660432-43-9Relevant articles and documents
Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells
Herrlinger, Eva-Maria,Hau, Mirjam,Redhaber, Desiree Melanie,Greve, Gabriele,Willmann, Dominica,Steimle, Simon,Müller, Michael,Lübbert, Michael,Miething, Christoph Cornelius,Schüle, Roland,Jung, Manfred
, p. 2329 - 2347 (2020)
Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR+. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches.
A 2-aminopyrimidine heterocyclic compound and its applications
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Paragraph 0086; 0111-0115; 0125; 0134; 0137; 0146; 0149; ..., (2022/01/12)
The present invention discloses a 2-aminopyrimidine heterocyclic compound having a general formula I structure and its applications, which are kinase CDK4, CDK6 and / or CDK9 inhibitors, can be more widely used in the treatment of a variety of cancers, ha
A piperazine-containing aminopyrimidine derivative and its application
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Paragraph 0141-0144, (2022/01/12)
The present invention discloses a piperazine-containing aminopyrimidine derivative having a general formula I. structure, which belongs to kinase CDK4, CDK6 and / or CDK9 inhibitors, can be more widely used in the treatment of a variety of cancers, has gr
Discovery, Structure-Activity Relationships, and in Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain
Hartz, Richard A,Ahuja, Vijay T.,Nara, Susheel J.,Kumar, C.M. Vijaya,Brown, Jeffrey M.,Bristow, Linda J.,Rajamani, Ramkumar,Muckelbauer, Jodi K.,Camac, Daniel,Kiefer, Susan E.,Hunihan, Lisa,Gulianello, Michael,Lewis, Martin,Easton, Amy,Lippy, Jonathan S.,Surti, Neha,Pattipati, Sreenivasulu N.,Dokania, Manoj,Elavazhagan, Saravanan,Dandapani, Kumaran,Hamman, Brian D.,Allen, Jason,Kostich, Walter,Bronson, Joanne J.,Macor, John E.,Dzierba, Carolyn D.
, p. 11090 - 11128 (2021/08/03)
Effective treatment of chronic pain, in particular neuropathic pain, without the side effects that often accompany currently available treatment options is an area of significant unmet medical need. A phenotypic screen of mouse gene knockouts led to the d
Discovery of Nonpungent Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist as Strong Topical Analgesic
Ann, Jihyae,Kim, Ho Shin,Thorat, Shivaji A.,Kim, Hee,Ha, Hee-Jin,Choi, Kwanghyun,Kim, Young-Ho,Kim, Minseok,Hwang, Sun Wook,Pearce, Larry V.,Esch, Timothy E.,Turcios, Noe A.,Blumberg, Peter M.,Lee, Jeewoo
, p. 418 - 424 (2019/12/24)
Paradoxically, some TRPV1 agonists are, at the organismal level, both nonpungent and clinically useful as topical analgesics. Here, we describe the scaled-up synthesis and characterization in mouse models of a novel, nonpungent vanilloid. Potent analgesic activity was observed in models of neuropathic pain, and the compound blocked capsaicin induced allodynia, showing dermal accumulation with little transdermal absorption. Finally, it displayed much weaker systemic toxicity compared to capsaicin and was negative in assays of genotoxicity.
Discovery of dual-acting opioid ligand and TRPV1 antagonists as novel therapeutic agents for pain
Lee, Hobin,Ahn, Songyeon,Ann, Jihyae,Ha, Heejin,Yoo, Young Dong,Kim, Young Ho,Hwang, Ji-Young,Hur, Kwang-Hyun,Jang, Choon-Gon,Pearce, Larry V.,Esch, Timothy E.,Lewin, Nancy E.,Blumberg, Peter M.,Lee, Jeewoo
, (2019/09/03)
In order to discover a novel type of analgesic, we investigated dual activity ligands with TRPV1 antagonism and mu-opioid receptor affinity with the goal of eliciting synergistic analgesia while avoiding the side effects associated with single targeting.
COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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Page/Page column 436; 437, (2019/02/13)
In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured. The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging.
FUSED HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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Paragraph 0481; 0482, (2018/06/26)
The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton’ s tyrosine kinase (Btk), and for treating disorders mediated thereby.
FUSED HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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Paragraph 0479; 0481; 0482, (2014/11/13)
The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.
SUBSTITUTED PYRAZOLYL-BASED CARBOXAMIDE AND UREA DERIVATIVES BEARING A PHENYL MOIETY SUBSTITUTED WITH A CO-CONTAINING GROUP AS VANILLOID RECEPTOR LIGANDS
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, (2013/05/23)
The invention relates to substituted pyrazolyl-based carboxamide and urea derivatives bearing a phenyl moiety substituted with a CO-containing group as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.