Evaluation of Physicochemical Properties of Glacial Acetic Acid Mediated Solvent Free One Pot Synthesis of 1, 5-Benzodiazepines and Its Chloroacetylated Derivatives (original) (raw)
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Bioorganic Chemistry, 2020
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Synthesis of novel heterocyclic compounds containing 1, 5-benzodiazepine
Benzodiazepines, from the pharmacological standpoint, are very interesting molecules. Numerous studies have demonstrated anxiolytic effect on the human nervous system. They are used in the therapeutic field 1 and have important biological activities, particularly the 1,4-and 1,5-benzodiazepines 2. Benzodiazepines are also used as anticonvulsant agents 3 , anti-inflammatory and analgesic 4 , antidepressive of the central nervous system 5 and antibacterial 6. For instance, Valium (diazepam) is marketed as a sedative and noveril (dibenzepin) as an antidepressive. The strategy of using benzodiazepines essentially depends on the knowledge of their pharmacokinetics that can take advantage of their "qualities" but also to avoid some of their "side effects". In addition, benzodiazepines are the most powerful anticonvulsant substances known so far: they are able of antagonize, common amongst animal, convulsions induced by a wide variety of chemical substances e.g., isoniazid, picrotoxin, strychnine, pentetrazole. On the other hand, they are less effective in protecting seizures due to electric shock 7. Synthesis of 1,5-benzodiazepines structures were made from different lactones, such as tetronic acid, 4-hydroxy coumarin, demidone and dehydroacetic acid 8. It therefore seemed interesting to carry on further research by investigating the reactivity of the dehydroacetic acid and its derivatives which are susceptible to serve as starting material for the synthesis of other heterocyclic compounds such as benzodi
Synthesis, Pharmacological, and Biological Screening of Novel Derivatives of Benzodiazepines
Journal of Heterocyclic Chemistry, 2014
In the present study a new series of 4-substituted phenyl-6-(pyridin-2-yl)pyrimidin-2-ol (1-9) and 4-substituted phenyl-6-(pyridin-2-yl)pyrimidin-2-thiol (10-18) have been synthesized by cyclizing 3-substituted phenyl-1-(pyridin-2-yl)prop-2-en-1-one with urea/thiourea in the presence of NaOH as base (1a-18a). 3-Substituted phenyl-1-(pyridin-2-yl)prop-2-en-1-one was prepared by condensing 2-acetylpyridine with substituted benzaldehyde in the presence of 20 % NaOH as base. The structures of the newly synthesized compounds were characterized by elemental analysis, IR, 1 H NMR, 13 C NMR, and mass spectroscopic studies. Newly synthesized compounds were screened for their anti-inflammatory, analgesic, cytotoxic, and antitubercular activities studies. Few of the compounds exhibited excellent anti-inflammatory activities compared to standard drug diclofenac sodium. Some compounds have shown moderate analgesic activities compared to standard drug pentazocine. Also, some compounds have exhibited moderate cytotoxic and antitubercular activities.
American Journal of PharmTech Research, 2020
The presence of recurrent seizures is responsible for epilepsy, further which has been characterized in the era. A seizure can be mention as "an episodic disturbance of movement, feeling, or consciousness caused by sudden synchronous, inappropriate, and excessive electrical discharges in the cerebral cortex" 1. Epileptic convulsions are expected to have negative consequences on the patient's psychological and social life such as relationships, education and employment. Uncontrolled seizures are associated with physical and psychosocial morbidity, dependent behavior, poor quality of life and an increased risk of sudden unexpected death. The heterocyclic compound is a potential compound for the development of chemotherapeutic and pharmacotherapeutic agents containing nitrogen and sulphur atoms 2. Therefore the present investigation was made in direction to the synthesis of some newer 1, 5-benzothiazepine derivatives and their evaluation for anticonvulsant activity. Physicochemical and elemental analysis of all the 1, 5-benzothiazepine (1B-10B) is confirmed with a preliminary study like melting point, elemental analysis and hyphenated tool namely IR, NMR and Mass spectroscopy. Firstly Primarily, α,βunsaturated carbonyl compounds or chalcones were prepared by the well-known Claisen-Schmidt condensation of acetophenones and substituted aldehyde by using alcoholic KOH (10%) at room temperature. By adding diazonium salt in substituted chalcone ,substituted diazonium chalcone was prepared. A yield mixture and 0.01 mole of substituted mercapto anilines was dissolved in 2methoxyethanol to get final product 1, 5-benzothiazepine derivatives. These molecules were evaluated for possible anticonvulsant activity. Anti-seizure activities of all synthesized compounds 101B to 110B were explored using MES. The synthesized compounds from (101B to 110B) 108B and 109B had shown significant activity against the tonic seizure as compared to the other synthesized compounds.
Recent advances in synthesis and medicinal chemistry of benzodiazepines
Bioorganic Chemistry, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Indo American Journal of Pharmaceutical Research, 2013
Pyridine and its derivatives have been observed intensively active biodynamically. Which is presented in this work. Pyridine derivatives have also been synthesized with the help of nucleophilic substitution reactions. The constitutions of the synthesized derivatives have been characterized with the help of Elemental analysis, IR, 1H NMR, 13C and MS. All the newly synthesized compounds were screened for antibacterial and antifungal activities (MIC) in vitro by both dilution method with two Gram positive bacteria (S. Aureus MTCC 96 and S. pyogenes MTCC 442), two Gram negative bacteria (E. Coli MTCC 443 and P. aeruginosa MTCC 1688) and fungi A. Niger MTCC 282.
Convenient synthesis of novel tetrahydro-1,5- benzodiazepine amide oximes
2006
The pharmacological importance of substituted 1,4and 1,5-benzodiazepines has been well established and some derivatives are known as anxiolytic, anticonvulsant, antihypnotic agents [1–3]. In recent years, much effort has been taken in the benzodiazepine area to develop new members of this family. Among the new compounds, antagonists of the polypeptidic cholecystokinine receptors have been established [4, 5]. The synthesis of benzodiazepine derivatives with heterocyclic rings annealed to the “a”, “c”, “d” sides of heptatomic system has also attracted interest of several research groups. Such derivatives are known to possess antiviral (HIV-1) activity [6, 7]. In previous papers [8, 9] we have reported a cyclofunctionalization strategy of 1,5-benzodiazepine system, which exploited the reactivity of the thioxo group of the corresponding derivatives. As a continuation of our investigations on tricyclic benzodiazepines, we have extended this strategy to develop a synthetic pathway towards...
Synthesis of 1,4-Benzodiazepine- 2,5-dione Derivatives
HETEROCYCLES, 2002
A synthesis of a series of 1,4-benzodiazepine-2,5-dione derivatives with a carboxy group at the 3-position is realized in good yields by using methyl malonylchloride as a key reagent and intramolecular nucleophilic substitution as ring closure reaction. 1,4-Benzodiazepine-2,5-dione (BZD) and its derivatives whether it is natural 1,2 or synthetic 3,4,5 represent one of the most important bioactive molecules. The BZD systems exhibit bioactivities such as anticonvulsant, 3 anxiolytic, 4 antitumor 1,5 pain releasing, 6 platelet aggregation inhibiting 7,8 and even anti-AIDS activities. 9 It was recently reported that 10,11 the human receptor ET A subtype is selective to endothelin-1 (ET-1), a 21 amino acid peptide. ET-1 exhibits profound endogenous vasoconstriction and mitogenic activities. Antagonism on the vasoconstrictor endothelin is a potential new approach to the treatment of a variety of human diseases including ischemia, hypertension, congestive heart failure, pulmonary hypertension and subarachnoid hemorrhage. In the process of searching for the non-peptide antagonists selective for ET A and ET B receptors, it was found by Elliott 12 that two phenyls on the indane derivative SB 209670 (Figure 1) are restricted dipeptide mimetic to Try-13 and Phe-14 of ET-1. By molecular modeling, we have found that the N-phenyl and N-benzyl group of the BZD ring can be a perfect match to the two phenyls of SB209670. Thus it is possible that compound (1) (Scheme 3) and its derivatives may serve as alternative candidates for the non-peptide antagonists of ET A. Many efforts have been devoted toward the synthesis of this bioactive BZD and its derivatives. 9,13-15 For example, Keating and Armstrong recently published 3 a new synthetic method for BZD by using rearrangement (Scheme 1). In a primary attempt (Scheme 2), the N-benzylisatoic anhydride (2) was reacted with aniline to afford the amide (3). Then 3 was reacted with dimethyl chloromalonate to give 4. However, cyclization to seven membered ring by intramolecular amide formation to 5 from 4 was not successful.