Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
  • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
  • C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
• • 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
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
• • 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
  • A61K31/33—Heterocyclic compounds
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
  • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
  • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
• • 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
  • C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
  • C07D213/22—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing two or more pyridine rings directly linked together, e.g. bipyridyl

Definitions

• the compounds of this invention are 4'-phenoxyalkanesulfonanilides which can be represented by the formula wherein X can be halo, alkyl containing from 1 to 4 carbon atoms, inclusive, or alkoxy containing from 1 to 4 carbon atoms, inclusive; Y can be halo; R can be hydrogen, alkyl containing from 1 to 4 carbon atoms, inclusive, 3-piperidinopropyl, 2-piperidinoethyl, 3-(l-pyrrolidinyl)propyl, 2-(1-pyrrolidinyl)ethyl, 3-morpholinopropyl, 2-morpholinoethyl and dialkylaminoalkyl of the formula R8 --(CH2)kN where R and R can be alike or difierent and are alkyl containing from 1 to 4 carbon atoms, inclusive; and R can be alkyl containing from 1 to 6 carbon atoms, inclusive.
• the subscript k is an integer having a value of 2 or 3
• m and n are integers having a value of zero to 3, inclusive, and of zero to 2, inclusive, respectively.
• the instant compounds can be prepared by reacting a phenoxyaniline of the type O- NH Q Q l.
• Xm Yn where X, Y, m and n have the same meaning as above and R is hydrogen or alkyl containing from 1 to 4 carbon atoms, inclusive, with an alkanesulfonyl halide represented by the formula (HI) HalogenSO -R where R has the same meaning as above, and Halogen preferably is chlorine or bromine.
• halo radicals are fluoro, chloro, bromo, and iodo.
• alkyl radicals contemplated herein are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.- butyl, tert.-butyl, the pentyls, and the hexyls.
• Illustrative alkoxy radicals are methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec.-butoxy, and tert.-butoxy.
• phenoxyanilines represented by Formula II are a known group of compounds, some of which are commercially available.
• Illustrative phenoxyanilines (II) are p- (p-chlorophenoxy aniline,
• alkanesulfonyl halides of Formula III are also a known class of compounds, and some are commercially available. Methods of preparation can be found in I. Am. Chem. Soc. 58, 1348 (1936); J. Am. Chem. Soc. 59, 1837, 2439 (1937); and J. Am. Chem. Soc. 60, 1486 (1938).
• Illustrative alkanesulfonyl halides (III) are methanesulfonyl chloride, ethanesulfonyl chloride, butanesulfonyl chloride, propanesulfonyl chloride, l-methylethanesulfonyl chloride, sec.-butanesulfonyl chloride, isobutanesulfonyl chloride, pentanesulfonyl chloride, hexanesulfonyl chloride, etc.
• a 4-phenoxyalkanesulfonilide (I) where R is hydrogen can be alkylated by treatment, in an inert organic solvent such as benzene, tetrahydrofuran, or dioxane, with an alkylating agent which can be an alkyl halide or a sec.-aminoalkyl halide.
• the alkylation takes place in the presencepf a base, for example, an alkali metal alkoxide such as potassium tert.-butoxide, or an alkali metal hydride such as sodium hydride or potassium hydride.
• Reaction temperature for the alkylation reaction can range from about C. to about 100 C.
• the alkylating agent is a primary alkyl iodide
• room temperature is the preferred reaction temperature; however, for alkyl chlorides a temperature from about 50 C. to about 100 C. is preferred.
• sec.-aminoalkyl halides in the form of a hydrohalide salt are employed as the alkylating agent, sufiicient base is added to the reaction mixture to liberate the free sec.-aminoalkyl halide and to form the sulfonanilide alkali metal salt.
• alkyl halides which can be used as alkylating agents are methyl iodide, ethyl iodide, propyl iodide, butyl iodide, methtyl bromide, ethyl chloride, propyl bromide, butyl chloride, sec.-butyl bromide, and the like.
• Illustrative sec.-aminoalkyl halides suitable as alkylating agents are N,N-diethyl-2-chloroethylamine, N,N- dibutyl-2-chloro-ethylamine, N,N diethyl-3-chloropropylamine hydrochloride, N-methyl-N-propyl-3-bromopropylamine hydrochloride, N ethyl N-butyl-2-bromoethylamine, N-(Z-chloroethyl)piperidine, N-(3-chloropropyl) piperidine, N-(2-chloroethyl)pyrrolidine, N-(S-chloropropyl)pyrrolidine, N-(2-chloroethyl)morpholine, N-(3- chloropropyl)morpholine, and the like.
• R sec.-aminoalkyl
• amines which can eXist either in the nonprotonated or free-base form, or in the protonated or acid addition salt form, depending on the pH of the environment.
• Stable, pharmaceutically acceptable protonates can be formed on neutralization of the free-base form with suitable acids such as hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid, acetic acid, and the like.
• the compounds of this invention have lipid-normalizing activity and thus are useful as hypocholesterolemic agents and as hypotriglyceridemic agents in mammals.
• the amount of the active ingredient that is to be administered depends on the age, weight, and condition of the recipient, and also on factors such as the frequency and route of administration.
• the daily dose range can be from about 0.1 milligram per kilogram of body weight to about 50 milligrams per kilogram of body weight.
• the resulting admixture was stirred at about room temperature for about 4 hours, then diluted with water and ice. A precipitate was observed to form and was recovered by filtration. Upon recrystallization from methanol, about 35 grams of a product melting at 125 C. to 126 C., and about 9 grams of the same product melting at 124 C.
• N-methyl-N-propyl-3-chloropropylamine hydrochloride the corresponding N-[3-(N-methyl-N-propylamino)propyl]-4'-phenoxymethanesulfonanilide can be prepared;
• N-(2-chloroethyl)morpholine the corresponding N-(2-morpholinoethyl)-4' phenoxymethanesulfonanilide can be prepared;
• X is a member of the grouping consisting of halo, alkyl containing from 1 to 4 carbon atoms, inclusive, and alkoxy containing from 1 to 4 carbon atoms, inclusive;
• Y is halo;
• R is dialkylaminoalkyl with R and R both ethyl and k has a value of 2, R is methyl, and mi and n have a value of zero.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
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• Life Sciences & Earth Sciences (AREA)
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• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Hydrogenated Pyridines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Citations (1)

• 1967
  • 1967-07-18 US US654064A patent/US3531522A/en not_active Expired - Lifetime
• 1968
  • 1968-06-12 GB GB27979/68A patent/GB1204946A/en not_active Expired
  • 1968-06-21 IL IL30223A patent/IL30223A/en unknown
  • 1968-07-17 FR FR1586894D patent/FR1586894A/fr not_active Expired
  • 1968-07-18 BE BE718228D patent/BE718228A/xx unknown

Patent Citations (1)

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