cas 13906-09-7, 2-MERCAPTO-4(3H)-QUINAZOLINONE

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NEW SYNTHESIS OF 2-THIOXOQUINAZOL-4-ONES
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Yangibaev, S.,Yun, L. M.,Shakhidoyatov, Kh. M.
p. 712
(1985)
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Synthesis of heterocycles via enamines-XIII1 1 H. Singh, S. Kumar, J. Chem. Soc., Perkin Trans 1, 1987, in press. Steric control on the mode of reactions of β-isothiocyanatoketones with amino-acids
Glycine and anthranilic acid with 4-isothiocyanato-butan-2-one (1) gives 3-(3-oxobutyl)-4-oxoimidazolidine-2-thione (11) and 3-(3-oxobutyl)-2-thioxoquinazolin-4-one (15) whereas with 4-isothiocyanato-4-methylpentan-2-one (2), having a gem-dimethyl group at the carbon bearing isothiocyanate group, tetrahydro-7,7,8a-trimethyl-5-thioxo-6H-oxazolo[3,2-c] pyrimidine-2(3H)-one (14) and 2,3,4,4a-tetrahydro-3,3,4a-trimethyl-1-thioxo-1H,6H-pyrimido[1,6a][3,1]-benzoxazin-6-one (17) are formed.
Singh, Harjit,Kumar, Subodh
p. 2177 - 2180
(1987)
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SYNTHESIS AND ALKYLATION OF 2-MERCAPTO-4-QUINAZOLONE AND THE FUNGICIDAL ACTIVITIES OF THE COMPOUNDS OBTAINED
A convenient method of obtaining 2-mercapto-4-quinazolone has been developed and the alkylation of its ambidentate anions has been studied.It has been found that they exhibit a dual reactivity in alkylation reactions.It has been shown that alkylated 2-mercapto-4-quinazolones possess a moderate fungicidal activity.
Shakhadoyatov, Kh. M.,Yangibaev, S.,Yun, L. M.,Kadyrov, Ch. Sh.
p. 106 - 111
(1982)
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NEW METHOD FOR THE SYNTHESIS OF 2-THIOXO-4-QUINAZOLONES
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Yun, L. M.,Yangibaev, S.,Shakhidoyatov, Kh. M.,Kadyrov, Ch. Sh.
p. 221
(1983)
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Synthesis, Cytotoxic Activity Evaluation of Novel 1,2,3-Triazole Linked Quinazoline Derivatives
A series of novel 1,2,3-triazole-quinazoline derivatives were synthesized in five steps starting from anthranilamide by conventional methods. All the title compounds 10a—10r were evaluated for cytotoxic activity against four human cancer cell lines (MGC-803, EC-109, MCF-7 and HGC-27) using MTT assay in vitro. Some of the synthesized compounds exhibited moderate to potent activity against tested cancer cell lines. Among them, compounds 10 h and 10q exhibited excellent growth inhibition against HGC-27 and compound 10 m also possessed excellent activity against MCF-7, with IC50 values less than 1 μmol/L. Especially, compound 10 h was more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines.
Song, Panpan,Cui, Fei,Li, Na,Xin, Jingchao,Ma, Qisheng,Meng, Xiangchuan,Wang, Chaojie,Cao, Qinpo,Gu, Yifei,Ke, Yu,Zhang, Qiurong,Liu, Hongmin
p. 1633 - 1639
(2017)
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2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium tuberculosis: Structure-Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization
Mycobacterium tuberculosis (MTb) possesses two nonproton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism. Furthermore, the structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose MTb whole-cell structure-activity relationships (SARs) for a series of 2-mercapto-quinazolinones which target the ndh encoded NDH-2 with nanomolar potencies. The compounds were inactivated by glutathione-dependent adduct formation as well as quinazolinone oxidation in microsomes. Pharmacokinetic studies demonstrated modest bioavailability and compound exposures. Resistance to the compounds in MTb was conferred by promoter mutations in the alternative nonessential NDH-2 encoded by ndhA in MTb. Bioenergetic analyses revealed a decrease in oxygen consumption rates in response to inhibitor in cells in which membrane potential was uncoupled from ATP production, while inverted membrane vesicles showed mercapto-quinazolinone-dependent inhibition of ATP production when NADH was the electron donor to the respiratory chain. Enzyme kinetic studies further demonstrated noncompetitive inhibition, suggesting binding of this scaffold to an allosteric site. In summary, while the initial MTb SAR showed limited improvement in potency, these results, combined with structural information on the bacterial protein, will aid in the future discovery of new and improved NDH-2 inhibitors.
Murugesan, Dinakaran,Ray, Peter C.,Bayliss, Tracy,Prosser, Gareth A.,Harrison, Justin R.,Green, Kirsteen,Soares De Melo, Candice,Feng, Tzu-Shean,Street, Leslie J.,Chibale, Kelly,Warner, Digby F.,Mizrahi, Valerie,Epemolu, Ola,Scullion, Paul,Ellis, Lucy,Riley, Jennifer,Shishikura, Yoko,Ferguson, Liam,Osuna-Cabello, Maria,Read, Kevin D.,Green, Simon R.,Lamprecht, Dirk A.,Steyn, Adrie J. C.,Ioerger, Thomas R.,Sacchettini, Jim,Rhee, Kyu Y.,Arora, Kriti,Barry, Clifton E.,Wyatt, Paul G.,Boshoff, Helena I. M.
p. 954 - 969
(2018)
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2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K
A series of novel 2,4-disubstituted quinazolines were synthesized and evaluated for their anti-tumor activity against five human cancer cells (MDA-MB-231, MCF-7, PC-3, HGC-27 and MGC-803) using MTT assay. Among them, compound 9n showed the most potent cytotoxicity against breast cancer cells. Compound 9n also significantly inhibited the colony formation and migration of MDA-MB-231 and MCF-7 cells. Meanwhile, compound 9n induced cell cycle arrest at G1 phase and cell apoptosis, as well as increased accumulation of intracellular ROS. Furthermore, compound 9n exerted anti-tumor effects in vitro via decreasing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 9n markedly decreased p-EGFR and p-PI3K expression, which revealed that compound 9n targeted breast cancer cells via interfering with EGFR-PI3K signaling pathway. Molecular docking suggested that compound 9n could indeed bind into the active pocket of EGFR. All the findings suggest that compound 9n might be a valuable lead compound for anti-tumor agents targeting breast cancer cells.
Li, Er-dong,Lin, Qiao,Meng, Ya-qi,Zhang, Lu-ye,Song, Pan-pan,Li, Na,Xin, Jing-chao,Yang, Peng,Bao, Chong-nan,Zhang, Dan-qing,Zhang, Yang,Wang, Ji-kuan,Zhang, Qiu-rong,Liu, Hong-min
p. 36 - 47
(2019)
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A facile and convenient method to the one-pot synthesis of 2-mercapto-4(3H)-quinazolinones
A facile and convenient method to the one-pot synthesis of 2-mercapto-4(3H)-quinazolinones is described from the reaction of anthranilic acid derivatives with thiourea in PEG.
Nikpour, Farzad,Mozafari, Roya,Paibast, Touraj
p. 1569 - 1571
(2009)
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An efficient ionic liquid mediated synthesis of substituted 5H[1,3]-thiazolo[2,3-b]quinazoline-3,5-(2H)-dione and 5H-thiazolo[2,3-b] quinazolin-5-one
A new, environmentally benign two-step synthesis of 5H[1,3]-thiazolo[2,3-b] quinazoline-3,5-(2H)-dione and 5H-thiazolo[2,3-b]quinazolin-5-one derivatives has been accomplished stepwise. The substituted 2-aminobenzoic acid upon condensation with thiourea in 1-butyl-3-methylimidazolium bromide at moderate temperature under nitrogen atmosphere yielded 2-thioxo-1H-4-quinazolinones. The resulting intermediate 2-thioxo-1H-4-quinazolinones, when reacted with 2-chloroethanoic acid/2-chloropropanal underwent cyclization to yield the desired product in excellent yields.
Yadav, Ashok K.,Dhakad, Pankaj,Sharma, Gopi Ram
p. 6061 - 6063
(2013)
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Preparation method and application of quinazolinone derivatives containing disulfide structure
The present invention relates to a class of disulfide-containing structure of quinazoline ketone derivative preparation method and application thereof. The compound having a structure as shown in formula (I): The present invention takes quinazolinone as the parent structure, the dishioalkyl (heterocyclic) structure is introduced into this system, a series of quinazolineone derivatives containing disulfide structure are synthesized, the series of compounds has a good inhibitory effect on plant pathogenic pathogenic bacteria, such as rice leaf blight, citrus canker fungus, kiwi canker bacteria and solanum subtilis and solanum subtilis.
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Paragraph 0041-0043

(2022/01/12)

2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn)
Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure-activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction of polar substituents on the quinazolinone core allowed reduction of bovine serum albumin (BSA) binding (63c, 63d). While most of the tested quinazolinones exhibited no cytotoxicity against MRC-5, the most potent compound 26 was found to be mutagenic via the Ames test. This analogue exhibited moderate inhibitory potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones that lies at the basis of the current analogues, indicating that the whole-cell antimycobacterial activity of the present S-substituted thioquinazolinones is likely due to modulation of alternative or additional targets. Diminished antimycobacterial activity was observed against mutants affected in cofactor F420 biosynthesis (fbiC), cofactor reduction (fgd), or deazaflavin-dependent nitroreductase activity (rv3547), indicating that reductive activation of the 3,5-dinitrobenzyl analogues is key to antimycobacterial activity.
Jian, Yanlin,Forbes, He Eun,Hulpia, Fabian,Risseeuw, Martijn D. P.,Caljon, Guy,Munier-Lehmann, Hélène,Boshoff, Helena I. M.,Van Calenbergh, Serge
p. 440 - 457
(2021/01/14)

1,2,3-Triazole structure unit-containing 2,4-disubstituted quinazoline compounds, and preparation method and use thereof
The invention belongs to the technical field of pharmaceutical chemistry synthesis, and discloses 1,2,3-triazole structure unit-containing 2,4-disubstituted quinazoline compounds, and a preparation method and a use thereof. A series of 1,2,3-triazole structure unit-containing 2,4-disubstituted quinazoline compounds are prepared from anthranilamide through cyclization, substitution, chlorination and aminolysis reactions. The compounds have a structure represented by general formula I. Preliminary in vitro antitumor activity evaluation finds that the series of the compounds have obvious inhibiting and killing effects on various tumor cells. The compounds can be processed to develop new medicines, and can be applied to clinic prevention and cancer treatment as an active component.
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(2017/06/22)

Use of dodecanoyl isothiocyanate as building block in synthesis of target benzothiazine, quinazoline, benzothiazole and thiourea derivatives
Dodecanoyl isothiocyanate (I) reacts additively with anthranilic acid to afford derivatives of thiourea II and benzothiazine III in a one-pot reaction. The cyclisation of thiourea II was achieved using acetic anhydride to form quinazoline derivative IV. The heating of quinazoline IV in acetic anhydride or butan-1-ol gave quinazoline derivatives V or VI, respectively. Benzothiazine III underwent trans-acylation to benzothiazine VII in boiling acetic anhydride. The treatment of IV with hydrazine hydrate, anthranilic acid or ethyl carbazate afforded derivatives of triazoloquinazoline VIII, quinazolinoquinazoline XI or thiosemicarbazide X, respectively. The reaction of I with 2aminophenol or 2-aminothiophenol afforded thiourea derivative XIII or benzothiazole derivative XIV, respectively. Most of the synthesised compounds bear a lauroyl (dodecanoyl) group (a hydrocarbon moiety). The structures of the synthesised compounds were confirmed by microanalytical and spectral data.
Hemdan, Magdy M.,El-Bordany, Eman A.
p. 1117 - 1125
(2016/06/01)

Conversion of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones to N(3)-unsubstituted 2-(het)arylquinazolin-4(3H)-ones by copper-mediated Pd-catalysed cross-coupling reactions
With the purpose of searching for new heterocyclic building blocks, a new method to access N(3)-unsubstituted 2-(het)arylquinazolin-4(3H)-ones from 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives was developed. The synthetic protocol was based on the copper-mediated palladium-catalysed cross-coupling reactions of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones with (het)arylstannanes or their S-benzylated derivatives with (het)arylboronic acids, using CuBr·Me2S and CuMeSal as promoters, respectively. A similar transformation was applied for the preparation of 2-aryl[1]benzothieno[3,2-d]pyrimidin-4(3H)-ones.
Kri??iūnien?, Vilija,Matulevi?iūt?, Gita,Paliulis, Osvaldas,Rollin, Patrick,?a?kus, Algirdas
p. 150 - 163
(2017/03/11)

One-Step Synthesis of 2-Chloropyrimidin-4-ol Derivatives: An Unusual Reactivity of Thiophosgene
A novel, high-yielding, one-step synthesis of 2-chloroquinazolin-4-ols and analogous bicycles from 2-aminoamides using thiophosgene is described. The scope of the reaction includes aminothioamides, amino acids, and fused heterocycle derivatives, furnishing quinazolines, oxazinones, and substituted fused pyrimidine bicycles, respectively. On the basis of observed results with substituted analogues, a mechanism for this transformation is thought to occur via an isothiocyanate intermediate followed by an unexpected chemoselective reaction of thiophosgene on the thiol intermediate.
Callingham, Michael,Blum, Francesca,Pavé, Grégoire
p. 4930 - 4932
(2015/10/12)

Green and efficient synthesis of 2-(4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydropthalazine-1,4-dione
2-Hydrazinoquinazolin-3H-4-ones 1a,b were reacts with each of the anhydrides, phthalic anhydride 2a, succinic anhydride 2b and maleic anhydride 2c independently in PEG-600 at RT to yield 2-(2-(4-oxo-3,4-dihydroquinazolin-2-yl)hydrazineecarbonyl) benzoic acid 3a,b, 4-oxo-4-(2-(4-oxo-3,4-dihydroquinazolin-2-yl)hydrazinyl)butanoic acid 3c,d and 4-oxo-4-(2-(4-oxo-3,4-dihydroquinazolin-2-yl)hydrazinyl)but-2-enoic acid 3e,f, respectively. 3a, b, 3c,d, 3e,f have been transformed into 2-(4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-dione 4a,b, 1-(4-oxo-3,4-dihydroquinazolin-2-yl)piperazine-3,6-dione 4c,d and 1-(4-oxo-3,4-dihydroquinazolin-2-yl)-1,2-dihydropyridazine-3,6-dione 4e,f, respectively by heating each in PEG-600 at 100°C for 3-3.5 hr in high yields and in high purity, involving a dehydrative ring closure. The final compounds 4a-f have also been prepared alternatively by reacting 1 with 2 in PEG-600 at 100°C for 3.5-4 hr.
Rafeeq,Srinivasa Reddy,Venkata Ramana Reddy,Naidu,Dubey
p. 412 - 417
(2015/03/31)

Lanthanide-catalyzed cyclocarbonylation and cyclothiocarbonylation: A facile synthesis of benzannulated 1,3-diheteroatom five- and six-membered heterocycles
La[N(SiMe3)2]3 proves to be an efficient catalyst system for the cyclocarbonylation of 1,2-disubstituted benzenes with isocyanates. In this approach, aryl/alkyl isocyanates react with o-phenylenediamine, o-aminophenol, o-aminothiophenol, catechols and anilines ortho-substituted by CH2NH2 and CONH2 to form, respectively, the corresponding benzimidazolones, benzoxazolones, benzothiazolones, benzodioxolones, 3,4-dihydroquinazolin-2(1H)-one, and quinazolinediones. These results represent the first example of lanthanide-catalyzed carbonylation. This methodology is also applicable for the preparation of various benzannulated 1,3-diheteroatom cyclic thioketones starting from aryl/alkyl isothiocyanates or CS2 in good to excellent yields. Based on the results of experiments performed using an o-aminobenzamido dianion lanthanide complex, a general mechanism, involving the tandem reaction of two lanthanide-ligand bonds with one heterocumulene molecule, is proposed as well.
Jing, Yufeng,Liu, Ruiting,Lin, Yanghui,Zhou, Xigeng
p. 1117 - 1125
(2014/08/18)

An expeditious microwave-assisted synthesis of mercapto benzazoles, quinazolinone and oxadiazoles
A simple, convenient and high yielding synthetic method for the preparation of various mercapto derivatives of benzimidazoles 2a-e, benzoxazole 2f, benzothiazole 2g, quinazolinone 2h, 5- substituted-1,3,4-oxadiazoles 4a-f by the treatment of a series of O, S and N heteroatoms containing bifunctional molecules with potassium isopropyldithiocarbonate under microwave irradiation technique is described.
Mahesh Kumar,Dubey
p. 1619 - 1622
(2013/01/15)

Design, synthesis and biological activity evaluation of 2-mercapto-4(3H)-quinazolinone derivatives as novel inhibitors of protein tyrosine phosphatase 1B
A series of novel 2-mercapto-4(3H)-quinazolinone derivatives have been synthesized and their inhibitory effects on PTP1B and TCPTP are evaluated for the first time. Most of these derivatives showed good inhibitory activity on PTP1B and reasonable selectivity for PTP1B over TCPTP, among them 32 was the most potent PTP1B inhibitor (IC50 = 1.50 μ ;g/mL), and 27 possessed the best selectivity of 3.0-fold.
Li, Hui,Wang, Jin-Ping,Yang, Fan,Liu, Ting,Qiu, Wen-Wei,Li, Jing-Ya,Li, Jia,Tang, Jie
p. 1897 - 1911
(2012/09/07)

Design, synthesis, and structure-activity relationships of highly potent 5-HT3 receptor ligands
The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure-activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [3H]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pKi > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.
Verheij, Mark H. P.,Thompson, Andrew J.,Van Muijlwijk-Koezen, Jacqueline E.,Lummis, Sarah C. R.,Leurs, Rob,De Esch, Iwan J. P.
p. 8603 - 8614
(2013/01/15)

Quinazolinediones and quinazolinethiones by intramolecular ester amidation
A new synthetic route was devised for synthesis of Quinazoline-2,4(1H,3H)- dione 5 in which salicylic acid 1 was treated with urea 2 to afford urea arylated ortho-urahydroxy benzoic acid 4. Ortho-urahydroxy benzoic acid 4 is the intermediate moiety which upon cyclization corroborated the cyclic formation of 2, 4-quinazolinedione 5. To form the quinazoline derivative 2, 3-dihydro-2-thioxoquinazolin-4(1H)-one 5a thiourea 3 is used in place of urea 2. Thiourahydroxy benzoic acid 4a is another intermediate compound formed by reacting salicylic acid 1 with thiourea 3. Thiourahydroxy benzoic acid 4a upon interamolecular ester amidation gave final product 2, 3-dihydro-2- thioxoquinazolin-4(1H)-one 5a. This new method replaces the isocyanates and cyanides usage for the formation of quinazolinediones because the incorporation of isocyanates and cyanides is extremely poisonous and cause fatal diseases and immediate death upon contact.
Ahmed, Ejaz,Manwar, Muhammad Ramzan,Sharif, Ahsan,Mukhtar-Ul-Hassan,Ahmed, Neman,Malik, Abdul,Mahmood, Zaid,Munawar, Munawar Ali
p. 417 - 420
(2012/04/04)

Synthesis of novel 2-[1-(1H-benzimidazol-2-yl)-ethylsulfanyl]-3H- quinazolin-4-ones
Condensation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanyl)-propionic acid (1) with o-phenylenediamine (2) gave 2-[1-(1H-benzimidazol-2-yl)-ethylsulfanyl] -3H-quinazolin-4-one (3). The latter can also be prepared by the reaction of 2-(1-chloroethyl)-1H-benzimidazole (4) with 2-mercapto-3W-quinazolin-4-one (5) either in acetone/ triethylamine or in DMF / K2CO3 in the presence of TBAB as phase transfer catalyst. 3 can also be prepared yet by an alternative method involving reaction of 4 with potassium ethylthioxanthate yielding dithiocarbonic acid S-[1 H-benzomidazol-2-yl) ethyl) ethyl ester (6) and subsequent condensation of the latter with o-aminobenzamide (7), in the presence of TFA, under reflux in toluene.
Srinivasa Reddy,Naidu,Dubey
p. 257 - 260
(2013/09/24)

Solvent-free syntheses of some quinazolin-4(3H)-ones derivatives
Solvent-free syntheses of quinazolin-4(3H)-ones were performed by reaction of anthranillic acid with different amides, such as nicotinamide, benzamide, formamide, etc., on montmorillonite K-10. Products were confirmed by FTIR, 1HNMR, and 13CNMR spectroscopic techniques. All synthesized compounds exhibited antioxidant properties and have been compared with standard antioxidant BHT.
Roopan, S. Mohana,Maiyalagan,Khan, F. Nawaz
experimental part
p. 1019 - 1025
(2009/02/08)

Synthesis of 2-aryl-5H-[1,3,4]-thiadiazolo[2,3-b]quinazolin-5-ones
3-Amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-ones were converted into 2-aryl-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-ones on treatment with carboxylic acids and POCl3. 3-Arylmethylidenamino-2-thioxo-1,2,3,4- tetrahydroquinazolin-4-ones also cyclized to 2-aryl-5H-[1,3,4]thiadiazolo[2,3-b] quinazolin-5-ones when oxidized with potassium chlorate in acetic acid, but on heating they were deaminated to give 2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one and aryl nitriles. 2006 Springer Science+Business Media, Inc.
Britsun,Esipenko,Lozinskii
p. 693 - 697
(2008/02/04)

Structure of the reaction product of anthranilic acid hydrazide with carbon disulfide in alkaline medium
The reaction of anthranilic acid hydrazide with carbon disulfide in alkaline medium yields 5-(2-aminophenyl)-2,3-dihydro-1,3,4-oxadiazole-2-thione rather than 3-amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one. The structure of the product was proved by spectral methods and chemical transformations.
Britsun,Esipenko,Kudryavtsev,Lozinskii
p. 1333 - 1336
(2007/10/03)

Generalized method for the production of 1,3-benzoxazine, 1,3-benzothiazine, and quinazoline derivatives from 2-(hydroxy, thio, or amino) aromatic acids using triphenylphosphine thiocyanogen
A modified one-pot method was developed for the synthesis of 1,3-benzoxazines, in which the preparation of unstable thiocyanogen was omitted. The method was found to be general for substituted (methyl, methoxy, halo, and hydroxy) 2-hydroxy benzoic acids and 2-hydroxy naphthoic acids. The method was extended to 2-thio, 2-amino, and N-methyl aminobenzoic acid with which the synthesis of 1,3-benzothiazine and quinazoline derivatives has been achieved, respectively. It was also found that 3-hydroxypyridine-2-carboxylic acid and 2-hydroxynicotinic acid using a modified method gave 2-thioxo-2,3-dihydro-4H- pyrido[2,3-e][1,3]oxazin-4-one and 2-thioxo-2,3-dihydro-4H-pyrido[3,2-e][1,3] oxazin-4-one, respectively. The structures of the new compounds were confirmed by the analysis of their IR, 1H, and 13C NMR spectra. Copyright Taylor & Francis, Inc.
Pritchard, Kaylene M.,Al-Rawi, Jasim M.,Hughes, Andrew B.
p. 1601 - 1611
(2007/10/03)

Kilogram-scale synthesis of a highly selective α1-adrenoceptor antagonist (DL-028A)
This work presents an improved eight-step process, leading to kilogram quantities of high-quality DL-028A, an antihypertensive agent. The improvements include reducing the levels of toxic reagents and the removal of dangerous processes and waste gas treatment. Moreover, specification and impurity profiles were determined.
Chou, Shan-Yen,Yin, Wei-Kung,Chung, Yuh-Shan,Chang, Lien-Shange,Liu, Chin-Wei,Chen, Shyh-Fong,Shih, Kae-Shyang
p. 273 - 278
(2013/09/06)

Synthesis and X-ray characterisation of a new polycondensed heterocycle obtained by a novel Mn(III)-mediated cascade reaction of 2-cyanophenyl isothiocyanate
2-Cyanophenyl isothiocyanate reacted with Mn(III) acetate in acetic acid or acetonitrile to give fair yields of a new polycondensed heterocycle arising from the joining together of two molecules of the starting isothiocyanate with loss of a CS moiety. The yields were close to 90% when the reaction was carried out in the presence of diethyl malonate. This compound was unambiguously identified by X-ray crystallography. Under the same conditions, 2-(methoxycarbonyl)phenyl isothiocyanate gave a quinazolinimine derivative instead which is likely to arise from cyclisation of an intermediate N,N′-diarylthiourea. The mechanism of formation of the former compound probably involves formation of a N,N′-bis(2-cyanophenyl)thiourea, followed by rearrangement and radical tandem ring closure of the corresponding cyclic imine derivative. This hypothesis is also supported by semiempirical calculations.
Calestani, Gianluca,Capella, Laura,Leardini, Rino,Minozzi, Matteo,Nanni, Daniele,Papa, Romina,Zanardi, Giuseppe
p. 7221 - 7233
(2007/10/03)

Synthesis of 2-aminoquinazoline-4(3H)-one derivatives as potential potassium channel openers
Starting from 2-thioxoquinazolin-4-one, the synthesis of 2-amino-4(3H)- one derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described.
Erb, Benedicte,Akue, Rufine,Rigo, Benoit,Pirotte, Bernard,Couturier, Daniel
p. 253 - 260
(2007/10/03)

Synthesis and enantioselective cleavage of chiralic quinazoline carboxylic acid esters
The synthesis of chiralic propionic acid ethylesters of 3-alkyl-4-oxo- 2-thioxo-1,2,3,4-tetrahydroquinazolines was described and their chromatographic behaviour was investigated on the chiralic phases (S,S)- Whelk-01 and Chiralcel-OD-H. The enantioselective cleavage succeeded by means of lipase of Candida cylindracea (CCL, E.C. 3.1.1.3.), of pork liver esterase (PLE, E.C. 3.1.1.1.) and of the enzymes of screening set Chirazyme, too. The results pointed out that the modification at the C3-alkyl group has a significant influence to the cleavage rate and the enantioselectivity. The highest selectivity is to obtain in presence of π-electrons in the 3- substituent whereas voluminous aryl groups block up the effectiveness of the enzymes used.
Beyrich, Thorsten,Theiss
p. 853 - 858
(2007/10/03)

Studies on quinazolines and 1,2,4-benzothiadiazine 1,1-dioxides. 8. Synthesis and pharmacological evaluation of tricyclic fused quinazolines and 1,2,4-benzothiadiazine 1,1-dioxides as potential α1-adrenoceptor antagonists
A series of 2-substituted methyl 2,3-dihydroimidazo[1,2-c]quinazolin- 5(6H)-ones (4), 3-substituted methyl 2,3-dihydroimidazo[1,2-c]quinazolin- 5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3- b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1- b]quinazolin-5(1H)-ones (16a,b), 3-substituted methyl 2,3-dihydro-1H- imidazo[1,2-b][1,2,4]benzothiadiazine 5,5-dioxides (33a,b), 2-substituted methyl imidazo[1,2-c]quinazolin-5(6H)-ones (42-45a,b), 3-substituted methyl imidazo[1,2-c]quinazolin-5(6H)-ones (50-53a,b), 3-substituted methyl 5H- thiazolo[2,3-b]quinazolin-5-ones (55-56a,b), and 3-substituted methyl 5- (methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (57) were synthesized as compound 1 conformational rigid congeners for pharmacological evaluation as potential α1-adrenoceptor antagonists. Compounds 4, 5, 33a,b, 44a,b, 45a,b, 52a,b, 53a,b, and 57 were found to possess high affinity for the α1- adrenoceptor. Compounds 5 and 57 were the most highly selective and potent α1 antagonists with K(i) = 0.21 ± 0.02 and 0.90 ± 0.08 nM, respectively. The S-enantiomers of these two compounds (K(i) = 0.13 ± 0.01 nM for (S)-(- )-5; K(i) = 1.0 ± 0.2 nM for (S)-(+)-57) were 144-200-fold more potent than the R-enantiomers (K(i) = 26 ± 8 nM for (R)-(+)-5; K(i) = 144 ± 23 nM for (R)-(-)-57). Compound 4 showed 8-fold higher affinity to α1A-AR better than α1B-AR. These compounds possessed weak to no activity against the 5-HT1A receptor.
Chern, Ji-Wang,Tao, Pao-Luh,Wang, Kuang-Chao,Gutcait, Alexander,Liu, Shiou-Wen,Yen, Mao-Hsiung,Chien, Shu-Lan,Rong, Jiann-Kuo
p. 3128 - 3141
(2007/10/03)

Molecular rearrangement of sulfur compounds pyrolysis of 2-(n-substituted carboxamidomethylthio) 5-phenyl-1,3,4-oxadiazole derivatives
Pyrolysis of 2-(N-phenyl carboxamidomethylthio) 5-phenyl-1,3,4-oxadiazole at ca 200°C in a sealed tube affords carbon dioxide, hydrogen sulfide, water, benzonitrile, benzamide, aniline, p-aminoacetophenone, indole, thioglycolic acid, 3-phenyl-2-thiohydantoin and 2-mercaptoquinazolinone. Furthermore pyrolysis of 2-(N-p-tolyl carboxamidomethylthio)5-phenyl-1,3,4-oxadiazole give rise to analogous products. A free radical mechanism has been suggested to account for the obtained products.
Atalla,Bakhite,Hussein,Kamal El-Dean
p. 1 - 6
(2007/10/03)

3,1-Benzothiazin-4-ones and 3,1-benzoxazin-4-ones: Highly different activities in chymotrypsin inactivation
3,1-Benzothiazin-4-ones are sulfur analogs of the potent serine protease inactivators of the 3,1-benzoxazin-4-one type, which acylate the serine residue within the active site of the enzymes. A series of 2-amino-3,1-benzothiazinones was synthesized, but these compounds showed only very little inhibitory activity toward chymotrypsin, a model serine protease. Detailed investigations revealed that benzothiazinones and benzoxazinones react with identical mechanisms, but benzothiazinones acylate chymotrypsin with much lower rate constants. Investigations of nonenzymatic hydrolysis showed the benzothiazinones to be intrinsically more stable than benzoxazinones. It was concluded from spectroscopic results, that benzoxazinones are highly activated due to the absence of ester-like resonance. 2-Benzoylamino-4H-3,1-benzoxazin-4-one was found to be a new, highly active chymotrypsin inactivator. In contrast, benzothiazinones were found to be resonance stabilized. The contribution of a resonance structure with an exocyclic oxanion to the overall structure of the benzothiazinones and its nonproductive binding to the active site explained their low reactivity toward chymotrypsin.
Neumann,Guetschow
p. 72 - 88
(2007/10/02)

MOLECULAR REARRANGEMENT OF SULFUR COMPOUNDS. PART V: PYROLYSIS OF MERCAPTOOXADIAZOLE DERIVATIVES
Pyrolysis of 5-phenyl-2-benzylthio-1,3,4-oxadiazole (1) by heating at ca. 250 deg C in a sealed tube gives rise to CO2 , H2S, H2O, benzyl thiocyanate, benzonitrile, benzyl sulfide, aniline, benzamide, benzaldehyde, 2-mercaptoquinazolinone, dibenzyl, stilbene, and tetraphenylthiophene.Furthermore pyrolysis of 5-phenyl-2-phenacylthio-1,3,4-oxadiazole (9) gives analogous results, besides phenacyl thiocyanate.Pyrolysis of 5(2-hydroxyphenyl)-2-benzylthio-1,3,4-oxadiazole (11) gives 2-hydroxybenzonitrile, 5(2-hydroxyphenyl)-1,3,4-oxadiazole-2-thiol, and 2-hydroxybenzamide, in addition to the previous obtained results.The mechanism of these results has been discussed.Key words: Molecular rearrangement; pyrolysis; mercaptooxadiazoles.
Atalla, A. A.,El-Dean, A. M. Kamal,Gaber, A. M.,Radwan, Sh. M.
p. 233 - 240
(2007/10/02)

Polycyclic azines, XXV: 2-amino-3,1-benzothiazin-4-ones: Synthesis, Dimroth-Rearrangement to quinazolin-4(3H)-on-2(1H)-thiones, and MS/MS-fragmentation
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Leistner,Gutschow,Stach
p. 857 - 862
(2007/10/02)

A FACILE PREPARATION OF 3-SUBSTITUTED 2-THIOXO-TETRAHYDROQUINAZOLIN-4-ONES BY THE REACTION OF ANTHRANILAMIDE WITH ISOTHIOCYANATES
3-Substituted 2-thioxo-tetrahydroquinazolin-4-ones (4a-d) can be synthesized in a convenient procedure directly by a treatment of anthranilamide with isothiocyanates at room temperature.However, anthranilamide was reacted with 4-isothiocyanato-1-benzylpiperidine (2e) leading to the formation of 2-thioureidobenzamide (3e) which was subsequently cyclized to 4e under a basic condition.
Chan, Chao-Han,Shish, Fang-Jy,Liu, Kang-Chien,Chern, Ji-Wang
p. 3193 - 3196
(2007/10/02)

Photochemical Reactions of Pyrimidinethiones with Alkenes
Photochemical addition reactions of pyrimidinethiones and related compounds with alkenes have been examinated.Irradiation of pyrimidine-4(3H)-thiones (1a) in the presence of electron-poor alkenes gave the 4-mercaptoalkylated pyrimidines (5), whereas irradiation of (1a) in the presence of electron-rich alkenes gave 4-alkylthiopyrimidines (6).Irradiation of quinazoline-4(3H)-thiones (1c-e) and electron-poor alkenes gave 4-subtituted quinazolines (9) and (10).This ready mode of carbon-carbon bond formation provides an efficient and novel method for alkylation of pyrimidine rings.
Nishio, Takehiki,Fujisawa, Masaru,Omote, Yoshimori
p. 2523 - 2530
(2007/10/02)

Synthesis of Substituted Thiazoloquinazolines
1,2-Dihydro-5H-thiazoloquinazolin-5-ones with carboxy, carbmethoxy or carbethoxy group in position 2 (IX) have been synthesised by the condensation of ethylanthranilatethiocyanate (I) as well as 2-mercapto-4-ketotetrahydroquinazoline (III) with α,β-dibromopropionic acid or its esters (IV).The products by both the routes have been found to be identical.The structure has been established on the basis of analysis and pmr of one of the compounds.
Gakhar, H. K.,Kiran, Sushma,Gupta, Shashi Bhushan
p. 666 - 667
(2007/10/02)

REACTIONS OF N-BENZOYL ISOTHIOCYANATE WITH ANTHRANILIC ACID AND METHYL ANTHRANILATE
N-Benzoyl-N'-(2-carboxy- and -2-methoxycarbonylphenyl)thioureas have been obtained by the reaction of N-benzoyl isothiocyanate with anthranilic acid and methyl anthranilate, respectively.Kinetics of cyclization of these compounds into 2-mercapto-3,4-dihydro-4-quinazolone have been studied in water and in methanol.In the base-catalyzed cyclization of N-benzoyl-N'-(2-carboxyphenyl)thiourea the proper cyclization is preceded by solvolysis of the benzoyl group.In the case of N-benzoyl-N'-(2-methoxycarbonylphenyl)thiourea the reaction rate is limited by the base-catalyzed cyclization of the starting benzoyl derivative; the benzoyl group is split off in a subsequent rapid step.
Kavalek, Jaromir,Kotyk, Milan,El Bahaie, Said,Sterba, Vojeslav
p. 246 - 255
(2007/10/02)