US3855406A - Thiaxanthene derivatives useful for treating peptic ulcers - Google Patents

Thiaxanthene derivatives useful for treating peptic ulcers Download PDF

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Publication number
US3855406A
US3855406A US00352504A US35250473A US3855406A US 3855406 A US3855406 A US 3855406A US 00352504 A US00352504 A US 00352504A US 35250473 A US35250473 A US 35250473A US 3855406 A US3855406 A US 3855406A
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composition
hydroxy
compound
thiaxanthenylurea
thiaxanthen
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US00352504A
Inventor
S Adams
B Armitage
N Bristow
B Heathcote
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Boots Co PLC
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Boots Co PLC
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Priority to SE11350/62A priority Critical patent/SE311024B/xx
Priority to GB05692/67A priority patent/GB1181673A/en
Priority to US662586A priority patent/US3558779A/en
Priority to CA998,489A priority patent/CA962686A/en
Priority to US662587A priority patent/US3644420A/en
Priority to FR119237A priority patent/FR8016M/fr
Priority to ES344599A priority patent/ES344599A1/en
Priority to NL6711975A priority patent/NL150793B/en
Priority claimed from NL6711975A external-priority patent/NL150793B/en
Priority to DE19671643244 priority patent/DE1643244A1/en
Priority to AT806467A priority patent/AT296324B/en
Priority to CS6700006243A priority patent/CS186702B2/en
Priority to CS7000000526A priority patent/CS186704B2/en
Priority to SE12168/67A priority patent/SE349028B/xx
Priority to CH1226067A priority patent/CH491104A/en
Priority to AT249371A priority patent/AT296328B/en
Priority to DK440567AA priority patent/DK123355B/en
Priority to AT605769A priority patent/AT289824B/en
Priority to CH881169A priority patent/CH514576A/en
Priority to US858183A priority patent/US3686218A/en
Priority to US00191111A priority patent/US3754005A/en
Priority to US00276670A priority patent/US3755593A/en
Priority to US00277410A priority patent/US3842178A/en
Priority to US00277333A priority patent/US3755594A/en
Priority to US00344570A priority patent/US3855244A/en
Application filed by Boots Co PLC filed Critical Boots Co PLC
Priority to US00352504A priority patent/US3855406A/en
Priority to US408378A priority patent/US3927029A/en
Priority to US410570A priority patent/US3897547A/en
Priority to US423925A priority patent/US3886169A/en
Priority to US05/426,799 priority patent/US3948947A/en
Priority to US05/492,399 priority patent/US3957821A/en
Publication of US3855406A publication Critical patent/US3855406A/en
Application granted granted Critical
Priority to US05/549,535 priority patent/US3978226A/en
Assigned to BOOTS COMPANY PLC THE reassignment BOOTS COMPANY PLC THE CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE MARCH 13.1982 Assignors: BOOTS COMPANY LIMITED THE
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    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom

Definitions

  • R is hydrogen, halogen, alkyl or alkoxy
  • R is hydroxy or alkanoyloxy; and R is hydrogen or alkyl.
  • alkyl, alkoxy and alkanoyloxy indicate such groups containing up to 7 carbon atoms.
  • compounds of formula I are anti-secretory agents, with a specific activity against gastric secretion and without any anticholinergic activity.
  • the anti-secretory activity has been demonstrated in the stimulated, pylorus-ligated rat, and varies with values of R R and R
  • the compounds of the invention may be administered orally, r'ectally or parenterally, preferably orally, the optimum dosage rate varying with the activity of the compounds.
  • a preferred dosage rate for oral administration is of theorder of 0025-2 g. daily, optionally in divided doses. g
  • compositions which comprise a compound of the hereinbefore described formula I in association with pharmaceutical excipients known for the production of compositions suitable for oral. rectal or parenteral administration.
  • compositions for oral administration include for example aqueous suspensions containing a compound of formula I in aqueous media in the presence of a non-toxic suspending agent e.g. sodium carboxymethylcellulose and dispersing agents, and oily suspensions containing a compound of formula I in a vegetable oil for example arachis oil.
  • a non-toxic suspending agent e.g. sodium carboxymethylcellulose and dispersing agents
  • oily suspensions containing a compound of formula I in a vegetable oil for example arachis oil for example arachis oil.
  • compositions of the invention suitable for rectal administration are the known pharmaceutical forms for such administration, such as for example suppositories I with cocoa butter or polyethylene glycol bases.
  • compositions of the invention suitable for parenteral administration are the known pharmaceutical forms for such administration, for example sterile suspensions in aqueous and oily media or sterile solutions in propylene glycol.
  • the compounds of formula I may if desired be associated with other compatible pharmacologically active ingredients.
  • antacids and acid absorbents such as aluminum hydroxide and magnesium trisilicate may be included in compositions for oral administration to give an immediate antacid effect.
  • Other pharmacologically active agents which may be associated with the compounds of formula 1 include compounds active on the central nervous system, including short and long acting sedatives such as the barbiturates and methaqualone, antihistaminic and/or antiemetic agents such as cyclizine and diphenhydramine, and anti-cholinergic agents such as atropine.
  • compositions of the invention include liquid and solid compositions based on milk and milk solids.
  • the compounds of formula I in the form of particles of very small size, such as for example, as obtained by fluid energy milling.
  • a method of treating peptic ulcer which comprises administering to a patient 0.025-2 grams daily of a compound of formula I; in a preferred embodiment of this aspect of the invention, administration is by the oral route.
  • compositions of the invention preferably contain 01-90% by weight of a compound of formula I.
  • compositions for oral administration are the preferred compositions of the invention, and these are the known pharmaceutical forms for such administration, such as for example tablets, capsules, syrups and aqueous and oily suspensions.
  • the excipients used in the preparation of these compositions are the excipients known in the pharmacists art.
  • Preferred compositions are tablets wherein a compound of formula I is mixed with an inert diluent such as calcium phosphate in the presence of disintegrating agents e.g. maize starch and lubricating agents e.g. magnesium stearate.
  • Such tablets may, if desired, be provided with enteric coatings by known methods, for example by the use of cellulose acetate phthalate.
  • capsules for example hard or soft gelatin capsules, containing a compound of for-
  • the starting materials employed in the preparation of compounds of formula I are in many cases known compounds; where they are new, they are prepared by methods analagous to those employed for known com pounds, and as such will be apparent to those skilled in the art. By way of example the preparation of some new intermediates is given below.
  • EXAMPLE 1 A suspension of N-9-thiaxanthenylhydroxylamine (2.3 g.) in methylene chloride (20 ml.) was treated with methyl isocyanate (0.8 ml.). After 30 minutes the mixture was diluted with light petroleum b.p. 4060C. (100 ml.). The resulting precipitate was recrystallised from chloroform/light petroleum b.p. 4060C. to give N-hydroxy-N'-methyl-N-9-thiaxanthenylurea, mp. 165C.
  • N'-ethyl-N-hydroxy-N-9-thiaxanthenylurea as a hydrate, m.p. l57l59C.
  • N-acetoxy-N-(2-methyl-9-thiaxanthenyl)urea as a hydrate, m.p. l74.5C.
  • N-acetoxy-N-( l-fluoro-9-thiaxanthenyl )urea mp.
  • EXAMPLE 4 In the preparation of tablets, mixtures of the following type may be tabletted in conventional manner:
  • EXAMPLE 5 The following mixture was formed into tablets in conventional manner, each tablet containing 50 mg. of acmagnesium stearate l% microcrystalline cellulose to by weight EXAMPLE 6
  • enteric coated tablets tablets prepared as described in Example 5 were coated with sanderac varnish and then coated with cellulose acetate phthalate using a solution of 20% cellulose acetate I pared by dissolving phthalate and 3% diethyl phthalate in a mixture of equal parts of industrial alcohol and acetone.
  • EXAMPLE 7 N-hydroxy-N-9-thiaxanthenylurea l lactose calcium phosphate 5 main: starch 5
  • EXAMPLE 8 In the preparation of enteric coated tablets, the tablets described in Example 7 were given a thin coat of shellac followed by 20 coats of cellulose acetate phthalate.
  • EXAMPLE 9 In the preparation of capsules, a mixture of the ingredients described in Example 7 was encapsulated in hard gelatin capsules. Enteric coating was applied by conventional dipping in cellulose acetate phthalate.
  • EXAMPLE I In the preparation of capsules, a mixture of equal parts by weight of .N-hydroxy-N-9-thiaxanthenylurea and calcium phosphate was encapsulated in hard gelatin capsules, each capsule containing 50 mg. of N- hydroxy-N-9-thiaxanthenylurea.
  • EXAMPLE 12 In the preparation of enteric coated capsules, the capsules of Example I l were coated with cellulose acetate phthalate in conventional manner.
  • EXAMPLE l3 Suppositories weighing 1 g. and containing 50 mg. of N-hydroxy-N-9-thiaxanthenylurea were prepared in conventional manner using a base consisting of:
  • EXAMPLE 14 A solution for parenteral administration was pre- 100 mg. of N-hydroxy-N-9- thiaxanathenylurea in 2 ml. of propylene glycol and sterilised by filtration.
  • compositions similar to those described in Examples 4-14 were prepared, containing the other preferred compounds described previously in place of N-hydroxy-N-9-thiaxanthenylurea.
  • a therapeutic composition useful for treating peptic ulcers which comprises an effective anti-secretory amount of a thiaxanthen compound of the formula in which R is a member selected from the group consisting of hydrogen, halogen, alkyl containing up to 7 carbon atoms and alkoxy containing up to 7 carbon atoms;
  • R is a member selected from the group consisting of hydroxy and alkanoyloxy containing up to 7 carbon atoms;
  • R is a member selected from the group consisting of hydrogen and alkyl containing up to 7 carbon atoms
  • composition of claim 1 in the form of a tablet or capsule.
  • composition of claim 4 wherein the said composition is enteric coated.
  • composition of claim 4 wherein said composition contains 25500 mg. of the thiaxanthen compound.
  • composition of claim 1 in the form of a suppository.
  • composition of claim 1 wherein said thiaxanthen compound is N-hydroxy-N-9-thiaxanthenylurea.
  • composition of claim 1 in the form of an enteric coated tablet or capsule useful for treating peptic ulcer comprising 25-500 mg. of N-hydroxy-N-9- thiaxanthenylurea and a pharmaceutically acceptable excipient.
  • a method of treating peptic ulcer which comprises administering to a patient in need of said treatment'a therapeutically effective anti-secretory amount of a thiaxanthen compound of the formula in which R, is a member selected from the group consisting of hydrogen, halogen, alkyl containing up to 7 carbon atoms and alkoxy containing up to 7 carbon atoms;
  • R is a member selected from the group consisting of hydroxy and alkanoyloxy containing up to 7 carbon atoms;
  • R is a member selected from the group consisting of hydrogen and alkyl containing up to 7 carbon atoms.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material 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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

N-Hydroxy-N-9-thiaxanthenylurea, its esters and substituted derivatives thereof are useful in the treatment of peptic ulcer. Pharmaceutical compositions thereof and method of treating therewith also disclosed.

Description

nite States atent I [1 1 Adams et al.
[4 1 Dec. 17, 1974 THIAXANTl-IENE DERIVATIVES USEFUL FOR TREATING PEPTIC ULCERS [73] Assignee: The Boots Company, Limited,
Nottingham, England [22] Filed: Apr. 19, 1973 [2]] Appl. No.: 352,504
Related U.S. Application Data [60] Division of Ser. No. 191,] ll, Oct. 20, 1971, Pat. No. 3,754,005, which is a continuation-in-part of Ser. No.
662,587, Aug. 23, 1967, Pat, No. 3,644,420.
[52 U.S. C1. 424/35, 424/275 51 Int. Cl ..A61k27/00 [58] Field of Search ..424/275 [56] References Cited UNITED STATES PATENTS 3,481,930 l2/l969 Childress ct al. 260/335 Primary Examiner-Frederick E. Waddell Attorney, Agent, or FirmGordon W. Hucschcn [57] ABSTRACT N-l-lydroxy-N-9-thiaxanthenylurea, its esters and substituted derivatives thereof are useful in the treatment of peptic ulcer. Pharmaceutical compositions thereof and method of treating therewith also disclosed.
13 Claims, No Drawings THIAXANTHENE DERIVATIVES This is a division of application Ser. No. 191,111, filed Oct. 20, 1971, now U.S. Pat. No. 3,754,005 issued Aug. 21, 1973, which is in a continuation-in-part of U.S. Patent application Ser. No. 662,587 filed on Aug. 23, 1967, now U.S. Pat. No. 3,644,420 issued Feb. 22, 1972 the disclosure of which is incorporated herein by reference.
According to the present invention there are provided compounds of formula I in which R, is hydrogen, halogen, alkyl or alkoxy;
R is hydroxy or alkanoyloxy; and R is hydrogen or alkyl.
And where the terms alkyl, alkoxy and alkanoyloxy indicate such groups containing up to 7 carbon atoms.
Methods for the preparation of the compounds of formula I are described in detail in our aforementioned U.S. Pat. application Ser. No. 662,587, now U.S. Pat. No. 3,644,420 issued Feb. 22, 1972.
It has been found that compounds of formula I are anti-secretory agents, with a specific activity against gastric secretion and without any anticholinergic activity. The anti-secretory activity has been demonstrated in the stimulated, pylorus-ligated rat, and varies with values of R R and R The compounds of the invention may be administered orally, r'ectally or parenterally, preferably orally, the optimum dosage rate varying with the activity of the compounds. A preferred dosage rate for oral administration is of theorder of 0025-2 g. daily, optionally in divided doses. g
In use, the compounds of the invention are administered in conventional formulationsfand therefore, according to a further aspect of the invention there are provided therapeutic compositions which comprise a compound of the hereinbefore described formula I in association with pharmaceutical excipients known for the production of compositions suitable for oral. rectal or parenteral administration.
mula l, with or without other excipients, may be prepared by conventional means and, if desired, provided with enteric coatings in known manner. The tablets and capsules may conveniently each contain 25-500 mg. of a compound of formula 1. Other compositions for oral administration include for example aqueous suspensions containing a compound of formula I in aqueous media in the presence of a non-toxic suspending agent e.g. sodium carboxymethylcellulose and dispersing agents, and oily suspensions containing a compound of formula I in a vegetable oil for example arachis oil.
Compositions of the invention suitable for rectal administration are the known pharmaceutical forms for such administration, such as for example suppositories I with cocoa butter or polyethylene glycol bases.
Compositions of the invention suitable for parenteral administration are the known pharmaceutical forms for such administration, for example sterile suspensions in aqueous and oily media or sterile solutions in propylene glycol.
In the compositions of the invention the compounds of formula I may if desired be associated with other compatible pharmacologically active ingredients. For example antacids and acid absorbents such as aluminum hydroxide and magnesium trisilicate may be included in compositions for oral administration to give an immediate antacid effect. Other pharmacologically active agents which may be associated with the compounds of formula 1 include compounds active on the central nervous system, including short and long acting sedatives such as the barbiturates and methaqualone, antihistaminic and/or antiemetic agents such as cyclizine and diphenhydramine, and anti-cholinergic agents such as atropine.
Milk and Milk solids are valuable in the treatment of peptic ulcer, and the compositions of the invention include liquid and solid compositions based on milk and milk solids. I
In some formulations it may be beneficial to use the compounds of formula I in the form of particles of very small size, such as for example, as obtained by fluid energy milling.
According to another aspect of the invention there is provided a method of treating peptic ulcer which comprises administering to a patient 0.025-2 grams daily of a compound of formula I; in a preferred embodiment of this aspect of the invention, administration is by the oral route.
The compositions of the invention preferably contain 01-90% by weight of a compound of formula I.
Compositions for oral administration are the preferred compositions of the invention, and these are the known pharmaceutical forms for such administration, such as for example tablets, capsules, syrups and aqueous and oily suspensions. The excipients used in the preparation of these compositions are the excipients known in the pharmacists art. Preferred compositions are tablets wherein a compound of formula I is mixed with an inert diluent such as calcium phosphate in the presence of disintegrating agents e.g. maize starch and lubricating agents e.g. magnesium stearate. Such tablets may, if desired, be provided with enteric coatings by known methods, for example by the use of cellulose acetate phthalate. Similarly capsules, for example hard or soft gelatin capsules, containing a compound of for- The starting materials employed in the preparation of compounds of formula I are in many cases known compounds; where they are new, they are prepared by methods analagous to those employed for known com pounds, and as such will be apparent to those skilled in the art. By way of example the preparation of some new intermediates is given below.
PREPARATION 1 A mixture of thiaxanthydrol (21.4 g.),' hydroxyammonium chloride (10 g), and dry pyridine ml.), was left overnight at room temperature and then poured into ice/water (1 litre). The resulting suspension was decanted from yellow gum, the solid collected on a filter, and recrystallized from chloroform/petroleum ether b.p. 4060C. to give N-9- thiaxanthenylhydroxylamine, m.p. C.
In a similar manner the following compounds are prepared:
160C. The following non-limitative examples illustrate the invention.
EXAMPLE 1 EXAMPLE 2 A suspension of N-9-thiaxanthenylhydroxylamine (2.3 g.) in methylene chloride (20 ml.) was treated with methyl isocyanate (0.8 ml.). After 30 minutes the mixture was diluted with light petroleum b.p. 4060C. (100 ml.). The resulting precipitate was recrystallised from chloroform/light petroleum b.p. 4060C. to give N-hydroxy-N'-methyl-N-9-thiaxanthenylurea, mp. 165C.
In a similar manner the following compounds are prepared:
N'-ethyl-N-hydroxy-N-9-thiaxanthenylurea, as a hydrate, m.p. l57l59C.
Nhydroxy-N'-propyl-N-9-thiaxanthenylurea, m.p.
l 28l 29C. N'-butyl-N-hydroxy-N-9-thiaxanthenylurea, m.p.
N-( l-fluoro-9-thiaxanthenyl)-N-hydroxy-N'- methylurea, mp. 180C.
N'-ethyl-N-( l-fluoro-9-thiaxanthenyl)-N- hydroxyurea, mp. 155C.
N-( l-fluoro-9-thiaxanthenyl)-N-hydroxy-N'- propylurea, mp. 155C.
N-(2-chloro-9-thiaxanthenyl)-N-hydroxy-N'- methylurea, m.p.
N-hydroxy-N-(2-methoxy-9-thiaxanthenyl)-N'- methylurea, m.p.
N-hyd roxy-N -methyl-N-( 2-methyl-9- thiaxanthenyl)urea, as a chloroform solvate, m.p. 145l47C.
EXAMPLE 3 A suspension of N-hydroxy-N-9-thiaxanthenylurea (0.9 g.) in dry pyridine (9 ml.) at C. was treated with 4-dimethylaminopyridine (25 mg.) and propionic anhydride (0.65 ml.), the temperature of the reaction mixture being maintained at 04C. during addition and for a further 20 hours. The mixture was then poured on to ice (300 g.) and the resulting precipitate recrystallised from ethyl acetate to give propionyloXy-N-9-thiaxanthenylurea, mp. 173C.
In a similar manner the following compounds are prepared:
N-acetoxy'N-9-thiaxanthenylurea, m.p. l67l 68C.
N-butyryloxy-N-9-thiaxanthenylurea, m.p.
l 73l 74C. N-isobutyryloxy-N-9-thiaxanthenylurea, mlp.
148l49C. N-acetoxy-N-methyl-N-9-thiaxanthenylurea, m.p.
163164C. N-methyl-N-propionyloxy-N-9-thiaxanthenylurea,
m.p. l69170C. N-butyryloxy-N-methyl-N-9-thiaxanthenylurea m.p.
l60-l6lC. N-acetoxy-N'-ethyl-N-9-thiaxanthenylurea,
166l67C. N'-ethyl-N-propionyloxy-N-9-thiaxanthenylurea,
m.p. l53-l54C. N-butyryloxy-N-ethyl-N-9-thiaxanthenylurea, as a chloroform solvate, m.p. l5l-l53C. N-acetoxy-N-propyl-N-9-thiaxanthenylurea,
l58-l59C. N-propionyloxy-N'-propyl-N-9-thiaxanthenylurea,
m.p. l6l-l62C. N-butyryloxy-N'-propyl-N-9-thiaxanthenylurea, m.p.
154155C. N-acetoxy-N'-butyl-N-9-thiaxanthenylurea,
l-166C. N-acetoxy-N-( 2-methoxy-9-thiaxanthenyl)urea, mp.
163C. N-acetoxy-N-(2-methyl-9-thiaxanthenyl)urea, as a hydrate, m.p. l74.5C. N-acetoxy-N-( l-fluoro-9-thiaxanthenyl )urea, mp.
207C. N-acetoxy-N-(2-chloro-9-thiaxanthenyl)urea, m.p.
l66-l68C.
EXAMPLE 4 In the preparation of tablets, mixtures of the following type may be tabletted in conventional manner:
compound of fonnula l l0-90% calcium phosphate 0-80% maize starch 5-l0% magnesium stearate ca. 1%
microcrystalline cellulose 0-90% (by weight) EXAMPLE 5 The following mixture was formed into tablets in conventional manner, each tablet containing 50 mg. of acmagnesium stearate l% microcrystalline cellulose to by weight EXAMPLE 6 In the preparation of enteric coated tablets, tablets prepared as described in Example 5 were coated with sanderac varnish and then coated with cellulose acetate phthalate using a solution of 20% cellulose acetate I pared by dissolving phthalate and 3% diethyl phthalate in a mixture of equal parts of industrial alcohol and acetone.
EXAMPLE 7 N-hydroxy-N-9-thiaxanthenylurea l lactose calcium phosphate 5 main: starch 5 EXAMPLE 8 In the preparation of enteric coated tablets, the tablets described in Example 7 were given a thin coat of shellac followed by 20 coats of cellulose acetate phthalate.
EXAMPLE 9 In the preparation of capsules, a mixture of the ingredients described in Example 7 was encapsulated in hard gelatin capsules. Enteric coating was applied by conventional dipping in cellulose acetate phthalate.
EXAMPLE 10 The following mixture was compressed into tablets in the conventional manner:
N-hydroxy-N-9-thiaxanthenylurea 25% sodium bicarbonate 75% peppermint oil q.s.
EXAMPLE I I In the preparation of capsules, a mixture of equal parts by weight of .N-hydroxy-N-9-thiaxanthenylurea and calcium phosphate was encapsulated in hard gelatin capsules, each capsule containing 50 mg. of N- hydroxy-N-9-thiaxanthenylurea.
EXAMPLE 12 In the preparation of enteric coated capsules, the capsules of Example I l were coated with cellulose acetate phthalate in conventional manner.
EXAMPLE l3 Suppositories weighing 1 g. and containing 50 mg. of N-hydroxy-N-9-thiaxanthenylurea were prepared in conventional manner using a base consisting of:
polyethylene glycol 4000 33% polyethylene glycol 6000 47% water EXAMPLE 14 A solution for parenteral administration was pre- 100 mg. of N-hydroxy-N-9- thiaxanathenylurea in 2 ml. of propylene glycol and sterilised by filtration.
Compositions similar to those described in Examples 4-14 were prepared, containing the other preferred compounds described previously in place of N-hydroxy-N-9-thiaxanthenylurea. We claim: l. A therapeutic composition useful for treating peptic ulcers which comprises an effective anti-secretory amount of a thiaxanthen compound of the formula in which R is a member selected from the group consisting of hydrogen, halogen, alkyl containing up to 7 carbon atoms and alkoxy containing up to 7 carbon atoms;
R is a member selected from the group consisting of hydroxy and alkanoyloxy containing up to 7 carbon atoms; and
R is a member selected from the group consisting of hydrogen and alkyl containing up to 7 carbon atoms;
in association with a pharmaceutically acceptable excipient.
2. The composition of claim 1 wherein R is hydrogen and R is hydroxy.
3. The composition of claim- 1 wherein R is alkoxy and R is hydroxy.
4. The composition of claim 1 in the form of a tablet or capsule.
5. The composition of claim 4 wherein the said composition is enteric coated.
6. The composition of claim 4 wherein said composition contains 25500 mg. of the thiaxanthen compound.
7. The composition of claim 1 in the form of a suppository.
8. The composition of claim 1 wherein said thiaxanthen compound is N-hydroxy-N-9-thiaxanthenylurea.
9. The composition of claim 1 in the form of an enteric coated tablet or capsule useful for treating peptic ulcer comprising 25-500 mg. of N-hydroxy-N-9- thiaxanthenylurea and a pharmaceutically acceptable excipient.
10. A method of treating peptic ulcer which comprises administering to a patient in need of said treatment'a therapeutically effective anti-secretory amount of a thiaxanthen compound of the formula in which R,, is a member selected from the group consisting of hydrogen, halogen, alkyl containing up to 7 carbon atoms and alkoxy containing up to 7 carbon atoms;
R is a member selected from the group consisting of hydroxy and alkanoyloxy containing up to 7 carbon atoms; and
R is a member selected from the group consisting of hydrogen and alkyl containing up to 7 carbon atoms.
11. The method of claim 10 wherein said thiaxanthen compound is administered orally.
12. The method of claim 10 wherein said thiaxanthen compound is administered at a dosage rate of 0025-2 grams per day.
13. The method of claim 10 wherein said thiaxanthen compound is N-hydroxy-N-9-thiax anthenylurea.

Claims (13)

1. A THERAPEUTIC COMPOSITION USEFUL FOR TREATING PEPTIC ULCERS WHICH COMPRISES AN EFFECTIVE ANTI-SECRETORY AMOUNT OF A THIAXANTHEN COMPOUND OF THE FORMULA
2. The composition of claim 1 wherein Ro is hydRogen and R1 is hydroxy.
3. The composition of claim 1 wherein Ro is alkoxy and R1 is hydroxy.
4. The composition of claim 1 in the form of a tablet or capsule.
5. The composition of claim 4 wherein the said composition is enteric coated.
6. The composition of claim 4 wherein said composition contains 25-500 mg. of the thiaxanthen compound.
7. The composition of claim 1 in the form of a suppository.
8. The composition of claim 1 wherein said thiaxanthen compound is N-hydroxy-N-9-thiaxanthenylurea.
9. The composition of claim 1 in the form of an enteric coated tablet or capsule useful for treating peptic ulcer comprising 25-500 mg. of N-hydroxy-N-9-thiaxanthenylurea and a pharmaceutically acceptable excipient.
10. A method of treating peptic ulcer which comprises administering to a patient in need of said treatment a therapeutically effective anti-secretory amount of a thiaxanthen compound of the formula
11. The method of claim 10 wherein said thiaxanthen compound is administered orally.
12. The method of claim 10 wherein said thiaxanthen compound is administered at a dosage rate of 0.025-2 grams per day.
13. The method of claim 10 wherein said thiaxanthen compound is N-hydroxy-N-9-thiaxanthenylurea.
US00352504A 1966-09-02 1973-04-19 Thiaxanthene derivatives useful for treating peptic ulcers Expired - Lifetime US3855406A (en)

Priority Applications (31)

Application Number Priority Date Filing Date Title
SE11350/62A SE311024B (en) 1967-04-05 1962-10-23
GB05692/67A GB1181673A (en) 1966-09-02 1966-09-02 Derivatives of Xanthen and Thiaxanthen and Preparation Thereof
US662586A US3558779A (en) 1966-09-02 1967-08-23 Anti-secretory compositions containing xanthen derivatives and uses therefor
CA998,489A CA962686A (en) 1966-09-02 1967-08-23 Xanthen derivatives
US662587A US3644420A (en) 1966-09-02 1967-08-23 Xanthene derivatives
FR119237A FR8016M (en) 1966-09-02 1967-08-29
ES344599A ES344599A1 (en) 1966-09-02 1967-08-30 Anti-secretory compositions containing xanthen derivatives and uses therefor
NL6711975A NL150793B (en) 1966-09-02 1967-08-31 PROCEDURE FOR PREPARING A MEDICINAL PRODUCT WITH AN ACTION AGAINST Ulceration AND PREPARED MEDICINAL PRODUCTS OBTAINED UNDER THIS METHOD AND PROCEDURE FOR THE PREPARATION OF SUITABLE MEDICINAL PRODUCTS OR THIS MEDICINAL PRODUCTS.
AT605769A AT289824B (en) 1966-09-02 1967-09-01 Process for the production of new xanthene derivatives, their esters, amides and salts
AT806467A AT296324B (en) 1966-09-02 1967-09-01 Process for the production of new xanthene derivatives
CS6700006243A CS186702B2 (en) 1966-09-02 1967-09-01 Method of producing n-9-xanthenyl- and n-9-thoaxanthenyl ureas and thioureas
CS7000000526A CS186704B2 (en) 1966-09-02 1967-09-01 Method of producing novel n-9-xanthenyl and n-9-thiaxanthenyl ureas and thioureas
SE12168/67A SE349028B (en) 1967-04-05 1967-09-01
CH1226067A CH491104A (en) 1966-09-02 1967-09-01 Process for the preparation of xanthene derivatives
AT249371A AT296328B (en) 1967-04-05 1967-09-01 Process for the production of new xanthene derivatives
DK440567AA DK123355B (en) 1967-04-05 1967-09-01 Analogous process for the preparation of 9-xanthenylurea derivatives.
DE19671643244 DE1643244A1 (en) 1966-09-02 1967-09-01 New Xanthene Derivatives
CH881169A CH514576A (en) 1966-09-02 1967-09-01 Xanthene derivs for the treatment of intestinal ulcers
US858183A US3686218A (en) 1966-09-02 1969-09-15 Xanthenyl semicarbazides
US00191111A US3754005A (en) 1966-09-02 1971-10-20 Thiaxanthene derivatives
US00276670A US3755593A (en) 1966-09-02 1972-07-31 Treatment of peptic ulceration with xanthene derivatives
US00277333A US3755594A (en) 1966-09-02 1972-08-02 Anti secretory composition containing xanthene derivatives and uses therefor
US00277410A US3842178A (en) 1966-09-02 1972-08-02 Xanthenyl semicarbazides as gastric antisecretory agents
US00344570A US3855244A (en) 1966-09-02 1973-03-26 Xanthen derivatives
US00352504A US3855406A (en) 1966-09-02 1973-04-19 Thiaxanthene derivatives useful for treating peptic ulcers
US408378A US3927029A (en) 1966-09-02 1973-10-23 Xanthen derivatives
US410570A US3897547A (en) 1966-09-02 1973-10-29 Thiaxanthenyl semicarbazides as anti-secretory agents
US423925A US3886169A (en) 1966-09-02 1973-12-12 Xanthenyl and thiaxanthenyl semicarbazides
US05/426,799 US3948947A (en) 1966-09-02 1973-12-20 Thiazanthenyl semicarbazides
US05/492,399 US3957821A (en) 1966-09-02 1974-07-29 Xanthenyl semicarbazides
US05/549,535 US3978226A (en) 1966-09-02 1975-02-13 Xanthen derivatives such as n,n'-dimethyl-n-9-xanthenylurea and the like in anti-secretory compositions, and method of treating therewith

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB3938466 1966-09-02
NL6711975A NL150793B (en) 1966-09-02 1967-08-31 PROCEDURE FOR PREPARING A MEDICINAL PRODUCT WITH AN ACTION AGAINST Ulceration AND PREPARED MEDICINAL PRODUCTS OBTAINED UNDER THIS METHOD AND PROCEDURE FOR THE PREPARATION OF SUITABLE MEDICINAL PRODUCTS OR THIS MEDICINAL PRODUCTS.
US19111171A 1971-10-20 1971-10-20
US00352504A US3855406A (en) 1966-09-02 1973-04-19 Thiaxanthene derivatives useful for treating peptic ulcers

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4687667A (en) * 1977-08-04 1987-08-18 J. B. Tillott Limited Method of treating functional bowel disorders by the administration of peppermint oil to the intestive
US20030050344A1 (en) * 2001-07-02 2003-03-13 Alberto Garavani Pharmaceutical formulations for thyroid hormones

Citations (1)

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Publication number Priority date Publication date Assignee Title
US3481930A (en) * 1966-11-21 1969-12-02 American Home Prod Xanthene and thioxanthene-9 ureas and propionamides

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
US3481930A (en) * 1966-11-21 1969-12-02 American Home Prod Xanthene and thioxanthene-9 ureas and propionamides

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4687667A (en) * 1977-08-04 1987-08-18 J. B. Tillott Limited Method of treating functional bowel disorders by the administration of peppermint oil to the intestive
US20030050344A1 (en) * 2001-07-02 2003-03-13 Alberto Garavani Pharmaceutical formulations for thyroid hormones
US7723390B2 (en) * 2001-07-02 2010-05-25 Altergon S.A. Pharmaceutical formulations for thyroid hormones

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