Wayne D Kornreich

US Patent:

45699674, Feb 11, 1986

Filed:

Oct 24, 1983

Appl. No.:

6/545077

Inventors:

Wayne D. Kornreich - San Diego CA
Harry A. Anderson - San Diego CA
John S. Porter - Leucadia CA
Jean E. F. Rivier - La Jolla CA

Assignee:

The Salk Institute for Biological Studies - San Diego CA

International Classification:

C08L 8900
C07C10352

US Classification:

525 5411

Abstract:

Peptide N-alkylamides, and other C-terminal N-substituted amides, can be synthesized using solid-phase synthesis on a benzene-containing resin which is suitably methylated. Reactive amino groups are attached directly or indirectly to the methyl groups, for example, such as by reacting commercially available chloromethylated polystyrene resins with an alkylamine to create a resin-amine. The C-terminal amino acid of the desired peptide is linked to the resin-amine via an amide linkage, and the peptide is thereafter built in normal fashion. Treatment of the completed peptide intermediate with HF is effective to both effect deprotection and cleave the peptide from the resin in the form of the N-substituted amide. Examples include peptide N-ethylamides, N-fluoroethylamide, N-anilides and other substituted N-benzylamides.

US Patent:

55104584, Apr 23, 1996

Filed:

Dec 14, 1993

Appl. No.:

8/162178

Inventors:

Wayne D. Kornreich - San Diego CA
Jean F. Hernandez - Noyarey, FR
Jean E. Rivier - La Jolla CA
Catherine L. Rivier - La Jolla CA
Wylie W. Vale - La Jolla CA

Assignee:

The Salk Institute For Biological Studies - La Jolla CA

International Classification:

C07K 14695

US Classification:

530306

Abstract:

Disclosed are improved CRF peptide antagonists such as those having the formula: Y-D-Phe-Xaa. sub. 13 -Leu-Leu-Arg-Xaa. sub. 17 -Xaa. sub. 18 -Leu-Xaa. sub. 20 -Nle-Xaa. sub. 22 -Xaa. sub. 23 -Xaa. sub. 24 -Xaa. sub. 25 -Xaa. sub. 26 -Leu-Xaa. sub. 28 -Xaa. sub. 29 -Gln-Xaa. sub. 31 -Xaa. sub. 32 -Xaa. sub. 33 -Xaa. sub. 34 -Arg-Xaa. sub. 36 -Xaa. sub. 37 -Nle-Xaa. sub. 39 -Xaa. sub. 40 -Xaa. sub. 41 -NH. sub. 2 wherein Y is Ac or hydrogen; Xaa. sub. 13 is His, Tyr or Glu; Xaa. sub. 17 is CML, Glu, Asn or Lys; Xaa. sub. 18 is Val, Nle or Met; Xaa. sub. 20 is Glu, D-Glu, Aib or D-Ala; Xaa. sub. 22 is Ala, Aib, Thr, Asp or Glu; Xaa. sub. 23 is Arg, Orn, Har or Lys; Xaa. sub. 24 is Ala or Aib; Xaa. sub. 25 is Asp or Glu; Xaa. sub. 26 is Gln, Asn or Lys; Xaa. sub.

US Patent:

52350363, Aug 10, 1993

Filed:

May 31, 1991

Appl. No.:

7/709091

Inventors:

Wayne D. Kornreich - San Diego CA
Jean-Francois Hernandez - Oullins, FR
Jean E. F. Rivier - La Jolla CA
Wylie W. Vale - La Jolla CA

Assignee:

The Salk Institute for Biological Studies - San Diego CA

International Classification:

C07K 738
C07K 710

US Classification:

530306

Abstract:

Analogs of CRF, which are based upon hCRF, oCRF and alpha-helical CRF, are disclosed that can be administered to achieve a substantial elevation of ACTH,. beta. -endorphin,. beta. -lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels. Analogs include those having the formula: Y-R. sub. 1 -R. sub. 2 -R. sub. 3 -R. sub. 4 -R. sub. 5 -Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-R. sub. 20 -R. sub. 21 -R. sub. 22 -R. sub. 23 -R. sub. 24 -R. sub. 25 -Gln-Leu-Ala-Gln-Gln-Ala-R. sub. 32 -Ser-Asn-Arg-Lys-Leu-R. sub. 38 -R. sub. 39 -Ile-R. sub. 41 -NH. sub. 2, wherein Y is an acyl group having 7 or fewer carbon atoms or hydrogen; R. sub. 1 is Ser or desR. sub. 1 ; R. sub. 2 is Glu, Gln or desR. sub. 2 ; R. sub. 3 is Glu or desR. sub. 3 ; R. sub.

US Patent:

54398851, Aug 8, 1995

Filed:

Aug 10, 1993

Appl. No.:

8/104862

Inventors:

Wayne D. Kornreich - San Diego CA
Jean-Francois Hernandez - Noyarey, FR
Jean E. F. Rivier - La Jolla CA
Wylie W. Vale - La Jolla CA

Assignee:

The Salk Institute for Biological Studies - San Diego CA

International Classification:

C07K 14695
A61K 3835

US Classification:

514 12

Abstract:

Analogs of CRF, which are based upon hCRF, oCRF and alpha-helical CRF, are disclosed that can be administered to achieve a substantial elevation of ACTH,. beta. -endorphin,. beta. -lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels. Analogs include those having the formula (see SEQ ID NO:9): Y-Ser-Xaa. sub. 2 -Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Xaa. sub. 12 -His-Leu-Leu-Arg-Glu-Val-Leu-Xaa. sub. 20 -Xaa. sub. 21 -Xaa. sub. 22 -Xaa. sub. 23 -Xaa. sub. 24 -Xaa. sub. 25 -Gln-Leu-Ala-Gln-Gln-Ala-Xaa. sub. 32 -Ser-Asn-Arg-Xaa. sub. 36 -Leu-Xaa. sub. 38 -Xaa. sub. 39 -Ile-Xaa. sub. 41 -NH. sub. 2, wherein Y is an acyl group having 7 or fewer carbon atoms or hydrogen; Xaa. sub. 2 is Glu or Gln; Xaa. sub. 12 is Phe or D-Phe; Xaa. sub.

US Patent:

47014997, Oct 20, 1987

Filed:

Feb 3, 1986

Appl. No.:

6/799339

Inventors:

Wayne D. Kornreich - San Diego CA
Harry A. Anderson - San Diego CA
John S. Porter - Leucadia CA
Jean E. F. Rivier - La Jolla CA

Assignee:

The Salk Institute for Biological Studies - San Diego CA

International Classification:

C08F 818
C08F 1208
C08F11208
C08F21208

US Classification:

5253333

Abstract:

Peptide N-alkylamides, and other C-terminal N-substituted amides, can be synthesized using solid-phase synthesis on a benzene-containing resin which is suitably methylated. Reactive amino groups are attached directly or indirectly to the methyl groups, for example, such as by reacting commercially available chloromethylated polystyrene resins with an alkylamine to create a resin-amine. The C-terminal amino acid of the desired peptide is linked to the resin-amine via an amide linkage, and the peptide is thereafter built in normal fashion. Treatment of the completed peptide intermediate with HF is effective to both effect deprotection and cleave the peptide from the resin in the form of the N-substituted amide. Examples include peptide N-ethylamides, N-fluoroethylamide, N-anilides and other substituted N-benzylamides.

US Patent:

52450090, Sep 14, 1993

Filed:

Jun 14, 1991

Appl. No.:

7/715752

Inventors:

Wayne D. Kornreich - San Diego CA
Jean-Francois Hernandez - Qullins, FR
Jean E. F. Rivier - La Jolla CA
Catherine L. Rivier - La Jolla CA
Wylie W. Vale - La Jolla CA

Assignee:

The Salk Institute for Biological Studies - San Diego CA

International Classification:

C07K 738
C07K 760
C07K 710

US Classification:

530306

Abstract:

Disclosed are improved CRF peptide antagonists such as those having the formula: Y-D-Phe-R. sub. 13 -Leu-Leu-Arg-R. sub. 17 -R. sub. 18 -Leu-R. sub. 20 -Nle-R. sub. 22 -R. sub. 23 -R. sub. 24 -R. sub. 25 -R. sub. 26 -Leu-R. sub. 28 -R. sub. 29 -Gln-R. sub. 31 -R. sub. 32 -R. sub. 33 -R. sub. 34 -Arg-R. sub. 36 -R. sub. 37 -Nle-R. sub. 39 -R. sub. 40 -R. sub. 41 -NH. sub. 2 wherein Y is Ac or hydrogen; R. sub. 13 is His, Tyr or Glu; R. sub. 17 is Cys, Glu, Asn or Lys; R. sub. 18 is Val, Nle or Met; R. sub. 20 is D-Cys, Glu, D-Glu, Aib or D-Ala; R. sub. 22 is Ala, Aib, Thr, Asp or Glu; R. sub. 23 is Arg, Orn, Har or Lys; R. sub. 24 is Ala or Aib; R. sub. 25 is Asp or Glu; R. sub. 26 is Gln, Asn or Lys; R. sub. 28 is Ala or Aib; R. sub. 29 is Gln, Aib or Glu, R. sub.