Introduction: TrkA/B/C receptor activation supports growth, survival, and differentiation of discrete neuronal populations during development, adult life, and ageing but also plays numerous roles in human disease onset and progression. Trk-specific inhibitors have therapeutic applications in cancer and pain and thus constitute a growing area of interest in oncology and neurology. There has been substantial growth in the number of structural classes of Trk inhibitors and the number of industrial entrants to the Trk inhibitor field over the past six years.Areas covered: In Part II of this two-part review, the discussion of recent patent literature covering Trk family inhibitors is continued from Part I and clinical research with Trk inhibitors is considered.Expert opinion: Trk has been molecularly targeted for over a decade resulting in the progressive evolution of structurally diversified Trk inhibitors arising from scaffold hopping and HTS efforts. Correspondingly, there have been a growing number...

Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 – Part I

Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.

Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors

Introduction: Tropomyosin receptor kinases (Trks) are a family of three similar tyrosine kinases activated by peptide hormones of the neurotrophin family. The nerve growth factor antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA pathway in pain. As an alternative modality, small-molecule inhibitors of the Trks have been pursued in recent years to probe the role of these neurotrophin pathways in pain, cancer and other indications.Areas covered: This paper reviews the patent literature between mid-2009 and 2013, claiming inhibitors of Trk family members as the primary biological targets. Additional patents have been reviewed where Trk is not the main kinase of interest but in which high Trk potency is observed and the chemical matter is particularly noteworthy. Patents pre-dating this period have been reviewed previously. Scifinder and Google were used to find relevant patents and clinical information using Trk or Tropomyosin as the search term.Expert opinion: Considerable...

Tropomyosin receptor kinase inhibitors: a patent update 2009 - 2013.

Provided is Compound (I) or a pharmaceutically acceptable salt thereof, which is an inhibitor of TrkA kinase and is useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation and inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, pelvic pain syndrome, diseases related to an imbalance of the regulation of bone remodeling, and diseases resulting from Connective Tissue Growth Factor aberrant signaling.

1-((3s,4r)-4-(3-fluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(4-methyl-3-(2-methylpyrimidin-5-yl)-1-phenyl-1h-pyrazol-5-yl)urea as a trka kinase inhibitor

Compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.

N-pyrrolidinyl, n'-pyrazolyl- urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors

The present invention is directed to benzyl urea compounds of formula (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence may be useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C.

Chun Sing Li

Papers

TrkA kinase inhibitors, compositions and methods thereof