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US4369181A
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Process for treating proliferative skin diseases using certain 6,8-substituted ribofuranosylpurine-3',5'-cyclic phosphates
Assignee: SRI International Inc
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Filing: 1981-08-05
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Granted: 1983-01-18
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Expires: 2001-08-05
Abstract
Abstract Proliferative skin diseases such as psoriasis are treated by topically administering cAMP analogs of the following formula to the afflicted skin site at a dose that preferentially and significantly activates type II protein kinase: <IMAGE> where: R6 is: (i) -NR1 R2 where R1 and R2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, and cyclopentyl or are joined together with the nitrogen atom to form a hetrocyclic group having 4 to 5, inclusive, annular carbon atoms with the proviso that the total number of carbon atoms in the -NR1 R2 group is 4 or 5, or (ii) -XR where X is a chalcogen atom of atomic number 8 or 16 and R is alkyl of 4 or 5 carbon atoms, R8 is: (i) -X-(CH2)n R3 where X is defined previously, n is an integer in the range of 1 to 3, inclusive, R3 is hydrogen, alkyl of 1 to 7 carbon atoms, or phenyl substituted with 0 to 1, inclusive, nitro, halo of atomic number 9 to 35, inclusive, methoxy, hydroxy or methyl, or (ii) -NR4 R5 wherein R4 and R5 are independently selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, and phenalkyl of 7 to 9 carbon atoms with the provisos that only one of R4 and R5 may be hydrogen and the total number of carbon atoms in the -NR4 R5 group is in the range of 1 to 9, inclusive, and Z is hydrogen, an alkali metal cation or ammonium.
Inventors
- 👤 Jon P. Miller
- 👤 Wesley W. Zmolek
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 16:02
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/16; C07H19/20; A; A61; A61P; A61P17/00
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
276 words
A method of treating a proliferative skin disease comprising topically administering to an afflicted site on the skin of a patient a therapeutically effective amount of a compound of the formula: ##STR3## where: R 6 is: (i) --NR 1 R 2 where R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, and cyclopentyl or are joined together with the nitrogen atom to form a hetrocyclic group having 4 to 5, inclusive, annular carbon atoms with the proviso that the total number of carbon atoms in the --NR 1 R 2 group is 4 or 5, or (ii) --XR where X is a chalcogen atom of atomic number 8 or 16 and R is alkyl of 4 or 5 carbon atoms, R 8 is: (i) --X--(CH 2 ) n R 3 where X is defined previously, n is an integer in the range of 1 to 3, inclusive, R 3 is hydrogen, alkyl of 1 to 7 carbon atoms, or phenyl substituted with 0 to 1, inclusive, nitro, halo of atomic number 9 to 35, inclusive, methoxy, hydroxy or methyl, or (ii) --NR 4 R 5 wherein R 4 and R 5 are independently selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms and phenalkyl of 7 to 9 carbon atoms, with the provisos that only one of R 4 and R 5 may be hydrogen and the total number of carbon atoms in the --NR 4 R 5 group is in the range of 1 to 9, inclusive, and Z is hydrogen, an alkali metal cation or ammonium.
Claim 2
Independent Claim
276 words
A method of treating a proliferative skin disease comprising topically administering to an afflicted site on the skin of a patient a therapeutically effective amount of a compound of the formula: ##STR3## where: R 6 is: (i) --NR 1 R 2 where R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, and cyclopentyl or are joined together with the nitrogen atom to form a hetrocyclic group having 4 to 5, inclusive, annular carbon atoms with the proviso that the total number of carbon atoms in the --NR 1 R 2 group is 4 or 5, or (ii) --XR where X is a chalcogen atom of atomic number 8 or 16 and R is alkyl of 4 or 5 carbon atoms, R 8 is: (i) --X--(CH 2 ) n R 3 where X is defined previously, n is an integer in the range of 1 to 3, inclusive, R 3 is hydrogen, alkyl of 1 to 7 carbon atoms, or phenyl substituted with 0 to 1, inclusive, nitro, halo of atomic number 9 to 35, inclusive, methoxy, hydroxy or methyl, or (ii) --NR 4 R 5 wherein R 4 and R 5 are independently selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms and phenalkyl of 7 to 9 carbon atoms, with the provisos that only one of R 4 and R 5 may be hydrogen and the total number of carbon atoms in the --NR 4 R 5 group is in the range of 1 to 9, inclusive, and Z is hydrogen, an alkali metal cation or ammonium.
Claim 3
Dependent Claim
22 words
The method of claim 1 wherein R 6 is n-butylamino, n-pentylamino, n-butylmethylamino, or pyrrolidyl, R 8 is benzylthio, and Z is hydrogen.
Claim 4
Dependent Claim
18 words
The method of claim 1 wherein R 6 is n-butylamino, R 8 is methylthio, and Z is hydrogen.
Claim 5
Dependent Claim
18 words
The method of claim 1 wherein R 6 is diethylamino, R 8 is diethylamino, and Z is hydrogen.
Claim 6
Dependent Claim
18 words
The method of claim 1 wherein R 6 is n-butylamino, R 8 is benzylthio, and Z is hydrogen.
Claim 7
Dependent Claim
12 words
The method of claim 1,2,3,4 or 5 wherein the disease is psoriasis.
Claim 8
Dependent Claim
23 words
The method of claim 1,2,3,4 or 5 wherein the amount is sufficient to effect preferential and significant activation of type II protein kinase.
Claim 9
Dependent Claim
25 words
The method of claim 1,2,3,4 or 5 wherein the amount is in the range of about 0.01 to about 10 mcg/cm 2 of skin treated.
Claim 10
Dependent Claim
21 words
The method of claim 5 wherein the amount is in the range of 0.1 to 1 mcg/cm 2 of skin treated.
Claim 11
Dependent Claim
45 words
The method of claim 1 wherein the compound is administered to the afflicted site via a controlled release dosage form that releases the compound to the skin at a rate that maintains the concentration of the compound in the epidermis at a therapeutically effective level.
Claim 12
Dependent Claim
278 words
A topical dosage form for treating a patient for a proliferative skin disease comprising a therapeutically effective amount of at least one compound of the formula: ##STR4## where: R 6 is: (i) --NR 1 R 2 where R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, and cyclopentyl or are joined together with the nitrogen atom to form a hetrocyclic group having 4 to 5, inclusive, annular carbon atoms with the proviso that the total number of carbon atoms in the --NR 1 R 2 group is 4 or 5, or (ii) --XR where X is a chalcogen atom of atomic number 8 or 16 and R is alkyl of 4 or 5 carbon atoms, R 8 is: (i) --R--(CH 2 ) n R 3 where X is defined previously, n is an integer in the range of 1 to 3, inclusive, R 3 is hydrogen, alkyl of 1 to 7 carbon atoms, or phenyl substituted with 0 to 1, inclusive, nitro, halo of atomic number 9 to 35, inclusive, methoxy, hydroxy or methyl, or (ii) --NR 4 R 5 wherein R 4 and R 5 are independently selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms and phenalkyl of 7 to 9 carbon atoms, with the provisos that only one of R 4 and R 5 may be hydrogen and the total number of carbon atoms in the --NR 4 R 5 group is in the range of 1 to 9, inclusive, and Z is hydrogen, an alkali metal cation or ammonium admixed with a pharmaceutically acceptable topical carrier.
Claim 13
Dependent Claim
278 words
A topical dosage form for treating a patient for a proliferative skin disease comprising a therapeutically effective amount of at least one compound of the formula: ##STR4## where: R 6 is: (i) --NR 1 R 2 where R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, and cyclopentyl or are joined together with the nitrogen atom to form a hetrocyclic group having 4 to 5, inclusive, annular carbon atoms with the proviso that the total number of carbon atoms in the --NR 1 R 2 group is 4 or 5, or (ii) --XR where X is a chalcogen atom of atomic number 8 or 16 and R is alkyl of 4 or 5 carbon atoms, R 8 is: (i) --R--(CH 2 ) n R 3 where X is defined previously, n is an integer in the range of 1 to 3, inclusive, R 3 is hydrogen, alkyl of 1 to 7 carbon atoms, or phenyl substituted with 0 to 1, inclusive, nitro, halo of atomic number 9 to 35, inclusive, methoxy, hydroxy or methyl, or (ii) --NR 4 R 5 wherein R 4 and R 5 are independently selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms and phenalkyl of 7 to 9 carbon atoms, with the provisos that only one of R 4 and R 5 may be hydrogen and the total number of carbon atoms in the --NR 4 R 5 group is in the range of 1 to 9, inclusive, and Z is hydrogen, an alkali metal cation or ammonium admixed with a pharmaceutically acceptable topical carrier.
Claim 14
Dependent Claim
22 words
The dosage form of claim 11 wherein R 6 is n-butylamino-n-pentylamino, n-butylmethylamino, or pyrrolidyl, R 8 is benzylthio, and Z is hydrogen.
Claim 15
Dependent Claim
19 words
The dosage form of claim 11 wherein R 6 is n-butylamino, R 8 is methylthio, and Z is hydrogen.
Claim 16
Dependent Claim
19 words
The dosage form of claim 11 wherein R 6 is diethylamino, R 8 is diethylamino, and Z is hydrogen.
Claim 17
Dependent Claim
18 words
The dosage of claim 11, wherein R 6 is n-butylamino, R 8 is benzylthio, and Z is hydrogen.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-01-17 | 1986-07-19 | 1987-01-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-01-17 | 1990-07-19 | 1991-01-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-01-17 | 1994-07-19 | 1995-01-18 | $7700.00 | Window Closed / Lapsed |