Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/13—Amines
  • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
  • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
  • C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
  • C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
  • C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
  • C07C215/32—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton containing hydroxy groups and carbon atoms of two six-membered aromatic rings bound to the same carbon atom of the carbon skeleton

Definitions

• This invention relates to the tertiary amines of 3,3-diphenyl propyl amine compounds of the formula Wherein R is alkyl, for example alkyl having up to 8 carbon atoms, preferably having 28 carbon atoms, for example ethyl, propyl, butyl;
• R and R is each selected from the group consisting of alkyl and cycloalkyl, and preferably each is a lower alkyl or lower cycloalkyl and is a group as is conventionally present in organic amino compounds for therapeutic use and preferably containing up to about 6 carbon atoms, and each of the groups can be, for example, methyl, butyl, ethyl, propyl, isopropyl, isobutyl, secondary butyl, isoamyl, hexyl, isohexyl, and cyclohexyl.
• Preferred products of formula (I) are those wherein R is ethyl, propyl or butyl, especially ethyl.
• Particular compounds found to be well suited for the purposes of the invention are: N,N-dimethyl-2-ethyl-3,3- diphenyl-propene-(Z)-yl-arnine, N,N-dipropyl-2-ethyl-3,3- diphenyl-propene- (2 -yl-amine, N,N-methyl cyclohexyl-2- ethyl-3,3-diphenyl-propene-(2)-yl-amine, and medicinally acceptable acid addition salts of these compounds or other medicinally acceptable salts.
• the compounds of the above formula valuable therapeutic properties which render them useful as vasopressors and in particular for increasing blood pressure, stimulating the heart muscle, accelerating the heart rate and 3,489,760 Patented Jan. 13, 1970 increasing cardiac output. Of outstanding importance is that they diminish or eliminate the undesirable depressive side effects of morphine or respiration.
• the compounds can be used in the form of medically acceptable acid addition salts.
• the vasopressor effect is accomplished by administration of a therapeutic amount of the compound used.
• ethyl-3,3-diphenyl-propene-(2)-yl-amine and medicinally acceptable acid addition salts with hydrochloric, hydrobromic, or hydroiodic acid. Acid addition salts are preferred.
• the salts are crystalline solids which are soluble in water and therefore constitute an advantageous embodiment of this invention.
• the disclosed organic bases form salts with a variety of inorganic and organic acids conventionally used for therapeutic application or organic amino or imino bases and including hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric, citric, lactic, maleic, acetic, benzoic, oxalic and related or similar acids.
• the resulting salt crystallizes out of suitably concentrated solution on chilling or standing or may be precipitated by addition of a solvent, such as ether or benzene in which the salt is insoluble.
• the invention is characterized in that the Leuckart reaction is used for preparation of the compounds.
• the corresponding primary or secondary amine that is, a compound as in Formula I above, except that R and/or R is hydrogen
• the organic acid is formic acid.
• the starting primary or secondary amines can be produced by the methods disclosed in application Ser. No. 231,018, filed Oct. 16, 1962, and now abandoned and assigned to the assignee hereof.
• the residue is made alkaline, extracted with ether, and the separated ether part, dried with sodium sulfate, and distilled.
• the residue is dissolved in methanolic hydrochloric acid and through addition of ether is obtained the N,N-dipropyl-Z-ethyl-3,3- diphenyl-propene- (2 -ylamine hydrochloride.
• EXAMPLE 3 14.1 g. of 2-ethyl-3,3-diphenyl-propene-(2)-yl-amine are added under cooling to a mixture of 13.8 g. formic acid and 1.5 ml. water. To the reaction mixture are added 11.4 ml. of 35% aqueous formaldehyde solution, and the whole subsequently heated for 15 hours to 110 C. After the cooling one acidifies with 54 ml. concentrated hydrochloric acid, and the excess formic acid/formaline solution is distilled-01f in vacuum on the Water bath. The residue is made alkaline with soda lye, extracted with ether, the separated ether part dried with sodium sulfate and distilled.
• 2-alkyl such as 2-propyl derivatives can be made by the procedure of the examples by corresponding change in the starting material.
• I.V. Blood pressure increase of 20-30 mm.
• I.V. Blood pressure increase of 30-60 mm.
• the 1-(3- hydroxyphenyl)-1-hydroxy-2-N-ethyl-amino ethane hydrochloride in a dosage of 1-4 mg./kg., a blood pressure increase of 20-60 mm. Hg, lasting 4 to 8 minutes, is found.
• the compounds may be given in dosage form hypo dermically or intramuscularly in the form of HCl salt, or in the form of their salts in isotonic physiologically acceptable solutions, as for example water saline or peanut oil. Locally, they may be used in solution as a spray and in ointment.
• the compounds of the invention also constitute valuable tools for use in medical research, as for instance in connection with animal experiments and in particular in the study of their effect on the blood pressure by stimulating the contraction of the muscular tissue of the capillaries and arterioles.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Citations (4)

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• 1961
  • 1961-10-19 DE DEG33376A patent/DE1149002B/de active Pending
• 1962
  • 1962-10-04 FR FR19889A patent/FR1395525A/fr not_active Expired
  • 1962-10-18 GB GB39471/62A patent/GB960302A/en not_active Expired
• 1967
  • 1967-04-24 US US634430A patent/US3489760A/en not_active Expired - Lifetime

Patent Citations (4)

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