Bendamustine hydrochloride

Bendamustine hydrochloride is a DNA cross-linking agent that causes DNA breaks, with alkylating and antimetabolite properties.

Bendamustine is a parenterally administered alkylating agent used alone and in combination with other antineoplastic agents in the treatment of chronic lymphocytic leukemia and refractory forms of non-Hodgkin lymphoma. Bendamustine therapy is associated with minor transient serum enzyme elevations during treatment and to rare instances of clinically apparent liver injury, with jaundice generally arising as a part of a generalized hypersensitivity syndrome. Bendamustine also has potent immunosuppressive activity and can cause reactivation of chronic hepatitis B that can be severe and even fatal.|Bendamustine Hydrochloride is the hydrochloride salt of bendamustine, a bifunctional mechlorethamine derivative with alkylator and antimetabolite activities. Bendamustine possesses three active moieties: an alkylating group; a benzimidazole ring, which may act as a purine analogue; and a butyric acid side chain. Although its exact mechanism of action is unknown this agent appears to act primarily as an alkylator. Bendamustine metabolites alkylate and crosslink macromolecules, resulting in DNA, RNA and protein synthesis inhibition, and, subsequently, apoptosis. Bendamustine may differ from other alkylators in that it may be more potent in activating p53-dependent stress pathways and inducing apoptosis; it may induce mitotic catastrophe; and it may activate a base excision DNA repair pathway rather than an alkyltransferase DNA repair mechanism. Accordingly, this agent may be more efficacious and less susceptible to drug resistance than other alkylators.|A nitrogen mustard compound that functions as an ALKYLATING ANTINEOPLASTIC AGENT and is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA and NON-HODGKIN'S LYMPHOMA.

HBI-ethylbutyrate (molecular weight = 349.42 g/mol) was dissolved in CHCICharge 600 ml lot I dichloromethane in round bottom flask at 25-30° C. and then charge stage E product. Slowly add 24 ml Thionyl chloride drop wise below 30° C. (exothermic reaction). Raise the temperature to 55-60° C. and maintained for 2 hrs. Cooled the reaction mass to 25-30° C. Added 400 ml of dichloromethane. Added 200 ml lot I purified water and separated the layer. Combined the organic layer and wash it with 200 ml saturated sodium bicarbonate solution. Combined the organic layer and wash it with 200 ml saturated sodium chloride solution. Settle and separated the layer. Combined the organic layer and dry it over sodium sulphate. Distill out the reaction mass under vacuum at 40° C. upto one volume. Then added 370 ml N-heptane into the reaction mass and stirred for 2 hrs at room temperature. Filter the reaction mass and washed it with 10 ml N-heptane and suck dried for 1 hr. Taken the insitu mass in round bottom flask and added 40 ml dilute hydrochloric acid into the reaction mass. Slowly heat the reaction mass to 55-60° C. Maintained for 7-8 hrs (checking and confirming the impurity profile). Cool the reaction mass to room temperature and stir for 3-4 hrs. Filter the reaction mass and wash it with 2 ml chilled water. [0174] Again Charge crude Bendamustine Hydrochloride monohydrate isolated in the wet stage in round bottom flask containing 136 ml purified water and 40 ml hydrochloric acid (Preparation of bendamustine hydrochloride. 4-{5-[Bis-(2- chIoroethyl)amino]-1-methyl-1 H-benzimidazol-2-yl}-butyric acid isopropyl ester (3 g) is charged into a round bottom flask and 50percent hydrochloric acid solution (21 mL) is slowly added. The mixture is heated to 35-40°C, maintained for about 90 minutes, and concentrated under vacuum at about 55-58°C, to give a viscous mass. Warm water (12 mL, 55-60°C) is added and the mixture is stirred for about 1 hour. The obtained solid is collected by filtration, , washed with water (3 mL), and dried under vacuum at 45-50°C for 4 hours to give bendamustinehydrochloride. Yield: 2.2 g (75percent).

alkylating agent recently approved by the FDA for treatment of Chronic Lymphocytic Leukemia

Molecular Weight:394.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:9
Exact Mass:393.077760
Monoisotopic Mass:393.077760
Topological Polar Surface Area:58.4
Heavy Atom Count:24
Complexity:380
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes