- A practical solid phase synthesis of quinazoline-2, 4-diones
-
We describe a practical solid phase synthesis of quinazoline-2,4-diones using a short-chain, high loading capacity, polyethyleneglycol polystyrene copolymer ('PEG4-PS' resin). The highlights of this synthesis include efficient acyl azide format
- Shao, Hui,Colucci, Marcus,Tong, Shaojing,Zhang, Hesheng,Castelhano, Arlindo L.
-
-
Read Online
- With anti-tumor effect of a quinazoline-urea derivative and its application (by machine translation)
-
The present invention relates to a of the general formula (II) anti-tumor function of said quinazoline-urea derivative and its application. The definition of the substituent in the general formula (II) in the specification. This invention, in order to SUO draw non-Buddhist nun and Geftinat compounds as the precursor, retention of SUO draw non-Buddhist nun the pharmocology-carbamido; at the same time, such as in reserved [...] EGFR-TKIs Geftinat, synthesis, and obtain a series of quinazoline-urea derivatives, by the in vitro activity tests, some compounds exhibit excellent anti-tumor activity, such derivatives have high research and utility value. (II). (by machine translation)
- -
-
Paragraph 0139-0142; 0172
(2016/11/02)
-
- Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents
-
Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure-activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization.
- Chen, Jia-Nian,Wang, Xian-Fu,Li, Ting,Wu, De-Wen,Fu, Xiao-Bo,Zhang, Guang-Ji,Shen, Xing-Can,Wang, Heng-Shan
-
-
- Quinazolinedione sulfonamides: A novel class of competitive AMPA receptor antagonists with oral activity
-
Quinazoline-2,4-diones with a sulfonamide group attached to the N(3) ring atom constitute a novel class of competitive AMPA receptor antagonists. One of the synthesized compounds, 28, shows nanomolar receptor affinity, whereas other examples of the series display oral anticonvulsant activity in animal models.
- Koller, Manuel,Lingenhoehl, Kurt,Schmutz, Markus,Vranesic, Ivan-Toma,Kallen, Joerg,Auberson, Yves P.,Carcache, David A.,Mattes, Henri,Ofner, Silvio,Orain, David,Urwyler, Stephan
-
scheme or table
p. 3358 - 3361
(2011/07/07)
-
- Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A
-
A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin.
- Shen, Hong C.,Szymonifka, Michael J.,Kharbanda, Divya,Deng, Qiaolin,Carballo-Jane, Ester,Wu, Kenneth K.,Wu, Tsuei-Ju,Cheng, Kang,Ren, Ning,Cai, Tian-Quan,Taggart, Andrew K.,Wang, Junying,Tong, Xinchun,Waters, M. Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
-
p. 6723 - 6728
(2008/04/03)
-
- Organosilicon synthesis of isocyanates: III. Synthesis of aliphatic, carbocyclic, aromatic, and alkylaromatic isocyanatocatboxylic acid esters
-
A series of aminoacid esters was prepared by treating the aminoacid suspensions in ethanol with thionyl chloride. Best conversion of aminoacid esters to corresponding isocyanates was achieved in the case of aromatic and carbocyclic aminoesters by phosgeneation of their N-silyl derivatives, and in the case of aliphatic and alkylaromatic aminoesters by phosgeneation of O-silyl or N,O-bissilylurethanes on their basis. In the last case additional step of esterification of the by-products isocyanatoalkylcarboxylic acid chlorides is required after phosgeneation. Unusual generation of cynnamates and intramolecular N→O-migration of trimethylsilyl group in the solutions of silylated alkylaromatic β-aminoacid esters were found. Pleiades Publishing, Inc., 2006.
- Lebedev,Lebedeva,Sheludyakov,Ovcharuk,Kovaleva,Ustinova
-
p. 1069 - 1080
(2008/02/05)
-
- SYNTHESIS OF PROTECTED PYRROLOBENZODIAZEPINES
-
A method of synthesis of a N-10 protected PBD compound of formula (I) via an intermediate of formula (II) or formula (V).
- -
-
Page/Page column 106
(2010/02/11)
-
- New phenylalanine derivatives
-
Specified phenylalanine derivatives and analogues thereof have an antagonistic activity to α4 integrin. They are used as therapeutic agents for various diseases concerning α4 integrin.
- -
-
-
- 2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease
-
A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by β-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2- iodophenyl)amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2- iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).
- Hays, Sheryl J.,Caprathe, Bradley W.,Gilmore, John L.,Amin, Nilam,Emmerling, Mark R.,Michael, Walter,Nadimpalli, Ravi,Nath, Rathna,Raser, Kadee J.,Stafford, Daniel,Watson, Desiree,Wang, Kevin,Jaen, Juan C.
-
p. 1060 - 1067
(2007/10/03)
-
- Quinaldoyl-amine derivatives of oxo-and hydroxy-substituted hydrocarbons
-
The present invention discloses the compounds of general formula (1) STR1 wherein R1, R2, R3 are optionally substituted carbonyl and amide derivatives which are useful as inhibitors of retroviral proteases, and are effecti
- -
-
-
- Tyrosine kinase inhibitors. 4. Structure-activity relationships among N- and 3-substituted 2,2'-dithiobis(1H-indoles) for in vitro inhibition of receptor and nonreceptor protein tyrosine kinases
-
A series of 3-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC50s 1-20 μM), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N- thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC50s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol- containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.
- Palmer,Rewcastle,Thompson,Boyd,Showalter,Sercel,Fry,Kraker,Denny
-
-
- SYNTHESIS OF CHIRAL 3-SUBSTITUTED 2,4-(1H,3H)-QUINAZOLINEDIONES
-
2-Carbomethoxyphenyl isocyanate and 6-nitro-2-carbomethoxyphenyl isocyanate were generated in situ from half-esters and then converted into the corresponding quainazolinediones using α-amino acids.This useful annelation process was found to be a general m
- Canonne, Persephone,Akssira, Mohamed,Dahdouh, Abdelaziz,Kasmi, Hicham,Boumzebra, Mohamed
-
p. 1305 - 1314
(2007/10/02)
-
- 5-Hydroxytryptamine (5-HT3) Receptor Antagonists. 3. Ortho-Substituted Phenylureas
-
A novel series of potent 5-HT3 receptor antagonists, ortho-substituted phenylureas 6a-z, is described in which the 5-membered ring of the previously reported indazoles and indolines has been replaced by an intramolecular hydrogen bond.High potency was found both for carbamate 6a and urea 6b.Granatane 6c was less potent than the equivalent tropane.Phenylurea 11c lacking the ortho substituent was inactive.Whereas further substitution could not be tolerated in the aromatic ring, activity was retained with a range of O-alkyl groups, compounds 6k-t.In addition, good activity was found for ortho ester 6u and sulfonamide 6x.The ortho-substituted phenylureas can therefore be regarded as bioisosteres of the 6,5-heterocycles indole, indazole, and indoline.
- Bermudez, Jose,Dabbs, Steven,King, Frank D.
-
p. 1932 - 1935
(2007/10/02)
-