- BIOAVAILABLE PROTEIN DISULFIDE ISOMERASE INHIBITORS
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Compounds according to formula (I) are described wherein R1 is an amino acid or a modified amino acid linked to the compound through a peptide bond, R2 is selected from CN, SO2CH3, NO2, CO2R3, CONHR3, NH2, NMe2 and CF3, and R3 is selected from H or lower alkyl, X is O or S, and Y is C-H or N, or a pharmaceutically acceptable salt thereof. The compounds can be used as protein disulfide isomerase inhibitors. The compounds can also be used in a method of treating or cancer in a subject.
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- Functionalized azobenzene platinum(II) complexes as putative anticancer compounds
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The synthesis and characterization of four platinum(II) complexes using azobenzenes conveniently functionalized as ligands has been carried out. The characteristic photochemical behavior of the complexes due to the presence of azobenzene-type ligands and the role of the ligands in the activation of the complexes has been studied. Their promising cytotoxicity observed in HeLa cells prompted us to study the mechanism of action of these complexes as cytostatic agents. The interaction of the compounds with DNA, studied by circular dichroism, revealed a differential activity of the Pt(II) complexes upon irradiation. The intercalation abilities of the complexes as well as their reactivity with common proteins present in the blood stream allows to confirm some of the compounds obtained as good anticancer candidates.
- Samper, Katia G.,Lorenzo, Julia,Capdevila, Mercè,Palacios, òscar,Bayón, Pau
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p. 435 - 453
(2021/05/11)
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- HETEROAROMATIC MACROCYCLIC DERIVATIVES AS PROTEIN KINASE INHIBITORS
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The present invention relates to a 2,7-substituted cyano[3,2-d]pyrimidine cyclic compound having protein kinase inhibitory activity, a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for preventing, alleviating, or treating a disease caused by abnormal cell growth, which includes the compound as an active ingredient. The novel 2,7-substituted cyano[3,2-d]pyrimidine cyclic compound of the present invention exhibits an excellent effect of inhibiting various protein kinases involved in the signal transduction of growth factors, and thus is effective as an agent for preventing, alleviating, or treating an abnormal cell growth disease caused by these protein kinases.
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- heteroaromatic macrocyclic derivatives as protein kinase inhibitors
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The present invention relates to: a 2,7-substituted cyano[3,2-d]pyrimidine cyclized compound having protein kinase inhibitory activity; a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing, alleviating or treating diseases caused by abnormal cell growth which contains the compound as an active component. A novel 2,7-substituted cyano[3,2-d]pyrimidine cyclized compound of the present invention exhibits excellent inhibitory effects on various protein kinases involved in the growth factor signal transduction, thereby being useful as an agent for preventing, alleviating or treating abnormal cell growth diseases caused by these protein kinases.COPYRIGHT KIPO 2020
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- OXOINDOLINE DERIVATIVES AS PROTEIN FUNCTION MODULATORS
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The present invention provides chimeric compounds of formula (II) that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CKl-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.
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Paragraph 0521
(2017/12/16)
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- MACROCYCLES AS KINASE INHIBITORS
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Compounds of the formula I in which X, Y, Q1, M, Q2 and B have the meanings indicated in Claim 1, are inhibitors of GCN2, and can be employed, inter alia, for the treatment of cancer.
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- INTEGRIN ANTAGONIST CONJUGATES FOR TARGETED DELIVERY TO CELLS EXPRESSING ALPHA-V-BETA-3
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The invention relates to compounds of formula (I): wherein R1, R2, and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula (I) for use in the manufacture and delivery of conjugated moieties such as small molecules, peptides, nucleic acids, fluorescent moieties, and polymers which are linked to alpha-V-beta-3 integrin antagonists to target cells expressing alpha-V-beta-3.
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- CHITOSAN COVALENTLY LINKED WITH SMALL MOLECULE INTEGRIN ANTAGONIST FOR TARGETED DELIVERY
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The invention relates to the chitosan polymer derivatives of formula I: and pharmaceutically acceptable salts and esters thereof, wherein Y, X1, X4, R1, R2, and n are defined in the detailed description and claims. The chitosan polymer derivatives of formula I bind to or associate with alpha-4-beta-1 (α4β1) and alpha-V-beta-3 (αVβ3) integrin dimers and can be used in delivery formulations to deliver drugs, nucleic acids, or other therapeutic compounds to tissues or cells expressing such integrins.
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- HETEROARYL COMPOUNDS AND USES THEREOF
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The present invention provides inhibitors of protein kinases of formula I-a and I-b, pharmaceutically acceptable compositions thereof, and methods of using the same.
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- DIAMINOTHIAZOLES
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The present invention is directed to novel diaminothiazoles of formula These compounds inhibit cyclin-dependent kinase 4 (Cdk4) and are selective against Cdk2 and Cdk1. These compounds and their pharmaceutically acceptable salts and esters have antiproliferative activity and are useful in the treatment or control of cancer, in particular solid tumors. This invention is also directed to pharmaceutical compositions containing such compounds and to methods of treating or controlling cancer, most particularly the treatment 6r control of breast, lung and colon and prostate tumors.
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Page/Page column 54-55
(2010/02/05)
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- New beta-strand macrocyclic peptidomimetic analogues containing alpha-(O-, S- or NH-)aryl substituted glycine residues: synthesis, chemical and enzymatic properties.
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In so much as bis-macrocyclic peptidomimetics have been recognized as high affinity substrates for HIV-1 protease, we were interested in the design and synthesis of new bis-macrocyclic bioisosteric analogues whose general structure is displayed on Fig. 2. The structures of these new analogues are characterized by the specific replacement of the methylene of the benzyl group directly attached to the N-acyl glycine residue in the original molecule 1, by its main bioisosteres, i.e. O-, S- and NH-aryl groups. Knowing that an intermediate in which an heteroatomic aryl group is directly linked to a free amine glycine residue is not stable, we developed an original synthetic pathway which involved the coupling of a specific side chain to the exocyclic carboxylic acid function, followed by an elegant oxidation-nucleophilic substitution Steglich-type reaction. Analogues 2a-d were then submitted to chemical and enzymatic hydrolysis. We demonstrated that, as expected, the specific cleavage of the exocyclic N-acyl bond led to the release of aryl moieties (phenol, thiophenol and aniline species). These chemical and enzymatic stability studies brought to light the biological potential of such macrocyclic analogues in infected cells.
- Quelever, Gilles,Bihel, Frederic,Kraus, Jean-Louis
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p. 1676 - 1683
(2007/10/03)
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