Originator
Darbid,SKF,US,1957
Definition
ChEBI: Isopropamide iodide is a diarylmethane.
Manufacturing Process
γ-Diisopropylamino-α,α-diphenylbutyronitrile (60 g) was added in several
portions to a mixture of sulfuric acid (150 ml) and water (15 ml) and the
solution was heated 3% hours on the steam bath and then poured on ice and
made basic with NH4OH. The γ-diisopropylamino-α,α-diphenylbutyramide
precipitated as a solid, which was taken up in methylene chloride from an
aqueous slurry. The methylene chloride was separated and dried by filtering
through anhydrous K2CO3. The solvent was removed by distillation, leaving
the amide which was crystallized from Skellysolve B five times and found then
to have MP 87.0° to 88.5°C.
γ-Diisopropylamino-α,α-diphenylbutyramide in propanol was refluxed 4 hours
in the presence of excess methyl iodide. Upon dilution of the solution with
ethyl acetate (100 ml per 50 ml isopropyl alcohol) and cooling γ-
diisopropylamino-α,α-diphenylbutyramide methiodide precipitated, was
collected by filtration and recrystallized (9.0 g) by dissolving in a hot mixtureof 100 ml isopropyl alcohol and 10 ml methanol and then diluting with 90 ml
Skellysolve B, to give 8.3 g recrystallized product, MP 182° to 184°C.
Brand name
Darbid (GlaxoSmithKline).
Therapeutic Function
Spasmolytic
General Description
Isopropamide iodide, 3-carbamoyl-3,3-diphenylpropyl)diisopropylmethylammoniumiodide (Darbid), occurs as a bitter, white to pale yellow, crystallinepowder that is only sparingly soluble in water butfreely soluble in chloroform and alcohol.
This drug, introduced in 1957, is a potent anticholinergic,producing atropine-like effects peripherally. Even with itsquaternary nature, it does not cause sympathetic blockade atthe ganglionic level except at high dosages. Its principal distinguishingfeature is its long duration of action. A singledose can provide antispasmodic and antisecretory effects foras long as 12 hours.
Clinical Use
ISOPROPAMIDE IODIDE is used as adjunctive therapy in the treatment of pepticulcer and other conditions of the GI tract associated withhypermotility and hyperacidity. It has the usual side effectsof anticholinergics (dryness of mouth, mydriasis, difficulturination) and is contraindicated in glaucoma, prostatic hypertrophy,etc.
Synthesis
Isopropamide, (3-carbamoyl-3,3-diphenylpropyl)di-iso-propylmethyl
ammonium iodide (14.1.25), is synthesized by alkylating diphenylacetonitrile with di-isopropylaminoethylchloride in the presence of sodium amide, and the subsequent hydrolysis
of the nitrile group of the resulting compound (14.1.23) to an amide group (14.1.24).
Alkylation of this compound with methyliodide gives isopropamide (14.1.25) [19¨C22].
