- PYRIDO[3,2-D]PYRIMIDINE COMPOUNDS AS IMMUNOMODULATORS
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The present disclosure is directed to compounds of Formula (I): which modulate PD-1/PD-L1 protein/protein interaction, compositions, and methods of treating various diseases, including infectious diseases and cancer.
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Paragraph 0181-0182
(2021/04/02)
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- 2-aminopyrimidine compound as well as pharmaceutical composition and application thereof
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The invention relates to a 2-aminopyrimidine compound as well as a pharmaceutical composition and application thereof. Specifically, the compound disclosed by the invention has a structure shown as aformula I in the specification, and all the groups and substituents in the formula I are as defined in the specification. The invention further discloses application of the compound in the fields of virus resistance, infection resistance, autoimmunity, tumors and other diseases.
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Paragraph 0194-0198
(2021/02/24)
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- CD73 INHIBITORS
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Disclosed are compounds that are inhibitors of CD73 and are useful in treating CD73-associated diseases or conditions, and compositions containing the compounds.
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Paragraph 215; 216
(2020/10/27)
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- COMBINATION OF HEPATITIS B VIRUS (HBV) VACCINES AND PYRIDOPYRIMIDINE DERIVATIVES
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Therapeutic combinations of hepatitis B virus (HBV) vaccines and a pyridopyrimidine derivative are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the disclosed therapeutic combinations are also described. The invention provides therapeutic combinations or compositions and methods for inducing an immune response against hepatitis B viruses (HBV) infection.
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Page/Page column 270; 271
(2021/01/22)
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- Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity
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There is an urgent need for strategies to combat dengue and other emerging viral infections. We reported that cyclin G-associated kinase (GAK), a cellular regulator of the clathrin-associated host adaptor proteins AP-1 and AP-2, regulates intracellular trafficking of multiple unrelated RNA viruses during early and late stages of the viral lifecycle. We also reported the discovery of potent, selective GAK inhibitors based on an isothiazolo[4,3-b]pyridine scaffold, albeit with moderate antiviral activity. Here, we describe our efforts leading to the discovery of novel isothiazolo[4,3-b]pyridines that maintain high GAK affinity and selectivity. These compounds demonstrate improved in vitro activity against dengue virus, including in human primary dendritic cells, and efficacy against the unrelated Ebola and chikungunya viruses. Moreover, inhibition of GAK activity was validated as an important mechanism of antiviral action of these compounds. These findings demonstrate the potential utility of a GAK-targeted broad-spectrum approach for combating currently untreatable emerging viral infections.
- Pu, Szu-Yuan,Wouters, Randy,Schor, Stanford,Rozenski, Jef,Barouch-Bentov, Rina,Prugar, Laura I.,O'Brien, Cecilia M.,Brannan, Jennifer M.,Dye, John M.,Herdewijn, Piet,De Jonghe, Steven,Einav, Shirit
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p. 6178 - 6192
(2018/07/09)
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- TOLL LIKE RECEPTOR MODULATOR COMPOUNDS
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The present disclosure relates generally to toll like receptor modulator compounds, such as diamino pyrido[3,2 D]pyrimidine compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR-8), and methods of making and using them.
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Paragraph 0627; 0628
(2016/10/27)
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- GAK MODULATORS AS ANTIVIRALS
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The present invention relates to the use of a class of novel isothiazolo[4,3-b]pyridine derivatives as well as to pharmaceutical compositions comprising one or more of said isothiazolo[4,3- b]pyridine derivatives and one or more pharmaceutically acceptable excipients as biologically active ingredients, more specifically as medicaments for the treatment of disorders and pathologic conditions such as viral diseases.
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Page/Page column 31; 32
(2016/02/18)
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- SUBSTITUTED PYRIDINES AND METHOD OF USE
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The invention discloses compounds of Formula (I) wherein X, R1, R2, and R3 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.
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Paragraph 00329
(2016/12/22)
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- NOVEL GAK MODULATORS
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The present invention relates to a class of novel isothiazolo[4,3-b]pyridine derivatives and a method for their preparation, as well as to pharmaceutical compositions comprising one or more of said isothiazolo[4,3-b]pyridine derivatives and one or more pharmaceutically acceptable excipients. The present invention further relates to the use of said novel isothiazolo[4,3-b]pyridine derivatives as biologically active ingredients, more specifically as medicaments for the treatment of disorders and pathologic conditions such as, but not limited to, cell-proliferative and neurodegenerative diseases.
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Page/Page column 35
(2015/01/16)
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- Selective inhibitors of cyclin G associated kinase (GAK) as anti-hepatitis C agents
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Cyclin G associated kinase (GAK) emerged as a promising drug target for the treatment of viral infections. However, no potent and selective GAK inhibitors have been reported in the literature to date. This paper describes the discovery of isothiazolo[5,4-
- Kovackova, Sona,Chang, Lei,Bekerman, Elena,Neveu, Gregory,Barouch-Bentov, Rina,Chaikuad, Apirat,Heroven, Christina,?ála, Michal,De Jonghe, Steven,Knapp, Stefan,Einav, Shirit,Herdewijn, Piet
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p. 3393 - 3410
(2015/05/05)
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- BRIDGED BICYCLIC AMINO THIAZINE DIOXIDE COMPOUNDS AS INHIBITORS OF BETA-SECRETASE AND METHODS OF USE THEREOF
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The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, R1, R2, R3, R7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.
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Paragraph 0891
(2015/02/19)
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- Substituted Amino-Pyrimidine Derivatives
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The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.
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Page/Page column 0177-0179
(2014/02/16)
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- SUBSTITUTED QUINAZOLINE AND PYRIDO-PYRIMIDINE DERIVATIVES
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The present application provides novel substituted quinazoline and pyrido- pyrimidine compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.
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Page/Page column 117
(2012/05/19)
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- AZAQUINOLONE BASED COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, COMPOSITIONS, AND USES THEREOF
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Compounds of Formula (I) are useful as inhibitors of HIF prolyl hydroxylases where the definitions of the variables are provided herein.
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Page/Page column 32-33
(2008/12/06)
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- QUINOLONES AND AZAQUINOLONES THAT INHIBIT PROLYL HYDROXYLASE
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Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.
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Page/Page column 56
(2008/12/08)
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- QUINAZOLINE DERIVATIVE
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This invention provides a compound or its pharmaceutically-acceptable salt of formula (I) wherein R 1 represents a lower alkyl group et al; R 2 and R 3 are same and different and represents hydrogen atm et al; R 4 represents the substituent of the formula (II) et al; X 1 represents NH, O or S; Y represents N or C; Ar is a divalent substituent derived from aryl et al, by removing two hydrogen atoms therefrom; the ring A represents a 5- or 6-membered heteroaryl group; this compounds has a histamine-H3 receptor antagonistic effect or a histamine-H3 receptor inverse-agonistic effect and is useful for preventive or remedy of metabolic system diseases, circulatory system diseases or nervous system diseases.
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Page/Page column 77
(2010/11/25)
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- Bradykinin B1 antagonists: Biphenyl SAR studies in the cyclopropanecarboxamide series
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SAR study of the biphenyl region of cyclopropanecarboxamide derived bradykinin B1 antagonists was examined. Incorporation of a pyridine in place of the proximal phenyl ring and chlorination of the distal phenyl ring proved to be well tolerated
- Kuduk, Scott D.,DiPardo, Robert M.,Chang, Ronald K.,Di Marco, Christina N.,Murphy, Kathy L.,Ransom, Richard W.,Reiss, Duane R.,Tang, Cuyue,Prueksaritanont, Thomayant,Pettibone, Douglas J.,Bock, Mark G.
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p. 3608 - 3612
(2008/02/08)
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- INDOLE SULFONAMIDE MODULATORS OF PROGESTERONE RECEPTORS
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Compounds of Formula (I), wherein n is 1 or 2, and R1, R2, R3, R4, R5, R6, R7, and R8 are as defined herein, their preparation, pharmaceutical compositions, and methods of use are disclosed.
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Page/Page column 23
(2008/06/13)
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- ALPHA-HYDROXY AMIDES AS BRADYKININ ANTAGONISTS OR INVERSE AGONISTS
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α-Hydroxy amide derivatives of the general formula (I) are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway. R2a is selected from (1) a group selected from Ra. (2) (CH2)nNRbC(O)Ra. (3)(CH2)nNRbSO2Rd.(4)(CH2)nNRbCO2Ra.(5)(CH2)k-heterocycle optionally substituted with 1 to 3 groups independently selected from halogen.nitro, cyano.ORa.SRa.C1-4 alkyl and C1-3 haloakyl wherein said heterocycle is (a) a 5-membered heteroaromatic ring having a ring heteroatom selected from N.O and S. and optionally having up to 3 additional ring nitrogen atoms wherein said ring is optionally benzo-fused; or(b) a 6-membered heteromatic ring containing from 1 to 3 ring nitrogen atoms and N-oxydes thereof. Wherein said ring is optionally benzo-fused. (6)(CH2)kCO2Ra.and (7)(CH2)C(O)NRbRc. R2b is OH or a group selected from R2a; or R2a and R2b together with the carbon atom to which they are attached form a 3-to 7-membered carbocyclic ring optionally substituted with 1 to 4 groups independently selected from halogen. ORa. C1-4 alkyl and C1-4 haloalkyl;
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Page/Page column 25
(2008/06/13)
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- AMINO CYCLOPROPANE CARBOXAMIDE DERIVATIVES AS BRADYKININ ANTAGONISTS
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Compounds disclosed herein are bradykinin Bl antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
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Page/Page column 20
(2008/06/13)
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