- HETEROCYCLIC COMPOUNDS AND USES THEREOF
-
Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, lI-P, or III. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH).
- -
-
Paragraph 0232
(2021/07/31)
-
- Eco-friendly reactions in PEG-400: A highly efficient and green approach for stereoselective access to multisubstituted 3,4-dihydro-2(1: H)-quinazolines using 2-aminobenzylamines
-
An efficient and stereoselective synthesis of novel 3,4-dihydro-2(1H)-quinazolines has been developed through cyclization reactions of 2-aminobenzylamines with α-oxoketene dithioacetals using PEG-400 as an inexpensive, easy to handle, non-toxic and recycl
- Sharma, Nutan,Sharma, Pankaj,Bhagat, Sunita
-
p. 8721 - 8731
(2018/03/08)
-
- Stable and Rapid Thiol Bioconjugation by Light-Triggered Thiomaleimide Ring Hydrolysis
-
Maleimide-mediated thiol-specific derivatization of biomolecules is one of the most efficacious bioconjugation approaches currently available. Alarmingly, however, recent work demonstrates that the resulting thiomaleimide conjugates are susceptible to breakdown via thiol exchange reactions. Herein, we report a new class of maleimides, namely o-CH2NHiPr phenyl maleimides, that undergo unprecedentedly rapid ring hydrolysis after thiol conjugation to form stable thiol exchange-resistant conjugates. Furthermore, we overcome the problem of low shelf lives of maleimide reagents owing to their propensity to undergo ring hydrolysis prior to bioconjugation by developing a photocaged version of this scaffold that resists ring hydrolysis. UV irradiation of thiol bioconjugates formed with this photocaged maleimide unleashes rapid thiomaleimide ring hydrolysis to yield the desired stable conjugates within 1 h under gentle, ice-cold conditions.
- Kalia, Dimpy,Pawar, Sharad P.,Thopate, Jyoti S.
-
p. 1885 - 1889
(2017/02/05)
-
- Quinazolinones, Quinazolinthiones, and Quinazolinimines as Nitric Oxide Synthase Inhibitors: Synthetic Study and Biological Evaluation
-
The synthesis of different compounds with a quinazolinone, quinazolinthione, or quinazolinimine skeleton and their in vitro biological evaluation as inhibitors of inducible and neuronal nitric oxide synthase (iNOS and nNOS) isoforms are described. These d
- Camacho, M. Encarnación,Chayah, Mariem,García, M. Esther,Fernández-Sáez, Nerea,Arias, Fabio,Gallo, Miguel A.,Carrión, M. Dora
-
p. 638 - 650
(2016/08/27)
-
- Three-component (Domino) reaction affording substituted pyrroloquinazolines: Cyclization regioselectivity and stereoselectivity
-
The cyclization involving 2-(aminomethyl)aniline, methyl 3,3,3-trifluoropyruvate, and various oxo compound afforded linearly annulated pyrroloquinazolines, for example, (2R,3aS)-2-hydroxy-3a-phenyl-2- trifluoromethyl-3,3a,4,9-tetrahydropyrrolo[2,1-b]quina
- Paleta, Oldrich,Dolensky, Bohumil,Palecek, Jiri,Kvicala, Jaroslav
-
supporting information
p. 1262 - 1270
(2013/04/10)
-
- Sustainable synthesis of diverse privileged heterocycles by palladium-catalyzed aerobic oxidative isocyanide insertion
-
Heterocycles containing a guanidine moiety are of great importance in medicinal chemistry (Scheme 1).[1] As a result, several methods for the synthesis of these "privileged scaffolds" have been reported.[2, 3] Classical approaches, such as the addition of diamines to isothiocyanates followed by condensation and the coupling of diamines with cyanogen bromide,[2, 4] have some clear limitations, such as the availability and toxicity of reagents. Moreover, these procedures suffer from poor atom and/or step efficiency, thus making them unattractive from a sustainability point of view.
- Vlaar, Tj?stil,Cioc, Razvan C.,Mampuys, Pieter,Maes, Bert U. W.,Orru, Romano V. A.,Ruijter, Eelco
-
supporting information
p. 13058 - 13061
(2013/02/26)
-
- 4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors
-
Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.
- Pechulis, Anthony D.,Beck, James P.,Curry, Matt A.,Wolf, Mark A.,Harms, Arthur E.,Xi, Ning,Opalka, Chet,Sweet, Mark P.,Yang, Zhicai,Vellekoop, A. Samuel,Klos, Andrew M.,Crocker, Peter J.,Hassler, Carla,Laws, Mia,Kitchen, Douglas B.,Smith, Mark A.,Olson, Richard E.,Liu, Shuang,Molino, Bruce F.
-
p. 7219 - 7222
(2013/01/15)
-
- NEW COMPOUNDS
-
The present invention encompasses compounds of general Formula (I) wherein R2, R3, Q, W, X, Y and Z are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation
- -
-
Page/Page column 22
(2009/01/24)
-
- The endocyclic restriction test: The geometries of nucleophilic substitutions at sulfur(VI) and sulfur(II)
-
(Chemical Equation Presented) The trajectories for nucleophilic substitutions at sulfur(VI) and sulfur(II) have been investigated by the endocyclic restriction test. On the basis of double-labeling experiments, the sulfur(VI) transfer in the conversion of 1 to 2 is found to be intramolecular, while the sulfur(VI) transfer in the conversion of 3 to 4 and the sulfur(II) transfer in the conversion of 5 to 6 are found to be intermolecular. These results are taken to be consistent with transition structures for these sulfur transfer reactions which require a large angle between the entering and leaving group, a geometry analogous to apical group positions in trigonal bipyramidal transition states.
- Jarboe, Stephen G.,Terrazas, Michael S.,Beak, Peter
-
supporting information; experimental part
p. 9627 - 9632
(2009/04/07)
-
- Experimental and computational studies on the mechanism of N-heterocycle C-H activation by Rh(I)
-
Evidence is presented for a proposed mechanism of C-H activation of 3-methyl-3,4-dihydroquinazoline (1) by (PCy3)2RhCl. One intermediate (3), a coordination complex of 1 with (PCy3) 2RhCl, was identified along t
- Wiedemann, Sean H.,Lewis, Jared C.,Ellman, Jonathan A.,Bergman, Robert G.
-
p. 2452 - 2462
(2007/10/03)
-
- Synthesis of methyl carbamates from primary aliphatic amines and dimethyl carbonate in supercritical CO2: Effects of pressure and cosolvents and chemoselectivity
-
(Chemical Equation Presented) At 130 °C, in the presence of CO 2 (5-200 bar), primary aliphatic amines react with dimethyl carbonate (MeOCO2Me, DMC) to yield methyl carbamates (RNHCO2Me) and N-methylation side-products (RNHMe and RNMe2). The pressure of CO2 largely influences both the reaction conversion and the selectivity toward urethanes: in general, conversion goes through a maximum (70-80%) in the midrange (40 bar) and drops at lower and higher pressures, whereas selectivity is continuously improved (from 50% up to 90%) by an increase of the pressure. This is explained by the multiple role of CO2 in (i) the acid/base equilibrium with aliphatic amines, (ii) the reactivity/solubility of RNHCO2- nucleophiles with/in DMC, and (iii) the inhibition of competitive N-methylation reaction of the substrates. Cosolvents also affect the reaction: in particular, a drop in selectivity is observed with polar protic media (i.e., MeOH), plausibly because of solvation effects (through H-bonds) of RNHCO2- moieties. The reaction shows also a good chemoselectivity: bifunctional aliphatic amines bearing either aromatic NH2 or OH substituents [XC6H4(CH2)nNH2, X = NH2, OH; n = 1 2], undergo methoxycarbonylation reactions exclusively at aliphatic amino groups and give the corresponding methyl carbamates [XC 6H4(CH2)nNHCO2Me] in 39-65% isolated yields.
- Selva, Maurizio,Tundo, Pietro,Perosa, Alvise,Dall'Acqua, Federico
-
p. 2771 - 2777
(2007/10/03)
-
- The development of a manufacturing route for the GPIIb/IIIa receptor antagonist SB-214857-A. Part 1: Synthesis of the key intermediate 2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester, SB-235349
-
The development of an efficient manufacturing route to 2,3,4,5-tetrahydro-4-methyl-3-Oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester SB-235349, a key intermediate in the synthesis of lotrafiban is described. The synthesis starts with 2-nitrobenzyl alcohol which is mesylated, reacted with methylamine and then dimethylacetylene dicarboxylate followed by reduction of the nitro group. Treatment of the resultant aniline with acid gives an intermediate quinazoline which rearranges on treatment with base to give a 1,4-benzodiazapine. Reduction of the exocyclic double bond affords SB-235349. The process can be run without isolation of any of the intermediates and has been used to prepare several tons of SB-235349.
- Andrews, Ian P.,Atkins, Richard J.,Breen, Gary F.,Carey, John S.,Forth, Michael A.,Morgan, David O.,Shamji, Amin,Share, Andrew C.,Smith, Stephen A. C.,Walsgrove, Timothy C.,Wells, Andrew S.
-
p. 655 - 662
(2013/09/05)
-
- Regioselective N-alkylation of 2-aminobenzylamine via chelation to 9- BBN
-
A selective synthesis of 2-amino-N-alkylbenzylamines by direct mono alkylation of 2-aminobenzylamine is achieved by a potassium tert- butoxide/alkyl halide treatment of a 9-BBN amine-aminoborane chelate.
- Bar-Haim, Galia,Kol, Moshe
-
p. 2643 - 2644
(2007/10/03)
-
- A New Synthesis of 1,2,3,4-Tetrahydro-2-methyl-4-phenylisoquinolines
-
1,2,3,4-Tetrahydro-2-methyl-4-phenylisoquinolines 6 are obtained from aromatic aldehydes 1, methyl amine and α-haloacetophenones 2 in the presence of sodium borohydride followed by cyclization with sulfuric acid and zinc in methanol.
- Venkov, Atanas P.,Vodenicharov, Daniel M.
-
p. 253 - 255
(2007/10/02)
-