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US5021450A
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New class of compounds having a variable spectrum of activities for capsaicin-like responses, compositions and uses thereof
Assignee: United States Department of Health and Human Services
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Filing: 1989-05-30
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Granted: 1991-06-04
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Expires: 2009-05-30
Abstract
Abstract The present invention relates to a new class of compounds having a variable spectrum of activities for capsaicin-like responses, compositions thereof, processes for preparing the same, and uses thereof. Compounds of the invention are prepared by combining phorbol related diterpenses and homovanillac acid analogs via esterification at the exocyclic hydroxy group of the diterpene. Examples of these compounds include 20-homovanillyl-mezerein and 20-homovanillyl-12-deoxyphorbol-13-phenylacetate.
Inventors
- 👤 Peter M. Blumberg
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 18:59
CPC Classifications
C; C07; C07D; C07D493/00; C07D493/02; C07D493/10; A; A61; A61P; A61P11/00; A61P11/06; A61P25/00; A61P25/04; A61P29/00; A61P37/00; A61P37/08; C07C; C07C69/00; C07C2603/00; C07C2603/02; C07C2603/40; C07C2603/56; C07C2603/86
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
203 words
A compound selected from the group consisting of formulas (I)-(IV): ##STR17## wherein in formula (I), R 2 is ##STR18## R 3 is H or ##STR19## R 4 is H or OH, R 5 is CH 3 or ##STR20## and wherein at least one of R', R" and R"' is an aromatic group and the remainder are (CH 2 ) n' --CH 3 wherein n' is 0-14; said aromatic group having the formula: ##STR21## wherein R 6 -R 10 each independently represents OH, ##STR22## or H; and n is 0-10; ##STR23## wherein in formula (II), R 3 is H, OH or ##STR24## R 4 is H or ##STR25## and R', R" and R"' are as defined above; ##STR26## wherein in formula (III), R 3 , R 4 , R', R" and R"' are the same as defined in formula (II); and ##STR27## wherein in formula (IV), R 2 is ##STR28## R 3 is CH 3 or ##STR29## and R 4 is H or ##STR30## and R', R" and R"' are as defined above; wherein R 1 in formulas (I)-(IV) represents ##STR31## with the proviso that in formula (II), R' is not ##STR32## R 3 and R 4 are not H at the same time.
Claim 2
Dependent Claim
203 words
A compound selected from the group consisting of formulas (I)-(IV): ##STR17## wherein in formula (I), R 2 is ##STR18## R 3 is H or ##STR19## R 4 is H or OH, R 5 is CH 3 or ##STR20## and wherein at least one of R', R" and R"' is an aromatic group and the remainder are (CH 2 ) n' --CH 3 wherein n' is 0-14; said aromatic group having the formula: ##STR21## wherein R 6 -R 10 each independently represents OH, ##STR22## or H; and n is 0-10; ##STR23## wherein in formula (II), R 3 is H, OH or ##STR24## R 4 is H or ##STR25## and R', R" and R"' are as defined above; ##STR26## wherein in formula (III), R 3 , R 4 , R', R" and R"' are the same as defined in formula (II); and ##STR27## wherein in formula (IV), R 2 is ##STR28## R 3 is CH 3 or ##STR29## and R 4 is H or ##STR30## and R', R" and R"' are as defined above; wherein R 1 in formulas (I)-(IV) represents ##STR31## with the proviso that in formula (II), R' is not ##STR32## R 3 and R 4 are not H at the same time.
Claim 3
Dependent Claim
8 words
The compound of claim 1, which is 20-homovanillyl-mezerein.
Claim 4
Dependent Claim
8 words
The compound of claim 1, which is 20-homovanillyl-12-deoxyphorbol-13-phenylacetate.
Claim 5
Dependent Claim
23 words
The compound of claim 1, wherein the aromatic group of R', R" and R"' in formulas (I)-(IV) is ##STR33## wherein n is 0-10.
Claim 6
Independent Claim
268 words
A method for desensitizing a subject animal, which comprises administering to said subject animal a therapeutically effective desensitizing amount of a compound selected from the group consisting of formulas (I)-(IV): ##STR34## wherein in formula (I), R 2 is ##STR35## R 3 is H or ##STR36## R 4 is H or OH, R 5 is CH 3 or ##STR37## and wherein at least one of R', R" and R"' is an aromatic group and the remainder are (CH 2 ) n' --CH 3 wherein n' is 0-14, said aromatic group having the formula: ##STR38## wherein R 6 -R 10 each independently represents OH, OCH 3 or H; and n is 0-10; wherein R 1 is homovanillic acid or an analog thereof possessing a pattern of substitution which would confer capsaicin-like activity were it in a capsaicin-like structure; ##STR39## wherein in formula (II), R 3 is H, OH or ##STR40## R 4 is H or ##STR41## and R 1 , R', R" and R"' are as defined above; ##STR42## wherein in formula (III), R 1 , R 3 , R 4 , R', R" and R"' are the same as defined in formula (II); and ##STR43## wherein in formula (IV), R 2 is ##STR44## R 3 is CH 3 or ##STR45## and R 4 is H or ##STR46## and R 1 , R', R" and R"' are as defined above, for desensitizing the subject to neurogenic inflammation, to chemically and thermally induced pain, to responses involving sensory afferent pathways sensitive to capsaicin and to responses involving the hypothalamic temperature control region, with the proviso that said compound is not resiniferatoxin.
Claim 7
Independent Claim
268 words
A method for desensitizing a subject animal, which comprises administering to said subject animal a therapeutically effective desensitizing amount of a compound selected from the group consisting of formulas (I)-(IV): ##STR34## wherein in formula (I), R 2 is ##STR35## R 3 is H or ##STR36## R 4 is H or OH, R 5 is CH 3 or ##STR37## and wherein at least one of R', R" and R"' is an aromatic group and the remainder are (CH 2 ) n' --CH 3 wherein n' is 0-14, said aromatic group having the formula: ##STR38## wherein R 6 -R 10 each independently represents OH, OCH 3 or H; and n is 0-10; wherein R 1 is homovanillic acid or an analog thereof possessing a pattern of substitution which would confer capsaicin-like activity were it in a capsaicin-like structure; ##STR39## wherein in formula (II), R 3 is H, OH or ##STR40## R 4 is H or ##STR41## and R 1 , R', R" and R"' are as defined above; ##STR42## wherein in formula (III), R 1 , R 3 , R 4 , R', R" and R"' are the same as defined in formula (II); and ##STR43## wherein in formula (IV), R 2 is ##STR44## R 3 is CH 3 or ##STR45## and R 4 is H or ##STR46## and R 1 , R', R" and R"' are as defined above, for desensitizing the subject to neurogenic inflammation, to chemically and thermally induced pain, to responses involving sensory afferent pathways sensitive to capsaicin and to responses involving the hypothalamic temperature control region, with the proviso that said compound is not resiniferatoxin.
Claim 8
Dependent Claim
19 words
The method of claim 5, wherein the compound is selected from the group consisting of tinyatoxin, 20-homovanillyl-mezerein and 20-homovanillyl-12-deoxyphorbol-13-phenylacetate.
Claim 9
Dependent Claim
16 words
The method of claim 5, wherein said compound is administered topically, subcutaneously, intraperitoneally, intravenously, or orally.
Claim 10
Dependent Claim
23 words
The method of claim 5, wherein said compound is administered in the range of 1×10 -5 mg/kg to 10 mg/kg to the subject.
Claim 11
Dependent Claim
11 words
The method of claim 5, wherein the subject is a mammal.
Claim 12
Dependent Claim
17 words
The method of claim 9, wherein the subject mammal is a mouse, rat, domestic animal, or human.
Claim 13
Dependent Claim
19 words
The method of claim 10, wherein the domestic animal is a dog, cat, horse, cow, pig, goat or sheep.
Claim 14
Dependent Claim
15 words
The method of claim 7, wherein the compound is administered by single or multiple application.
Claim 15
Dependent Claim
50 words
A composition comprising a therapeutically effective amount of the compound of claim 1 for desensitizing the subject to neurogenic inflammation, to chemically and thermally induced pain, to responses involving sensory afferent pathways sensitive to capsaicin and to responses involving the hypothalamic temperature control region, and a pharmaceutically acceptable carrier therefor.
Claim 16
Dependent Claim
15 words
The composition of claim 13, which comprises 0.0001 to 10% by weight of said compound.
Claim 17
Dependent Claim
11 words
The method of claim 5, wherein R 1 is homovanillic acid.
Claim 18
Dependent Claim
10 words
The method of claim 5, wherein R 1 is ##STR47##
Claim 19
Dependent Claim
10 words
The method of claim 5, wherein said compound is tinyatoxin.
Claim 20
Dependent Claim
56 words
A method for desensitizing a subject animal, which comprises administering to said subject animal a therapeutically effective desensitizing amount of a compound of claim 1 for desensitizing the subject to neurogenic inflammation, to chemically and thermally induced pain, to responses involving sensory afferent pathways sensitive to capsaicin and to responses involving the hypothalamic temperature control region.
References Cited (Backward Citations)
No citation records indexed.
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