OPC-41061 was determined to be a potent and orally active agent. Copyright (C) 1999 Elsevier Science Ltd.
- Kondo, Kazumi,Ogawa, Hidenori,Yamashita, Hiroshi,Miyamoto, Hisashi,Tanaka, Michinori,Nakaya, Kenji,Kitano, Kazuyoshi,Yamamura, Yoshitaka,Nakamura, Shigeki,Onogawa, Toshiyuki,Mori, Toyoki,Tominaga, Michiaki
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p. 1743 - 1754
(2007/10/03)
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