Patent US5100880A successfully refreshed from Google Patents.
US5100880A
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US
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Novel betalactam elastase inhibitors containing phosphorous acid derivatives at the 4-position of the 2-azetidinone
Assignee: Merck and Co Inc
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Filing: 1991-03-20
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Granted: 1992-03-31
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Expires: 2011-03-20
Abstract
Abstract New substituted azetidinones of the general formula (A), which have been found to be potent elastase inhibitors and thereby useful as anti-inflammatory and antidegenerative agents, are described. ##STR1##
Inventors
- 👤 Philippe L. Durette
- 👤 Malcolm MacCoss
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 22:32
CPC Classifications
C; C07; C07F; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/568; A; A61; A61P; A61P29/00
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
285 words
A compound Formula (A) ##STR7## or a pharmaceutically acceptable salt thereof wherein: R is H, C 1-6 alkyl, or C 2-6 alkenyl; R 1 is H, C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkoxy-C 1-6 alkyl; M is (1) hydrogen, (2) C 1-6 alkyl, (3) hydroxy C 1-6 -alkyl, (4) halo C 1-6 -alkyl, (5) C 2-6 alkenyl, or (6) C 1-6 alkoxy-C 1-6 alkyl; R 2 and R 3 are each independently (1) hydrogen, (2) C 1-6 alkyl, (3) halo, (4) carboxy, (5) C 1-6 alkoxy, (6) phenyl, (7) C 1-6 alkylcarbonyl, (8) C 1-6 alkyloxycarbonyl, (9) di-(C 1-6 alkyl)amino, (10) phenoxy, or R 2 and R 3 are joined together with the carbon atoms to which they are attached to form a ring selected from furan, thiophene, and dioxacyclopentane; R 4 is (a) hydrogen, (b) C 1-6 alkyl, (c) halo, or (d) C 1-6 alkoxy; n is 0, 1, 2, 3, or 4; R 5 and R 6 are each independently (a) hydrogen, (b) C 1-6 alkyl, (c) substituted C 1-6 alkyl wherein the substituent is halo, hydroxy, C 1-6 alkoxy, C 1-6 alkylcarbonyloxy, amino, C 1-6 alkylamino, or di-(C 1-6 alkyl)- amino, (d) C 6-10 aryl wherein the aryl group is selected from the group consisting of (1) phenyl, (2) naphthyl, (3) pyridyl, (4) furyl, (5) pyrryl, (6) thienyl, (7) imidazolyl, (8) benzimidazolyl, (9) pyrazinyl, (10) pyrimidyl, (11) quinolyl, (12) isoquinolyl, (13) benzofuryl, and (14) benzothienyl, and mono and di-substituted C 6-10 aryl as defined above in items (1) to (14) wherein the substituents are independently C 1-6 alkyl, halo, hydroxy, C 1-6 alkyloxy, C 1-6 alkylcarbonyl, C 1-6 alkoxy C 1-6 alkyl; (e) C 1-6 alkyl carbonyloxy-C 1-6 alkyl.
Claim 2
Dependent Claim
285 words
A compound Formula (A) ##STR7## or a pharmaceutically acceptable salt thereof wherein: R is H, C 1-6 alkyl, or C 2-6 alkenyl; R 1 is H, C 1-6 alkyl, C 2-6 alkenyl or C 1-6 alkoxy-C 1-6 alkyl; M is (1) hydrogen, (2) C 1-6 alkyl, (3) hydroxy C 1-6 -alkyl, (4) halo C 1-6 -alkyl, (5) C 2-6 alkenyl, or (6) C 1-6 alkoxy-C 1-6 alkyl; R 2 and R 3 are each independently (1) hydrogen, (2) C 1-6 alkyl, (3) halo, (4) carboxy, (5) C 1-6 alkoxy, (6) phenyl, (7) C 1-6 alkylcarbonyl, (8) C 1-6 alkyloxycarbonyl, (9) di-(C 1-6 alkyl)amino, (10) phenoxy, or R 2 and R 3 are joined together with the carbon atoms to which they are attached to form a ring selected from furan, thiophene, and dioxacyclopentane; R 4 is (a) hydrogen, (b) C 1-6 alkyl, (c) halo, or (d) C 1-6 alkoxy; n is 0, 1, 2, 3, or 4; R 5 and R 6 are each independently (a) hydrogen, (b) C 1-6 alkyl, (c) substituted C 1-6 alkyl wherein the substituent is halo, hydroxy, C 1-6 alkoxy, C 1-6 alkylcarbonyloxy, amino, C 1-6 alkylamino, or di-(C 1-6 alkyl)- amino, (d) C 6-10 aryl wherein the aryl group is selected from the group consisting of (1) phenyl, (2) naphthyl, (3) pyridyl, (4) furyl, (5) pyrryl, (6) thienyl, (7) imidazolyl, (8) benzimidazolyl, (9) pyrazinyl, (10) pyrimidyl, (11) quinolyl, (12) isoquinolyl, (13) benzofuryl, and (14) benzothienyl, and mono and di-substituted C 6-10 aryl as defined above in items (1) to (14) wherein the substituents are independently C 1-6 alkyl, halo, hydroxy, C 1-6 alkyloxy, C 1-6 alkylcarbonyl, C 1-6 alkoxy C 1-6 alkyl; (e) C 1-6 alkyl carbonyloxy-C 1-6 alkyl.
Claim 3
Dependent Claim
60 words
A compound of Formula A' according to claim 1, wherein R 5 is (1) Hydrogen, (2) C 1-6 alkyl, (3) C 6-10 aryl wherein the aryl group is selected from the group consisting of (a) phenyl, (b) pyridyl, (c) furyl, (d) thienyl, (e) imidazolyl, (f) benzimidazolyl, (g) pyrimidyl, (h) benzofuryl, and (i) benzothienyl; or (4) C 1-6 alkylcarbonyloxy-C 1-6 alkyl.
Claim 4
Dependent Claim
78 words
A compound of Formula A' according to claim 2, wherein R 6 is (a) hydrogen, (b) C 1-6 alkyl, (c) substituted C 1-6 alkyl wherein the substituent is halo, hydroxy, C 1-6 alkoxy, C 1-6 alkylcarbonyloxy, amino, C 1-6 alkylamino, or di-(C 1-6 alkyl)-amino, (d) C 6-10 aryl wherein the aryl group is selected from the group consisting of (1) phenyl, (2) pyridyl, (3) furyl, (4) thienyl, (5) imidazolyl, (6) benzimidazolyl, (7) pyrimidyl, (8) benzofuryl, and (9) benzothienyl.
Claim 5
Dependent Claim
52 words
A compound of Formula A' according to claim 3, wherein R 5 is (1) Hydrogen, (2) C 1-6 alkyl, (3) C 6-10 aryl wherein the aryl group is selected from the group consisting of (a) phenyl, (b) thienyl, (c) isothiazolyl, (d) benzofuryl, and (e) benzothienyl, or (4) C 1-6 alkylcarbonyloxy-C 1-6 alkyl.
Claim 6
Dependent Claim
59 words
A compound of Formula A' according to claim 4, wherein R 6 is (a) hydrogen, (b) C 1-6 alkyl, (c) substituted C 1-6 alkyl wherein the substituent is halo, hydroxy, C 1-6 alkyloxy, or amino, (d) C 6-10 aryl wherein the aryl group is selected from the group consisting of (1) phenyl, (2) thienyl, (3) benzofuryl, and (4) benzothienyl.
Claim 7
Dependent Claim
110 words
A compound of Formula A' according to claim 5, wherein M, R, and R 1 are each independently C 1-6 alkyl or C 2-6 alkenyl; R 2 and R 3 are each independently hydrogen, C 1-6 alkyl, C 1-6 alkala, or R 2 and R 3 are joined together with the carbon atoms to which they are attached to form a ring selected from furan, thiophene, or dioxacyclopentane; R 4 is hydrogen, C 1-6 alkyl, fluoro or chloro; n is 0 or 1; R 5 is hydrogen, C 1-6 alkyl, C 1-6 -alkylcarbonyloxy-C 1-6 alkyl; and R 6 is hydrogen, C 1-6 alkyl, or C 1-6 -alkyl carbonyloxy-C 1-6 alkyl.
Claim 8
Dependent Claim
93 words
A compound according to claim 6 of Formula A' wherein M, R and R 1 are each independently C 1-6 alkyl; R 2 is hydrogen, and R 3 is C 1-6 alkyl, C 1-6 alkyloxy, or R 2 and R 3 are joined together with the carbon atoms to which they are attached to form a ring selected from furan or dioxacyclopentane; R 4 is hydrogen, C 1-6 alkyl, fluoro, or chloro; n is 0 or 1; R 5 is hydrogen or C 1-6 alkyl; R 6 is hydrogen or C 1-6 alkyl.
Claim 9
Dependent Claim
76 words
A compound according to claim 7 wherein M is n-propyl; R and R 1 , are ethyl; n is 0 or 1; R 2 is hydrogen, and R 3 is methyl, or methoxy, or R 2 and R 3 are joined together with the carbon atoms to which they are attached to form a ring selected from furan or dioxacyclopentane; R 5 is hydrogen or C 1-6 alkyl; and R 6 is hydrogen, C 1-6 alkyl.
Claim 10
Dependent Claim
20 words
A compound of Formula A' according to claim 8 selected from the group consisting of (a) (4S)-3,3-Diethyl-1-[(R)-α-n-propyl-(4-methyl)benzylaminocarbonyl]-4-[4-(diethoxy-phosphinylmethyl-phenoxy]azetidin-2-one; and (b) (4S)-3,3-Diethyl-1-[(R)-α-n-propyl-(4-methyl)benzylaminocarbonyl]-4-[4-(dihydroxy-phosphinylmethyl)-phenoxy]azetidin2-one.
Claim 11
Dependent Claim
27 words
A pharmaceutical composition for the inhibition of leukocyte elastase which comprises a nontoxic therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 12
Dependent Claim
27 words
A pharmaceutical composition for the inhibition of leukocyte elastase which comprises a nontoxic therapeutically effective amount of a compound of claim 9 and a pharmaceutically acceptable carrier.
Claim 13
Dependent Claim
34 words
A method of treatment for the inhibition of human leukocyte elastase which comprises the administration to a subject in need of such inhibition a nontoxic therapeutically effective amount of a compound of claim 1.
Claim 14
Dependent Claim
34 words
A method of treatment for the inhibition of human leukocyte elastase which comprises the administration to a subject in need of such inhibition a nontoxic therapeutically effective amount of a compound of claim 9.
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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) | 1995-03-31 | 1995-09-30 | 1996-03-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-03-31 | 1999-09-30 | 2000-03-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-03-31 | 2003-09-30 | 2004-03-31 | $7700.00 | Window Closed / Lapsed |