60285-00-9Relevant academic research and scientific papers
Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer
Akwii, Racheal,Alvina, Karina,Ashraf-Uz-Zaman, Md,Farshbaf, Mohammad Jodeiri,German, Nadezhda A.,Kallem, Raja Reddy,Mikelis, Constantinos M.,Putnam, William,Sajib, Md Sanaullah,Shahi, Sadisna,Trippier, Paul C.,Wang, Wei,Zhang, Ruiwen
supporting information, (2020/10/12)
Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.
NEW HETEROCYCLIC COMPOUNDS
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Page/Page column 69-70, (2019/06/17)
The invention provides new heterocyclic compounds having the general formula (IA) wherein A, L, X, Y, m, n, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
Synthesis, Calcium-Channel-Blocking Activity, and Antihypertensive Activity of 4-(Diarylmethyl)-1-piperidines and Structurally Related
Shanklin, James R.,Johnson, Christopher P.,Proakis, Anthony G.,Barrett, Richard J.
, p. 3011 - 3022 (2007/10/02)
A series of 4-(diarylmethyl)-1-piperidines and structurally related compounds were synthesized as calcium-channel blockers and antihypertensive agents.Compounds were evaluated for calcium-channel-blocking activity by determineng their ability to antagonize calcium-induced contractions of isolated rabbit aortic strips.The most potent compounds were those with fluoro substituents in the 3- and/or 4-positions of both rings of the diphenylmethyl group.Bis(4-fluorophenyl)acetonitrile analogue 79 was similar in potency to bis(4-fluorophenyl)methyl compound 1.The methylene analogue of 1 (78) and derivatives of 1 that contained a hydroxyl (76), carbamoyl (80), amino (81), or acetamido (82) substituent on the methyl group were less potent.In most cases substituents on the phenoxy ring, changes in the distance between the aryloxy group and the piperidine nitrogen, and the substitution of S, N(CH3), or CH2 for the oxygen atom of the aryloxy group had only a small to moderate effect on the potency.The best compounds in this series were more potent than verapamil, diltiazem, flunarizine, and lidoflazine, but were less potent than nifedipine.Compounds were evaluated for antihypertensive activity in spontaneusly hypertensive rats (SHR) at an oral dose of 30 mg/kg.Of the 55 compounds tested, only nine produced a statistically significant (p-1-piperidinyl>propoxy>-3-methoxyphenyl>ethanone (63), which produced a 35percent reduction in blood pressure and was similar in activity to nifedipine.At lower doses, however, 4--1-piperidine (93) was one of the most effective antihypertensive agents, producing reductions in blood pressure of 17 and 11percent at oral doses of 10 and 3 mg/kg, respectively; 63 was inactive at 10 mg/kg.
Aryl(alkyland alkylene)-N-((phenoxy and phenylthio)alkyl) aminoheterocyclics as cardiovascular, anthihistaminic, antisecretory and antiallergy agents
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, (2008/06/13)
A method of treating cardiac dysfunction, the effects of histamine, and gastric secretion excesses with aryl(alkyl and alkylene)-N-[(phenoxy and phenythio)alkyl]aminoheterocyclics corresponding to the formula: STR1 wherein Ar is phenyl or substituted phenyl; R is phenyl, substituted phenyl, pyridinyl or cycloalkyl; A is hydrogen, hydroxy, cyano, amido and amino; Q is --CH2 --, --CH--, or --CHOH--; d and n are zero or one and the dotted lines form double bonds consistent with the valence of carbon; p is zero, one or two; m is one to six inclusive; B is oxygen, nitrogen, sulfur, sulfinyl or sulfonyl; z is zero or one; l is zero or one; W is hydrogen, loweralkyl, halo, nitro, loweralkoxy or hydroxy; X is hydrogen, loweralkyl, halogen, loweralkoxy or hydroxy; Y is --CH(OH)CH2 OH, --CH(OH)C(O)OH, --C(O)C(O)OH, --C(O)CH2 OH,--C(O)C(O)OCH3, --C(O)C(O)OC2 H5, --CH2 C(O)OC2 H5, --CH(OH)C(O)OCH3, --CH(OH)C(O)OC2 H5 or --C(O)CH2 OC(O)CH3 ; and the pharmaceutically acceptable salts thereof; in addition to the above methods of treatment, compounds wherein (B)z is oxygen are useful in a method of treating Gell and Coombs type 1 allergic responses in mammals.
New xanthine derivatives with potent and long lasting anti-bronchoconstrictive activity
Regnier, Gilbert L.,Guillonneau, Claude G.,Duhault, Jacques L.,Tisserand, Francoise P.,Saint-Romas, Guy,Holstorp, Sophie M.
, p. 243 - 250 (2007/10/02)
Twenty eight new derivatives of 8-aminoalkyl substituted xanthine have been synthesized.They all have demonstrated a potent anti-bronchoconstrictive effect in the guinea pig and some of them have a very long duration of action (>48 h).Among them, one compound: 1-methyl 3-isobutyl 8-(4-benzhydryl piperazino ethyl)xanthine (57) (S 9795) has been selected for clinical trials in asthmatic patients because of its long duration of action, its lack of CNS stimulating effects and its inhibiting action on mast cell degranulation and phosphodiesterase activity.Keywords - 8-aminoalkyl substituted xanthines / benzhydryl piperazine / piperidine / ethylenediamine / anti-bronchoconstrictors / phosphodiesterase inhibitors / asthma
Substituted N-benzyl-4-(benzhydryl) piperidines
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, (2008/06/13)
The invention relates to compounds of the formula: STR1 which are useful cardiovascular agents.
