.

Deeper Knowledge, Faster

  • Plan your formulary budget
  • Predict branded drug patent expiration
  • Uncover prior art in expired and abandoned patents

► See Plans & Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

Serving 500+ biopharmaceutical companies globally:

Federal Trade Commission
Moodys
Cipla
McKinsey
AstraZeneca
Novartis
Harvard Business School
Cantor Fitzgerald
Fish and Richardson
Express Scripts

Generated: June 26, 2017

DrugPatentWatch Database Preview

Claims for Patent: 4,800,191

« Back to Dashboard

Claims for Patent: 4,800,191

Title: LHRH antagonists
Abstract:The present invention deals with LHRH antagonists which possess improved water solubility and while having the high antagonist potency of the basic peptides, are free of the edematogenic effects. These compounds are highly potent in inhibiting the release of gonadotropins from the pituitary gland in mammals, including humans. The compounds of this invention are represented by the formula wherein X is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms, R.sup.1 is D- or L-Pro, D- or L- .DELTA. .sup.3 -Pro, D-Phe, D-Phe(4-H1), D-Ser, D-Thr, D-Ala, D-Nal (1) or D-Nal (2), R.sup.2 is D-Phe or D-Phe(4-H1) R.sup.3 is D-Trp, D-Phe, D-Pal, D-Nal(1) or D-Nal (2), R.sup.6 is D-Cit, D-Hci, D-Cit(Q) or D-Hci(Q) and R.sup.10 is Gly or D-Ala where Q is lower alkyl of 1-3 carbon atoms and H1 is fluoro, chloro or bromo, and the pharmaceutically acceptable acid addition salts thereof and methods of use pertaining to these compounds.
Inventor(s): Schally; Andrew V. (Metarie, LA), Bajusz; Sandor (New Orleans, LA)
Assignee:
Application Number:07/074,126
Patent Claims: 1. A peptide selected from the group of peptides having the formula:

wherein

X is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms,

R.sup.1 is D- or L-Pro, D- or L-.DELTA..sup.3 -Pro, D-Phe, D-Phe(4-H1), D-Ser, D-Thr, D-Ala, D-Nal(1) or D-Nal (2),

R.sup.2 is D-Phe or D-Phe(4-H1),

R.sup.3 is D-Trp, D-Phe, D-Pal, D-Nal(1) or D-Nal (2),

R.sup.6 is D-Cit, D-Hci, D-Cit(Q) or D-Hci(Q) and

R.sup.10 is Gly or D-Ala,

where Q2 is lower alkyl of 1-3 carbon atoms and H1 is fluoro, chloro or bromo,

and the pharmaceutically acceptable acid addition salts thereof.

2. A peptide of claim 1 wherein

R.sup.1 is D- or L-Pro, D-Phe, D-Phe(4-Cl), D-Nal (2),

R.sup.2 is D-Phe(4-F) or D-Phe(4-Cl), and

R.sup.3 is D-Trp.

3. A peptide selected from the group of peptides having the formula:

wherein

X is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms, t-Boc or hydrogen,

X.sup.4 is hydrogen or a protecting group for the Ser hydroxyl group,

X.sup.5 is hydrogen or a protecting group for the Tyr phenolic hydroxyl group,

X.sup.6 is hydrogen or a protecting group for the Lys or Orn side chain amino group,

X.sup.8 is hydrogen or a protecting group for the Arg guanidino group,

X.sup.10 is hydrogen or a resin support containing benzhydryl or methylbenzhydryl groups,

R.sup.1 is D- or L-Pro, D- or L.DELTA..sup.3 -Pro, D-Phe, D-Phe(4-H1), D-Ser, D-Thr, D-Ala, D-Nal(1) or D-Nal (2),

R.sup.2 is D-Phe or D-Phe(4-H1),

R.sup.3 is D-Trp, D-Phe, D-Pal, D-Nal(1) or D-Nal (2),

R.sup.6 is D-Lys or D-Orn and R.sup.10 is Gly or D-Ala,

where H1 is fluoro, chloro or bromo, provided that where X is t-Boc or hydrogen, X.sup.4, X.sup.5, X.sup.6, and X.sup.8 must be other than hydrogen.

4. A Peptide of claim 3 wherein

X.sup.4 is hydrogen or 2,6-dichloro-benzyl,

X.sup.5 is hydrogen or Z(2-Br) or 2,6-dichlorobenzyl,

X.sup.6 is hydrogen or Z(2-Cl) and

X.sup.8 is hydrogen, nitro, Tos, methyl-(t-butylbenzyl)sulfonyl or 4-methoxy-2,3,6-trimethyl benzylsulfonyl.

5. A Peptide of claim 4 wherein

X.sup.4 and X.sup.5 are hydrogen or benzyl,

X.sup.6 is hydrogen or Z(2Cl), and

X.sup.8 is hydrogen or Tos.

6. A peptide of claim 2 wherein X is acetyl.

7. A peptide of claim 6 wherein R.sup.1 is Pro.

8. A peptide of claim 6 wherein R.sup.1 is D-Nal(2).

9. A peptide of claim 6 wherein R.sup.1 is D-Phe(4-Cl).

10. A peptide of claim 6 wherein R.sup.1 is D-Phe.

11. A peptide of claim 7 wherein R.sup.6 is D-Cit or D-Cit(Et).

12. A peptide of claim 7 wherein R.sup.6 is D-Hci or D-Hci(Et).

13. A peptide of claim 8 wherein R.sup.6 is D-Hci or D-Cit.

14. A peptide of claim 9 wherein R.sup.6 is D-Hci or D-Cit.

15. A peptide of claim 10 wherein R.sup.6 is D-Cit or D-Cit(Et).

16. A peptide of claim 10 wherein R.sup.6 is D-Hci or D-Hci(Et).

17. A pharmaceutical composition for reducing the physiological availability of pituitary gonadotropins in a mammal which comprises a reductively effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

18. A method of reducing the physiological availability of pituitary gonadotropins in mammals in need of such reduction which comprises administering thereto a reductively effective amount of a compound of claim 1.

19. A method of claim 18 wherein the amount is between 0.1 and 2.5 mg/kg body weight per day.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Serving 500+ biopharmaceutical companies globally:

Accenture
Johnson and Johnson
US Department of Justice
Citi
Chinese Patent Office
Federal Trade Commission
Dow
US Army
McKinsey
Cantor Fitzgerald

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

Copyright 2002-2017 thinkBiotech LLC
ISSN: 2162-2639

Secure SSL Encrypted

Follow DrugPatentWatch:



Google
Twitter
Google Plus
botpot