US3907895A - Keto-quaternary compounds - Google Patents
Keto-quaternary compounds Download PDFInfo
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- US3907895A US3907895A US445542A US44554274A US3907895A US 3907895 A US3907895 A US 3907895A US 445542 A US445542 A US 445542A US 44554274 A US44554274 A US 44554274A US 3907895 A US3907895 A US 3907895A
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- Prior art keywords
- compounds
- keto
- bromide
- quaternary ammonium
- quaternary compounds
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- 150000001875 compounds Chemical class 0.000 title claims description 17
- IKONLTRHPFIXAA-UHFFFAOYSA-N [1-(1-adamantyl)-1-oxotetradecan-3-yl]-dimethylazanium bromide Chemical compound [Br-].C12(CC3CC(CC(C1)C3)C2)C(=O)CC(CCCCCCCCCCC)[NH+](C)C IKONLTRHPFIXAA-UHFFFAOYSA-N 0.000 claims 1
- OGKGXSSRQYMVOR-UHFFFAOYSA-N [Br-].C12(CC3CC(CC(C1)C3)C2)C(=O)CC(CCCCCCCCCCCCC)[NH+](C)C Chemical compound [Br-].C12(CC3CC(CC(C1)C3)C2)C(=O)CC(CCCCCCCCCCCCC)[NH+](C)C OGKGXSSRQYMVOR-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001453 quaternary ammonium group Chemical group 0.000 abstract description 4
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical group C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000468 ketone group Chemical group 0.000 abstract description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- -1 adamantyl radical Chemical class 0.000 description 3
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 3
- 125000005228 aryl sulfonate group Chemical group 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- ZVJUTDORASFVHU-UHFFFAOYSA-N 1,3-bis(1-adamantyl)-1,3-dibromopropan-2-one Chemical compound C1C(C2)CC(C3)CC2CC13C(Br)C(=O)C(Br)C1(C2)CC(C3)CC2CC3C1 ZVJUTDORASFVHU-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical group [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- UBLAMKHIFZBBSS-UHFFFAOYSA-N 3-Methylbutyl pentanoate Chemical compound CCCCC(=O)OCCC(C)C UBLAMKHIFZBBSS-UHFFFAOYSA-N 0.000 description 1
- XGRSAFKZAGGXJV-UHFFFAOYSA-N 3-azaniumyl-3-cyclohexylpropanoate Chemical compound OC(=O)CC(N)C1CCCCC1 XGRSAFKZAGGXJV-UHFFFAOYSA-N 0.000 description 1
- 208000020154 Acnes Diseases 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000206575 Chondrus crispus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241001134658 Streptococcus mitis Species 0.000 description 1
- WKQQCBZRBJMIPF-UHFFFAOYSA-M [4-(1-adamantyl)-4-oxobutyl]-dimethyl-tetradecylazanium;bromide Chemical compound [Br-].C1C(C2)CC3CC2CC1(C(=O)CCC[N+](C)(C)CCCCCCCCCCCCCC)C3 WKQQCBZRBJMIPF-UHFFFAOYSA-M 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002272 anti-calculus Effects 0.000 description 1
- 230000000675 anti-caries Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical class C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 229910000400 magnesium phosphate tribasic Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- SFBHPFQSSDCYSL-UHFFFAOYSA-N n,n-dimethyltetradecan-1-amine Chemical compound CCCCCCCCCCCCCCN(C)C SFBHPFQSSDCYSL-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 1
- 229960004711 sodium monofluorophosphate Drugs 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
- A61K8/416—Quaternary ammonium compounds
Definitions
- the present invention relates to novel quaternary ammoniumcompounds represented by the general formula:
- R is l-am adantyl '(C Hi R is a long chain alkyl group of l l 8 carbon atoms, 11 is an integer from 1 to 3 and X is a compatible anion such as the halides (Cl' Br, I), sulfates (i.e.. methyl sulfateynitrate. aryl sulfonates, etc.
- the quaternary compounds possess superior anti-microbial. anti-caries and anti-calculus activity.
- the adamantyl radical is derived from tricyclo- [3.3. l l ldeeane showing four fused chair cyelohexane rings as follows:
- quaternary ammonium compounds which may be used in this invention are: 2adamantylearbonylethyldimethyldeeylammonium bromide. 3-adamantylcarbonylpropyldimethyltetradecylammonium bromide, Z-adamantylcarbonylethyldimethylhexadecylammonium bromide, l-adamantylearbonylethyldimethyloctadeeylammonium bromide, l-adamantylcarbonylmethyldimethyltetradecylammonium bromide, l-adamantylcarbonylmethyldimethyldodecylammonium bromide.
- Other halides such as the chlorides, iodides and analogous compounds such as the sulfates, nitrate, aryl sulfonates, ctc.. may also be employed herein as effective anti-
- test tube serial dilution test in which an appropriate number of test tubes of broth containing decreasing concentrations of the test agent was inoculated with the test organism. After a suitable period of incubation the tubes were examined for the presence or absence of growth. The activity of the test agent was the lowest concentration which inhibited the growth of the organism and 'is expressed as the minimal inhibitory concentration in ug/ml.
- compounds of the instant invention When used against bacteria or fungi. compounds of the instant invention may he applied directly to the surface to be protected or may be dissolved in a pharmaceutical carrier.'Typically. an effective amount, e.g. 0.] to about-10% by weight ofthe' eompound.-is included in an inert carrier and a dispersing or. surface active agent. Alternatively. an effective amount. eg 0.] to about' l0 /z by weight may be incorporated into a solid carrier which may be inert. such as talc. clay. diatomaceous earth. flour. etc.
- the oral preparation is a dentrifrice.
- a dental cream. tablet or powder containing as a vehicle about 20-95% by weight of a waterinsoluble polishing material. preferably including water-insoluble phosphate such as dicalcium phosphate, tricalcium phosphate. trimagnesium phosphate.
- the dentrifrice may also include water; binders such as glyeerine. sorbitol, propylene glycol.
- detergents such as Irish moss and sodium carboxymethyl cellulose; additional antibacterial agents. coloring or whitening agents; preservatives; silieones; chlorophyll compounds; additional ammoniated materials; flavoring or sweetening materials; and compounds which provide fluorine-containing ion such as sodium flouride, stannous flouride and sodium monofluorophosphate.
- the oral preparation may also be a liquid such as mouth rinse which typically contains 20-997! by weight of an aqueous lower aliphatic alcohol, preperably having about 1-3071 by weight alcohol, such as ethanol. n-propyl. or isopropyl alcohol.
- aqueous lower aliphatic alcohol preperably having about 1-3071 by weight alcohol, such as ethanol. n-propyl. or isopropyl alcohol.
- Such oral preparations are typically applied by brushing the teeth or rinsing the oral cavity for 30-90 seconds at least once daily.
- Typical oral preparations of the invention which can be applied in this manner are set forth below.
- EXAMPLE 4 The dodecyl homolog was prepared by the procedure of Example 3 yielding white crystals of melting point l40-l4l.5C and with the following analysis.
- R is l-adamantyl.
- R is a long chain alkyl group of 10 to 18 carbon atoms
- n is an integer from 1 to 3.
- X is an anion selected from the group consisting of chloride. bromide, iodide. methyl sulfate. nitrate and arylsulfonates.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Novel keto-quaternary ammonium compounds which include the adamantane ring system linked to the quaternary ammonium group by a keto group.
Description
United States Patent Bauman Sept. 23, 1975 KETO-QUATERNARY COMPOUNDS [56] References Cited [75] Inventor: Robert Andrew Bauman, New UNITED STATES PATENTS Brunswick, 3,565,942 2/1971 Krimmel 260/468 G 3,591,642 v7/1971 Szinai et al. [73] Asslgnee' gg f g New 3,663,617 511972 Pedrazzoli et al 260/563 P I ER P BLI A [22] Filed: Feb. 25, 1974 GT U TIONS Stepanov et aI.,- Zh. Organ. Khlm 2(4), pp. 644-648.
[21] Appl. No.: 445,542
Related U.S. Application Data Continuation-in-part of Ser. No. 400,097, Sept. 24, 1973, which is a continuation of Ser. No. 39,536, May 21, 1970, abandoned.
U.S. Cl 260/567.6 M; 424/329; 424/54;
260/501.15; 260/459 Int. Cl. C07c 87/00 Field of Search 260/567.6 M, 468 G, 584 R,
[57] ABSTRACT Novel keto-quaternary ammonium compounds which include the adamantane ring system linked to the quaternary ammonium group by a keto group.
4 Claims, No Drawings I KETO-QUATERNARY COMPOUNDS The present application is a continuation-in-part of copending application Ser. No. 400.097 filed Sept. 24. 1973, which is a continuation of patent application Ser. No. 39. 536 filed May 21. l970.'now abandoned.
The present invention relates to novel quaternary ammoniumcompounds represented by the general formula:
whereinR is l-am adantyl '(C Hi R is a long chain alkyl group of l l 8 carbon atoms, 11 is an integer from 1 to 3 and X is a compatible anion such as the halides (Cl' Br, I), sulfates (i.e.. methyl sulfateynitrate. aryl sulfonates, etc. The quaternary compounds possess superior anti-microbial. anti-caries and anti-calculus activity.
The adamantyl radical is derived from tricyclo- [3.3. l l ldeeane showing four fused chair cyelohexane rings as follows:
Typical examples of the quaternary ammonium compounds which may be used in this invention are: 2adamantylearbonylethyldimethyldeeylammonium bromide. 3-adamantylcarbonylpropyldimethyltetradecylammonium bromide, Z-adamantylcarbonylethyldimethylhexadecylammonium bromide, l-adamantylearbonylethyldimethyloctadeeylammonium bromide, l-adamantylcarbonylmethyldimethyltetradecylammonium bromide, l-adamantylcarbonylmethyldimethyldodecylammonium bromide. Other halides such as the chlorides, iodides and analogous compounds such as the sulfates, nitrate, aryl sulfonates, ctc.. may also be employed herein as effective anti-bactericides.
It has been observed that the compounds generally described by the foregoing formula are particularly effective against gram positive organisms such as Staphylococcus our-cur. Streptococcus mitis, Bacillus .s'ubti lis. Coryncbacterium acnes. and against fungi. such as Candida albicans, 'I'riclzop/zyrrm menlogrophytes and Aspergillus niger. and moderately effective against Ext-heric/n'a coli which is a gram negative bacterium. Compounds wherein R is a benzyl radical in lieu of instant higher alkyl radical would be devoid of anti-bacterial activity.
The anti-microbial nature of the instant novel compounds was shown by a standard test tube serial dilution test in which an appropriate number of test tubes of broth containing decreasing concentrations of the test agent was inoculated with the test organism. After a suitable period of incubation the tubes were examined for the presence or absence of growth. The activity of the test agent was the lowest concentration which inhibited the growth of the organism and 'is expressed as the minimal inhibitory concentration in ug/ml.
In general. smaller concentrations of the subject compounds are required to inhibit the growth of the organisms than of analogous compounds which contain substantially the'same number of carbon atoms.
When used against bacteria or fungi. compounds of the instant invention may he applied directly to the surface to be protected or may be dissolved in a pharmaceutical carrier.'Typically. an effective amount, e.g. 0.] to about-10% by weight ofthe' eompound.-is included in an inert carrier and a dispersing or. surface active agent. Alternatively. an effective amount. eg 0.] to about' l0 /z by weight may be incorporated into a solid carrier which may be inert. such as talc. clay. diatomaceous earth. flour. etc.
When compounds of the instant invention are intended for use in compositions which reduce formation of caries and inhibit formation of oral calculus. they are typically incorporated in oral preparations in effective amounts up to about 5% by weight. preferably .025] '7! and most'preferably 0.050.5'/1'by weight of the oral preparation. Typically. the oral preparation is a dentrifrice. such as a dental cream. tablet or powder. containing as a vehicle about 20-95% by weight of a waterinsoluble polishing material. preferably including water-insoluble phosphate such as dicalcium phosphate, tricalcium phosphate. trimagnesium phosphate. The dentrifrice may also include water; binders such as glyeerine. sorbitol, propylene glycol. and polyethylene glycol 400; detergents; gelling agents such as Irish moss and sodium carboxymethyl cellulose; additional antibacterial agents. coloring or whitening agents; preservatives; silieones; chlorophyll compounds; additional ammoniated materials; flavoring or sweetening materials; and compounds which provide fluorine-containing ion such as sodium flouride, stannous flouride and sodium monofluorophosphate.
The oral preparation may also be a liquid such as mouth rinse which typically contains 20-997! by weight of an aqueous lower aliphatic alcohol, preperably having about 1-3071 by weight alcohol, such as ethanol. n-propyl. or isopropyl alcohol.
Such oral preparations are typically applied by brushing the teeth or rinsing the oral cavity for 30-90 seconds at least once daily. Typical oral preparations of the invention which can be applied in this manner are set forth below.
EXAMPLE 1 Dental Cream Quaternary ammonium 0.50 adamantylkctonc *Nonionic detergent L00 Glycerine 22.00 Sodium pyrophosphate 0.25 Carboxymethyl cellulose 0.85 Sodium saccharin 0.20 Sodium henzoate 0.50 Calcium carbonate (precipitated) 5.00 Dicalcium phosphate dihydrate 46.75 Flavor 0.80 Water 2215 *Tween Polyuxyethylene (20 moles ethylene oxide) sorhitan monooleale EXAMPLE 2 !\1oulh Wash Quaternary ammonium 0.05 adamnntylketune *Nonionic detergent (Pluronic F478) 1.00 Ethyl alcohol (containing Flavor) 15.00 Gl 'eerine 10.00 Saceharin 0.02 Water 73.93
EXAMPLE 3 Preparation of l-adamantylcarbonylmethyldimethyltetradecylammonium bromide.
A mixture of 1.3g. (0.005 mole) l-adamantyl bromomethyl ketone and 1.23g. (0.005 mole) dimethyltetradecylamine was solubilized by the addition of cc acetone. The next day the solidified mixture was washed with ether and recrystallized from ethyl acetate to yield 2.1g. white crystals, m.p. l34l35.5C.
Found Calculated Carbon 67.72 (17.45
Hydrogen 10.65 10.5l
EXAMPLE 4 The dodecyl homolog was prepared by the procedure of Example 3 yielding white crystals of melting point l40-l4l.5C and with the following analysis.
Found Calculated Carbon 66.55 (16.36 Hydrogen 9.87 10.18
Although this invention has been described with reference to specific examples. it will be apparent to one skilled in the art that various modifications may be made thereto which will fall within its scope.
What is claimed is: v
1. A chemical compound having the structural formula:
wherein R is l-adamantyl. R is a long chain alkyl group of 10 to 18 carbon atoms, n is an integer from 1 to 3. and X is an anion selected from the group consisting of chloride. bromide, iodide. methyl sulfate. nitrate and arylsulfonates.
2. A chemical compound as set forth in claim 1, wherein X is a halide.
3. l-adamantanecarbonylmethyldimethyldodeeylammonium bromide.
4. l-adamantanecarbonylmethyldimethyltet-
Claims (4)
1. A CHEMICAL COMPOUND HAVING THE STRUCTURAL FORMULA.
2. A chemical compound as set forth in claim 1, wherein X is a halide.
3. 1-adamantanecarbonylmethyldimethyldodecylammonium bromide.
4. 1-adamantanecarbonylmethyldimethyltetradecylammonium bromide.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US445542A US3907895A (en) | 1973-09-24 | 1974-02-25 | Keto-quaternary compounds |
| CA209,689A CA1059124A (en) | 1973-09-24 | 1974-09-20 | Quaternary compounds and oral compositions containing said compounds |
| GB4125174A GB1475899A (en) | 1974-02-25 | 1974-09-23 | Oral compositions containing quaternary ammonium compounds |
| DE19742450707 DE2450707A1 (en) | 1974-02-25 | 1974-10-25 | NEW QUATERNAERE CONNECTIONS AND THESE ORAL CARE PRODUCTS |
| FR7501676A FR2272651B1 (en) | 1974-02-25 | 1975-01-20 | |
| US05/576,082 US3961074A (en) | 1974-02-25 | 1975-05-09 | Keto-quaternary compositions |
| FR7735917A FR2366261A1 (en) | 1974-02-25 | 1977-11-29 | NEW QUATERNARY AMMONIUM DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR APPLICATION |
| FR7735918A FR2366267A1 (en) | 1974-02-25 | 1977-11-29 | IMPROVEMENT IN QUATERNARY AMMONIUM DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR APPLICATION |
| FR7735919A FR2366260A1 (en) | 1974-02-25 | 1977-11-29 | IMPROVEMENT WITH QUATERNARY AMMONIUM COMPOUNDS, THEIR PREPARATION PROCESS AND THEIR APPLICATION |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US400097A US3928411A (en) | 1970-05-21 | 1973-09-24 | New quaternary compounds having anti-microbial activity |
| US445542A US3907895A (en) | 1973-09-24 | 1974-02-25 | Keto-quaternary compounds |
| GB41256/74A GB1483508A (en) | 1970-05-21 | 1974-09-23 | Quaternary ammonium compounds and oral compositions containing them |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US400097A Continuation-In-Part US3928411A (en) | 1970-05-21 | 1973-09-24 | New quaternary compounds having anti-microbial activity |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US05/576,082 Division US3961074A (en) | 1974-02-25 | 1975-05-09 | Keto-quaternary compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3907895A true US3907895A (en) | 1975-09-23 |
Family
ID=27259694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US445542A Expired - Lifetime US3907895A (en) | 1973-09-24 | 1974-02-25 | Keto-quaternary compounds |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3907895A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4046873A (en) * | 1973-09-24 | 1977-09-06 | Colgate Palmolive Company | Alicyclic amido-quaternary ammonium anti-bacterial agents |
| US4288609A (en) * | 1976-11-24 | 1981-09-08 | Rotta Research Laboratorium S.P.A. | Quaternary ammonium derivatives of adamantane with antimicrobic activity |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3565942A (en) * | 1966-06-13 | 1971-02-23 | Searle & Co | Dialkylaminoalkyl esters of adamantanecarboxylic acids |
| US3591642A (en) * | 1966-10-24 | 1971-07-06 | Lilly Co Eli | Adamantane compounds |
| US3663617A (en) * | 1968-10-21 | 1972-05-16 | Rech Et D Applic Scient Et Med | 1-(adamantylmethyloxy) - 2 - hydroxy-3-substituted amino propanes and acid addition salts thereof |
-
1974
- 1974-02-25 US US445542A patent/US3907895A/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3565942A (en) * | 1966-06-13 | 1971-02-23 | Searle & Co | Dialkylaminoalkyl esters of adamantanecarboxylic acids |
| US3591642A (en) * | 1966-10-24 | 1971-07-06 | Lilly Co Eli | Adamantane compounds |
| US3663617A (en) * | 1968-10-21 | 1972-05-16 | Rech Et D Applic Scient Et Med | 1-(adamantylmethyloxy) - 2 - hydroxy-3-substituted amino propanes and acid addition salts thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4046873A (en) * | 1973-09-24 | 1977-09-06 | Colgate Palmolive Company | Alicyclic amido-quaternary ammonium anti-bacterial agents |
| US4288609A (en) * | 1976-11-24 | 1981-09-08 | Rotta Research Laboratorium S.P.A. | Quaternary ammonium derivatives of adamantane with antimicrobic activity |
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