US3629434A - Use of 1-alkylsulfonylalkyl-2-alkyl-5 - nitroimidazoles in controlling amebiasis - Google Patents
Use of 1-alkylsulfonylalkyl-2-alkyl-5 - nitroimidazoles in controlling amebiasis Download PDFInfo
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- US3629434A US3629434A US833731A US3629434DA US3629434A US 3629434 A US3629434 A US 3629434A US 833731 A US833731 A US 833731A US 3629434D A US3629434D A US 3629434DA US 3629434 A US3629434 A US 3629434A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
- C07D233/94—Nitro radicals attached in position 4 or 5 with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to other ring members
Definitions
- R and R are each alkylene having 1 to 7 carbon atoms and X is lower alkylsulfonyl, for the control of amebiasis is described.
- This invention relates to the use of various l-alkylsulfonylalkyl 2 alkyl 5 nitroimidazoles in controlling amebiasis.
- Amebiasis is the generic term given to an infectious parasitic disease caused by Entameba histolytica.
- the disease causes inflammation of the colon, characterized in some cases by the passage of bloody stools.
- the mild form of the disease usually occurring in the temperate climates, is usually characterized by ill-defined gastrointestinal complaints, diarrhea, constipation, fatigue, and in some cases abdominal discomfort.
- the disease takes a more severe course (amebic dysentery) and is manifested by the daily passage of numerous fluid or semi-fluid stools, usually containing enormous numbers of active trophozoites. This acute stage of the disease is very debilitating with the patient becoming emaciated and anemic.
- a serious complication which may occur in the advanced stages of the disease is the possible involvement of the liver by intestinal infection giving rise to amebic hepatitis and the formation of amebic abscesses.
- the therapeutic objective is the elimination of all amebae from the affected tissues, the exact mode of treatment depending upon the severity of the infection.
- Two widely used drugs in treating the disease are emetine and Resotren.
- R and R are each alkylene having from 1 to 7 carbon atoms and X is lower alkylsulfonyl; and their pharmaceutically-acceptable acid addition salts.
- the invention also provides an amebicidal composition
- a compound having the herein above mentioned formula and a pharmaceutically acceptatble carrier.
- fl-bromoethyl alkyl sulfides are conveniently prepared by reacting ethyl rnereaptan, bromine, and ethylene in carbon tetrachloride at low temperatures.
- the compounds of this invention are basic in nature, they Will form water-soluble salts with the appropriate acids. Although such salts must be pharmaceutically acceptable, since the final products are intended for animal and human consumption, it is possible to convert the desired compound to a pharmaceutically unacceptable salt and subsequently convert the latter salt to the free organic compound by treatment with a base; the imidazole so obtained is then converted to a pharmaceutically acceptbale acid addition salt there of in the manner hereinafter indicated.
- the acid addition salts of the compounds of this invention can be prepared by treating free base with a substantially equivalent amount of the chosen acid in an aqueous solution or in a suitable organic solvent such as methanol or ethanol. Upon careful evaporation of the solvent, the solid salt is obtained.
- a suitable organic solvent such as methanol or ethanol.
- the acids which are used to prepare the pharmaceutically acceptable acid addition salts of this invention must, of course, be those which necessarily form nontoxic acid addition salts containing a pharmaceutically acceptable anion, such as the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bitartrate, oxalate, succinate, maleate, gluconate, saccharate, methanesulfonate, ethanesulfonate, benzenesulfonte and p-t-oluenesulfonate salts, etc.
- a pharmaceutically acceptable anion such as the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bitartrate
- the compounds of the present invention In the treatment of amebiasis, it is generally preferred to administer the compounds of the present invention orally.
- the compounds are usually administered at a dosage level of from 0.300 g. to 3.00 g. per day. The exact amount will depend upon the amebicidal activity of the particular compound chosen.
- a preferred regimen is to administer 0.100 to 1.00 grams of compound three times a day.
- dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger dosages may be employed without causing any harmul or deleterious side effects to occur provided that such higher dose levels are first divided into several smaller doses that are to be administered throughout the day.
- tablets containing various excipients such as sodium citrate, calcium carbonate and dicalcium phosphate may be employed along with various disintegrants such as starch and preferably potato or tapioca starch, alginic acid and certain complex silicates, together with binding agents such as polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting purposes.
- Solid compositions of a similar type may also be employed as fillers in soft elastic and hard-filled gelatin capsules; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols.
- the essential active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes and, if so desired, emulsifying and/or suspending agents, together with such diluents as water, ethanol, propylene glycol, glycerin and various like combinations thereof.
- solutions of these particular compounds in sesame or peanut oil or in aqueous-propylene glycol may be employed, as Well as sterile aqueous solutions of the corresponding water-soluble acid addition salts previously enumerated.
- aqueous solutions should be suitably bufiered if necessary and the liquid diluent rendered isotonic with sulficient saline or glucose.
- these particular aqueous solutions are especially suitable for intravenous, intramuscular and subcutaneous injection purposes.
- the sterile aqueous media employed are readily obtained by standard techniques well known to those skilled in the art.
- distilled water is ordinarily used as the liquid diluent and the final preparation is passed through a suitable bacterial filter, such as a sintered-glass filter or a diatomaceous-earth or unglazed porcelain filter.
- a suitable bacterial filter such as a sintered-glass filter or a diatomaceous-earth or unglazed porcelain filter.
- Preferred filters of this type include the Berkefeld.
- the 2-alkyl-S-nitroimidazoles in Part I-A are reacted with the B-bromo-ethyl alkyl sulfides in Part I-B according to the procedure of Part II-A, and the resulting tosylates are then converted to the sulfones according to the procedure of Part II-B.
- a suitable acid 0.1 mole of a suitable acid.
- the solvent is removed by evaporation under reduced pressure or lyophilization and the solid acid addition salt is filtered and dried.
- acids that can be used in this procedure are hydrochloric acid, acetic acid, sulfuric acid, citric acid and oxalic salt.
- suitable solvents are ethanol, water, and mixtures thereof.
- EXAMPLE I The compounds of the present invention are elfective in the treatment and control of amebiasis. Table I below contains test results showing the efiicacy of a typical compound with rats infected with Entamoeba histolytica, the causative agent of humanamebiasis. These tests were conducted as follows:
- Laparotomies were performed on 35-45 gram, male, albino rats in order to inject approximately 200,000 Entamoeba histolytica trophozites intracecally.
- the inoculum was prepared from pooled 48 hour cultures maintained on Lockes egg slant-Lockes overlay medium in the presence of an undetermined flora.
- the test drug was administered for four consecutive days commencing 48 hours post-infection.
- the efficacy of the therapy was evaluated 24 hours after the administration of the fourth dose.
- the percent of the rats (7-12 per group) cleared of infection, the average degree of infection (A.D.I.) and the percent efficiency (A.D.I. of treated group divided by A.D.I. of infected control times 100) were determined.
- the minimum eifective dose (MED) of the experimental drug was the lowest dose which produced a percent efficiency equal to or greater than 90.
- a tablet base is prepared by blending the following ingredients in the proportions indicated:
- Oral administration of these tablets 3 times a day to a human host suffering from amebiasis provides effective control of the disease.
- a method for combatting amebiasis in a human which comprises orally administering to said human an amebicidae amount of a compound having the formula:
- R and R are each alkylene having 1 to 7 carbon atoms; X is lower alkylsulfonyl and the pharmaceuticallyacceptable acid addition salts thereof.
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Abstract
WHEREIN R AND R1 ARE EACH ALKYLENE HAVING 1 TO 7 CARBON ATOMS AND X IS LOWER ALKYLSULFONYL, FOR THE CONTROL OF AMEBIASIS IS DESCRIBED.
1-(X-R-),2-(H-R1-),5-(NO-)IMIDAZOLE
THE USE OF COMPOUNDS OF THE FORMULA:
1-(X-R-),2-(H-R1-),5-(NO-)IMIDAZOLE
THE USE OF COMPOUNDS OF THE FORMULA:
Description
United States Patent 3,629,434 USE OF 1-ALKYLSULFONYLALKYL-2-ALKYL- 5 NITROIMIDAZOLES IN CONTROLLING AMEBIASIS Max W. Miller, Stonington, Conn., assignor to Pfizer Inc., New York, N.Y. No Drawing. Filed June 16, 1969, Ser. No. 833,731 Int. Cl. A61k 27/00 U.S. Cl. 424-473 5 Claims ABSTRACT OF THE DISCLOSURE The use of compounds of the formula:
7* NO N )R -H I tX wherein R and R are each alkylene having 1 to 7 carbon atoms and X is lower alkylsulfonyl, for the control of amebiasis is described.
BACKGROUND OF THE INVENTION This invention relates to the use of various l-alkylsulfonylalkyl 2 alkyl 5 nitroimidazoles in controlling amebiasis.
Amebiasis is the generic term given to an infectious parasitic disease caused by Entameba histolytica. The disease causes inflammation of the colon, characterized in some cases by the passage of bloody stools. The mild form of the disease, usually occurring in the temperate climates, is usually characterized by ill-defined gastrointestinal complaints, diarrhea, constipation, fatigue, and in some cases abdominal discomfort. In the tropics the disease takes a more severe course (amebic dysentery) and is manifested by the daily passage of numerous fluid or semi-fluid stools, usually containing enormous numbers of active trophozoites. This acute stage of the disease is very debilitating with the patient becoming emaciated and anemic.
A serious complication which may occur in the advanced stages of the disease is the possible involvement of the liver by intestinal infection giving rise to amebic hepatitis and the formation of amebic abscesses.
' The therapeutic objective is the elimination of all amebae from the affected tissues, the exact mode of treatment depending upon the severity of the infection. Two widely used drugs in treating the disease are emetine and Resotren.
We have now found that the compounds described in the present invention are eifective against amebiasis.
SUMMARY OF THE INVENTION The present invention provides a method for combatting amebiasis in a human host comprising orally administering to the infected patient an amebicidal amount of a compound having the formula:
3,629,434 Patented Dec. 21, 1971 ice Where R and R are each alkylene having from 1 to 7 carbon atoms and X is lower alkylsulfonyl; and their pharmaceutically-acceptable acid addition salts.
The invention also provides an amebicidal composition comprising a compound having the herein above mentioned formula and a pharmaceutically acceptatble carrier.
DETAILED DESCRIPTION OF THE INVENTION rm N 1. Prepare tosylate salt 2. NaOCl T NO -L J R -H l CH CH X R =alkylene having 1 to 7 carbon atoms X=lower alkylsulfonyl In the above procedure the appropriate Z-alkyl-S-nitroimidazole and ,B-bromo-ethyl alkyl sulfide is reacted in formic acid to give the corresponding alkyl-[2-(2-alkyl- S-nitro-l-imidazolyl)ethyl]sulfide, which is then converted to the tosylate salt. Oxidation of the tosylate salt with NaOCl in chloroform affords the desired alkyl[2- (2-alkyl-5-nitro-l-imidazolyl)ethyl] sulfone.
The necessary fl-bromoethyl alkyl sulfides are conveniently prepared by reacting ethyl rnereaptan, bromine, and ethylene in carbon tetrachloride at low temperatures.
In view of the fact that the compounds of this invention are basic in nature, they Will form water-soluble salts with the appropriate acids. Although such salts must be pharmaceutically acceptable, since the final products are intended for animal and human consumption, it is possible to convert the desired compound to a pharmaceutically unacceptable salt and subsequently convert the latter salt to the free organic compound by treatment with a base; the imidazole so obtained is then converted to a pharmaceutically acceptbale acid addition salt there of in the manner hereinafter indicated.
For instance, the acid addition salts of the compounds of this invention can be prepared by treating free base with a substantially equivalent amount of the chosen acid in an aqueous solution or in a suitable organic solvent such as methanol or ethanol. Upon careful evaporation of the solvent, the solid salt is obtained. Alternatively,
other recovery techniques are also applicable, such as freeze-drying when the solvent is water or the use of an anti-solvent in the case of an organic solution, e.g., the addition of diethyl ether to an ethanolic solution of the product will cause precipitation of the desired product to occur.
The acids which are used to prepare the pharmaceutically acceptable acid addition salts of this invention must, of course, be those which necessarily form nontoxic acid addition salts containing a pharmaceutically acceptable anion, such as the hydrochloride, hydrobromide, hydriodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bitartrate, oxalate, succinate, maleate, gluconate, saccharate, methanesulfonate, ethanesulfonate, benzenesulfonte and p-t-oluenesulfonate salts, etc.
In the treatment of amebiasis, it is generally preferred to administer the compounds of the present invention orally. The compounds are usually administered at a dosage level of from 0.300 g. to 3.00 g. per day. The exact amount will depend upon the amebicidal activity of the particular compound chosen. A preferred regimen is to administer 0.100 to 1.00 grams of compound three times a day.
Nevertheless, it is to be appreciated that still other variations may also occur in this respect, depending upon the individual response to said medicament, as well as on the particular type of pharmaceutical formulation chosen and the time period and interval at which such administration is carried out. In some instances, dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger dosages may be employed without causing any harmul or deleterious side effects to occur provided that such higher dose levels are first divided into several smaller doses that are to be administered throughout the day.
For purposes of oral administration, tablets containing various excipients such as sodium citrate, calcium carbonate and dicalcium phosphate may be employed along with various disintegrants such as starch and preferably potato or tapioca starch, alginic acid and certain complex silicates, together with binding agents such as polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting purposes. Solid compositions of a similar type may also be employed as fillers in soft elastic and hard-filled gelatin capsules; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols. When aqueous suspension and/or elixirs are desired for oral administration, the essential active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes and, if so desired, emulsifying and/or suspending agents, together with such diluents as water, ethanol, propylene glycol, glycerin and various like combinations thereof.
Although the preferred mode of administration of the herein described compounds is oral, they may be administered parenterally as well.
For purposes of parenteral administration, solutions of these particular compounds in sesame or peanut oil or in aqueous-propylene glycol may be employed, as Well as sterile aqueous solutions of the corresponding water-soluble acid addition salts previously enumerated. Such aqueous solutions should be suitably bufiered if necessary and the liquid diluent rendered isotonic with sulficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous, intramuscular and subcutaneous injection purposes. In this connection, the sterile aqueous media employed are readily obtained by standard techniques well known to those skilled in the art. For instance, distilled water is ordinarily used as the liquid diluent and the final preparation is passed through a suitable bacterial filter, such as a sintered-glass filter or a diatomaceous-earth or unglazed porcelain filter. Preferred filters of this type include the Berkefeld. the
4 Chamberland and the asbestos disc-metal Seitz filter, wherein the fluid is sucked through the filter candle into a sterile container with the aid of a suction pump. Needless to say, the necessary step should be taken throughout the preparation of these injectable solutions to ensure that the final products are obtained in a sterile condition.
(I) Preparation of Starting Materials (A) Preparation of 2-alkyl-5-nitroimidazoles To 300 ml. of 98% H SO was added 136 g. (1.66 moles) of Z-methylimidazole, allowing the temperature to rise to 132. To this hot solution was added a total of 240 ml. of 70% HNO at such a rate as to maintain a reaction temperature of ISO-170. After the addition of HNO was completed the mixture was stirred for 1.5 hours at ambient temperature, cooled and poured over ice. The pH was adjusted to 6.0, and the product collected by filtration to yield 305 g. (45.2% of theory) of 2- methyl-S-nitroimidazole; M.P. 250-252.
Using the above procedure and the appropriately substituted Z-aIkyI-imidazoles the following 2-alkyl-5-nitroimidazoles are similarly prepared:
2-n-heptyl-5-nitroin1idazole 2-n-butyl-S-nitroimidazole 2-i-propyl-5-nitroimidazole 2-n-pentyl-5-nitroimidazole (B) Preparation of B-bromoethyl alkyl sulfides To a solution of 400 ml. of CCL, and 141 g. (2.27 moles) of ethyl mercaptan which was cooled to 16 was added 359 g. (2.27 moles) of Br in 360 ml. CCL, so that the temperature of the mixture did not exceed l0. The resulting mixture was sparged for 20 hours with N then cooled again to 14. Next 81.2 g. (2.9 moles) of ethylene was added, maintaining a temperature of O or less. After the ethylene had been added the reaction was left at ambient temperature for 20 hours, the solvent stripped and the residue distilled to yield 239 g. of fi-bromoethyl ethyl sulfide (62.5% of theory), B.P. 68 (18 mm.).
Using the appropriate alkyl mercaptans, the following B-bromoethyl alkyl sulfides are also prepared:
,B-bromoethyl-n-propyl sulfide ,B-bromoethyl-n-methyl sulfide fi-bromoethyl-i-propyl sulfide fi-bromoethyl-n-butyl sulfide B-bromoethyl-n-pentyl sulfide fi-bromoethyl-i-butyl sulfide (II) Preparation of l-alkylsulfonylalkyl-Z-alkyl-S- nitroimidazoles (A) Preparation of ethyl[2-(2-ethyl-5-nitro-1- imidazolyl) ethyl] sulfide tosylate A solution of 178 ml. of CH COOH and 250 g. (1.96 mole) of 2-methyl-2-nitroirnidazole was heated to Then 166 g. (0.98 mole) of fl-bromoethyl ethyl sulfide was added and the mixture held at 90 for 1.5 hours. The CH COOH was removed at reduced pressure, and the residue quenched in 260 ml. of water. The unreacted 2- methyl-S-nitroimidazole was removed by filtration, and the pH of the aqueous phase adjusted to 7.0. The product was extracted with CHCl which after drying and concentration gave 166 g. of an oil. The oil was extracted with ether and the extract concentrated to yield 130.7 g. of product still contaminated with the 4-nitro isomer. The mixture was dissolved in ml. ethyl acetate and added to 55 6 g. of p-toluenesulfonic acid in 200 ml. ethyl acetate. On cooling to 2, ethyl[2-(2-methyl-5-nitro-1- imidazolyl)ethyl]sulfide tosylate precipitated and was collected to yield 126 g. (33% of theory), M.P. 112-114.
(B) Preparation of ethyl[2-(2-methyl-5-nitro-limidazolyl ethyl] sulfone A mixture of 530 ml. of H 0, 126 g. (0.326 mole) of tosylate salt from the preceding procedure A above and 200 ml. CHCl was cooled to 7, and 126 ml. of 12.5% NaOCl was added in one portion. The resulting mixture was stirred for minutes, then extracted with CHCl The combined extracts were washed with saturated NaI-ICO and the CHCl replaced with isopropyl alcohol. The solids were collected and dried to yield 39 g. (48% of theory), M.P. 125-126".
The 2-alkyl-S-nitroimidazoles in Part I-A are reacted with the B-bromo-ethyl alkyl sulfides in Part I-B according to the procedure of Part II-A, and the resulting tosylates are then converted to the sulfones according to the procedure of Part II-B.
(III) PREPARATION OF THE ACID ADDITION SALTS OF THE l-ALKYLSULFONYLALKYL-Z- ALKYL-S-NITROIMIDAZOLES The S-nitroimidazole compounds described herein are converted to their acid addition salts by the following general procedure.
To a methanolic solution containing 0.10 mole of the 5-nitr0imidazole is added 0.1 mole of a suitable acid. The solvent is removed by evaporation under reduced pressure or lyophilization and the solid acid addition salt is filtered and dried. Among the acids that can be used in this procedure are hydrochloric acid, acetic acid, sulfuric acid, citric acid and oxalic salt. Other suitable solvents are ethanol, water, and mixtures thereof.
The following examples are provided to illustrate more fully the scope of the present invention; however, they should not be construed to be limitations thereof.
EXAMPLE I The compounds of the present invention are elfective in the treatment and control of amebiasis. Table I below contains test results showing the efiicacy of a typical compound with rats infected with Entamoeba histolytica, the causative agent of humanamebiasis. These tests were conducted as follows:
Laparotomies were performed on 35-45 gram, male, albino rats in order to inject approximately 200,000 Entamoeba histolytica trophozites intracecally. The inoculum was prepared from pooled 48 hour cultures maintained on Lockes egg slant-Lockes overlay medium in the presence of an undetermined flora. The test drug was administered for four consecutive days commencing 48 hours post-infection. The efficacy of the therapy was evaluated 24 hours after the administration of the fourth dose. The percent of the rats (7-12 per group) cleared of infection, the average degree of infection (A.D.I.) and the percent efficiency (A.D.I. of treated group divided by A.D.I. of infected control times 100) were determined. The A.D.I. was determined using the following lesion scoring system: 0=no cecal lesions; 1:few amebae; 2=many amebae, no cecal inflammation; 3=many amebae, cecal inflammation; 4=rnany amebae. cecal inflammation and/or ulceration and mucous. The minimum eifective dose (MED) of the experimental drug was the lowest dose which produced a percent efficiency equal to or greater than 90.
TABLE I A tablet base is prepared by blending the following ingredients in the proportions indicated:
Parts Sucrose, U.-S.P. 82 Tapioca starch 14 Magnesium stearate 4 This base is then blended with sufficient amounts of the 2-nitroimidazoles of the present invention to give after tabletting tablets containing from 100 to 1000 mg. of active ingredient.
Oral administration of these tablets 3 times a day to a human host suffering from amebiasis provides effective control of the disease.
What is claimed is:
1. A method for combatting amebiasis in a human which comprises orally administering to said human an amebicidae amount of a compound having the formula:
wherein R and R are each alkylene having 1 to 7 carbon atoms; X is lower alkylsulfonyl and the pharmaceuticallyacceptable acid addition salts thereof.
2. The method of claim 1 wherein said compound is such that R is alkylene having 1 to 7 carbon atoms, X is lower alkylsulfonyl and R is methylene.
3. The method of claim 1 wherein said compound is such that R is ethylene, X is ethylsulfonyl and R is methylene.
4. The method of claim 1 wherein said compound is such that R is ethylene, X is propylsulfonyl and R is methylene.
5. The method of claim 1 wherein said compound is such that R is ethylene, X is methylsulfonyl and R is methylene.
References Cited UNITED STATES PATENTS 3,399,211 8/1968 Sarrett et al. 424273 SAM ROSEN, Primary Examiner g UNITED STATES PATENT 0 11 11 CERTIFICATE 0F. N v
Patent. Nd. 3,629,434 Date Inventor(s) -Max H 1 MillJ:, assig or t f' Tn'v N It is certified that error appears in the above-identified 15atent and that said Letters Patent are hereby corrected .as shown below; v
[ 061. 1, lines 13-18, N should-read l N I LLR -H l I Signed and sealed this-30th day of May-1972;
(SEAL) Attest:
EDWARD M.FLETCHER,JR. ROBERT GOTTSC HALK Attest ing Officer Commissioner of Patents
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US83373169A | 1969-06-16 | 1969-06-16 |
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US3629434A true US3629434A (en) | 1971-12-21 |
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US833731A Expired - Lifetime US3629434A (en) | 1969-06-16 | 1969-06-16 | Use of 1-alkylsulfonylalkyl-2-alkyl-5 - nitroimidazoles in controlling amebiasis |
Country Status (5)
Country | Link |
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US (1) | US3629434A (en) |
BE (1) | BE751302A (en) |
BR (1) | BR6915182D0 (en) |
FR (1) | FR2052970B1 (en) |
GB (1) | GB1277993A (en) |
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DE2645172C2 (en) * | 1976-10-07 | 1982-02-18 | Basf Ag, 6700 Ludwigshafen | Process for the preparation of 4-nitroimidazoles |
EP0903341A1 (en) * | 1997-07-22 | 1999-03-24 | Akzo Nobel N.V. | "Novel ortho-mercaptoaniline compounds" |
-
1969
- 1969-06-16 US US833731A patent/US3629434A/en not_active Expired - Lifetime
- 1969-12-16 BR BR215182/69A patent/BR6915182D0/en unknown
-
1970
- 1970-05-21 GB GB24764/70A patent/GB1277993A/en not_active Expired
- 1970-06-02 FR FR7020202A patent/FR2052970B1/fr not_active Expired
- 1970-06-02 BE BE751302D patent/BE751302A/en not_active IP Right Cessation
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BE751302A (en) | 1970-12-02 |
GB1277993A (en) | 1972-06-14 |
BR6915182D0 (en) | 1973-02-13 |
FR2052970A1 (en) | 1971-04-16 |
FR2052970B1 (en) | 1974-05-24 |
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