Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
  • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
  • C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
  • C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
  • C07C331/02—Thiocyanates
  • C07C331/10—Thiocyanates having sulfur atoms of thiocyanate groups bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen 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
  • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/55—Acids; Esters
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
  • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
  • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
  • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
  • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
  • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
  • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
  • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
  • C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
  • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
  • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
  • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
  • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

• the new 4-(hetero cyclic)salicyclic acid compounds described have antiinflammatory, anti-pyretic and analgesic activity.
• This invention relates to new heterocyclic phenyl compounds and to processes for producing the same. More specifically, it relates to 4-(heterocyclic)-salicylic acid compounds (2-hdroxy -4-heterocyclic benzoic acids). Still more specifically, this invention relates to compounds having the following general formula:
• Het is a 6- membered ring structure containing from one to three hetero atoms or a five-membered ring structure containing from one to four hetero atoms.
• the hetero atoms are either nitrogen, sulphur, or oxygen;
• R is hydrogen, lower alkyl, lower alkoxy, halogen, or
• R is hydrogen, alkyl (preferably lower alkyl, such as methyl, ethyl, propyl, isopropyl, butyl or pentyl), halo (such as, chlorine, bromine or iodine or fluorine), amino, alkyl amino, (preferably lower alkyl amino, such as methyl amino or isopropyl amino), dialkyl amino, (preferably diloweralkyl amino such as dimethyl amino or diethyl amino), hydroxy or alkoxy (preferably lower alkoxy, such as methoxy or ethoxy).
• alkyl preferably lower alkyl, such as methyl, ethyl, propyl, isopropyl, butyl or pentyl
• halo such as, chlorine, bromine or iodine or fluorine
• dialkyl amino preferably diloweralkyl amino such as di
• the six-membered ring structure containing from one to three hetero atoms are 2,3 or 4-pyridyl, 2 or 3 pyrazinyl, 2,4 or S-pyrimidyl, 3 or 4 pyridazinyl, s-triazinyl, 3,4 or b-as-triazinyl (1,2,3- triazinyl; 1,3,5-Triazinyl; l ,2,4-triazinyl).
• Preferred examples of five-membered heterocyclic ring structures containing from one to four hetero atoms are:
• heterocyclic ring structures are the oxazole, thiazolyl and pyrole rings in that order of importance.
• the R substituent on the heterocyclic nucleus can be in any available position and may be in one or more positions.
• the compounds described above have anti-inflammatory activity and are effective in the prevention and inhibition of edema and granuloma tissue formation.
• some of them have a useful degree of anti-pyretic and analgesic activity.
• they are normally administered orally in tablets or capsules, the optimum dosage depending on the particular compound being used and the type and severity of the condition being treated.
• oral dose levels of preferred compounds in the range of 50 mg. to 10 g. per day are useful in the control of said conditions, depending on the activity of the specific compound and the reaction sensitivity of the patient.
• the compounds of the instant invention can be prepared by a carboxylation reaction wherein the appropriate starting material is reacted with carbon dioxide, preferably in the presence of potassium carbonate.
• the reaction is usually carried out in a pressurized vessel at a wide range of temperatures especially from about 50 to 200 C., preferably at about 175 C. at 800 p.s.i. initial pressure. The pressure can also vary from atmospheric pressure on up.
• the reaction mixture is carried out for a sufficient time to consume the stoimetric amount of carbon dioxide.
• the desired product can be isolated by extraction with water, the water layer then acidified and the precipitated product recrystallized.
• EXAMPLE 1 EXAMPLE Preparation of 4-(2-oxazolyl-salicylic acid A. m-(Diethoxy ethylaminomethyl)-nitrobenzene 22.7 Gms. (0.15 moles) of 3-nitro-benzaldehyde and 20.0 gms. (0.15 moles) of diethoxyethyl amine were mixed together and heated in an oil bath for about 1 hour until no more water is given off. The mixture was then cooled and diluted with an ether-hexane mixture at which time a solid material crystallized. The solid material was filtered and dried yielding 34.3 gms. of m- (diethoxy ethylaminomethyl)-nitrobenzene, m.p.
• This solid was a boron complex of 2-chloro-4-(mhydroxyphenyl)-thiazole. It was decomposed by heating it with a saturated sodium bicarbonate solution for about one-half hour on a steam bath. The crude solid was filtered, dried and crystallized from petroleum ether. A yield of 0.9 g. of 2-chloro-4-(m-hydroxyphenyl)-thiazole was obtained, n1.p. 89-90 C. D. 4-[4-(2-chlorotl'iiazolyl)]-salicylic acid 2,3 gms. of 2-chloro-4-( m-hydroxyphenyl)-thiazole and 5.1 gms.
• R is hydrogen, lower alkyl, lower alkoxy, halogen or haloloweralkyl
• R is hydrogen, lower alkyl, halo, amino, lower alkylamino, di( lower a1kyl)amino, hydroxy or lower alkoxy.

Landscapes

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

Applications Claiming Priority (1)

Publications (1)

Family

ID=21954809

Family Applications (1)

Country Status (6)

Cited By (9)

Families Citing this family (2)

Family Cites Families (4)

• 1970
  • 1970-06-22 US US48479A patent/US3687971A/en not_active Expired - Lifetime
• 1971
  • 1971-06-07 NL NL7107784A patent/NL7107784A/xx unknown
  • 1971-06-14 GB GB1295570D patent/GB1295570A/en not_active Expired
  • 1971-06-15 CA CA115,727A patent/CA952116A/en not_active Expired
  • 1971-06-21 DE DE19712130709 patent/DE2130709A1/de active Pending
  • 1971-06-22 FR FR7122592A patent/FR2100810B1/fr not_active Expired

Also Published As

Similar Documents