FIELD OF INVENTION

[001] The present invention concern with the design and synthesis of a novel heterocyclic bismuthine and characterized by Melting point, Elemental analysis along with spectral techniques. The synthesized compound show prominent biomedicinal activity.

[002] More particularly, the present invention relates a novel heterocyclic bismuthine compound for bio-medicinal application and method of synthesis thereof.

BACKGROUND & PRIOR ART

[003] The subject matter discussed in the background section should not be assumed to be prior art merely as a result of its mention in the background section. Similarly, a problem mentioned in the background section or associated with the subject matter of the background section should not be assumed to have been previously recognized in the prior art. The subject matter in the background section merely represents different approaches, which in-and-of-themselves may also be inventions.

[004] As per the latest research data about 85% of the compounds involved in various organic synthesis focusing on the medicinal drugs comprises of the heterocyclic moieties. Amidst the devastating effects implicated by the corona virus covid -19 the compound hydroxychloroquine which belongs to the heterocyclic compounds has been successful to some extent in providing relief against the viral disease. Thus the exploration of the heterocyclic scaffold as a powerful tool in the realms of clinical medicine is all the more significant today.

[005] The organobismuth compounds have also attracted the attention in this area owing to their microbiological and gastroprotective utility. It was found that organobismuth compounds were active against the treatment of gastrointestinal disorders like dyspepsia, diarrhea and in peptic ulcers by inhibiting E. coli. The salts of organobismuth compounds, such as colloidal bismuth sub-salicylate (CBS), bismuth sub-citrate (BSC) and ranitidine bismuth citrate (RBC) are now common for controlling bacterial and fungal infections. The ranitidine bismuth citrate, used as H2 antagonist is an analog of histamine which involve in the control of gastric secretion.

[006] The major advantage of bismuth compounds is their less toxicity and the Bi-C bond is biodegradable. The extensive chemical, biochemical, biomedicinal and pharmacological studies of bismuth compounds have enabled the medical applications of clinically used bismuth compounds to be extended. Bismuth compounds offer potentials in gastro-protection and cancer therapy not only by directly but also by indirectly reducing the side-effect of the clinically used antiulcer and anticancer drugs.

[007] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[008] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.

[009] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context.

[0010] The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0011] The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.

OBJECTIVE OF THE INVENTION

[0012] The principle objective of the present invention is to provide novel heterocyclic compound and method of synthesis thereof.

[0013] The principle objective of the present invention is to provide novel heterocyclic compound and method of synthesis thereof.

SUMMARY

[0014] The present invention discloses a novel heterocyclic bismuthine compound for bio-medicinal application and method of synthesis thereof.

[0015] An aspect of the present disclosure relates to a method for synthesis of a novel heterocyclic bismuthine compound for bio-medicinal application, wherein the method comprising steps of: preparing of tris(p- aminophenyljbismuth through steps comprises of adding solution of bismuth trichloride (O.lmol) and bromoaniline (O.lmol) in benzene (200 ml) drop wise to a boiling suspension of sodium in the same solvent, reflexing of obtain mixture for some hours with occasional shaking and then filtered ho, & performing distilled off after extraction of the residue with hot benzene; preparing of bis(p-aminophenyl)bismuth(iii)chloride through steps comprises of use of metal halides and an organometallic compound in presence of or in absence of an appropriate solvent (neat/without solvent); adding 2-((4-((7-chloroquinolin-4- ylamino)pentyl)(ethyl)amino)ethanol (lmmol) in the stirring solution of bis(p-aminophenyl)bismuth(iii)chloride(0.1mmol), in presence of triethylamine in benzene ; and stirring anhydrous oxygen free, nitrogen conditions for some hours , followed by refluxing for some hours to ensure completion of the reaction.

BRIEF DESCRIPTION OF DRAWINGS

[0016] To clarify various aspects of some example embodiments of the present invention, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings. It is appreciated that these drawings depict only illustrated embodiments of the invention and are therefore not to be considered limiting of its scope. The invention will be described and explained with additional specificity and detail through the use of the accompanying drawings.

[0017] In order that the advantages of the present invention will be easily understood, a detailed description of the invention is discussed below in conjunction with the appended drawings, which, however, should not be considered to limit the scope of the invention to the accompanying drawings, in which:

[0018] Figure 1 shows diagram of chemical reaction of method of synthesis for novel heterocyclic compound a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention.

[0019] Figure 2 shows structure of a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention. [0020] Figure 3 shows IR SPACTRA & NMR SPECTRA analysis of a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention.

[0021] Figure 4 shows Molecular Docking Studies of a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention.

DETAIL DESCRIPTION

[0022] .The present invention disclosure is related to a novel heterocyclic bismuthine compound for bio-medicinal application and method of synthesis thereof.

[0023] Figure 1 shows diagram of chemical reaction of method of synthesis for novel heterocyclic compound a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention.

[0024] Although the present disclosure has been described with the purpose of a novel heterocyclic bismuthine compound for bio-medicinal application and method of synthesis thereof, it should be appreciated that the same has been done merely to illustrate the invention in an exemplary manner and to highlight any other purpose or function for which explained structures or configurations could be used and is covered within the scope of the present disclosure.

[0025] Novel Synthesis:

[0026] Different L.R. Grade solvent (BDH, SISCO, E. Merck and RANBAXY) were used. Solvent purified and dried by conventional methods prior to their use. [0027] The L.R. grade of Liquid amines, alcohols, benzenes etc of CDH and SISCO were used without purification.

[0028] All other chemicals (CDH, SISCO, E. Merck and RANBAXY) used, were prior checked for their purities.

[0029] The physiochemical techniques employed viz. melting point, elemental analysis for carbon, hydrogen, nitrogen, infra-red (IR), mass and nuclear magnetic resonance (NMR) spectra for characterization and structure determination of compounds are performed by standard methods.

[0030] The melting points for the synthesized compounds were determined in open glass capillary tubes using a Khera instruments model no RI214 (220Volt/watt) melting point apparatus.

[0031] The infrared (IR) spectra of the compounds were recorded in region 4000- 400 cm ¹ using KBr discs a Perkin-Elmer (Grating) spectrophotometer model

337 at Umversity of Lucknow, Lucknow.

[0032] The nuclear magnetic resonance (NMR) studies were carried out on at 800 MHz NMR Spectrometer (Make: Bruker GmbH, Germany Model: AVANCE III equipped with Cryoprobe) at Center of Biomedical Research (CBMR) SGPGI,

Lucknow using CDC1 ₃ or DMSO as solvent. In all the cases trimethylsilane (TMS) were used as an internal indicator and the values of chemical shift were given in d-scales.

[0033] Mostly, all compounds were dried finally in vacuum desiccators.

[0034] The molecular docking studies were perfomed by standard software of computational studies.

[0035] Novel Route of Synthesis: 1. Preparation of Tris(/>-aminophcn l)hismuth: A solution of bismuth trichloride (O.lmol) and bromoaniline (O.lmol) in benzene (200 ml) was added drop wise to a boiling suspension of sodium (0.6mol) in the same solvent (300 ml). The reaction mixture was refluxed for 5 hr with occasional shaking and then filtered hot. The residue was extracted twice with hot benzene. The solvent was completely distilled off and the remaining residue was recrystallised from alcohol/pet-ether (60-80°) mixture. Yield - (78%)

2. Preparation of bis(p-aminophenyl)bismuth(III)chloride: This reaction involves the use of metal halides and an organometallic compound in presence of or in absence of an appropriate solvent (neat/without solvent). The formation of the compounds can be represented in the form of equation shown below.

2R ₃ Bi + BiCl ₃ > 3R ₂ BiCl

Tris (p-aminophcnvl) bismuth (2mmol) and bismuth trichloride (lmmol) on mixing followed by shaking are rapidly liquefied and redistribution was completed in about three hour at 25°C. The off white color viscous oil of the compound was crystallized from dichloromethane and diethyl ether.

3. Complexation Reaction: In the stirring solution of bis(p- aminophenyl)bismuth(lll)chloride(0. lmmol), 2-((4-((7-chloroquinolin-4- ylamino)pentyl)(ethyl)amino)ethanol (lmmol) was added in presence of triethylamine (1 ml) in benzene and was stirred in anhydrous oxygen free, nitrogen conditions for 6h, followed by refluxing for 2h to ensure completion of the reaction. A flocculent white precipitate of Et ₃ N.HCl (M.P.240°C) was formed which was filtered off. The fdtrate on concentration gave a light brown solid which was recrystallised by petroleum ether (40°-

60°C).

2-((4-((bis(4-aminophenyl)bismuthino)(7-chloroquinolin-4- yl)amino)pentyl)(ethyl)amino)ethanol Molecular Formula: C ₃₀ H ₃₇ B1CIN ₅ O Molecular weight: 727.25 Melting Point: 166°C

Elemental Analysis: C = 49.49; H = 5.12; N = 9.62;

Figure 2 shows structure of a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention.

Figure 3 shows IR SPACTRA & NMR SPECTRA analysis of a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention.

[0036] Figure 4 shows Molecular Docking Studies of a novel heterocyclic bismuthine compound for bio-medicinal application, according to present invention