900456-21-5Relevant articles and documents
Discovery of Orally Efficacious Phosphoinositide 3-Kinase δ Inhibitors with Improved Metabolic Stability
Patel, Leena,Chandrasekhar, Jayaraman,Evarts, Jerry,Forseth, Kristen,Haran, Aaron C.,Ip, Carmen,Kashishian, Adam,Kim, Musong,Koditek, David,Koppenol, Sandy,Lad, Latesh,Lepist, Eve-Irene,McGrath, Mary E.,Perreault, Stephane,Puri, Kamal D.,Villase?or, Armando G.,Somoza, John R.,Steiner, Bart H.,Therrien, Joseph,Treiberg, Jennifer,Phillips, Gary
, p. 9228 - 9242 (2016)
Aberrant signaling of phosphoinositide 3-kinase δ (PI3Kδ) has been implicated in numerous pathologies including hematological malignancies and rheumatoid arthritis. Described in this manuscript are the discovery, optimization, and in vivo evaluation of a novel series of pyridine-containing PI3Kδ inhibitors. This work led to the discovery of 35, a highly selective inhibitor of PI3Kδ which displays an excellent pharmacokinetic profile and is efficacious in a rodent model of rheumatoid arthritis.
PYRAZOLOPYRIMIDINE COMPOUND AS PI3K INHIBITOR AND USE THEREOF
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, (2019/08/30)
The present application relates to a pyrazolopyrimidine compound of Formula (I) and a pharmaceutically acceptable salt thereof. Such compounds can be used to inhibit the activity of a lipid kinase PI3K, and can also be used to treat diseases mediated by P
Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856
Perreault, Stephane,Chandrasekhar, Jayaraman,Cui, Zhi-Hua,Evarts, Jerry,Hao, Jia,Kaplan, Joshua A.,Kashishian, Adam,Keegan, Kathleen S.,Kenney, Thomas,Koditek, David,Lad, Latesh,Lepist, Eve-Irene,McGrath, Mary E.,Patel, Leena,Phillips, Bart,Therrien, Joseph,Treiberg, Jennifer,Yahiaoui, Anella,Phillips, Gary
, p. 1555 - 1567 (2017/03/08)
Phosphoinositide 3-kinase (PI3K) β signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation
QUINOLINE ANALOGS AS PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 081; 082, (2017/09/27)
The present disclosure provides selective phosphoinositide 3-kinase inhibitors of formula (A), or pharmaceutically acceptable salts thereof. These compounds are useful for the treatment of conditions mediated by one or more P13K isoforms, such as PI3K delta (PI3K?). The present disclosure further provides methods of inhibiting phosphoinositide 3-kinase inhibitors using these compounds for treatment of disorders related to phosphatidylinositol 3-kinase activity.
2,4,6-Triaminopyrimidine as a Novel Hinge Binder in a Series of PI3Kδ Selective Inhibitors
Patel, Leena,Chandrasekhar, Jayaraman,Evarts, Jerry,Haran, Aaron C.,Ip, Carmen,Kaplan, Joshua A.,Kim, Musong,Koditek, David,Lad, Latesh,Lepist, Eve-Irene,McGrath, Mary E.,Novikov, Nikolai,Perreault, Stephane,Puri, Kamal D.,Somoza, John R.,Steiner, Bart H.,Stevens, Kirk L.,Therrien, Joseph,Treiberg, Jennifer,Villase?or, Armando G.,Yeung, Arthur,Phillips, Gary
, p. 3532 - 3548 (2016/05/19)
Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) is an appealing target for several hematological malignancies and inflammatory diseases. Herein, we describe the discovery and optimization of a series of propeller shaped PI3Kδ inhibitors comprising a novel triaminopyrimidine hinge binder. Combinations of electronic and structural strategies were employed to mitigate aldehyde oxidase mediated metabolism. This medicinal chemistry effort culminated in the identification of 52, a potent and highly selective inhibitor of PI3Kδ that demonstrates efficacy in a rat model of arthritis.
PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 0623; 0624, (2015/12/30)
The present application provides the compounds of formula (J), or pharmaceutically acceptable salts, isomers, or a mixture thereof, wherein n, m, q, A′, W1, W2, W3, R1, R2, and R3 are descr
PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 00164, (2016/01/01)
The present application provides the compounds of formula (J), or pharmaceutically acceptable salts, isomers, tautomer, or a mixture thereof wherein n, m, R1, R2, R3, R4, and R5 are described herein. The compounds are inhibitors to the activities of phosphatidylinositol 3-kinase (ΡI3Κ) and are useful for treating conditions mediated by one or more PI3K isoforms. The present application further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts, isomers, tautomer, or mixture thereof, and methods of using these compounds and compositions for treating conditions mediated by one or more ΡI3Κ isoforms.
PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 0274, (2015/12/30)
The present application provides the compounds of formula (J), or pharmaceutically acceptable salts, isomers, tautomer, or a mixture thereof, wherein X, Y, Z, n, m′, A′, R1, R2, and R3 are described herein. The compounds a
PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 00233; 00234; 00235, (2016/01/25)
The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (J), or pharmaceutically acceptable salts thereof, in which A, n, m, R1, R2, R3 R4, R5, R6 and R7 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more ΡI3Κ isoforms. The present disclosure further provides pharmaceutical compositions that include a compound of formula (J), or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms.
PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
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Paragraph 0667, (2014/07/08)
The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts thereof, in which n, m, R1, R2, and R3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.