US4684620A
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Cyclic polypeptides having mu-receptor specificity
Assignee: University Patents Inc
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Filing: 1984-09-04
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Granted: 1987-08-04
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Expires: 2004-09-04
Abstract
Abstract Novel compounds which are capable of binding with enhanced specificity to the mu opioid receptor are disclosed. The compounds are analogs of somatostain and have the formula: -D-AA 1NH <IMAGE> +TR COThrX wherein X is CONH2 or CH2OH; Y and Z are independently sulfur or CH2; R1 and R2, which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms; R3 and R4, which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms, provided, however, that R1, R2, R3, and R4 may not all be hydrogen; AA1 is Phe, D-Phe, phenyl-Gly, D-phenyl-Gly, Tyr, D-Tyr, L-1-Naphthylalanine, D-1-Naphthylalanine, or D-Phe(4-Me); AA2 is Tyr, Phe, Tyr(OMe), Phe(4-Me), Tyr(OEt), or Phe(4-Et); and AA3 is Lys, Arg, Orn or homo-Arg. The novel compounds have antagonist activity and may be used to induce pharmacological or therapeutic effects in humans and other animals.
Inventors
- 👤 Victor J. Hruby
- 👤 John T. Pelton
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 14:03
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/655; C07K14/6555; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/808; Y10S530/809; Y10S930/00; Y10S930/01; Y10S930/16
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
134 words
A polypeptide having the formula: ##STR43## wherein X is CONH 2 or CH 2 OH; Y and Z are independently sulfur or CH 2 ; R 1 and R 2 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms; R 3 and R 4 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms, provided, however, that R 1 , R 2 , R 3 , and R 4 may not all be hydrogen; AA 1 is Phe, D-Phe, phenyl-Gly, D-phenyl-Gly, Tyr, D-Tyr, L-1-Naphthylalanine, D-1-Naphthylalanine, or D-Phe(4-Me); AA2 is Tyr, Phe, Tyr(OMe), Phe(4-Me), Tyr(OEt), or Phe(4-Et); and AA 3 is Lys, Arg, Orn or homo-Arg.
Claim 2
Dependent Claim
134 words
A polypeptide having the formula: ##STR43## wherein X is CONH 2 or CH 2 OH; Y and Z are independently sulfur or CH 2 ; R 1 and R 2 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms; R 3 and R 4 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms, provided, however, that R 1 , R 2 , R 3 , and R 4 may not all be hydrogen; AA 1 is Phe, D-Phe, phenyl-Gly, D-phenyl-Gly, Tyr, D-Tyr, L-1-Naphthylalanine, D-1-Naphthylalanine, or D-Phe(4-Me); AA2 is Tyr, Phe, Tyr(OMe), Phe(4-Me), Tyr(OEt), or Phe(4-Et); and AA 3 is Lys, Arg, Orn or homo-Arg.
Claim 3
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR44##
Claim 4
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR45##
Claim 5
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR46##
Claim 6
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR47##
Claim 7
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR48##
Claim 8
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR49##
Claim 9
Dependent Claim
10 words
A polypeptide according to claim 1 having the formula: ##STR50##
Claim 10
Dependent Claim
24 words
A compound according to claim 1 wherein either R 1 and R 2 both methyl or R 3 and R 4 are both methyl.
Claim 11
Dependent Claim
14 words
A compound according to claim 1 wherein said compound is a mu receptor antagonist.
Claim 12
Dependent Claim
22 words
A process for treating irritable bowel disease comprising administering a safe and effective amount of an opioid receptor antagonist of claim 10.
Claim 13
Dependent Claim
26 words
A process for ameliorating opioid effects in humans and other mammals comprising administering a safe and effective amount of an opioid receptor compound of claim 1.
Claim 14
Dependent Claim
26 words
A process for treating digestive diseases in humans and other mammals comprising administering a safe and effective amount of an opioid receptor compound of claim 1.
Claim 15
Dependent Claim
16 words
The process of claim 12 wherein said opioid effects are opiate addiction, constipation or, respiratory depression.
Claim 16
Dependent Claim
164 words
A pharmaceutical composition comprising an effective amount of an opioid receptor antagonist having enhanced specificity for the mu opioid receptors of the formula: ##STR51## wherein X is CONH 2 or CH 2 OH; Y and Z are independently sulfur or CH 2 ; Rhu 1 and R 2 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms; R 3 and R 4 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms, provided, however, that R 1 , R 2 , R 3 , and R 4 may not all be hydrogen; AA 1 is Phe, D-Phe, phenyl-Gly, D-phenyl-Gly, Tyr, D-Tyr, L-1-Naphthylalanine, D-1-Naphthylalanine, or D-Phe(4-Me); AA 2 is Tyr, Phe, Tyr(OMe), Phe(4-Me), Tyr(OEt), or Phe(4-Et); and AA 3 is Lys, Arg, Orn or homo-Arg or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.
Claim 17
Dependent Claim
164 words
A pharmaceutical composition comprising an effective amount of an opioid receptor antagonist having enhanced specificity for the mu opioid receptors of the formula: ##STR51## wherein X is CONH 2 or CH 2 OH; Y and Z are independently sulfur or CH 2 ; Rhu 1 and R 2 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms; R 3 and R 4 , which may be the same or different, are hydrogen, methyl, ethyl, cyclopentamethylene, or a lower alkyl group having five or less carbon atoms, provided, however, that R 1 , R 2 , R 3 , and R 4 may not all be hydrogen; AA 1 is Phe, D-Phe, phenyl-Gly, D-phenyl-Gly, Tyr, D-Tyr, L-1-Naphthylalanine, D-1-Naphthylalanine, or D-Phe(4-Me); AA 2 is Tyr, Phe, Tyr(OMe), Phe(4-Me), Tyr(OEt), or Phe(4-Et); and AA 3 is Lys, Arg, Orn or homo-Arg or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.
Claim 18
Dependent Claim
21 words
The pharmaceutical composition of claim 15 wherein Rl and R 2 are hydrogen and R 3 and R 4 are methyl.
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) | 1990-08-03 | 1991-02-02 | 1991-08-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-08-03 | 1995-02-02 | 1995-08-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-08-03 | 1999-02-02 | 1999-08-04 | $7700.00 | Window Closed / Lapsed |