14474-56-7Relevant articles and documents
NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
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Page/Page column 77, (2016/04/20)
This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
2-Amino-1,3,5-triazine chemistry: hydrogen-bond networks, Takemoto thiourea catalyst analogs, and olfactory mapping of a sweet-smelling triazine
Hintermann, Lukas,P?thig, Alexander,Xiao, Li
supporting information, p. 1529 - 1539 (2015/08/18)
Abstract The chemistry of 4,6-dialkyl-2-amino-1,3,5-triazines with bulky alkyl substituents was investigated and their use as building blocks for preparing chiral thiourea organocatalysts explored. Reaction of ammonia with 4,6-di-tert-butyl-2-chloro-1,3,5-triazine gave 4,6-di-tert-butyl-1,3,5-triazin-2-amine which formed extended hydrogen-bond networks in the solid state according to X-ray crystallography. Selected heterocyclic amines were converted to isothiocyanates, and the latter reacted with (S,S)-2-(dimethylamino)cyclohexylamine to give enantiopure 1-hetaryl-3-[2-(dimethylamino)cyclohexyl]thioureas, with hetaryl representing either 4,6-dimethyl-1,3-diazin-2-yl, 4,6-diisopropyl-1,3,5-triazin-2-yl, or 4,6-di-tert-butyl-1,3,5-triazin-2-yl groups. These compounds are structural analogs of Takemotos's chiral thiourea organocatalysts (1-[3,5-bis(trifluoromethyl)phenyl]-3-[(1S,2S)-2-(dimethylamino)cyclohexyl]thiourea) with an aza-aryl instead of the 3,5-bis(trifluoromethyl)phenyl group. They feature a strong intramolecular N-H to N-1 hydrogen bond, as shown by X-ray crystallography of 1-(4,6-di-tert-butyl-1,3,5-triazin-2-yl)-3-[2-(dimethylamino)cyclohexyl]thiourea in the solid state and by 1H NMR spectroscopy of all derivatives in CDCl3 solution, which prevents them from acting as bifunctional organocatalyst. In the reaction of 4,6-di-tert-butyl-2-chloro-1,3,5-triazine with ammonia, 4,6-di-tert-butyl-2-ethoxy-1,3,5-triazine was identified as side-product displaying a mildly sweet, floral odor that is unusual for a 1,3,5-triazine. Analogs (>35) of 4,6-di-tert-butyl-2-ethoxy-1,3,5-triazine were prepared to define the important structural factors of the olfactophore.
PYRIDINE DERIVATIVES AS REARRANGED DURING TRANSFECTION (RET) KINASE INHIBITORS
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Page/Page column 128; 45, (2014/09/29)
This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
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Paragraph 0238; 0239, (2014/09/30)
This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
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Page 201, (2010/02/06)
The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.
THE MOLECULAR COMPLEX OF 4-(N-PYRIDINIUM)PYRIDINE-N-OXIDE CHLORIDE WITH TETRACYANOETHYLENE IN THE SYNTHESIS OF SUBSTITUTED PYRIDINE N-OXIDES
Rodina, L. L.,Ryzhakov, A. V.,Alekseeva, O. O.
, p. 157 - 159 (2007/10/03)
The structure of the complex of 4-(N-pyridinium)pyridine-N-oxide chloride with tetracyanoethylene was studied by 13C NMR spectroscopy.The results of the investigation, suggesting the use of this complex in the synthesis of substituted pyridine derivatives, were confirmed experimentally by its reaction with oxygen and with nitrogen-containing nucleophiles.
New description of substituent effect on electronic spectra by means of substituent constants-VI. Ultraviolet spectra of 4-substituted pyridine N-oxides and blue shifted iodine bands of their EDA complexes with iodine
Uno, Bunji,Kano, Kenji,Kaida, Naoki,Kubota, Tanekazu
, p. 937 - 944 (2007/10/02)
Electronic spectra of 4-substituted pyridine N-oxides and their EDA complexes with iodine were studied.The substituent effect on the near u.v. 1A1 intramolecular CT bands of the N-oxides and on the blue shifted iodine bands caused by CT complex formation are discussed in terms of a general equation, theoretically derived in order to describe the substituent effect on electronic spectra by means of substituent constants.The results are quite successful and supported by semi-empirical SCFMO-Cl calculations.Based on the results mentioned above, the character of n-? type N-oxide-iodine CT complexes is also examined.The complex formation constants(log K) and pKa values of the N-oxides correlate especially well, indicating that the CT interaction mechanism cannot be neglected in proton addition reactions such as hydrogen bonding and pKa values.
