- Artificial Macrocycles as Potent p53-MDM2 Inhibitors
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Based on a combination of an Ugi four component reaction and a ring closing metathesis, a library of novel artificial macrocyclic inhibitors of the p53-MDM2 interaction was designed and synthesized. These macrocycles, alternatively to stapled peptides, target for the first time the large hydrophobic surface area formed by Tyr67, Gln72, His73, Val93, and Lys94 yielding derivatives with affinity to MDM2 in the nanomolar range. Their binding affinity with MDM2 was evaluated using fluorescence polarization (FP) assay and 1H-15N two-dimensional HSQC nuclear magnetic resonance experiments.
- Estrada-Ortiz, Natalia,Neochoritis, Constantinos G.,Twarda-Clapa, Aleksandra,Musielak, Bogdan,Holak, Tad A.,D?mling, Alexander
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Read Online
- Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin αvβ3 Receptors in the Treatment of Neuroblastoma
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Therapeutic targeting of the norepinephrine transporter (NET) function with benzylguanidine (BG), conjugated with the high-affinity thyrointegrin αvβ3 antagonist triazole tetraiodothyroacetic acid, TAT, via noncleavable bonding to poly(ethylene glycol) (PEG400) (P) might allow for effective treatment options in neuroblastoma. BG-P-TAT is a dual-targeting agent, targeting the NET function and the thyrointegrin αvβ3 receptors that are overexpressed in neuroblastoma and other neuroendocrine tumors. Various cancer cells and actively dividing tumor-endothelial cells express the thyrointegrin αvβ3 receptors. In this work, the novel compound BG-P-TAT was synthesized and evaluated in the neuroblastoma SK-N-FI cell line for improved targeting and to offer a new strategy for patients with neuroblastoma. BG-P-TAT demonstrated significant suppression of neuroblastoma tumor progression, growth, and viability in a dose-dependent manner. In conclusion, BG-P-TAT represents a potential lead candidate for the treatment of neuroblastoma and other neuroendocrine tumors.
- Karakus, Ozlem Ozen,Godugu, Kavitha,Rajabi, Mehdi,Mousa, Shaker A.
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Read Online
- Synthesis of novel 2-pyrrolidinone and pyrrolidine derivatives and study of their inhibitory activity against autotaxin enzyme
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Autotaxin (ATX), a glycoprotein (~125 kDa) isolated as an autocrine motility factor from melanoma cells, belongs to a seven-membered family of ectonucleotide pyrophosphatase/phosphodiesterase (ENPP), and exhibits lysophospholipase D activity. ATX is responsible for the hydrolysis of lysophosphatidylcholine (LPC) to produce the bioactive lipid lysophosphatidic acid (LPA), which is upregulated in a variety of pathological inflammatory conditions, including fibrosis, cancer, liver toxicity and thrombosis. Given its role in human disease, the ATX-LPA axis is an interesting target for therapy, and the development of novel potent ATX inhibitors is of great importance. In the present work a novel class of ATX inhibitors, optically active derivatives of 2-pyrrolidinone and pyrrolidine heterocycles were synthesized. Some of them exhibited interesting in vitro activity, namely the hydroxamic acid 16 (IC50 700 nM) and the carboxylic acid 40b (IC50 800 nM), while the boronic acid derivatives 3k (IC50 50 nM), 3l (IC50 120 nM), 3 m (IC50 180 nM) and 21 (IC50 35 nM) were found to be potent inhibitors of ATX.
- Afantitis, Antreas,Aidinis, Vassilis,Gerokonstantis, Dimitrios Triantafyllos,Kokotos, George,Magkrioti, Christiana,Moutevelis-Minakakis, Panagiota,Nikolaou, Aikaterini
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Read Online
- Efficient oxidative self-coupling of polystyrene bearing chain-end primary amines
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A series of well-defined linear polystyrenes (PSs) with different degree of polymerization (DP) was synthesized via atom transfer radical polymerization (ATRP) using tert-butyloxycarbonyl (t-boc)-protected 4-(aminomethyl)phenyl 2-bromoisobutyrate (BAPB) a
- Kim, HyeMi,Lee, Hyung-Il
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Read Online
- Diarylcarbonates are a new class of deubiquitinating enzyme inhibitor
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Promiscuous inhibitors of tyrosine protein kinases, proteases and phosphatases are useful reagents for probing regulatory pathways and stabilizing lysates as well as starting points for the design of more selective agents. Ubiquitination regulates many cr
- Long, Marcus J.C.,Lawson, Ann P.,Baggio, Rick,Qian, Yu,Rozhansky, Lior,Fasci, Domenico,El Oualid, Farid,Weerapana, Eranthie,Hedstrom, Lizbeth
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Read Online
- Novel derivatives of urea and use thereof
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The present invention relates to a novel urea derivative compound and 5HT thereof. 2A The present invention relates to the use of antagonists as antagonists for the prevention or treatment of neuropsychiatric disorders, degenerative brain diseases, propagated disorders and/or metabolic diseases.
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Paragraph 0097; 0099-0102
(2021/10/27)
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- Heptamethine indocyanine dye as well as preparation method and application thereof
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The invention provides a heptamethine indocyanine dye as well as a preparation method and an application thereof, and belongs to the technical field of fine chemical engineering. The heptamethine indocyanine dye provided by the invention has a structure a
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Paragraph 0131; 0146-0148; 0151
(2021/10/05)
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- Design, synthesis, and biological evaluation of novel bifunctional thyrointegrin antagonists for neuroblastoma
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Receptor-mediated cancer therapy has received much attention in the last few decades. Neuroblastoma and other cancers of the sympathetic nervous system highly express norepinephrine transporter (NET) and cell plasma membrane integrin αvβ3. Dual targeting
- Karakus, Ozlem Ozen,Godugu, Kavitha,Fujioka, Kazutoshi,Mousa, Shaker A.
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- Rapid and High-Yield Synthesis of [23]Crown Ether: Applied as a Wheel Component in the Formation of Pseudo[2]rotaxane and Synthesis of [2]Catenane with a Dibenzylammonium Dumbbell
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A facile, rapid, and high yield synthesis of [23]crown ether (X23C7) has been developed from commercially available starting materials, in one step with good to excellent yield. The reaction is completed in 6 h under room temperature conditions, with the highest yield being 81%. The X23C7 macrocycle formed pseudo[2]rotaxane with a dibenzylammonium ion (DBA+) dumbbell, exhibiting strong association (Ka = 2.61 × 103 M-1). Consequently, a [2]catenane was synthesized from a DBA+-based diolefin terminated salt and X23C7 in 81% yield, using a threading-followed-ring-closing-metathesis approach.
- Dasgupta, Suvankar,Prakashni, Manisha,Shukla, Rasendra
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p. 7825 - 7831
(2021/06/28)
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- Discovery of dual targeting PEGylated BG-P1600-TAT to norepinephrine transporter (NET) and thyrointegrin αvβ3 in the treatment of neuroblastoma
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Polymer-drug conjugates are growing in interest as novel anticancer agents for targeted cancer therapy. The aim of this study was to synthesize a poly(ethylene glycol) (PEG) conjugated anticancer drug for neuroblastoma, which is the most common extracrani
- Godugu, Kavitha,Mousa, Shaker A.,Ozen Karakus, Ozlem
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- Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease
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Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide, causing serious liver complications, including nonalcoholic steatohepatitis. Recent findings suggest that peripheral serotonin (5-hydroxytryptamine, 5HT) regulates energy homeostasis, including hepatic lipid metabolism. More specifically, liver-specific 5HT2A knockout mice exhibit alleviated hepatic lipid accumulation and hepatic steatosis. Here, structural modifications of pimavanserin (CNS drug), a 5HT2A antagonist approved for Parkinson's disease, led us to synthesize new peripherally acting 5HT2A antagonists. Among the synthesized compounds, compound 14a showed good in vitro activity, good liver microsomal stability, 5HT subtype selectivity, and no significant inhibition of CYP and hERG. The in vitro and in vivo blood-brain barrier permeability study proved that 14a acts peripherally. Compound 14a decreased the liver weight and hepatic lipid accumulation in high-fat-diet-induced obesity mice. Our study suggests new therapeutic possibilities for peripheral 5HT2A antagonists in NAFLD.
- Kim, Minhee,Hwang, Inseon,Pagire, Haushabhau S.,Pagire, Suvarna H.,Choi, Wonsuk,Choi, Won Gun,Yoon, Jihyeon,Lee, Won Mi,Song, Jin Sook,Yoo, Eun Kyung,Lee, Seung Mi,Kim, Mi-Jin,Bae, Myung Ae,Kim, Dooseop,Lee, Heejong,Lee, Eun-Young,Jeon, Jae-Han,Lee, In-Kyu,Kim, Hail,Ahn, Jin Hee
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supporting information
p. 4171 - 4182
(2020/04/30)
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- Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction
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Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient α-helical N-terminal ‘‘lid’’ segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds.
- Neochoritis, Constantinos G.,Atmaj, Jack,Twarda-Clapa, Aleksandra,Surmiak, Ewa,Skalniak, Lukasz,K?hler, Lisa-Maria,Muszak, Damian,Kurpiewska, Katarzyna,Kalinowska-T?u?cik, Justyna,Beck, Barbara,Holak,D?mling, Alexander
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supporting information
(2019/08/20)
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- Composition and method for dual targeting in treatment of neuroendocrine tumors
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Chemical compositions and methods of synthesis thereof. The compositions disclosed and described herein are directed toward thyroid hormone αvβ3 integrin receptor antagonists conjugated to targets of the norepinephrine transporter (NET) or the catecholamine transporter. The compositions have a dual targeting effect and increased targeting efficiency in the treatment and diagnostic imaging of neuroendocrine tumors.
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Page/Page column 14-15
(2019/07/12)
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- Synthesis and structure-activity relationships of small-molecular di-basic esters, amides and carbamates as flaviviral protease inhibitors
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Inhibitors of the flaviviral serine proteases, which are crucial for the replication of dengue and West-Nile virus, have attracted much attention over the last years. A dibasic 4-guanidinobenzoate was previously reported as inhibitor of the dengue protease with potency in the low-micromolar range. In the present study, this lead structure was modified with the intent to explore structure-activity relationships and obtain compounds with increased drug-likeness. Substitutions of the guanidine moieties, the aromatic rings, and the ester with other functionalities were evaluated. All changes were accompanied by a loss of inhibition, indicating that the 4-guanidinobenzoate scaffold is an essential element of this compound class. Further experiments indicate that the target recognition of the compounds involves the reversible formation of a covalent adduct.
- Sundermann, Tom R.,Benzin, Clarissa V.,Dra?i?, Tonko,Klein, Christian D.
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p. 187 - 194
(2019/05/21)
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- PAIN TREATING COMPOUNDS AND USES THEREOF
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The present invention relates to compounds useful in the modulation of ion channel activity in cells. The invention also relates to use of these compounds in the treatment of pain, and pharmaceutical compositions containing these compounds and methods for their preparation.
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Page/Page column 42; 43
(2019/12/04)
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- STEROIDS AND PROTEIN-CONJUGATES THEREOF
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Described herein protein steroid conjugates that are useful, for example, for the target-specific delivery of glucocorticoids (GCs) to cells.
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Paragraph 0584; 0586
(2018/05/27)
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- An Electron Transport Layer Material and the Application Thereof
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The present invention belongs to the technical field of optoelectronic devices, and discloses an electron transport layer material and its application. This material has the following structure: wherein n is a natural number of 1 to 10000, B is a strongly polar group, A1 and A2 are the same or different aromatic ring derivatives or conjugated units containing carbon-carbon double bonds and carbon-nitrogen bonds, M is a connection unit between A2 and B and is an alkyl group containing 1 to 20 carbon atoms, or is an alkyl group in which one or more carbon atoms are replaced by one or more functional groups selected from oxygen atoms, alkenyl groups, alkynyl groups, aryl groups or ester groups, and the hydrogen atom is replaced by a fluorine atom, a chlorine atom, a bromine atom, an iodine atom or the above-mentioned functional groups.
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Paragraph 0031; 0042; 0043
(2018/02/28)
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- Rational design and synthesis of 1,5-disubstituted tetrazoles as potent inhibitors of the MDM2-p53 interaction
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Using the computational pharmacophore-based ANCHOR.QUERY platform a new scaffold was discovered. Potent compounds evolved inhibiting the protein-protein interaction p53-MDM2. An extensive SAR study was performed based on our four-point pharmacophore model
- Surmiak, Ewa,Neochoritis, Constantinos G.,Musielak, Bogdan,Twarda-Clapa, Aleksandra,Kurpiewska, Katarzyna,Dubin, Grzegorz,Camacho, Carlos,Holak, Tad A.,D?mling, Alexander
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p. 384 - 407
(2016/12/22)
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- Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation
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The noninvasive imaging of MMP activity in vivo could have a high impact in basic research as well as in clinical applications. This approach can be established using radiolabeled MMP inhibitors (MMPIs) as tracers for the detection of activated MMPs by means of PET. However, the complexity of diseases associated with dysregulated MMP expression necessitates the imaging of distinct MMPs or MMP subgroups to distinguish their individual role in specific diseases. To this end, selective and potent MMP-13 inhibitors based on a N,N′-bis(benzyl)pyrimidine-4,6-dicarboxamide core have been synthesized and successfully radiolabeled with carbon-11, fluorine-18, and gallium-68. Selected radiolabeled candidates were evaluated in vitro and in vivo regarding their pharmacokinetic properties and metabolic stability.
- Hugenberg, Verena,Wagner, Stefan,Kopka, Klaus,Sch?fers, Michael,Schuit, Robert C.,Windhorst, Albert D.,Hermann, Sven
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supporting information
p. 307 - 321
(2017/04/26)
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- OXAZOLIDINE-BASED COMPOUND AND SELECTIVE ANDROGEN RECEPTOR AGONIST COMPRISING SAME
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Provided are novel selective androgen receptor agonists, a preparation method thereof, and a pharmaceutical composition including the same at a pharmaceutically effective amount. The selective androgen receptor agonists according to the present invention
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Paragraph 0072; 0073
(2017/03/14)
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- ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.
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Page/Page column 130; 131
(2017/12/14)
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- Quinolone amides as antitrypanosomal lead compounds with In Vivo activity
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Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei. Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments, respectively. Spray-dried GHQ168 demonstrated exciting antitrypanosomal efficacy.
- Hiltensperger, Georg,Hecht, Nina,Kaiser, Marcel,Rybak, Jens-Christoph,Hoerst, Alexander,Dannenbauer, Nicole,Müller-Buschbaum, Klaus,Bruhn, Heike,Esch, Harald,Lehmann, Leane,Meinel, Lorenz,Holzgrabe, Ulrike
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supporting information
p. 4442 - 4452
(2016/08/02)
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- HETEROCYCLIC SULFONAMIDE DERIVATIVE AND MEDICINE COMPRISING SAME
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The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. The compound has a superior TRPA1 antagonist activity, and can provide a medicament useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.
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Paragraph 0411; 0412
(2016/12/01)
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- Post-synthetic modifications of cadmium-based knots and links
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Three topologically non-trivial cadmium(ii)-based complexes - Cd-[2]C, Cd-TK and Cd-SL - were simultaneously self-assembled in a dynamic library, individually isolated and fully characterized using solid-state, gas-phase and solution-phase techniques. Post-synthetic modifications, including reduction and transmetalation, were subsequently achieved. Imine bond reduction followed by demetallation led to the isolation of the corresponding organic molecules [2]C, TK and SL. Transmetalation of Cd-TK and Cd-SL with the zinc(ii) cation resulted in isolation of the corresponding zinc(ii)-containing complexes Zn-TK and Zn-SL.
- Prakasam, Thirumurugan,Bilbeisi, Rana A.,Lusi, Matteo,Olsen, John-Carl,Platas-Iglesias, Carlos,Trabolsi, Ali
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p. 7398 - 7401
(2016/06/14)
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- HETEROCYCLIC AMIDE DERIVATIVE AND MEDICINE CONTAINING SAME
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Compound represented by formula (I): wherein each symbol is as defined herein, exhibit TRPA1 antagonist activity, and are useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.
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Paragraph 0323
(2015/10/28)
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- Dynamic stereoisomerization in inherently chiral bimetallic [2]catenanes
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Stereoisomerization and the unprecedented phenomenon of metal translocation in the absence of redox processes were probed in two inherently chiral bimetallic [2]catenanes by using a combination of variableerature 1H NMR and CD spectroscopies, X-ray crystallography, and DFT calculations.
- Prakasam, Thirumurugan,Lusi, Matteo,Nauha, Elisa,Olsen, John-Carl,Sy, Mohamadou,Platas-Iglesias, Carlos,Charbonnière, Lo?c J.,Trabolsi, Ali
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p. 5840 - 5843
(2015/03/31)
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- Structure-based design of type II inhibitors applied to maternal embryonic leucine zipper kinase
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A novel Type II kinase inhibitor chemotype has been identified for maternal embryonic leucine zipper kinase (MELK) using structure-based ligand design. The strategy involved structural characterization of an induced DFG-out pocket by protein-ligand X-ray
- Johnson, Christopher N.,Adelinet, Christophe,Berdini, Valerio,Beke, Lijs,Bonnet, Pascal,Brehmer, Dirk,Calo, Frederick,Coyle, Joseph E.,Day, Phillip J.,Frederickson, Martyn,Freyne, Eddy J. E.,Gilissen, Ron A. H. J.,Hamlett, Christopher C. F.,Howard, Steven,Meerpoel, Lieven,Mevellec, Laurence,McMenamin, Rachel,Pasquier, Elisabeth,Patel, Sahil,Rees, David C.,Linders, Joannes T. M.
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supporting information
p. 31 - 36
(2015/01/30)
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- INHIBITORS OF DEUBIQUITINATING PROTEASES
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Disclosed are small molecule inhibitors of deubiquitinating enzymes (DUBs), and methods of using them. Certain compounds display a preference for specific ubiquitin specific proteases (USPs).
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Page/Page column 58
(2014/11/11)
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- SUBSTITUTED 4-PHENOXYPHENOL ANALOGS AS MODULATORS OF PROLIFERATING CELL NUCLEAR ANTIGEN ACTIVITY
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In one aspect, the invention relates to substituted 4-phenoxyphenol analogs, derivatives thereof, and related compounds,which are useful as inhibitors of proliferating cell nuclear antigen (PCNA); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating hyperproliferative disorders associated with PCNA using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention
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Paragraph 00572
(2013/03/26)
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- Simultaneous self-assembly of a [2]catenane, a trefoil knot, and a solomon link from a simple pair of ligands
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A topological triptych: Three molecular links, a [2]catenane, a trefoil knot, and a Solomon link, were obtained in one pot through the self-assembly of two simple ligands in the presence of ZnII (see picture). The approach relied on dynamic covalent chemistry and metal templation.
- Prakasam, Thirumurugan,Lusi, Matteo,Elhabiri, Mourad,Platas-Iglesias, Carlos,Olsen, John-Carl,Asfari, Zouhair,Cianferani-Sanglier, Sarah,Debaene, Francois,Charbonniere, Loic J.,Trabolsi, Ali
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p. 9956 - 9960
(2013/10/01)
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- COFERONS AND METHODS OF MAKING AND USING THEM
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The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.
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Page/Page column 183
(2012/12/13)
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- THIAZOLIDINE DERIVATIVES AND METHODS FOR THE PREPARATION THEREOF
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The present invention relates to novel 2-carbonyl-3-acyl-1,3-thiazolidines having a β-amino group on the acyl chain, in free, prodrug form or pharmaceutically acceptable salt thereof, including their enantiomers, diastereomers and racemates, as efficient inhibitors against DPP-IV. The invention further relates to the pharmaceutical compositions comprising the disclosed compounds. The present invention also relates to methods for preparing the disclosed compounds and for treating DPP-IV-mediated diseases.
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Page/Page column 45
(2010/03/31)
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- N-SUBSTITUTED PIPERIDINE DERIVATIVES AS SEROTONIN RECEPTOR AGENTS
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Disclosed herein are substantially pure forms of the compounds of Formula (I), (II), (III), (IV) and (V), or a pharmaceutically acceptable salt, prodrug, hydrate, solvate, polymorph, stereoisomer or ester thereof. Also disclosed are methods of inhibiting an activity of a serotonin receptor, methods inhibiting an activation of a serotonin receptor, and methods of alleviating or treating various disease conditions and side effects.
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Page/Page column 49-50
(2010/11/04)
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- PTERIDINE DERIVATIVES AS POLO-LIKE KINASE INHIBITORS USEFUL IN THE TREATMENT OF CANCER
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Compound of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful in treatment of cell proliferative diseases: wherein R1 and R2 are hydrogen, or an optionally substituted (C1-C6)alkyl, (C2- Cs
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Page/Page column 44
(2008/12/05)
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- Structural modifications of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1- piperazinehexanamides: Influence on lipophilicity and 5-HT7 receptor activity. Part III
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Starting from the previously reported 5-HT7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)pipe
- Leopoldo, Marcello,Lacivita, Enza,De Giorgio, Paola,Fracasso, Claudia,Guzzetti, Sara,Caccia, Silvio,Contino, Marialessandra,Colabufo, Nicola A.,Berardi, Francesco,Perrone, Roberto
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experimental part
p. 5813 - 5822
(2009/09/08)
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- 2-(ARYLOXY)ACETAMIDE FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
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The present invention relates generally to novel 2-(aryloxy)acetamides of Formula (I) or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables W, Y, Z, R7, R8, and R9 are as defined herein. These compounds are selective inhibitors of the serine protease coagulation factor VIIa which can be used as medicaments.
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Page/Page column 87
(2008/06/13)
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- Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1
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A structurally unique and new class of opioid receptor antagonists (OpRAs) that bear no structural resemblance with morphine or endogenous opioid peptides has been discovered. A series of carboxamido-biaryl ethers were identified as potent receptor antagonists against mu, kappa and delta opioid receptors. The structure-activity relationship indicated para-substituted aryloxyaryl primary carboxamide bearing an amine tether on the distal phenyl ring was optimal for potent in vitro functional antagonism against three opioid receptor subtypes.
- Takeuchi, Kumiko,Holloway, William G.,McKinzie, Jamie H.,Suter, Todd M.,Statnick, Michael A.,Surface, Peggy L.,Emmerson, Paul J.,Thomas, Elizabeth M.,Siegel, Miles G.,Matt, James E.,Wolfe, Chad N.,Mitch, Charles H.
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p. 5349 - 5352
(2008/02/13)
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- Facile N-tert-butoxycarbonylation of amines using La(NO3)3·6H2O as a mild and efficient catalyst under solvent-free conditions
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Facile N-tert-butoxycarbonylation of amines is described by the treatment of various primary, secondary, benzylic and aryl amines with di-tert-butyl dicarbonate in the presence of catalytic amounts of La(NO3)3·6H2O under solvent-free conditions at room temperature to afford N-tert-butylcarbamates in excellent yields.
- Suryakiran,Prabhakar,Reddy, T. Srikanth,Rajesh,Venkateswarlu
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p. 8039 - 8042
(2007/10/03)
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- Substituted compounds derived from N-(benzyl)phenylacetamide, preparation and uses
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This invention relates to poly-substituted derivatives of the N-(benzyl)phenylacetamide type, pharmaceutical compositions comprising same, therapeutic uses thereof, more particularly in the fields of human and animal health. This invention also relates to a process for the preparation of such derivatives.
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Page/Page column 39
(2010/10/20)
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- Phenyl derivatives comprising an acetylene group
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This invention is concerned with compounds of the formula I: wherein one of R5, R6 and R7 is and X1, X2, R1 to R12, m, n and o are as defined in the description, and pharmaceutically acceptable salts and/or esters thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are modulated by PPARδ and/or PPARα agonists.
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Page/Page column 30
(2010/02/15)
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- Nanoscale borromeates
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In addition to a parent zinc(II) Borromean ring (BR) complex, the preparation and characterization of two hexasubstituted BR complexes with either 4-acetoxymethylphenyl or 4-methylthiophenyl substituents associated in turn with all six pyridyl rings has b
- Chichak, Kelly S.,Peters, Andrea J.,Cantrill, Stuart J.,Stoddart, J. Fraser
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p. 7956 - 7962
(2007/10/03)
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- MEDICINE COMPRISING DICYANOPYRIDINE DERIVATIVE
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Compounds having a high conductance-type of calcium-activated K channel opening effect and a smooth muscle relaxant effect for bladder based on the K-channel opening effect, which can be used in treating pollakiuria and urinary incontinence, are provided. 3,5-Dicyanopyridine derivatives or their salts.
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- Medicine comprising dicyanopyridine derivative
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Compounds having a high conductance-type of calcium-activated K channel opening effect and a smooth muscle relaxant effect for bladder based on the K-channel opening effect, which can be used in treating pollakiuria and urinary incontinence, are provided.
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- Bicyclic fibrinogen antagonists
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This invention relates to compounds of the formulae: wherein A1is O, S, N—R1or CHR1; A4is N—R4or CHR4; R2is a sidechain containing an acid or ester group; R1, R4and R5are substituents such as H, alkyl and aryl alkyl, and R6is a sidechain containing a nitrogen group; and pharmaceutically acceptable salts thereof, which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, and a method for inhibiting platelet aggregation.
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- Cyclic imino derivatives and pharmaceutical compositions containing them
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The invention relates to cyclic imino compounds which have, inter alia, valuable pharmacological properties, especially inhibitory effects on cell aggregation, pharmaceutical compositions which contain these compounds and processes for preparing them.
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