US3551436A - Certain 4-(thiazolyl) and 4-(oxazolyl) pyridinium salts - Google Patents

Certain 4-(thiazolyl) and 4-(oxazolyl) pyridinium salts Download PDF

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Publication number
US3551436A
US3551436A US875525A US87552569A US3551436A US 3551436 A US3551436 A US 3551436A US 875525 A US875525 A US 875525A US 87552569 A US87552569 A US 87552569A US 3551436 A US3551436 A US 3551436A
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US
United States
Prior art keywords
thiazolyl
oxazolyl
methyl
pyridinium
pyridine
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 - Lifetime
Application number
US875525A
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English (en)
Inventor
Victor John Bauer
Gretchen Ellen Wiegand
Sidney Robert Safir
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.)
Wyeth Holdings LLC
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American Cyanamid Co
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
Priority to NL6813336A priority Critical patent/NL6813336A/xx
Priority to CH1413168A priority patent/CH521371A/de
Priority to FR166957A priority patent/FR1598975A/fr
Priority to BE721158D priority patent/BE721158A/xx
Priority to FR166958A priority patent/FR8478M/fr
Priority to DE19681795369 priority patent/DE1795369A1/de
Priority to US875527A priority patent/US3551437A/en
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Priority to US875526A priority patent/US3555036A/en
Priority to US875525A priority patent/US3551436A/en
Application granted granted Critical
Publication of US3551436A publication Critical patent/US3551436A/en
Priority to US127023A priority patent/US3703577A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B63—SHIPS OR OTHER WATERBORNE VESSELS; RELATED EQUIPMENT
    • B63H—MARINE PROPULSION OR STEERING
    • B63H1/00—Propulsive elements directly acting on water
    • B63H1/02—Propulsive elements directly acting on water of rotary type
    • B63H1/04—Propulsive elements directly acting on water of rotary type with rotation axis substantially at right angles to propulsive direction
    • B63H1/06—Propulsive elements directly acting on water of rotary type with rotation axis substantially at right angles to propulsive direction with adjustable vanes or blades
    • B63H1/08—Propulsive elements directly acting on water of rotary type with rotation axis substantially at right angles to propulsive direction with adjustable vanes or blades with cyclic adjustment

Definitions

  • R is selected from the group consisting of hydrogen and lower alkyl; R is lower alkoxy(lower)alkyl; X is a sulfur or an oxygen atom, and Y is a pharmaceutically acceptable anion such as, for example, chloride, bromide, iodide, and the like.
  • the term lower alkoxy as well as the term lower alkyl is intended to include those having 1 to 4 carbon atoms present.
  • the compounds are crystalline solids, soluble in water.
  • the quaternary compounds of the present invention may be prepared by reaction of a thiazolylpyridine or an oxazolylpyridine with a lower alkoxy(lower)alkyl halide at a temperature of 0 to 150 C. with or without a sol vent, suchas an alcohol, for a period of time of several minutes to twenty-four hours in an open vessel or a sealed bomb.
  • a sol vent suchas an alcohol
  • quaternary compounds of the present invention are, for example:
  • the quaternary compounds of the present invention may be used to lower blood sugar levels in warm-blooded animals at a dose of from 0.5 to milligrams per kilogram of body weight.
  • the quaternary compounds of this invention can be used in composition such as tablets; the principal active ingredient is mixed with conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate, gums, and fractionally similar materials as pharmaceutical diluents or carriers.
  • the tablets or pills of the novel compositions can be laminated or otherwise compounded to provide a dosage form affording the advantage of prolonged or delayed action or predetermined successive action of the enclosed medication.
  • the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former
  • the two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permits the inner component to pass intact into the duodenum or to be delayed in release.
  • enteric layers or coatings such materials including a number of polymeric acids or mixtures of polymeric acids with such materials as shellac, shellac and cetyl alcohol, cellulose acetate and the like.
  • a particularly advantageous enteric coating comprises a styrene maleic acid copolymer together with known materials contributing to the enteric properties of the coating.
  • dosage form as described herein refers to physically discrete units suitable as unitary dosage for warm-blooded animal subjects, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical diluent, carrier or vehicle.
  • suitable oral dosage forms in accord with this invention are tablets, capsules, pills, powder packets, granules, wafers, cachets, teaspoonfuls, dropperfulls, ampules, vials, segregated multiples of any of the foregoing and other forms as herein described.
  • EXAMPLE 2 Preparton of 4-(5-methyl-2thiazolyl)pyridine A mixture of 2 g. of a-isonicotinamidoacetone and 3 g. of phosphorus pentasulfied is heated in an oil bath at 110-140 C. until gas evolution ceases. The solid mass is heated with excess 1 N potassium hydroxide solution and the resulting mixture is extracted with chloroform. The chloroform solution is dried and concentrated to give a tan solid. Sublimation at C./0.05 mm. provides yellow crystals, melting point 8890 C.
  • EXAMPLE 4 Preparation of 4-(2-methyl-5-thiazolyl) pyridine A mixture of 1.5 g. of 4-acetylaminoacetylpyridine and 2.3 g. of phosphorus pentasulfide is heated in an oil bath at 110140 C. until gas evolution ceases. The solid mass is heated with excess 1 N potassium hydroxide solution, and the resulting mixture is extracted with chloroform. The chloroform solution is dried and concentrated to an amber oil. The material is sublimed at C./0.05 mm. to provide colorless crystals, melting point 30 C.
  • EXAMPLE 8 Preparation of 4-(2-methyl-5-oxazolyl)pyridine
  • EXAMPLE 9 Preparation of l-(2-ethoxyethyl)-4-(4-methyl-2-thiazolyl) pyridinium chloride
  • a mixture of 5.2 g. of 4-(4-methyl-2-thiazolyl)pyridine and 5 ml. of 2-chloroethyl ethyl ether is heated at C. in a bomb for 18 hours. The excess 2-chloroethyl ethyl ether is evaporated and the solid residue is recrystallized from acetonitrile-ether to afford yellow crystals. Recrystallization from acetone affords pale yellow needles, melting point 89-92 C.
  • EXAMPLE 11 Preparation of 1-(2-ethoxyethyl)-4-(2-oxazolyl)pyridinium chloride A mixture of 2.1 g. of 4-(2-oxazolyl)pyridine and 10 ml. of ethoxyethyl chloride is heated at C. in a bomb for 4 hours. The excess 2-ethoxyethyl chloride is allowed to escape, and the residual solid is recrystallized from isopropyl alcohol to provide crystals.
  • R is selected from the group consisting of hydrogen and lower alkyl; R is lower alkoxy(lower)alkyl; X is selected from the group consisting of sulfur and oxygen and Y is a pharmaceutically acceptable anion.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Combustion & Propulsion (AREA)
  • Mechanical Engineering (AREA)
  • Ocean & Marine Engineering (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
US875525A 1967-09-22 1969-11-10 Certain 4-(thiazolyl) and 4-(oxazolyl) pyridinium salts Expired - Lifetime US3551436A (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
NL6813336A NL6813336A (nl) 1967-09-22 1968-09-18 Werkwijze voor het bereiden van pyridinederivaten.
BE721158D BE721158A (fr) 1967-09-22 1968-09-20
FR166958A FR8478M (fr) 1967-09-22 1968-09-20 Nouveaux dérivés de pyridine et leurs sels de pyridinium, utiles comme relaxants musculaires et antiépileptiques.
DE19681795369 DE1795369A1 (de) 1967-09-22 1968-09-20 Neue Pyridiniumsalze und Verfahren zu ihrer Herstellung
CH1413168A CH521371A (de) 1967-09-22 1968-09-20 Verfahren zur Herstellung neuer Cyclopropyl-1,2,4-oxadiazolylpyridine
FR166957A FR1598975A (fr) 1967-09-22 1968-09-20 Procédé de préparation de sels de pyridinium.
US875527A US3551437A (en) 1967-09-22 1969-11-10 Certain 4-(1,2,4-oxadiazole-3 or 5-yl) pyridinium salts and derivatives thereof
US875526A US3555036A (en) 1967-09-22 1969-11-10 Cyclopropyl-1,2,4-oxadiazolylpyridines
US875525A US3551436A (en) 1967-09-22 1969-11-10 Certain 4-(thiazolyl) and 4-(oxazolyl) pyridinium salts
US127023A US3703577A (en) 1967-09-22 1971-03-22 4-(thiazolyl) pyridinium salts and 4-(oxazolyl) pyridinium salts for lowering blood glucose levels

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US66970567A 1967-09-22 1967-09-22
US67670667A 1967-10-20 1967-10-20
US69038267A 1967-12-14 1967-12-14
US875527A US3551437A (en) 1967-09-22 1969-11-10 Certain 4-(1,2,4-oxadiazole-3 or 5-yl) pyridinium salts and derivatives thereof
US875526A US3555036A (en) 1967-09-22 1969-11-10 Cyclopropyl-1,2,4-oxadiazolylpyridines
US875525A US3551436A (en) 1967-09-22 1969-11-10 Certain 4-(thiazolyl) and 4-(oxazolyl) pyridinium salts
US127023A US3703577A (en) 1967-09-22 1971-03-22 4-(thiazolyl) pyridinium salts and 4-(oxazolyl) pyridinium salts for lowering blood glucose levels

Publications (1)

Publication Number Publication Date
US3551436A true US3551436A (en) 1970-12-29

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ID=27568835

Family Applications (4)

Application Number Title Priority Date Filing Date
US875525A Expired - Lifetime US3551436A (en) 1967-09-22 1969-11-10 Certain 4-(thiazolyl) and 4-(oxazolyl) pyridinium salts
US875526A Expired - Lifetime US3555036A (en) 1967-09-22 1969-11-10 Cyclopropyl-1,2,4-oxadiazolylpyridines
US875527A Expired - Lifetime US3551437A (en) 1967-09-22 1969-11-10 Certain 4-(1,2,4-oxadiazole-3 or 5-yl) pyridinium salts and derivatives thereof
US127023A Expired - Lifetime US3703577A (en) 1967-09-22 1971-03-22 4-(thiazolyl) pyridinium salts and 4-(oxazolyl) pyridinium salts for lowering blood glucose levels

Family Applications After (3)

Application Number Title Priority Date Filing Date
US875526A Expired - Lifetime US3555036A (en) 1967-09-22 1969-11-10 Cyclopropyl-1,2,4-oxadiazolylpyridines
US875527A Expired - Lifetime US3551437A (en) 1967-09-22 1969-11-10 Certain 4-(1,2,4-oxadiazole-3 or 5-yl) pyridinium salts and derivatives thereof
US127023A Expired - Lifetime US3703577A (en) 1967-09-22 1971-03-22 4-(thiazolyl) pyridinium salts and 4-(oxazolyl) pyridinium salts for lowering blood glucose levels

Country Status (6)

Country Link
US (4) US3551436A (fr)
BE (1) BE721158A (fr)
CH (1) CH521371A (fr)
DE (1) DE1795369A1 (fr)
FR (2) FR8478M (fr)
NL (1) NL6813336A (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3985754A (en) * 1975-05-08 1976-10-12 American Cyanamid Company Para-fluorobenzoylpropyl-N-heterocyclic substituted quaternary salts
US4488647A (en) * 1983-07-18 1984-12-18 Paramount Packaging Corporation Flexible package with easy opening peel seal
US4571402A (en) * 1982-06-22 1986-02-18 Schering Corporation Anti-bronchoconstriction 2-(4'-pyridinyl)-thiazole derivatives, composition, and method of use therefor
US20080108799A1 (en) * 2004-09-02 2008-05-08 Andre Weiss Use Of Thiazolyl-Pyridinium Based Dyes In Optical Layers For Optical Data Recording

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4528291A (en) * 1982-06-22 1985-07-09 Schering Corporation 2-(4'-Pyridinyl)-thiazole compounds and their use in increasing cardiac contractility

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3985754A (en) * 1975-05-08 1976-10-12 American Cyanamid Company Para-fluorobenzoylpropyl-N-heterocyclic substituted quaternary salts
US4571402A (en) * 1982-06-22 1986-02-18 Schering Corporation Anti-bronchoconstriction 2-(4'-pyridinyl)-thiazole derivatives, composition, and method of use therefor
US4488647A (en) * 1983-07-18 1984-12-18 Paramount Packaging Corporation Flexible package with easy opening peel seal
US20080108799A1 (en) * 2004-09-02 2008-05-08 Andre Weiss Use Of Thiazolyl-Pyridinium Based Dyes In Optical Layers For Optical Data Recording
US7655767B2 (en) 2004-09-02 2010-02-02 Clariant Finance (Bvi) Limited Use of thiazolyl-pyridinium based dyes in optical layers for optical data recording

Also Published As

Publication number Publication date
NL6813336A (nl) 1969-03-25
US3551437A (en) 1970-12-29
BE721158A (fr) 1969-03-20
FR8478M (fr) 1972-06-09
CH521371A (de) 1972-04-15
FR1598975A (fr) 1970-07-15
US3555036A (en) 1971-01-12
DE1795369A1 (de) 1972-01-05
US3703577A (en) 1972-11-21

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