GB690274A - Antihistaminic substances - Google Patents

Antihistaminic substances

Info

Publication number
GB690274A
GB690274A GB27020/48A GB2702048A GB690274A GB 690274 A GB690274 A GB 690274A GB 27020/48 A GB27020/48 A GB 27020/48A GB 2702048 A GB2702048 A GB 2702048A GB 690274 A GB690274 A GB 690274A
Authority
GB
United Kingdom
Prior art keywords
pyridyl
phenyl
compounds
alkyl
imidazolinyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB27020/48A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme Corp
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Publication of GB690274A publication Critical patent/GB690274A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

A process for the manufacture of antihistaminic substances of the general formula <FORM:0690274/IV (b)/1> where Py represents a pyridine residue which may carry halogen, alkyl or alkoxyl as substituents, Y stands for an alkylene group having 2 or 3 carbon atoms, R represents a dialkylamino-, piperidino-, morpholino-, or iminazolino group and R1 stands for alkyl, aryl, aralkyl, cycloalkyl or a heterocyclic residue, which may carry as substituents alkyl, alkoxyl, dialkylamino, chlorine or bromine, and of salts of such compounds, comprises the hydrolysis and decarboxylation of a nitrile having the formula <FORM:0690274/IV (b)/2> by reaction with a strong acid, e.g. 80 per cent sulphuric acid. In the alkyl, alkoxy and dialkylamino groups, the alkyl group contains not more than four carbon atoms. The preparation of the nitriles is described in Specification 666,778. In an example, 3-phenyl-3-(21-pyridyl)-N,N-dimethylpropylamine is prepared by heating a - phenyl - a (b - dimethylaminoethyl)-2-pyridylacetonitrile with (a) 80 per cent sulphuric acid; (b) 48 per cent hydrobromic acid; (c) a mixture of 80 per cent sulphuric acid and 48 per cent hydrobromic acid; (d) concentrated hydrochloric acid. In (b) the product is isolated as the picrate. Other compounds obtainable by the above methods include 3 - phenyl - 3 - (21 - pyridyl) - N,N - diethylpropylamine; 3 - (21 - pyridyl) - N,N - dimethylbutylamine substituted at the 4-position by phenyl, 211-thienyl, or p-bromophenyl radicals; 4-phenyl-4-(21-pyridyl)-2-(dimethylamino) - butane; 4 - phenyl - 4 - (21 - pyridyl) - N,N - dimethylbutylamine; 3 - cyclohexyl - 4 - (21 - pyridyl) - N,N - dimethylbutylamine; 3 - (21 - pyridyl) - N,N - dimethylpropylamine substituted at the 3-position by 211-thienyl, p-methylphenyl, p-methoxyphenyl, p-isopropylphenyl, p-bromophenyl, phenyl, cyclohexyl or 511 - bromo - 211 - thienyl radicals; 3 - phenyl - 3 - (61 - methyl - 21 - pyridyl) - N,N - dimethylpropylamine. Salts mentioned are of hydrochloric, hydrobromic, sulphuric, phosphoric, salicylic, tartaric, maleic, succinic and lauric acids. The monohydrochloride, mono-hydrogen oxalate, mono-hydrogen succinate, and mono-hydrogen maleate of the product of the example are described. The compounds may be administered as tablets, creams, or injectible solutions. As open to inspection under Sect. 91, the Specification comprises compounds of the above general formula in which Y is an alkylene group of from 1 to 5 carbon atoms. Instead of strong acids, alkali metal amides or organometallic compounds may be employed for reaction with the nitriles. Additional examples describe carrying out the process of (1) above using in place of acid (d) sodamide, (e) lithium ethyl, (f) ethyl magnesium bromide; (2) the preparation of a -(2-pyridyl)-b -(2-imidazolinyl) ethylbenzene by reacting a -phenyl-a -(2-pyridyl)-b -2-(imidazolinyl) propionitrile with 80 per cent sulphuric acid; (3) the preparation of b -(2-pyridyl)-g -(2-imidazolinyl) propylbenzene from b - phenyl - a - (2 - pyridyl) - a - (2 - imidazolinyl) propionitrile. There are also mentioned as obtainable by the procedure of example (1), derivatives of 3-(2-pyridyl)-N,N-dimethylpropylamine substituted at the 3-position by an o- or p-chlorophenyl-, 2-pyridyl-, 2-thiazyl, 2-furyl-, or 2-pyrimidyl radical; and 3-(2-thiazyl) - 3 - (2 - pyridyl) - N,N - diethylpropylamine. For use in examples (2) and (3), a -phenyl-a -(2 - pyridyl) - b - (2 - imidazolinyl) propionitrile is prepared by condensing phenylacetonitrile and 2-(chloromethyl) imidazoline in the presence of sodamide, and b -phenyl-a -(2-pyridyl)-a -(2-imidazolinylmethyl) propionitrile is obtained by condensing b -phenylpropionitrile with 2-bromopyridine and 2-(chloromethyl) imidazoline. This subject-matter does not appear in the Specification as accepted.ALSO:Antihistaminic preparations comprise compounds of the general formula <FORM:0690274/VI/1> where Py represents a pyridine residue which may carry halogen, alkyl or alkoxyl as substituents, Y is an alkylene group of 2 or 3 carbon atoms, R is a dialkylamino-, piperidino-, morpholino-, or iminazolino group, and R1 is alkyl, aryl, aralkyl, cycloalkyl or a heterocyclic residue, which may carry as substituents alkyl, aryl, alkoxyl, dialkylamino, chlorine or bromine, and salts of such compounds. Salts mentioned are the hydrochloride, hydrobromide, sulphate, phosphate, salicylate, tartrate, maleate, succinate, citrate, lactate and oxalate, some being the monohydrogen salts. The compounds may be used as tablets, creams or as aqueous solutions, the latter being preferably of the salts in admixture with sodium carbonate and boric acid. The preparation of such substances is described (see Group IV (b)). Products of the above formula mentioned are 3-phenyl-3-(21-pyridyl)-N,N-dimethyl- or diethyl-propylamine; 3-(21-pyridyl)-N,N-dimethylbutylamine substituted at the 4-position by phenyl, 211-thienyl or p-bromophenyl radicals; 4-phenyl-4-(21-pyridyl)-2-(dimethylamino)-butane; 4-phenyl-4-(21-pyridyl)-N,N-dimethylbutylamine; 3-cyclohexyl-4-(21-pyridyl)-N,N-dimethylbutylamine; 3-(21-pyridyl)-N,N-dimethylpropylamine substituted at the 3- position by 211-thienyl, p-methylphenyl, p-methoxyphenyl, p-isopropylphenyl, p-bromphenyl, phenyl, cyclohexyl or 511-bromo-211-thienyl radicals; 3-phenyl-3-(61methyl-21-pyridyl)-N, N-dimethyl-propylamine. Specification 666,778 is referred to. The Specification as open to inspection under Sect. 91, comprises compounds of the above formula in which Y is an alkylene group of from 1 to 5 carbon atoms. Mentioned are a -(2-pyridyl)-b -(2-imidazolinyl) ethylbenzene; b -(2-pyridyl)-g -(2-imidazolinyl) propylbenzene; 3-(2-pyridyl)-N,N-dimethylpropylamines substituted at the 3-position by an o- or p-chlorophenyl-, 2-pyridyl-, 2-thiazyl, 2-furyl-, or 2-pyrimidyl radical; and 3-(2-thiazyl)-3-2-(pyridyl)-N,N-diethyl propylamine. This subject-matter does not appear in the Specification as accepted.
GB27020/48A 1947-10-28 1948-10-18 Antihistaminic substances Expired GB690274A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US690274XA 1947-10-28 1947-10-28

Publications (1)

Publication Number Publication Date
GB690274A true GB690274A (en) 1953-04-15

Family

ID=22086245

Family Applications (1)

Application Number Title Priority Date Filing Date
GB27020/48A Expired GB690274A (en) 1947-10-28 1948-10-18 Antihistaminic substances

Country Status (5)

Country Link
BE (1) BE497819A (en)
DE (1) DE922825C (en)
FR (1) FR1013691A (en)
GB (1) GB690274A (en)
NL (1) NL70759C (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7230030B2 (en) 1998-05-12 2007-06-12 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines
US7989654B2 (en) 2003-04-08 2011-08-02 Ucb Pharma Gmbh High purity bases of 3,3-diphenylpropylamino monoesters

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4605661A (en) * 1984-06-18 1986-08-12 Eli Lilly And Company Aromastase inhibiting α,α-diarylimidazole-4(5)-propionitriles, α,α-diarylimidazole-4(5)-propionamides, and 4(5)-(2,2-diarylethyl)imidazoles
US4882343A (en) * 1987-08-28 1989-11-21 G. D. Searle & Co. Biarylalkylimidazole derivatives as anti-depressants

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7230030B2 (en) 1998-05-12 2007-06-12 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines
US7384980B2 (en) 1998-05-12 2008-06-10 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines
US7855230B2 (en) 1998-05-12 2010-12-21 Ucb Pharma Gmbh Derivatives of 3,3-diphenylpropylamines
US7985772B2 (en) 1998-05-12 2011-07-26 Ucb Pharma Gmbh Derivatives of 3,3-diphenylpropylamines
US8338478B2 (en) 1998-05-12 2012-12-25 Ucb Pharma Gmbh Derivatives of 3,3-diphenylpropylamines
US7989654B2 (en) 2003-04-08 2011-08-02 Ucb Pharma Gmbh High purity bases of 3,3-diphenylpropylamino monoesters

Also Published As

Publication number Publication date
FR1013691A (en) 1952-08-01
NL70759C (en)
DE922825C (en) 1955-01-27
BE497819A (en)

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