US4339453A
Expired / Lapsed
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Antimicrobial aminopyrimidinium salts
Assignee: Merck and Co Inc
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Filing: 1979-07-23
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Granted: 1982-07-13
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Expires: 1999-07-23
Abstract
Abstract 4-Amino- and 2,4-diaminopyrimidines with a quaternized ring nitrogen and an oxygen bearing substituent such as hydroxyalkyl, alkoxyalkyl, or alkanoyl on one of the exo- or endocyclic nitrogens and a C6-18 alkyl on another, are highly active antimicrobial agents with a relatively low acute mammalian toxicity.
Inventors
- 👤 Nathaniel Grier
- 👤 Elbert E. Harris
- 👤 Henry Joshua
- 👤 Arthur A. Patchett
- 👤 Bruce E. Witzel
- 👤 Richard A. Dybas
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 17:32
CPC Classifications
C; C07; C07D; C07D239/00; C07D239/02; C07D239/24; C07D239/28; C07D239/32; C07D239/42; A; A01; A01N; A01N43/00; A01N43/48; A01N43/54; C07D239/46; C07D239/48
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
208 words
A compound of structural formula: ##STR59## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N--; R 1 is (1) C 2-5 alkenyl (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy, (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gem-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or (6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 2
Dependent Claim
208 words
A compound of structural formula: ##STR59## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N--; R 1 is (1) C 2-5 alkenyl (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy, (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gem-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or (6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 3
Dependent Claim
13 words
The compound of claim 1, wherein R is R 2 R 3 N--.
Claim 4
Dependent Claim
62 words
The compound of claim 2, wherein R 1 is C 1-5 alkyl, hydroxy-C 1-5 alkyl, or C 3-5 alkenyl; one of R 2 R 3 N-- and R 4 R 5 N-- is hydroxy-C 1-5 alkyl-NH-- and the other is C 12 alkyl-NH- or di(C 6 alkyl)N--; R 6 is hydrogen or C 1-3 alkyl; and A - is halide, or acetate.
Claim 5
Dependent Claim
13 words
The compound of claim 3 which is 4-(n-dodecylamino)-2-(2-hydroxyethylamino)-1-methylpyrimidinium chloride, bromide, iodide, or acetate.
Claim 6
Dependent Claim
11 words
The compound of claim 3 which is 4-(n-dodecylamino)-2-(2-hydroxyethylamino)-1-(2-methyl-2-propenyl)pyrimidinium chloride or bromide.
Claim 7
Dependent Claim
12 words
The compound of claim 3 which is 2-(n-dodecylamino)-1-(3-hydroxypropyl)-4-(3-hydroxypropylamino)pyrimidinium chloride, bromide or iodide.
Claim 8
Dependent Claim
9 words
The compound of claim 3 which is 4-(di-n-hexylamino)-2-(2-hydroxyethylamino)-1-methylpyrimidinium bromide.
Claim 9
Dependent Claim
9 words
The compound of claim 3 which is 1,6-dimethyl-4-(n-dodecylamino)-2-(2-hydroxyethylamino)pyrimidinium acetate.
Claim 10
Dependent Claim
2 words
2,4-Bis-(n-hexylamino)-1-(3-hydroxypropyl)pyrimidinium bromide.
Claim 11
Dependent Claim
2 words
2,4-Bis-(n-hexylamino)-1-(3-hydroxypropyl)pyrimidinium bromide.
Claim 12
Dependent Claim
2 words
4-n-Dodecylamino-1-(3-hydroxypropyl)pyrimidinium bromide.
Claim 13
Dependent Claim
2 words
4-n-Dodecylamino-1-(3-hydroxypropyl)pyrimidinium bromide.
Claim 14
Dependent Claim
2 words
1-n-Dodecyl-4-[(2-methoxyethyl)amino]pyrimidinium bromide.
Claim 15
Dependent Claim
2 words
1-n-Dodecyl-4-[(2-methoxyethyl)amino]pyrimidinium bromide.
Claim 16
Dependent Claim
220 words
An antimicrobial composition comprising a carrier and an effective antimicrobial amount of a compound of structural formula: ##STR60## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N-; R 1 is (1) C 2-5 alkenyl, (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gem-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or (6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 17
Dependent Claim
220 words
An antimicrobial composition comprising a carrier and an effective antimicrobial amount of a compound of structural formula: ##STR60## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N-; R 1 is (1) C 2-5 alkenyl, (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gem-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or (6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 18
Dependent Claim
13 words
The composition of claim 12 wherein R is R 2 R 3 N--.
Claim 19
Dependent Claim
61 words
The composition of claim 13, wherein R 1 is C 1-5 alkyl, hydroxy-C 1-5 alkyl, or C 3-5 alkenyl; one of R 2 R 3 N- and R 4 R 5 N- is hydroxy-C 1-5 alkyl-NH-- and the other is C 12 -alkyl-NH-- or di(C 6 alkyl)N--; R 6 is hydrogen or C 1-5 alkyl; and A.sup.⊖ is halide, or acetate.
Claim 20
Independent Claim
224 words
A method of inhibiting microbial growth which comprises the application of an effective antimicrobial amount of a compound of structural formula: ##STR61## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N-; R 1 is (1) C 2-5 alkenyl, (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy, (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gemi-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or (6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 21
Independent Claim
224 words
A method of inhibiting microbial growth which comprises the application of an effective antimicrobial amount of a compound of structural formula: ##STR61## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N-; R 1 is (1) C 2-5 alkenyl, (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy, (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gemi-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or (6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 22
Dependent Claim
13 words
The method of claim 15, wherein R is R 2 R 3 N--.
Claim 23
Dependent Claim
61 words
The method of claim 16, wherein R 1 is C 1-5 alkyl, hydroxy-C 1-5 alkyl, or C 3-5 alkenyl; one of R 2 R 3 N- and R 4 R 5 N- is hydroxy-C 1-5 alkyl-NH-- and the other is C 12 -alkyl-NH-- or di(C 6 alkyl)N--; R 6 is hydrogen or C 1-3 alkyl; and A.sup.⊖ is halide, or acetate.
Claim 24
Independent Claim
160 words
The method of protecting seeds and plants against fungal and bacterial attack which comprises applying to the soil, seed or plant an antifungal and antibacterial amount of a composition the active ingredient of which is a compound of structural formula: ##STR62## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N-; R 1 is (1) C 2-5 alkenyl, (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy, (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gem-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or
Claim 25
Independent Claim
160 words
The method of protecting seeds and plants against fungal and bacterial attack which comprises applying to the soil, seed or plant an antifungal and antibacterial amount of a composition the active ingredient of which is a compound of structural formula: ##STR62## wherein R is hydrogen, C 1-5 alkyl or R 2 R 3 N-; R 1 is (1) C 2-5 alkenyl, (2) C 1-3 alkoxycarbonyl-C 2-5 alkenyl, (3) C 1-18 alkyl, or (4) C 1-18 alkyl mono-substituted with (a) hydroxy (b) C 1-3 alkoxy (c) carboxy, (d) C 1-3 alkoxycarbonyl, (e) C 2-5 alkanoyloxy, (f) C 3-6 cycloalkyl, (g) gem-di (C 1-3 alkoxy), (h) tetrahydrofuranyl, (i) hydroxy-C 1-3 alkoxy, or (j) C 2-3 alkanoyl, R 2 , R 3 , R 4 and R 5 are independently (1) hydrogen, or (2) R 1 ; R 6 is (1) hydrogen, (2) C 1-11 alkyl, (3) C 1-5 alkoxy-C 1-11 alkyl, (4) C 1-5 alkoxycarbonyl-C 1-11 alkyl, (5) C 1-3 alkylsulfinyl, or
Claim 26
Dependent Claim
83 words
(6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 27
Dependent Claim
83 words
(6) --(CH 2 ) n -- wherein n is 3 or 4 and the group --(CH 2 ) n -- is joined to the 5 and 6 carbons of the pyrimidine ring; and A.sup.⊖ is a non-toxic anion derived from an organic or inorganic acid; with the proviso that; (1) at least one of R 1-5 is C 6-18 alkyl, (2) at least one of R 1-5 is oxygen bearing, and (3) at least one exocyclic nitrogen is a secondary or tertiary amine.
Claim 28
Dependent Claim
13 words
The method of claim 18, wherein R is R 2 R 3 N--.
Claim 29
Dependent Claim
61 words
The method of claim 19, wherein R 1 is C 1-5 alkyl, hydroxy-C 1-5 alkyl, or C 3-5 alkenyl; one of R 2 R 3 N-- and R 4 R 5 N- is hydroxy-C 1-5 alkyl-NH-- and the other is C 12 alkyl-NH-- or di(C 6 alkyl)N--; R 6 is hydrogen or C 1-3 alkyl; and A.sup.⊖ is halide, or acetate.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-07-12 | 1986-01-11 | 1986-07-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-07-12 | 1990-01-11 | 1990-07-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-07-12 | 1994-01-11 | 1994-07-13 | $7700.00 | Window Closed / Lapsed |