- Heterocyclic phosphodiesterase inhibitor and uses thereof
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The present invention belongs to the technical field of medicine, and particularly relates to a heterocyclic phosphodiesterase inhibitor compound represented by a formula (I), or a pharmaceutically acceptable salt and a stereoisomer thereof, and a pharmaceutical preparation, a pharmaceutical composition and applications of the compound, wherein R1, R2, R3, R4, ring A, m and n are defined in the specification. According to the present invention, the compound can be used for preparing drugs for treatment or prevention of diseases associated with PDE9 kinase.
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Paragraph 0159-0163
(2019/11/04)
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- Improving the Selectivity of PACE4 Inhibitors through Modifications of the P1 Residue
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Paired basic amino acid cleaving enzyme 4 (PACE4), a serine endoprotease of the proprotein convertases family, has been recognized as a promising target for prostate cancer. We previously reported a selective and potent peptide-based inhibitor for PACE4, named the multi-Leu peptide (Ac-LLLLRVKR-NH2 sequence), which was then modified into a more potent and stable compound named C23 with the following structure: Ac-dLeu-LLLRVK-Amba (Amba: 4-amidinobenzylamide). Despite improvements in both in vitro and in vivo profiles of C23, its selectivity for PACE4 over furin was significantly reduced. We examined other Arg-mimetics instead of Amba to regain the lost selectivity. Our results indicated that the replacement of Amba with 5-(aminomethyl)picolinimidamide increased affinity for PACE4 and restored selectivity. Our results also provide a better insight on how structural differences between S1 pockets of PACE4 and furin could be employed in the rational design of selective inhibitors.
- Dianati, Vahid,Navals, Pauline,Couture, Frédéric,Desjardins, Roxane,Dame, Anthony,Kwiatkowska, Anna,Day, Robert,Dory, Yves L.
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p. 11250 - 11260
(2019/01/04)
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- Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use
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In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, -L2-, and -L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.
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Paragraph 0589
(2015/11/16)
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- THERAPEUTIC AGENT FOR CEREBRAL INFARCTION
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The present invention provides a novel therapeutic drug for cerebral infarction, which contains a piperazine compound as an active ingredient. The compound of the present invention can be provided as a novel therapeutic drug for cerebral infarction having
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Page/Page column 20; 21
(2010/03/04)
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- HETEROCYCLIC DERIVATIVES
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The invention relates to novel heterocyclic derivatives, processes for their preparation, and their use in medicaments, especially for the treatment of chronic obstructive pulmonary diseases, acute coronary syndrome, acute myocardial infarction and heart failure development.
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Page/Page column 29
(2010/02/13)
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- Mandelic acid derivatives and their use as throbin inhibitors
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There is provided a compound of formula I wherein Ra, R1, R2, Y and R3 have meanings given in the description and pharmaceutically acceptable derivatives (including prodrugs) thereof, which compounds and derivatives are useful as, or are useful as prodrugs of, competitive inhibitors of trypsin-like proteases, such as thrombin, and thus, in particular, in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.
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Page/Page column 41
(2008/06/13)
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- DIHYDROPYRIDINONE DERIVATIVES
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The invention relates to novel dihydropyridinone derivatives, processes for their preparation, and their use in medicaments, especially for the treatment of chronic obstructive pulmonary diseases, acute coronary syndrome, acute myocardial infarction and heart failure development.
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- PYRIMIDINONE DERIVATIVES AS THERAPEUTIC AGENTS AGAINST ACUTE AND CHRONIC INFLAMMATORY, ISCHAEMIC AND REMODELLING PROCESSES
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The invention relates to novel heterocyclic derivatives, processes for their preparation, and their use in medicaments, especially for the treatment of chronic obstructive pulmonary diseases.
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- PHARMACEUTICAL COMBINATION
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There is provided a combination product comprising: (1) a compound of claim 1 in WO 02/44145 or a compound of claim 20 in WO 02/44145 (or derivative thereof)or a pharmaceutically-acceptable derivative thereof; and (1) a compound as defined in claim 1 of WO 01/28992 or (2) a compound of Claim 34 of WO 01/28992 or (3) Compound A or B or C or D (or pharmaceutically-acceptable salts thereof) for use in treating arrhythmia or a coagulation controlled complication thereof.
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- Substituted phenyl farnesyltransferase inhibitors
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Compounds of formula (I) or pharmaceutically acceptable salts thereof, inhibit farnesyltransferase. Methods for making the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.
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- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
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