- ASPARAGINE DERIVATIVES AND METHODS OF USE THEREOF
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The present invention relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of them, pharmaceutical compositions comprising them, methods of preparation thereof, intermediate compounds useful for the preparation thereof, and methods of treatment or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using these. (A) (I)
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Paragraph 00778-00779
(2021/12/31)
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- A method for one-step synthesis of carboxylic acids with two extended carbon chains from olefins
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The invention relates to a method for one-step synthesis of carboxylic acid with two extended carbon chains from olefin, which comprises the following steps: under the protection of inert gas, sequentially adding an olefin substrate, a photocatalyst, a hydrogen atom transfer reagent, alpha-haloacetic acid, a reducing agent, a solvent and protonic acid into a reactor, and reacting at normal temperature under the irradiation of 25W blue light to obtain a reaction product; diluting, alkalizing, washing, acidifying and extracting the reaction product to obtain an organic phase; and finally, carrying out reduced pressure distillation and column chromatography on the organic phase to obtain a carboxylic acid product with two extended carbon chains; or carrying out reduced pressure distillation and column chromatography on the reaction product to obtain a carboxylic acid product with two extended carbon chains. The invention is simple to operate, direct synthesis conditions are mild, mutual conversion among various functional groups in the traditional carboxylic acid compound synthesis process is avoided, and the atom and step economy of the reaction is improved. Meanwhile, the method disclosed by the invention can also be applied to the simplified synthesis of the medicines cinacarbazide and tirofiban.
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Paragraph 0071-0072
(2020/10/12)
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- Incorporation of neutral C-terminal residues in 3-amidinophenylalanine-derived matriptase inhibitors
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A novel series of matriptase inhibitors based on previously identified tribasic 3-amidinophenylalanine derivatives was prepared. The C-terminal basic group was replaced by neutral residues to reduce the hydrophilicity of the inhibitors. The most potent co
- Schweinitz, Andrea,Doennecke, Daniel,Ludwig, Alexander,Steinmetzer, Peter,Schulze, Alexander,Kotthaus, Joscha,Wein, Silvia,Clement, Bernd,Steinmetzer, Torsten
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scheme or table
p. 1960 - 1965
(2009/11/30)
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- Pyrrolidine modulators of chemokine receptor activity
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The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
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- Dibasic inhibitors of human mast cell tryptase. Part 3: Identification of a series of potent and selective inhibitors containing the benzamidine functionality
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A survey of charged groups and linkers for a series of symmetrical and unsymmetrical dibasic inhibitors is described, leading to several classes of potent and selective inhibitors. In particular, the benzamidine functionality was identified as the most potent charged group investigated.
- Dener, Jeffrey M.,Rice, Kenneth D.,Newcomb, William S.,Wang, Vivian R.,Young, Wendy B.,Gangloff, Anthony R.,Kuo, Elaine Y.-L.,Cregar, Lynne,Putnam, Daun,Wong, Martin
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p. 1629 - 1633
(2007/10/03)
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- Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
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The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.
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- 2,3-diaminopropionic acid derivative
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The present invention relates to a 2,3-diaminopropionic acid derivative of the formula (1): STR1 or a pharmaceutically acceptable salt thereof. The compounds of the present invention are useful as a platelet aggregation inhibitor, a cancer metastasis inhibitor, a wound healing agent or a bone resorption inhibitor.
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- Design of a new class of orally active fibrinogen receptor antagonists
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The integrin receptor recognition sequence Arg-Gly-Asp was successfully used as a template from which to develop a series of potent, selective, orally active, peptide-based fibrinogen receptor antagonists with a long duration of action. Simple modifications centered on the Arg and Gly residues quickly led to a modified peptide (1) with significantly enhanced ability to inhibit in vitro platelet aggregation. Substitution of the guanidino group in 1 by piperidine provided 3, which showed not only a further increase in potency but also a modest degree of oral efficacy. Finally, exploration of the nature of the C-terminal amino acid, with respect to its side-chain functionality and the carboxy terminus, yielded a group of molecules that showed excellent in vitro potency for inhibiting platelet aggregation, excellent integrin selectivity, a high level of oral efficacy, and an extended duration of action.
- Klein, Scott I.,Molino, Bruce F.,Czekaj, Mark,Gardner, Charles J.,Chu, Valeria,Brown, Karen,Sabatino, Ralph D.,Bostwick, Jeffrey S.,Kasiewski, Charles,Bentley, Ross,Windisch, Vincent,Perrone, Mark,Dunwiddie, Christopher T.,Leadley, Robert J.
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p. 2492 - 2502
(2007/10/03)
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- Dipiperidine derivatives
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The present invention relates to an novel dipiperidine derivative represented by formula (1), or a pharmaceutically acceptable salt thereof; STR1 wherein R1 represents a hydrogen atom or a lower alkyl group; Y represents a single bond or an oxygen atom; n represents 1, 2 or 3; W represents a methylene group or an oxygen atom; R2 represents a hydrogen atom or a carboxyl modifying group which can be eliminated in vivo; X1 and X3 are the same or different and each represents a hydrogen atom or a lower alkyl group. This compound is useful as platelet aggregation inhibitors, cancer metastasis inhibitors, wound remedies or bone resorption inhibitors.
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- Tetrahydrothienopyridine derivatives as novel GPIIB/IIIA antagonists
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The tetrahydrothienopyridine derivatives were derived from aminomethylcyclohexylcarboxylic acid as a lead moiety. Evaluation of the antiplatelet activity and receptor binding assay revealed that compound 1 (Me3277) was a novel and potent non-peptide and n
- Katano, Kiyoaki,Shitara, Eiki,Shimizu, Masaro,Sasaki, Kazue,Miura, Tomoaki,Isomura, Yasuko,Kawaguchi, Mami,Ohuchi, Shokichi,Tsuruoka, Takashi
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p. 2601 - 2606
(2007/10/03)
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- Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp
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Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation.Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation.Compound 23m (L-700, 462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of >24000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors.Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions 0.1-10 μg/kg/min of 23m in anesthetized dogs, with 10 μg/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol.Platelet aggregatability returned rapidly after the termination of the 23m infusions.These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.
- Egbertson, Melissa S.,Chang, Charles T.-C.,Duggan, Mark E.,Gould, Robert J.,Halczenko, Wasyl,et al.
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p. 2537 - 2551
(2007/10/02)
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- Fibrinogen receptor antagonists
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The present invention comprises fibrinogen receptor antagonist compounds, compositions containing them and methods for using them to inhibit fibrinogen binding to blood platelets. Compounds of the invention have the following formula STR1 wherein Z is STR
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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 binding of fibrinogen to blood platelets and for inhibiting the aggregation of blood platelets.
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- Fibrinogen receptor antagonists
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Fibrinogen receptors antagonists of the Formula: are disclosed for use in inhibiting the binding of fibrinogen to blood platelets and inhibiting the aggregation of blood platelets.
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