- ISOINDOLINONE COMPOUNDS
-
Disclosed herein is a compound or pharmaceutically acceptable salts or stereoisomers thereof of of formula I wherein X1 is linear or branched C1-6 alkyl, C3-6 cycloalkyl, -C1-6 alkyl C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl C6-10 aryl, C1-6 alkyl 5-10 membered heteroaryl, wherein X1 is unsubstituted or substituted with one or more of halogen, linear or branched C1-6 alkyl, linear or branched C1-6 heteroalkyl, CF3, CHF2, -O-CHF2, -O-(CH2)2-OMe, OCF3, C1-6 alkylamino, -CN, -N(H)C(O)-C1- 6alkyl, -OC(O)-C1-6alkyl, -OC(O)-C1-4alkylamino, -C(O)O-C1-6alkyl, -COOH, - CHO, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-6 alkoxy or C1-6 alkylhydroxy; X2 is hydrogen, C6-10 aryl, 5-10 membered heteroaryl, -O-(5-10 membered heteroaryl), 4-8 membered heterocycloalkyl, C1-4 alkyl 4-8 membered heterocycloalkyl, -O-(4-8 membered heterocycloalkyl), -O-C1-4 alkyl-(4-8 membered heterocycloalkyl), -OC(O)-C1-4alkyl-4-8 membered heterocycloalkyl or C6 aryloxy, wherein X2 is unsubstituted or substituted with one or more of linear or branched C1-6 alkyl, NH2, NMe2 or 5-6 membered heterocycloalkyl; n is 0, 1 or 2.
- -
-
Page/Page column 168-169
(2021/04/17)
-
- METHOD FOR PRODUCING TRIAZOLIDINEDIONE COMPOUND
-
Provided is a method for industrially producing a triazolidinedione compound at a high purity and a high yield. A precipitation step for preparing a solution that contains a triazolidinedione compound represented by formula (1) and precipitating the triaz
- -
-
Paragraph 0072-0073
(2021/08/20)
-
- METHOD FOR PRODUCING SEMICARBAZIDE COMPOUND, AND METHOD FOR PRODUCING TRIAZOLIDINEDIONE COMPOUND
-
PROBLEM TO BE SOLVED: To provide a method for synthesizing a semicarbazide compound which gives the semicarbazide compound without passing through an acyl azide. SOLUTION: Carbonylating agents such as carbonyl diimidazole (CDI) and triphosgene (TCF) are brought into contact with either one of an amine compound and a carbazate compound to form an active intermediate. A semicarbazide compound is synthesized by reacting the resulting active intermediate with the remaining one of the amine compound and the carbazate compound. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
- -
-
Paragraph 0137-0141; 0145
(2020/02/14)
-
- A novel Cookson-type reagent for enhancing sensitivity and specificity in assessment of infant vitamin D status using liquid chromatography/tandem mass spectrometry
-
Rationale 25-Hydroxyvitamin D3 [25(OH)D3] is the best-established indicator of vitamin D status. 4-Phenyl-1,2,4-triazoline-3,5- dione (PTAD), a representative Cookson-type reagent, has often been employed for enhancing the sensitivit
- Ogawa, Shoujiro,Ooki, Satoshi,Morohashi, Misato,Yamagata, Kenichiro,Higashi, Tatsuya
-
p. 2453 - 2460
(2013/10/22)
-
- Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents
-
Novel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC50 values of 1.55 μM and 1.48 μM, respectively. Further investigation on tube formation assay in human vein umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3-ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with minimum effective dose of 25 nM (for 1) and 6.25 μM (for 6). The ED 50 of 1 and 6 were found to be 0.26 μM and 17.52 μM, respectively. The results from in vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases (VEGFR2, FGFR1 and PDGFRβ). The cytotoxicity of 1 against EGFR overexpressing cell line A431 (IC50 36 nM) was comparable to that of erlotinib. The binding mode of 1 from docking simulation in the EGFR active site revealed that the urea motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic pocket of EGFR. Compound 1 is considered as a potential lead for further optimization.
- Sanphanya, Kingkan,Wattanapitayakul, Suvara K.,Prangsaengtong, Orawin,Jo, Michiko,Koizumi, Keiichi,Shibahara, Naotoshi,Priprem, Aroonsri,Fokin, Valery V.,Vajragupta, Opa
-
supporting information; experimental part
p. 3001 - 3005
(2012/06/04)
-
- Carbonyldiimidazole-mediated lossen rearrangement
-
[Chemical Equation Presented] Carbonyldiimidazole (CDI) was found to mediate the Lossen rearrangement of various hydroxamic acids to isocyanates. This process is experimentally simple and mild, with imidazole and CO 2 being the sole stoichiometric byproduct. Significant for large-scale application, the method avoids the use of hazardous reagents and thus represents a green alternative to standard processing conditions for the Curtius and Hofmann rearrangements.
- Dube, Pascal,Fine Nathel, Noah F.,Vetelino, Michael,Couturier, Michel,Aboussafy, Claude Larrivee,Pichette, Simon,Jorgensen, Matthew L.,Hardink, Mark
-
supporting information; experimental part
p. 5622 - 5625
(2010/03/02)
-
- Novel carbamates as potent histamine H3 receptor antagonists with high in vitro and oral in vivo activity
-
The known histamine H3 receptor antagonists burimamide, thioperamide, clobenpropit, and a related homohistamine thioamide derivative were taken as templates in search for new leads. Novel histamine H3 receptor antagonists structurally described as carbamate derivatives of 3-(1H-imidazol-4- yl)propanol were prepared in high yields by treatment of the alcohol with corresponding isocyanates or carbamoyl chlorides and investigated for their H3 receptor antagonist activity. Different chain lengths and various substituents possessing different electronic and steric parameters were introduced and structure-activity relationships established. In different functional tests, the new antagonists showed high H3 receptor antagonist potencies in vitro (-log K(i) values of 6.4-8.4) at synaptosomes of rat cerebral cortex and low activities at histamine H1 and H2 receptor subtypes. They were also screened for their central in vivo activity in mice after peroral administration. The most promising compounds (2, 16, 19) showed ED50 values of about 1-2 mg/kg and thus are potential drugs for the therapy of H3 receptor dependent diseases. Some of the novel carbamate derivatives are H3 receptor selective compounds with high in vitro and in vivo activity.
- Stark, Holger,Purand, Katja,Ligneau, Xavier,Rouleau, Agnès,Arrang, Jean-Michel,Garbarg, Monique,Schwartz, Jean-Charles,Schunack, Walter
-
p. 1157 - 1163
(2007/10/03)
-
- PYRAZOLIDINONE CCK AND GASTRIN ANTAGONISTS AND PHARMACEUTICAL FORMULATIONS THEREOF
-
Novel substituted pyrazolidinones have been found to exhibit significant binding to cholecystokinin (CCK) receptors and gastrin receptors in the brain and/or peripheral sites such as the pancreas, stomach, and ileum. The pyrazolidinones are CCK and gastri
- -
-
-
