Patent US4086336A successfully refreshed from Google Patents.
US4086336A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Phosphonothioureide anthelmintics
Assignee: GlaxoSmithKline LLC
•
Filing: 1976-08-24
•
Granted: 1978-04-25
•
Expires: 1996-08-24
Abstract
Abstract Aryl- and heterocyclic substituted phosphonothioureide compounds useful as anthelmintics.
Inventors
- 👤 Ronald P. Owen
- 👤 George A. Miller
- 👤 Charles M. Schneider
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 04:47
CPC Classifications
A; A01; A01N; A01N57/00; A01N57/26; C; C07; C07F; C07F9/00; C07F9/02; C07F9/06; C07F9/22; C07F9/24; C07F9/2454; C07F9/2479; C07F9/2487
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
441 words
A compound of the formula: ##STR63## wherein A is a divalent arylene group optionally substituted with halo, cyano, thiocyano, carboxy, nitro, dialkylamino, vicinal alkylene, or a radical of the formula: R.sup.3 (X).sub.n wherein R 3 is an aliphatic group of from 1 to 18 carbon atoms, optionally substituted aryl, X is oxo, thio, sulfinyl, sulfonyl, or carbonyl and n is an integer of 0 to 1 with the proviso that when X is oxo and n is 1, R 3 is methyl; R is hydrogen, (C 1 -C 10 ) alkyl, (C 1 -C 10 ) haloalkyl, (C 3 -C 6 ) cycloalkyl, (C 2 -C 11 ) alkoxyalkyl, (C 1 -C 10 ) cyanoalkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) haloalkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) haloalkynyl, optionally substituted aralkyl of from 7 to 11 carbon atoms or optionally substituted (C 6 -C 10 ) aryl; R 1 is R', OR', N(R') 2 or SR' R 2 is OR', N(R') 2 or SR' wherein R' is an aliphatic group of from 1 to 18 carbon atoms or optionally substituted aryl; Z is a group of the formula: ##STR64## wherein R 4 and R 5 are hydrogen atoms or aliphatic groups of from 1 to 18 carbon atoms, Z is also --N═CHR 6 ; ##STR65## wherein R 6 is an aliphatic group of from 1 to 18 carbon atoms, optionally substituted aryl containing from 6 to 10 nuclear carbon atoms, R 7 and R 8 are independently hydrogen, (C 1 -C 10 ) alkyl, (C 1 -C 10 ) haloalkyl, (C 3 -C 6 ) cycloalkyl, (C 2 -C 11 ) alkoxyalkyl, (C 1 -C 10 ) cyanoalkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) haloalkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) haloalkynyl, optionally substituted aralkyl of from 7 to 11 carbon atoms, optionally substituted (C 6 -C 10 ) aryl; R 9 is R", OR", N(R") 2 or SR" and R 10 is R", N(R") 2 or SR" wherein R" is an aliphatic group of from 1 to 18 carbon atoms or optionally substituted aryl containing from 6 to 10 nuclear carbon atoms provided that R 9 and R 10 are not simultaneosly R"; R 11 is an aliphatic group of from 1 to 18 carbon atoms or optionally substituted aromatic group containing from 6 to 10 carbpn atoms in the aromatic ring; n' is an integer of 0 to 1; Y is carbonyl, sulfinyl or sulfonyl and the pharmaceutically acceptable metal salts, acid salts and metal salt complexes thereof.
Claim 2
Dependent Claim
441 words
A compound of the formula: ##STR63## wherein A is a divalent arylene group optionally substituted with halo, cyano, thiocyano, carboxy, nitro, dialkylamino, vicinal alkylene, or a radical of the formula: R.sup.3 (X).sub.n wherein R 3 is an aliphatic group of from 1 to 18 carbon atoms, optionally substituted aryl, X is oxo, thio, sulfinyl, sulfonyl, or carbonyl and n is an integer of 0 to 1 with the proviso that when X is oxo and n is 1, R 3 is methyl; R is hydrogen, (C 1 -C 10 ) alkyl, (C 1 -C 10 ) haloalkyl, (C 3 -C 6 ) cycloalkyl, (C 2 -C 11 ) alkoxyalkyl, (C 1 -C 10 ) cyanoalkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) haloalkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) haloalkynyl, optionally substituted aralkyl of from 7 to 11 carbon atoms or optionally substituted (C 6 -C 10 ) aryl; R 1 is R', OR', N(R') 2 or SR' R 2 is OR', N(R') 2 or SR' wherein R' is an aliphatic group of from 1 to 18 carbon atoms or optionally substituted aryl; Z is a group of the formula: ##STR64## wherein R 4 and R 5 are hydrogen atoms or aliphatic groups of from 1 to 18 carbon atoms, Z is also --N═CHR 6 ; ##STR65## wherein R 6 is an aliphatic group of from 1 to 18 carbon atoms, optionally substituted aryl containing from 6 to 10 nuclear carbon atoms, R 7 and R 8 are independently hydrogen, (C 1 -C 10 ) alkyl, (C 1 -C 10 ) haloalkyl, (C 3 -C 6 ) cycloalkyl, (C 2 -C 11 ) alkoxyalkyl, (C 1 -C 10 ) cyanoalkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) haloalkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) haloalkynyl, optionally substituted aralkyl of from 7 to 11 carbon atoms, optionally substituted (C 6 -C 10 ) aryl; R 9 is R", OR", N(R") 2 or SR" and R 10 is R", N(R") 2 or SR" wherein R" is an aliphatic group of from 1 to 18 carbon atoms or optionally substituted aryl containing from 6 to 10 nuclear carbon atoms provided that R 9 and R 10 are not simultaneosly R"; R 11 is an aliphatic group of from 1 to 18 carbon atoms or optionally substituted aromatic group containing from 6 to 10 carbpn atoms in the aromatic ring; n' is an integer of 0 to 1; Y is carbonyl, sulfinyl or sulfonyl and the pharmaceutically acceptable metal salts, acid salts and metal salt complexes thereof.
Claim 3
Dependent Claim
376 words
A compound according to claim 1 having the formula: ##STR66## wherein A is phenylene, naphthylene or phenanthrylene; R 13 and R 14 are the same or different radicals selected from OR 1 ', N(R 1 ') 2 or SR 1 ' wherein R 1 ' is (C 1 -C 4 ) alkyl, (C 2 -C 6 ) alkoxyalkyl, (C 1 -C 4 ) haloalkyl, (C 3 -C 4 ) alkenyl or phenyl; R 15 represents from 1 to 4 substituents when A is phenylene and from 1 to 6 substituents when A is naphthylene or phenanthrylene which substituents can be hydrogen, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, (C 3 -C 4 ) alkenyl, halogen, nitro, carboxy, benzoyl, phenylthio, phenylsulfinyl or phenylsulfonyl, provided that R 15 does not represents more than one of these groups and Z is a group of the formula: ##STR67## wherein R 16 is hydrogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 3 -C 6 ) alkenyl, (C 2 -C 8 ) alkoxyalkyl, optionally substituted aralkyl of up to 11 carbon atoms or optionally substituted (C 6 -C 10 ) aryl; Z is also --N═CHR 6' , ##STR68## wherein R 6' is (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, optionally substituted aralkyl of up to 11 carbon atoms, optionally substituted (C 6 -C 10 ) aryl, an optionally substituted heterocyclic group containing 5 or 6 nuclear members, an optionally substituted heterocyclic alkyl group wherein the alkyl group contains 1 to 4 carbon atoms; R 7' and R 8' are independently hydrogen, (C 1 -C 4 ) alkyl, (C 3 -C 4 ) alkenyl, (C 2 -C 4 ) alkoxyalkyl or optionally substituted aralkyl of up to 11 carbon atoms; R 9' is OR 1 ", SR 1 " or N(R 1 ") 2 and R 10' is SR 1 " or N(R 1 ") 2 wherein R 1 " is (C 1 -C 4 ) alkyl, (C 2 -C 6 ) alkoxyalkyl, (C 1 -C 4 ) haloalkyl, (C 3 -C 4 ) alkenyl or phenyl; R 11' is (C 1 -C 8 ) alkyl or optionally substituted phenyl and Y is carbonyl, sulfinyl or sulfonyl.
Claim 4
Dependent Claim
302 words
The compound of claim 2 having a formula selected from: ##STR69## wherein R 1' is OR 2 ' and R 2' is OR 2 ' or SR 2 ' wherein R 2' is (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl or phenyl; R 17 is hydrogen, (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, halo, benzoyl or carboxyl; Z" is a group of the formula: NH 2 , HNR 18 , wherein R 18 is (C 1 -C 8 ) alkyl, (C 2 -C 8 ) alkoxyalkyl, (C 3 -C 8 ) alkenyl, benzyl optionally substituted with one to two substituents selected from (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, (C 1 -C 4 ) haloalkyl, di-(C 1 -C 4 ) alkylamino, halo, nitro or cyano; --N═CHR 19 wherein R 19 is phenyl, optionally substituted with one to two substituents selected from (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, (C 1 -C 4 ) haloalkyl, di (C 1 -C.sub. 4) alkylamino, halo, nitro or cyano; ##STR70## wherein R 20 is (C 1 -C 4 ) alkoxycarbonyl or phenyl, optionally substituted with up to two substituents selected from (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, (C 1 -C 4 ) haloalkyl, di-(C 1 -C 4 ) alkylamino, halo, nitro or cyano; ##STR71## wherein R 21 is (C 1 -C 4 ) alkyl, (C 1 -C 4 ) haloalkyl, (C 2 -C 4 ) allyl or phenyl optionally substituted with one to two substituents selected from (C 1 -C 4 ) alkyl, (C 1 -C 4 ) alkoxy, (C 1 -C 4 ) haloalkyl, di-(C 1 -C 4 ) alkylamino, halo, nitro or cyano and Y' is carbonyl or sulfonyl.
Claim 5
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR72##
Claim 6
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR73##
Claim 7
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR74##
Claim 8
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR75##
Claim 9
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR76##
Claim 10
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR77##
Claim 11
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR78##
Claim 12
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR79##
Claim 13
Dependent Claim
10 words
A compound according to claim 3 of the formula: ##STR80##
Claim 14
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 15
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 2 and a pharmaceutically acceptable carrier.
Claim 16
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.
Claim 17
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 4 and a pharmaceutically acceptable carrier.
Claim 18
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 5 and a pharmaceutically acceptable carrier.
Claim 19
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 6 and a pharmaceutically acceptable carrier.
Claim 20
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 7 and a pharmaceutically acceptable carrier.
Claim 21
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 8 and a pharmaceutically acceptable carrier.
Claim 22
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 9 and a pharmaceutically acceptable carrier.
Claim 23
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 10 and a pharmaceutically acceptable carrier.
Claim 24
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 11 and a pharmaceutically acceptable carrier.
Claim 25
Dependent Claim
21 words
An anthelmintic composition for oral administration comprising an effective amount of the compound of claim 12 and a pharmaceutically acceptable carrier.
Claim 26
Dependent Claim
8 words
The composition of claim 13 in tablet form.
Claim 27
Dependent Claim
8 words
The composition of claim 14 in liquid form.
Claim 28
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 1.
Claim 29
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 2.
Claim 30
Dependent Claim
22 words
The method for combatting a helminth infection in a host which comprises administering an effective amount of the compound of claim 3.
Claim 31
Dependent Claim
23 words
The method for combatting a helminth infection in a host animals which comprises administering an effective amount of the compound of claim 4.
Claim 32
Dependent Claim
23 words
The method for combatting a helmith infection in a host animal which comprises administering an effective amount of the compound of claim 5.
Claim 33
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 6.
Claim 34
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 7.
Claim 35
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 8.
Claim 36
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 9.
Claim 37
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 10.
Claim 38
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 11.
Claim 39
Dependent Claim
23 words
The method for combatting a helminth infection in a host animal which comprises administering an effective amount of the compound of claim 12.
References Cited (Backward Citations)
DE2325036A1
Cited
US3845176A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-04-24 | 1981-10-24 | 1982-04-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-04-24 | 1985-10-24 | 1986-04-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-04-24 | 1989-10-24 | 1990-04-25 | $7700.00 | Window Closed / Lapsed |