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Publication numberUS3706834 A
Publication typeGrant
Publication dateDec 19, 1972
Filing dateJul 14, 1970
Priority dateNov 30, 1966
Also published asDE1617994A1
Publication numberUS 3706834 A, US 3706834A, US-A-3706834, US3706834 A, US3706834A
InventorsMax Duenncnherger, Max Schellenbaum
Original AssigneeCiba Geigy Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Method for combatting bacteria using certain 2-(2'-hydroxyphenyl)-oxazoles
US 3706834 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

United States Patent Office Patented Dec. 19, 1972 US. Cl. 424-272 Claims ABSTRACT OF THE DESCLOSURE A method for combatting harmful microorganisms, such as fungi and bacteria, by applying a 2-(2'-hydroxyphenyl)- oxazole.

CROSS-REFERENCE TO RELATED APPLICATION This is a continuation-in-part of our application Ser. No. 686,298, filed Nov. 28, 1967, now abandoned.

BACKGROUND OF THE INVENTION The present invention provides a method for combating harmful microorganisms, which comprises applying to a desired site an effective amount of a 2-(2'-hydroxyphenyl)- oxazole of the formula N i R CX or an alkali metal salt thereof, where R is an aromatic ring system containing at most 2 six-membered rings, which is fused on as indicated by the valency lines, and X represents a benzene residue substituted by a hydroxyl group in ortho-position relatively to the bond with the oxazole ring.

Of special value are 2-(2'-hydroxypheny1)-oxazoles of the formula in which R has the above meaning, Me is a hydrogen or alkali metal atom, and at least one of the symbols X and X represents a halogen atom, an amino group or an alkyl group containing up to 4 carbon atoms and the other is a hydrogen or halogen atom or an alkyl group with up to 4 carbon atoms. The present invention is specially concerned with a method for combating harmful microin which Me has the above meaning; at least one of the symbols X and X stands for a halogen atom or an alkyl group with up to 4 carbon atoms and the other for a hydrogen or halogen atom or for an alkyl group with up to 4 carbon atoms, and one to four of the symbols R to R represent hydrogen or halogen atoms and two of these symbols, not standing for hydrogen or halogen atoms, represent phenyl, alkyl, alkoxy, phenylalkyl, cyclohexyl, nitro, primary amino, alkylamino, acylamino, trihalomethyl, aminosulphonyl, methylaminosulphony groups or sulphonic acid groups (possibly in the form of their alkali metal salts); or two vicinal symbols R to R together form the complement to a fused-on carbocycle, which is preferably unsubstituted, and any alkyl carbon chains in the substituents contain at most 12 carbon atoms. Within the indicated meanings -R to R may be chosen independently of one another, that is to say for instance that one and the same molecule may contain 1 to 4 halogen atoms side by side with 0 to 3 hydrogen atoms and 0 to 2, preferably 0 to 1, of the other substituents of the kinds indicated above.

Preferred compounds are the 2-(2-hydroxyphenyl)- benzoxazoles of the formula in which one or both of the symbols R and R are hydrogen, chlorine or bromine atoms, methyl, methoxy or nitro groups and, when one of these symbols does not satisfy this definition, it stands for a phenyl, cyclohexyl group or a phenylalkyl group containing up to 9 carbon atoms; R represents a hydrogen or halogen atom; X a hydrogen, chlorine or bromine atom or a methyl group and X a chlorine or bromine atom.

In this group 2-(2-hydroxyphenyl)-benzoxazoles of the formula N HO X n I l o I O X n where R is a hydrogen, chlorine or bromine atom, an alkyl group with 1 to 4 carbon atoms, a phenyl, cyclohexyl or methoxy group; R represents a hydrogen, chlorine or bromine atom or a methyl group; R a hydrogen, chlorine or bromine atom, and X and X a chlorine or bromine atom eachare particularly valuable as active ingredients of antimicrobial preparations.

More especially, 2-(2-hydroxyphenyl)-benzoxazoles of theformula N HO X, l Q

on X:

where R is a hydrogen, chlorine or bromine atom, a methyl, phenyl or cyclohexyl group, and where R R X and X have the above meaningsare preferred because of their good antimicrobial activity. Extremely satisfactory results in combating microorganisms have been obtained with 2-(2'-hydroxyphenyl)benzoxazoles of the formula N HO Xa 53' where R and R each is a hydrogen, chlorine or bror mine atom or a methyl group, and R X and X have the above meanings. Specifically, the following compounds may be mentioned, for example:

/N\ HO $1 which display an excellent activity against microorganisms, e p c a y g i st bacteria.

4 The 2-(2-hydroxyphenyl)-oxazoles of the Formula 1 can be prepared by known methods by cyclizing an orthohydroxyamino compound of the formula where R has the above meaningwith a functional derivative of a 2-hydroxybenzene-l-carboxylic acid (HOOC-X) and, if desired, introducing further substituents, for example halogen atoms or sulphonic acid groups, into the resulting oxazole compound and/or converting it into an alkali metal salt thereof.

An especially unexpected feautre of the compound of the Formula 1 is their broad antibacterial activity spectrum which, in the case of some of these oxazoles, extends to both Gram-positive and Gram-negative bacteria. In this connection, as far as their application is concerned, the absence of odours and colours in the compound of the Formulas l to 11 is of special value.

The present invention includes also the use of the 2-(2'- hydroxyphenyl)-oxazoles in pest control quite generally. The antimicrobial compounds may be used on a very broad basis, especially for protecting organic substrates from infestation by destructive and pathogenic (including phytopathogenic) microorganisms. Accordingly, the aforementioned compounds may be used as preservatives or disinfectants for textile materials and other industrial products of many kinds, in plant protection, agriculture, veterinary medicine and cosmetics.

From among non-textile industrial products that can be protected with the aid of the oxazoles the following random examples may be given: Textile assistants and improving agents, glues, binders, paints, dyeing and printing pastes and similar preparations based on organic or inorganic dyestuffs or pigments, including those which contain a share of casein or other organic compounds. Likewise, wall and ceiling paints, for example those containing a proteinic dyestutf binder, may be protected from infestation by pests by the addition of the new compounds. Timber may likewise be protected.

Furthermore, the oxazoles may be used for producing preserving and disinfecting finishes on fibres and textile materials, including both natural and synthetic fibres on which they produce a durable protection against harmful (including pathogenic) microorganisms, for example fungi and bacteria. The compounds may be added before, during or after a treatment of such textile materials with other substances, for example dyeing or printing pastes, dressing agents etc.

Textile materials treated in this manner are also protected against body odour (perspiration) caused by microorganisms.

The oxazoles may also be used as preservatives in the cellulose and paper industry, inter alia for preventing the known slime formation in paper-making machines due to microorganisms.

Furthermore, when the oxazoles are combined with surface-active, especially detergent, substances, there are ob tained detergents and cleansing agents having a excellent antibacterial or antimycotic effect. The compounds of the Formulae 1 to 11 can be incorporated, for example, with soaps, or combined with soap-free detergents or surfaceactive substances or they may be combined with mixtures of soaps and soap-free detergents, and their antimicrobial activity is fully maintained in such combinations.

Cleansing preparations containing compounds of the formulae shown above may also be used in industry and the home, in the food industry, for example in dairies, breweries or abattoirs. They may also be used as ingred- 'ients of preparations used for cleansing or disinfecting hospitals or surgeries.

The effect of the oxazoles can also be utilized in pro vinding plastic materials with a preserving and disinfecting finish. When plasticizers are used it is advantageous to dissolve or disperse the antimicrobial compound in the plasticizer and then to incorporate it with the plastic material. It is advantageous to ensure that the additive is as evenly as possible distributed in the plastic material. Plastic materials having antimicrobial properties can be used for making utilitarian articles of all kinds in which an activity against a wide variety of germs, for example bacteria and fungi, is desirable, for example in doormats, bathroom curtains, seats, treads in swimming baths, wall coverings or the like. By incorporation with waxes and polishing compositions, floor and furniture polishes are obtained that have a disinfecting activity.

The antimicrobially active substances can be applied to the textile materials to be protected in a variety of ways, for example by impregnating or spraying with solutions or suspensions containing the above-mentioned compounds as active ingredients. Depending on the individual use, the content of active substance may vary from 1 to 30 g. per litre of treatment liquor.

In most cases textile materials of synthetic or natural origin will be adequately protected from infestation by fungi and bacteria by application of a preparation containing 0.1% to 3% of active substance. The active substances mentioned above may be used in combination with other textile assistants such as dressing agents, anticrease finishing agents or the like.

The form in which the active substances of this invention are applied may be similar to the conventional formulations of pesticidal preparations; for example, prepara tions containing the said active substances may, if desired, further contain additives such as vehicles, solvents, diluents, dispersants, wetting agents, adhesives or the like and also other pesticides.

Unless otherwise indicated, parts in the following manufacturing instructions and examples are by weight.

MANUFACTURING INSTRUCTIONS (A) A mixture of 20.7 parts of 3,5-dichlorosalicylic acid, 12.3 parts of 2 amino-4-methylphenol and 100 parts of polyphosphorio acid is stirred and heated for 3 hours at 195-200 C. under nitrogen. The reaction mixture is then poured in a thin jet over 2000 parts of ice water and the resulting suspension is stirred for 1 /2 hours. The compound A of the formula is filtered off, washed neutral with water and dried. Yield: 28 parts. Melting point: 158160 C. After purification by recrystallization from chloroform+petroleum ether the compound melts at l60l 6l C.

(B) A mixture of 20.7 parts of 3,5-dichlorosalicylic acid, 14.4 parts of 2-amino-4-chlorophenol and 0.4 part of aluminium chloride in 140 parts by volume of o-dichlorobenzene is mixed at 130 C. within 30 minutes with a solution of 12 parts of phosphorus trichlon'de in parts by volume of o-dichlorobenzene. The reaction mixture is then refluxed for 2 hours and poured over ice water. The aqueous layer is separated and the organic phase repeatedly washed with water. The o-dichlorobenzene is expelled with steam, to leave the compound B of in a yield of 22 parts, melting at 199201 C. After recrystallization from dioxane-l-methanol the compound melts at 204-205 C.

(C) 32.0 parts of bromine in 50 parts by volume of glacial acetic acid are added at 50-60 C. within minutes to a solution of 21.1 parts of 2-(2'-hydroxyphenyl)- benzoxazole in 150 parts by volume of glacial acetic acid. The resulting suspension is heated for 2 hours longer at 60 C., then cooled and at 25 C. 200 parts of water are added. The compound C of the formula 5) N HO 1'31 -Q l is filtered off, rinsed with water and dried. Yield: 34 parts. After recrystallization from dioxane-i-acetonitrile or from dimethylformamide the compound melts at 203-204 C.

(D) 56.0 parts of the compound of the formula 6) /N OH Cl (=Compound F in the Table) are stirred within 40 minutes into 130 parts by volume of chlorosulphonic acid. The temperature of the mixture rises gradually to 4550 C., and a clear solution is obtained which is heated for 2 hours at 105-110 C. and then poured in a thin jet over ice water. The precipitated compound of the formula 7) OH Cl hours and then cooled to 25 C., whereupon the compound of the formula NELHO S 1130/ 0 or settles out in light-yellow tflakes melting at 226-228 C. Yield: 17 parts.

A mixture of 4.05 parts of the dimethylamine salt and 20 parts by volume of 2 N sodium hydroxide solution is heated for 15 minutes on a water bath, during which dimethylamine is given off. The solution is cooled to 25 C. and acidified with 2 N hydrochloric acid. The precipitate is filtered off and once recrystallized from aqueous alcohol, to yield about 2.6 parts of the compound D of the formula melting above 400 C.

(E) A solution of 6.29 parts of the compound of the Formula (13) in 100 parts by volume of dimethylformamide is mixed at C. with a solution of 0.8 part of sodium hydroxide in 3.0 parts by volume of water. The

heating bath is removed and 100 parts by volume of alcobegins to settle out slowly. The reaction mixture is cooled hol are added at 45 C. The compound E of the formula to C. and the product filtered off and dried; it melts above 400 C. Yield: 5.4 parts.

B C1 As described in manufacturing instructions A to E 5 above, the 2-(2-hydroxyphenyl)benzoxazoles F to Z, AA

0 to BB of the following table can be prepared; they corre- 3 spond to the .above Formula 3 and the symbols R to R 0 1 X and X have the meanings shown in the table.

Analysis Calculated Found Meltin Compound R1 R R3 R4 X1 X2 point, C C H N O H N H H C1 Cl 160-161 51.17 3.08 4. 76 57. 02 3.17 4. 75 H H C1 Cl 204-205 49. 64 1. 92 4. 49. 84 1. 97 4. 44 H H Br Br 203-204 42. 31 1. 91 3. 80 41. 53 1. 95 4. 05 S OaNa. H C1 C1 700 39.91 1.80 3. 58 40.02 1. 93 3. 70 H H C1 C1 400 46. 40 1. 4. 16 46. 28 1. 43 4. 11 H H C1 C1 185. 5-186. 5 74 2. 52 5.00 55. 96 2. 31 4. 93 C1 H C1 Cl 218-219 49 64 1. 92 4. 45 49. 74 1. 97 4. 38 H H C1 158. 5-159. 5 55 2. 52 5. 00 55. 49 2. 59 5.04 CI H H 01 183-184 55 74 2. 52 5.00 55. 57 2. 53 4. 98 H C1 C1 Cl 201-202 44 74 1. 44 4. 01 44. 78 1. 52 4. 27 H 01 H 01 201-202 49. 64 1. 92 4. 45 49. 76 2.10 4. 42 H H H Br 174-176 48.11 21. 7 4. 32 47. 97 2. 25 4.05 H H Br Br 217-219 38. 70 1. 49 3. 47 38. 67 1. 65 3. 37 Cl H Br Br 224. 5-226. 5 38. 7 1. 49 3. 47 38. 71 1. 56 3. 42 CH H C1 Cl 170-180 57.17 3.08 4. 76 57.35 3.16 4. 59 H H H Cl 154-155 64.75 3.88 5. 39 64. 79 3. 83 5. 37 H H H Br 163-165 55. 29 3. 31 4. 61 55. 08 3. 53 4. 84 CH; H C1 Cl 232-233 58. 46 3. 4. 55 58. 25 3. 66 4. H H 01 Cl 149-151 60. 73 4. 50 4.17 61.02 4. 52 4. 26 H H Br Br 157-158. 5 48.03 3. 56 3. 29 47. 77 3. 54 3. 42

H C1 Cl 181-182 64.07 3.11 3. 3. 3.

H C1 Cl 151-152 63.00 4.73 3.87 63.09 4.90 3.83

: mmj I X H $113 11 C1 01 165166 66.31 4.30 3.52 66.05 4. 17 3.71

Y 11 H N Oz 11 C1 Cl 293-294 48. 03 1. 86 8. 62 18. 1O 2 O0 8. 60 Z H CH3 0 H H C1 C1 169-171 54. 21 2. 93 4. 52 54. 33 3 O6 4. 42

AA H H CHaNH 1'1 01 01 254-255 45. O6 2. 7O 7. 51 45. 35 2 7. 38

CH C1 C1 C1 278-279 78 2. 41. 3. 71 48. O6 2. 44 3. 58 H H CH; 131-132 74. 65 4. 92 6. 22 74. 53 5. 11 6. 19 H C1 B! B! 264-265 44. 74 1. 44 4. 01 45. O4 1. 69 4. 04 H Cl Br B1 291-292 33. O5 0. 2. 97 33. 25 O. 83 3. 02 11 H CH; 165. 6-166 5 64. 75 3. 88 5. 39 64. 54 4. 02 5.46 H H CH: 128-129 5 64. 75 3. 88 5. 39 64. 85 3. 87 5. 31 H H B1 B1 206-207 34. 86 1. 35 3. 13 34. 89 1. 42 3. 04 H H CH3 B1 163-164 56. 62 3. 80 4. 40 56. 76 4. 03 4. 42 H H CH] BI 183-134 49. 66 2. 68 4. 14 49. 73 2. 77 4. 11 H H Bl CH3 218-219 49. 66 2. 68 4. 14 49. 52 2. 62 4. 19 H H Bl CH; 168. 5-169 5 56. 62 3. 80 4. 40 56. 61 4. 0O 4. 16 H H 01 CH: 155. 5-156 5 65. 82 4. 42 5. 12 65. 67 4. 54 4. 89 H H Cl CH1 195-19 57. 17 3. 08 4. 76 57. 34 3. 17 4. 62 H H CH; 01 174-175 57. 17. 3. 98 4. 76 57. 07 2. 86 4. 98 H H CH: 01 160-161 65. 82 4. 42 5. 12 65. 84 4. 48 4. 99 H H B1 C1 160. 5-161 5 49. 66 2. 68 4. 14 49. 78 2. 84 4. 07 H H B1 C1 213. 5-215 43. 49 1. 68 3. 90 43. 73 2. 05 3. 92

(RH! H H 01 Cl 156-151 64. 29 5. 91 3. 57 64. 3'1 6. 99 3. 36 z):C-CHs- I AT H (3H3 H H B1 B1 160. 5-161 52. 41 4. 82 2. 91 52, 2O 4. 88 2 79 a)a-CCHn OF; H H C1 Cl 169-171 48. 1. 74 4. 02 29 16. 9 4. 23

CF H H 131 B1 192-193 5 38. 48 1. 38 3. 21 38. 56 1. 41 3. 38 OF; H H B1 140. 5-141 5 46. 1. 97 3. 91 47. 10 2. 11 3. 77 CF; H H Cl -146 53. 61 2. 25 4. 47 53. 76 2. 34 4. 28 $0311 H C1 Cl 327-329 43. 35 1. 96 3. B9 43. 12 2. 9O 4. 06 N0 H H C1 C1 223; 5-224 5 43. 03 1. 86 8. 62 47. 81 2. 04 8 60 NH; H H 01 Cl 265-266 52. 91 2. 73 9. 49 53. 12 2. 93 9. 72 NH: H C1 Cl 273-274 52. 91 2. 73 9. 49 53. U9 2. 73 9. 49

The following compounds are accessible in an analogous manner:

Analysis Calculated Found Melting Compound Formula point, C. C H N C H N I /N\ H0 31 l o 01 BE 01 N\ H( 272-273 59.90 3.48 10.76 59.77 3.77 10.53

EXAMPLE 1 EXAMPLE 2 Determining the minimal inhibitory concentration (MIC) against bacteria in the dilution test The MIC (minimal inhibitory concentration) is determined by a method adapted from the standard procedure, which furnishes an approximation to absolute minimal inhibitory values of an active substance.

A solution of 1% and 0.3% strength each of the above substances in dimethylsulphoxide are poured into small tubes containing glucose broth and with these solutions dilution series are prepared in which each member is a tenfold dilution of the preceding one. By combining the two series, the following continuous dilution series is obtained: 1000, 300, 100, 30, 10, 3 parts per million and so The solutions are inoculated with Staphylococcus aureus and then incubated for 48 hours at 37 C. (bacteriostatic test).

After the time mentioned, the minimal inhibitory values in parts per million, shown in the following table, are found:

Compound: Minimal inhibitory concentration (MIC) l 111 parts per million bacteriostatie test, Staphylococcus aureus.

Antibacterial soaps in cake form are manufactured by adding 1.2 g. of a compound of the Formula 1 to the following mixture:

120 g. of basic soap in flake form 0.12 g. of the disodium salt of ethylenediamine tetraacetic acid (dihydrate) 0.24 g. of titanium dioxide 6 g. ethyleneglycol 10, 3, 1, and so on, parts per million of active substance.

The solutions are inoculated with the bacteria Staphylococcus aureus, Escherichia coli, and incubated for 24 hours at 37 C. After this time, 0.05 ml. is withdrawn with a pipette from each solution and poured out over brain heart infusion slant-agar. 'Ihe agar tubes are then incubated for another 24 hours at 37 C., and then the minimal lethal concentration in parts per million is determined.

Staphylococ- Escherichiiq 2 Compound cus aureus co EXAMPLE 3 Specimens of a Woolen fabric are impregnated with an 0.1 solution of a compound of the Formula I in dioxane and then padded to a liquid content of 100%. The dried fabric specimens contain 0.1% active substance, referred to their own weight.

To test the effect against bacteria round blanks of mm. diameter of the impregnated fabrics are placed on glucose agar plates, which have previously been inoculated with Staphylococcus aureus, and the plates are then incubated for 24 hours at 37 C.

The valuation extends, on one hand, to the inhibitory zones (IZ in mm.) found around the blanks and, on the other hand, to the growth (6%) detected underneath them by microscopic examination:

Staphylococcus aureus Compound IZ (mm.) percent What is claimed is:

1. A method for combatting bacteria which comprises applying to said bacteria an anti-bacterially effective amount of a 2-(2-hydroxyphenyl)-benzoaxole of the formula in which R represents a member selected from the group consisting of hydrogen, chlorine, bromine, alkyl with up to 4 carbon atoms, phenyl, cyclohexyl and methoxy, R represents a member selected from the group consisting of hydrogen, chlorine, bormine and methyl and R is hydrogen, cholrine or bromine and X and X represent chlorine or bromine each.

2. The method of claim 1, wherein the 2-(2'-hydroxyphenyl)-benzoxazole has the formula.

l N HO X8 12 in which R represents a member selected from the group consisting of hydrogen, chlorine, bromine, methyl, phenyl and cyclohexyl.

3. The method of claim 1, wherein the 2'(2'-hydroxyphenyl) -benzoxazole has the formula 4. The method of claim 3, wherein the 2-(2'-hydroxyphenyl)-benzoxazole has the formula N H0 or 5. The method of claim 3, wherein the 2-(2'-hydroxyphenyl)-benzoxazole has the formula HO C1 References Cited FOREIGN PATENTS 957,438 5/ 1964 Great Britain. 372,871 10/1963 Switzerland. 1,000,819 1/1967 Germany.

217,997 11/1961 Austria 260-307 ALBERT T. MEYERS, Primary Examiner L. SCHENKMAN, Assistant Examiner 5-6062/E/CONT mgg UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 7 6, 3u Dated December 9 1972 Inventbfl) MAX SCHELLENBAUM ET AL It is certifiedthat error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, lines 5 and 6, delete "Corporation" and insert AG Signedand sealed this 2nd day of July 1974.

(SEAL) Attest: v

EDWARD MTFLETC HERJR. C. MARSHALL DANN Attesting Officer Commissioner of Patents

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US5216110 *Jan 10, 1992Jun 1, 1993The Dow Chemical CompanyMonomers useful in nucleophilic displacement synthesis of polybenzazole polymers
US5665737 *Oct 12, 1994Sep 9, 1997Euro-Celtique, S.A.Phosphodiesterase inhibitors
US5744473 *Sep 16, 1996Apr 28, 1998Euro-Celtique, S.A.Used for treating allergies, inflammation, asthma, and rhinitis
US5864037 *Jun 6, 1996Jan 26, 1999Euro-Celtique, S.A.Dethionating, halogenating and aminating a 2-thiocarbonyl-6-oxo-3,8-disubstituted-1,2,3,6-tetrahydro-3h-purine to obtain the 6-amino derivative; bronchodilators; antiinflammatory agents
US5889014 *Sep 20, 1996Mar 30, 1999Euro-Celtique, S.A.Heterocyclic compounds for inhibiting phosphodiesterase IV
US5922751 *Jan 10, 1997Jul 13, 1999Euro-Celtique, S.A.Aryl pyrazole compound for inhibiting phosphodiesterase IV and methods of using same
US5939422 *Jun 21, 1994Aug 17, 1999Euro-Celtique, S.A.An enzyme inhibitor as bronchodilator, relaxants, antiinflammatory agent for treating asthma, allergies, inflammation, depression, dementia, diseases associated with abnormal high level of cytokine
US5977119 *Sep 15, 1997Nov 2, 1999Euro-Celtique, S.A.Trisubstituted thioxanthines
US6025361 *Dec 12, 1995Feb 15, 2000Euro-Celtique, S.A.Effective pde iv inhibitors, asthma
US6066641 *Dec 12, 1995May 23, 2000Euro-Celtique S.A.Phosphodiesterases as molecular targets for anti-asthmatic agents
US6075016 *Apr 10, 1997Jun 13, 2000Euro-Celtique S.A.6,5-fused aromatic ring systems having enhanced phosphodiesterase IV inhibitory activity
US6153630 *Jan 11, 1996Nov 28, 2000Euro-Celtique, S.A.Phenylpyridyl compounds for inhibiting phosphodiesterase IV and methods of using same
US6166041 *Nov 3, 1997Dec 26, 2000Euro-Celtique, S.A.2-heteroaryl and 2-heterocyclic benzoxazoles as PDE IV inhibitors for the treatment of asthma
US6310205Jan 26, 1999Oct 30, 2001Euro-Celtique, S.A.Intermediates for preparing 3-substituted adenines and 3,8-di-substituted 6-aminopurine derivatives for use as phosphodiesterase inhibitors.
US6372770 *Sep 11, 1998Apr 16, 2002Euro-Celtique, S.A.Benzoxazoles
WO1996011917A1 *Oct 11, 1995Apr 25, 1996David J CavallaNovel benzoxazoles
Classifications
U.S. Classification514/375
International ClassificationC07D263/60, D06M16/00, C07D263/57, C07D263/56
Cooperative ClassificationD06M16/00, C07D263/57, C07D263/60
European ClassificationD06M16/00, C07D263/60, C07D263/57