Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
  • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
  • A61K51/04—Organic compounds
  • A61K51/0493—Steroids, e.g. cholesterol, testosterone
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2121/00—Preparations for use in therapy

Definitions

• This invention relates to 19-halocholesterols which can be utilized as fat producing agents and intermediates in the preparation of radioiodinated cholesterol which 10- calizes in the adrenal cortex to provide a definitive scan of this organ.
• This end product when injected into a patient localizes in the adrenal cortex and allows a radiologist to obtain a scan of the organism as its uptake ratio here is greater than in the adrenal per se. Scans of the organ utilizing known techniques would then enable a practitioner ot visualize anatomical and functional differences in the adrenal gland, e.g., adrenocortical carcinomas, cushings syndrome.
• the amount of the iodocholesterol to be utilized in each patient is determined by known procedures as the amount of radioactivity will determine the volume amount to be injected into a patient. Therefore, from 0.1 mCi. to 10 mCi. per dose with from about 0.5 mCi. to about 5 mCi. is the preferred range.
• the 19-ha1ocholesterols of this invention have the structure I:
• X is chloro, bromo, iodo or fluoro and R is hydrogen or acyl.
• the preferred acyl radicals are those of hydrocarbon carboxylic acids of less than twelve carbon atoms, as exemplified by the lower alkanoic acids (e.g., acetic, propionic butyric and pivalic acid), the lower alkanoic acids, the monocyclic aryl carboxylic acids (e.g., benzoic and toluic acids), the monocyclic aryl lower alkanoic acids (e.g., phenacetic and fi-phenylpropionic acid), the cycloalkane carboxylic acids and the cycloalkene carboxylic acids.
• the lower alkanoic acids e.g., acetic, propionic butyric and pivalic acid
• the monocyclic aryl carboxylic acids e.g., benzoic and toluic acids
• the compounds of this invention are prepared by reacting cholest-5-ene-3,l9-diol-3-acyl with a sulfonyl halide in an organic base such as pyridine.
• a sulfonyl halide is the preferred reactant, however, other sulfonyl halides such as methane sulfonyl bromide, ethoxy phenyl sulfonyl chloride and p-bromo phenyl sulfonyl chloride, and so forth, can be utilized.
• a tosylate of the structure H is thus formed:
• the acyl group is then hydrolyzed by utilizing a basic solution of an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide, and so forth; or other known means of hydrolyzing the 3-position of cholesterol as by utilizing an alkali metal carbonate or bicarbonate (e.g., sodium carbonate, potassium bicarbonate, etc.), an alkali metal (e.g., powdered sodium, potassium, etc.) or an alkali metal hydride (sodium hydride, potassium hydride, etc.).
• an alkali metal carbonate or bicarbonate e.g., sodium carbonate, potassium bicarbonate, etc.
• an alkali metal e.g., powdered sodium, potassium, etc.
• an alkali metal hydride sodium hydride, potassium hydride, etc.
• the hydroxide thus formed has the structure 111:
• the l9-iodo compounds of this invention can be labeled by isotope exchange of the compounds as by reaction with alkali metal halide, sodium iodide-125, potassium iodide- 131, and so forth.
• isotopes- 1 and I may also be placed in the 19-ha1o cholesterol of this invention.
• this position is resistant to dehalogenation in the adrenal and does not markedly alter the structure of the cholesterol molecule. It is to be understood that this compound is to be further utilized as a diagnostic tool in humans.
• the 19-iodocholesterol has the utility set forth above.
• the remaining 19-halocholesterol compounds of this instant invention have been found to increase the fat content in animals.
• a farm animal e.g., sheep, cattle, pigs, and so forth
• the injection can be administered as deemed necessary but for best results injection of a steroid of this invention should be within the first 6 months after birth.
• EXAMPLE 7 Twenty-six mongrel dogs weighing 7 to 13 kilograms are injected intravenously with 19- I-chloesterol. Ten to 90 ,aCL/kg. weight of the compound were administered to 13 dogs pretreated with 40 units of adrenal corticaltropic hormone gel daily for 2 to 4 days and continued to termination of the study period. The various daily intervals up to 8 days after the tracer dose scans were performed on the dogs and the results are as indicated in Table I.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Optics & Photonics (AREA)
• Physics & Mathematics (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Steroid Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

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ID=22124601

Family Applications (1)

Country Status (7)

Cited By (9)

Families Citing this family (1)

• 1970
  • 1970-09-24 US US00075269A patent/US3784576A/en not_active Expired - Lifetime
• 1971
  • 1971-09-24 GB GB4468771A patent/GB1353038A/en not_active Expired
  • 1971-09-24 CA CA123,635,A patent/CA951311A/en not_active Expired
  • 1971-09-24 CH CH1399771A patent/CH550587A/fr not_active IP Right Cessation
  • 1971-09-24 DE DE19712147849 patent/DE2147849A1/de active Pending
  • 1971-09-24 FR FR7134516A patent/FR2107954B1/fr not_active Expired
  • 1971-09-24 HU HURE507A patent/HU166763B/hu unknown

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