38275-55-7Relevant academic research and scientific papers
The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis
De Savi, Chris,Pape, Andrew,Cumming, John G.,Ting, Attilla,Smith, Peter D.,Burrows, Jeremy N.,Mills, Mark,Davies, Chris,Lamont, Scott,Milne, David,Cook, Calum,Moore, Peter,Sawyer, Yvonne,Gerhardt, Stefan
, p. 1376 - 1381 (2011)
Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described.
Use of ω-transaminase enzyme chemistry in the synthesis of a JAK2 kinase inhibitor
Frodsham, Lianne,Golden, Michael,Hard, Susan,Kenworthy, Martin N.,Klauber, David J.,Leslie, Kevin,Macleod, Claire,Meadows, Rebecca E.,Mulholland, Keith R.,Reilly, Julie,Squire, Christopher,Tomasi, Simone,Watt, Denise,Wells, Andrew S.
, p. 1123 - 1130 (2013)
ω-Transaminase enzyme chemistry provides an excellent methodology to build synthetically useful chiral amines from their corresponding ketones. An application of this methodology, providing a long-term commercial manufacturing route to a JAK2 kinase inhibitor, is reported herein.
COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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Page/Page column 138-139, (2019/09/18)
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol "APLNR"). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.
Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use
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Paragraph 0552, (2015/11/16)
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.
IMIDAZOTRIAZINONE COMPOUNDS
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Paragraph 0642; 0643; 0644, (2013/10/08)
The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.
Discovery of 5-chloro- N 2-[(1 S)-1-(5-fluoropyrimidin-2-yl) ethyl]- N 4-(5-methyl-1 H -pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the jak/stat pathway
Ioannidis, Stephanos,Lamb, Michelle L.,Wang, Tao,Almeida, Lynsie,Block, Michael H.,Davies, Audrey M.,Peng, Bo,Su, Mei,Zhang, Hai-Jun,Hoffmann, Ethan,Rivard, Caroline,Green, Isabelle,Howard, Tina,Pollard, Hannah,Read, Jon,Alimzhanov, Marat,Bebernitz, Geraldine,Bell, Kirsten,Ye, Minwei,Huszar, Dennis,Zinda, Michael
experimental part, p. 262 - 276 (2011/03/20)
The myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are a heterogeneous but related group of hematological malignancies characterized by clonal expansion of one or more myeloid lineages. The discovery of the Jak2 V617F gain of function mutation highlighted Jak2 as a potential therapeutic target in the MPNs. Herein, we disclose the discovery of a series of pyrazol-3-yl pyrimidin-4-amines and the identification of 9e (AZD1480) as a potent Jak2 inhibitor. 9e inhibits signaling and proliferation of Jak2 V617F cell lines in vitro, demonstrates in vivo efficacy in a TEL-Jak2 model, has excellent physical properties and preclinical pharmacokinetics, and is currently being evaluated in Phase I clinical trials.
2-(IMIDAZ0LYLAMIN0)-PYRIDINE DERIVATIVES AND THEIR USE AS JAK KINASE INHIBITORS
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Page/Page column 58, (2010/04/03)
The present inv ention relates to compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein Ring A is 5- or 6-membered heteroaryl, wherein said 5- or 6-membered heteroaryl is optionally substituted on carbon with one or more R6
HETEROCYCLIC JAK KINASE INHIBITORS
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Page/Page column 64-65, (2010/04/27)
The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer
Discovery of pyrazol-3-ylamino pyrazines as novel JAK2 inhibitors
Ioannidis, Stephanos,Lamb, Michelle L.,Davies, Audrey M.,Almeida, Lynsie,Su, Mei,Bebernitz, Geraldine,Ye, Minwei,Bell, Kirsten,Alimzhanov, Marat,Zinda, Michael
scheme or table, p. 6524 - 6528 (2010/05/18)
The design, synthesis and biological evaluation of a series of pyrazol-3-ylamino pyrazines as potent and selective JAK2 kinase inhibitors is reported, along with the pharmacokinetic and pharmacodynamic properties of lead compounds.
CHEMICAL COMPOUNDS 916-1
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Page/Page column 57, (2009/03/07)
The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.
