Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators

Hardtmann, Goetz E.; Koletar, G.; Pfister, Oskar R.; Gogerty, John H.; Iorio, Louis C.

doi:10.1021/jm00239a001

Cited by 42 publications

(14 citation statements)

References 2 publications

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“…In combination with the 2-chloroethylamino grouping, they form novel 2-chloroethylphosphamides chemically related to cyclophosphamide, [10] one of the most common cancerostatics today. Although a number of N-substituted anthranilamides are already known, [11] we intended to synthesize a series of N-methylanthranilamides containing either a quincorine or quincoridine unit as a bulky, functionalized substituent.…”

Section: Results and Discussion A) N-methylanthranilamidesmentioning

confidence: 99%

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Unusual Stabilization of 1,2‐Diamino Derivatives of Quincorine and Quincoridine by Carbon Dioxide: Persistent Crystalline prim‐Ammonium‐Carbamate Salts and Their Reactivity towards Isatoic Acid Anhydride

Neda¹,

Kaukorat²,

Fischer

2003

Eur J Org Chem

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The reaction of N‐methylisatoic anhydride 1 with a series of quincorine (QCI) and quincoridine (QCD) derivatives furnished the corresponding QCI‐ and QCD‐substituted anthranilic acid amides 4−9. In the synthesis of 4−9, we investigated the influence of the C5 substituent of 2‐aminomethyl derivatives of QCI and QCD on their basicity and polarity and, therefore, on their reactivity towards isatoic acid anhydride. By exposing a number of 2‐aminomethyl derivatives of QCI and QCD to (carbon dioxide from) air, the formation of carbon dioxide adducts 10−15 was observed. In an unusual reaction, we obtained the first set of chiral ammonium carbamates derived from primary amines, which provides a convenient method for purifying and stabilizing aminomethyl derivatives of QCI and QCD. All compounds were fully characterized by spectroscopic methods. In addition, the structure of 11 was proved by X‐ray crystal structure determination. The heterocyclic nitrogen atoms display trigonal‐pyramidal coordination geometries; the amido group is essentially planar. N‐2′ of the ammonium ion is a triple hydrogen bond donor to the carboxylato oxygen atoms of three different carbamate anions. The resulting net effect is a hydrophilic plane parallel to the ab plane. The crystal packing involves six classical hydrogen bonds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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Section: Results and Discussion A) N-methylanthranilamidesmentioning

confidence: 99%

“…[11] By reaction of 1 with the aminomethyl derivatives of QCD and QCI (2aϪc and 3aϪc), we synthesized the corresponding anthranilamides 4Ϫ9 (Scheme 2). Scheme 2 The course of the reaction was followed easily by monitoring the evolution of carbon dioxide.…”

Section: Results and Discussion A) N-methylanthranilamidesmentioning

confidence: 99%

Unusual Stabilization of 1,2‐Diamino Derivatives of Quincorine and Quincoridine by Carbon Dioxide: Persistent Crystalline prim‐Ammonium‐Carbamate Salts and Their Reactivity towards Isatoic Acid Anhydride

Neda¹,

Kaukorat²,

Fischer

2003

Eur J Org Chem

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“…and spectroscopic data (IR, 1 H and 13 C NMR) which are in good agreement with the reported values. These data are provided below in order of their entries in Table 1 as 7,64.1,55.3,28.9,26.8,23.7,19.9. N,.…”

Section: General Procedures For Condensation Of Amine and Carbon Disulmentioning

confidence: 99%

A simple and green procedure for the synthesis of N,N'-disubstituted thioureas on the surface of alumina under microwave irradiation

Ranu¹,

Dey²,

Bag³

2003

Arkivoc

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“…A literature survey revealed that imidazo [2,1-b]quinazolinones, imidazo [4,5-c]quinolin-4(5H)-one derivatives exhibited potent bronchodilatory activites [3,4]. Recent reports from these laboratories also indicate that fused heterocyclic quinazolinone ring systems exhibit potent bronchodilatory activity [5−7].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Evaluation and Structure-Activity Relationships of 5-Alkyl-2,3-dihydroimidazo[1,2-c]quinazoline, 2,3-Dihydroimidazo[1,2-c]quinazolin-5(6H)-thiones and their Oxo-analogues as New Potential Bronchodilators

Bahekar

Rao

2011

Arzneimittelforschung

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With an aim to obtain potent bronchodilators, two series of 5-alkyl-2,3-dihydroimidazo[1,2-c]quinazolines (Va-1), 2,3-dihydroimidazo[1,2-c]quinazolin-5-(6H)-thiones (VIIIa-d) and their oxo-analogues (IXa-d) have been designed. The compounds Va-1 were synthesized by two alternative routes. The former (Method A) based on the dehydrocyclization of 4-(1-hydroxyethyl)-aminoquinazoline (IV) and the latter (Method B) involves the usage of 2-aminobenzonitrile (VI) which on reaction with ethylenediamine leads to the formation of the key intermediate 2-(2-aminophenyl)-4,5-dihydro-1H-imidazoles (VII). Finally the intermediate VII on condensation with different acidanhydrides yielded the title compound V. In general method-A resulted the compound V in quantitatively higher yields. 2,3-Dihydroimidazo[1,2-c]quinazolin-5 (6H)-thiones (VIII) were obtained by condensing VII with carbon disulfide and a further oxidation of VIII gave their corresponding oxo-analogues (IX). The title compounds V, VIII and IX were evaluated for their bronchodilator activity using in vitro and in vivo (standard animal models) methods. All the test compounds exhibited bronchodilatory activity. The structure activity relationship studies indicated good correlation between the nature of the substituent and bronchodilatory activity. In the 5-alkyl substituted compounds V, a longer alkyl chain showed higher bronchodilatory activity. Compounds VIII and IX were found to be less potent and replacement of sulphur with oxygen showed no significant effect on the biological activity. The presence of halogens altered the biological activity in both the series. Among the compounds tested, 9-lodo-5-(n-propyl)-2,3-dihydroimidazo[1,2-c]quinazoline (VI) was found to be the most potent (percentage protection = 87.1%; relative activity = 1.1 compared to the standard aminophylline).

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Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators

Cited by 42 publications

References 2 publications

Unusual Stabilization of 1,2‐Diamino Derivatives of Quincorine and Quincoridine by Carbon Dioxide: Persistent Crystalline prim‐Ammonium‐Carbamate Salts and Their Reactivity towards Isatoic Acid Anhydride

Unusual Stabilization of 1,2‐Diamino Derivatives of Quincorine and Quincoridine by Carbon Dioxide: Persistent Crystalline prim‐Ammonium‐Carbamate Salts and Their Reactivity towards Isatoic Acid Anhydride

A simple and green procedure for the synthesis of N,N'-disubstituted thioureas on the surface of alumina under microwave irradiation

Synthesis, Evaluation and Structure-Activity Relationships of 5-Alkyl-2,3-dihydroimidazo[1,2-c]quinazoline, 2,3-Dihydroimidazo[1,2-c]quinazolin-5(6H)-thiones and their Oxo-analogues as New Potential Bronchodilators

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