- NOVEL IMIDAZOPYRAZINE DERIVATIVES
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The invention provides novel imidazopyrazine derivatives having the general formula (I), wherein Rx and R3 to R5 are as described herein (formula (I)) or pharmaceutically acceptable salts thereof. Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.
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Page/Page column 51; 238-239
(2021/12/31)
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- LABELLED COMPOUNDS THAT BIND TO ALPHA-V-BETA-3 INTEGRIN
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The present invention concerns in vivo imaging and in particular a novel in vivo imaging agent of formula (I). Also provided by the present invention is a method for the preparation of the in vivo imaging agent of the invention, and precursor compounds useful in said method. The in vivo imaging agent of the invention is useful in the diagnosis of conditions where there is a deviation from normal in the expression of integrin αvβ3.
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Page/Page column 23; 24
(2014/08/20)
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- Fluorescent non-peptidic RGD mimetics with high selectivity for αvβ3 vs αiIbβ3 integrin receptor: Novel probes for in vivo optical imaging
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Integrins are heterodimeric transmembrane protein receptors consisting of different α and β subunits. αvβ3 integrins are overexpressed on many tumor cells and tumor-associated angiogenic vessels, whereas αIIbβ3 is a receptor for, e.g., fibrinogen and mediates platelet aggregation. In this study, a near-infrared fluorescent imaging probe has been designed and synthesized by conjugating fluorescent dyes to a non-peptidic, pharmacophore-based ligand, based on a molecular modeling design approach. Affinity values were determined, and in vitro cell binding assays and preliminary in vivo xenograft studies in nude mice were performed to evaluate target binding. Competition assays revealed excellent binding and selectivity to αvβ3 compared to that for αIIbβ3. In vitro, the probe showed high target binding on αvβ3-positive M-21 cells and negligible binding to αvβ3-negative MCF-7 cells. In vivo, the tracer is able to image target expression in U-87 xenografts with a maximum signal-to-noise ratio (SNR) of 2.5:1 at 24 h after injection.
- Alsibai, Wael,Hahnenkamp, Anke,Eisenbl?tter, Michel,Riemann, Burkhard,Sch?fers, Michael,Bremer, Christoph,Haufe, Günter,H?ltke, Carsten
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p. 9971 - 9982
(2015/02/02)
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- Sulfate Encapsulation in Supramolecular Structures from L -Asparagine-Derived 2,5-Diketopiperazine Scaffolds: Anion Binding
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We report a new sulfate receptor, anchored onto 2,5-diketopiperazine units, which results in the formation of two types of supramolecules; one in which the sulfate ion guest fits snugly into extended cavities and the other in which the guest is sandwiched between layers. In each case, the anion is held by six hydrogen bonds from the host. 1H NMR spectroscopic solution studies enabled the construction of Job plots, and calculation of stoichiometry and association constants. These findings are of possible significance in drug design and for construction of combinatorial libraries.
- Naini, Santhosh Reddy,Lalancette, Roger A.,Gorlova, Olga,Ramakrishna, Kallaganti V. S.,Yadav, Jhillu Singh,Ranganathan, Subramania
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p. 7015 - 7022
(2016/02/19)
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- Hydantoin and thiohydantoin derivatives as antiviral drugs
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The present invention relates to a compound of the following formula (I), or a salt, solvate, tautomer, enantiomer, diastereoisomer or racemic mixture thereof: as well as its use as a drug, notably in the treatment of hepatitis C, its preparation process, and the pharmaceutical compositions containing such a compound.
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Paragraph 0298-0299
(2013/12/03)
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- HYDANTOIN AND THIOHYDANTOIN DERIVATIVES AS ANTIVIRAL DRUGS
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The present invention relates to a compound of the following formula (I), or a salt, solvate, tautomer, enantiomer, diastereoisomer or racemic mixture thereof: as well as its use as a drug, notably in the treatment of hepatitis C, its preparation process, and the pharmaceutical compositions containing such a compound.
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Page/Page column 149-150
(2013/12/03)
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- Compositions Comprising Enzyme-Cleavable Oxycodone Prodrug
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The embodiments provide Compound KC-7, N-1-[(S)-2-(oxycodone-6-enol-carbonyl-methyl-amino)-2-carbonyl-sarcosine-ethyl amine]-arginine-glycine-acetate, or acceptable salts, solvates, and hydrates thereof. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug, Compound KC-7, that provides controlled release of oxycodone. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of oxycodone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.
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- Iridium-catalyzed asymmetric allylic amination with polar amines: Access to building blocks with lead-like molecular properties
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The combination of an air-stable iridium catalyst and the dipolar aprotic solvent dimethyl sulfoxide (DMSO) allowed, for the first time, the systematic exploitation of highly polar, functionalized amines in asymmetric allylic substitutions: low molecular
- Tosatti, Paolo,Horn, Joachim,Campbell, Amanda J.,House, David,Nelson, Adam,Marsden, Stephen P.
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supporting information; experimental part
p. 3153 - 3157
(2011/03/18)
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- NOVEL ETHYLENEDIAMINE DERIVATIVES
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A compound represented by the following formula (1):Q-Q-T-N(R)-Q-N(R)-T-Q [wherein, R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may have a substituent, or the like; Q2 is a single bond or the like; Q3 represents the following group: -C(R3a)(R4a)-{C(R3b)(R4b)}m1-{C(R3c)(R4c)}m2-{C(R3d)(R4d)}m3-{C(R3e)(R4e)}m4-C(R3f)(R4f)- (in which, R3a to R4e represent hydrogen or the like); T0 represents a carbonyl group or the like; and T1 represents -COCONR- or the like]; or salt thereof, solvate thereof, or N-oxide thereof. The compound is useful as a preventive and/or therapeutic agent for cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
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Page/Page column 62
(2010/02/14)
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- Non-peptide GPIIb/IIIa inhibitors. 20. Centrally constrained thienothiophene α-sulfonamides are potent, long acting in vivo inhibitors of platelet aggregation
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The synthesis and pharmacology of 4, a potent thienothiophene non- peptide fibrinogen receptor antagonist, are reported. Compound 4 inhibited the aggregation of human gel-filtered platelets with an IC50 of 8 nM and demonstrated an 8-fold improvement in affinity for isolated GPIIb/IIIa receptors over analogues possessing an isoindolinone backbone. Flow cytometry studies revealed that the binding of 4 to resting platelets is a diffusion- controlled process (k(on) = 3.3 x 106 M-1 s-1) and that 4 binds to dog and human platelets with comparable affinity (K(d) = 0.04 and 0.07 nM, respectively). Ex vivo platelet aggregation in dogs was completely inhibited by an iv dose of 5 mg/kg, and an oral dose of 50-90 mg/kg followed by low daily doses of 10 mg/kg was sufficient to maintain ~80% inhibition of ex vivo platelet aggregation over several days. Inhibition of ADP-induced platelet aggregation in anesthetized dogs at 77 ± 7% resulted in a moderate 2.5-fold increase in bleeding time, while complete inhibition (100%) resulted in an approximately 10-min bleeding time. Additional doses were required to increase the bleeding time to the maximum time allowed in the protocol (15 min), thus indicating a potentially useful and safe separation of efficacy and bleeding time.
- Egbertson, Melissa S.,Cook, Jacquelynn J.,Bednar, Bohumil,Prugh, John D.,Bednar, Rodney A.,Gaul, Stanley L.,Gould, Robert J.,Hartman, George D.,Homnick, Carl F.,Holahan, Marie A.,Libby, Laura A.,Lynch Jr., Joseph J.,Lynch, Robert J.,Sitko, Gary R.,Stranieri, Maria T.,Vassallo, Laura M.
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p. 2409 - 2421
(2007/10/03)
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- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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The present invention comprises low molecular weight peptidyl compounds that inhibit the farnesyl-protein transferase. Furthermore, these compounds differ from the mono- or dipeptidyl analogs previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production
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- Fibrinogen receptor antagonists
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Novel fibrinogen receptor antagonists of the formula: X--Y--Z-Aryl-A--B and the pharmaceutically acceptable salts thereof, wherein Aryl is a 5-membered aromatic ring system containing 1 or 2 heteroatoms chosen from N, O or S wherein ring atoms may be unsubstituted or substituted with R5 and wherein S may be substituted with 0, 1 or 2 oxygen atoms; and X comprises various Nitrogen substituents including aromatic or nonaromatic systems; Y comprises, for example, alkyl or alkylaminocarbonylalkyl groups and Z and A are substituents which when present are independently chosen from alkyl or alkyloxyalkyl or other groups as defined herein; B is (a) or (b). The claimed compounds exhibit fibrinogen receptor antagonist activity, inhibit platelet aggregation and are therefore useful in modulating or preventing thrombus formation.
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- Integrin receptor antagonists
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This invention relates to novel heterocycles including 3-?1-?3-(imidazolin-2-ylamino)propyl!indazol-5-ylcarbonylamino!-2-(benzyloxycarbonylamino)propionic acid, which are useful as antagonists of the αv β3 integrin and related cell surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.
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- Fibrinogen receptor antagonists
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Fibrinogen receptor antagonists having the formula STR1 for example STR2
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- Design, synthesis and in vitro activities of a series benzimidazole/benzoxazole glycoprotein IIb/IIIa inhibitors
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A potent centrally constrained series of benzimidazole and benzoxazole glycoprotein IIb/IIIa inhibitors has been discovered based on the solution conformation of a cyclic RGD-containing peptide, DMP 728. The high potency of this series of compounds in the inhibition of platelet aggregation requires a benzamidine as the basic moiety and an α-carbamate or sulfonamide substituted β-alanine as the acidic moiety.
- Xue,Rafalski,Roderick,Eyermann,Mousa,Olson,DeGrado
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p. 339 - 344
(2007/10/03)
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- Non-peptide glycoprotein IIb/IIIa inhibitors. 9. Centrally constrained alpha-sulfonamides are useful tools for exploring platelet receptor function
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Two fluorescent, centrally constrained fibrinogen receptor antagonists were prepared to probe ligand receptor interactions.
- Egbertson,Bednar,Bednar,Hartman,Gould,Lynch,Vassallo,Young
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p. 1415 - 1420
(2007/10/03)
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- Fibrinogen receptor antagonists
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Fibrinogen receptor antagonists of the formula: STR1 are disclosed for use in inhibiting the aggregation of blood platelets. wherein G is: STR2
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- A selective protection of 2,3-diaminopropionic acid
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A two step selective protection of 2,3-diaminopropionic acid yields the useful diaminopropionic acid methyl ester 3a. Further manipulation yields 2(S)-(N-benzyloxycarbonylamino)-3-aminopropionic acid methyl ester hydrochloride 5 in >99.9%ee.
- Egbertson,Homnick,Hartman
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p. 703 - 709
(2007/10/02)
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- A Convenient Differential Protection Strategy for Functional Group Manipulation of Aspartic and Glutamic Acids
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Procedures are provided for selective protection of the α-carboxyl groups of aspartic and glutamic acids via the 5-oxazolidinones 2.A convenient synthesis of a differentially protected derivative of (S)-2,3-diaminopropanoic acid, 3, is described, along wi
- Scholtz, John M.,Bartlett, Paul A.
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p. 542 - 544
(2007/10/02)
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