Peptide antagonists of neurokinin B

• US 4,665,157 A
• Filed: 09/30/1985
• Issued: 05/12/1987
• Est. Priority Date: 09/30/1985
• Status: Expired due to Term

• Current Assignee: McNeilab, Inc.
• Original Assignee: McNeilab, Inc.
• Inventors: Wright, David E.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US06/781,839
• Time in Patent Office: 589 Days
• Field of Search: 530/328
• US Class Current: 530/328
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 7/22 Tachykinins, e.g. Eledoisins , Substance P; Related peptides

Abstract

Four decapeptides found to be analgesics and have antagonist activity to Neurokinin B which is also known as Neuromedin K. The decapeptides are of the following formula (I):

A.sup.1 -D-Pro.sup.2 -His.sup.3 -D.sup.4 -Phe.sup.5 -D-Trp.sup.6 -Val.sup.7

-D-Trp⁸ -Leu⁹ -Nle¹⁰ -NH₂ (I)

wherein A¹ and D⁴ are Asp or D-Asp amino acids. Also described is an HPLC separation method using piperidine.

Claims

1. A decapeptide of the following formula (I):

space="preserve" listing-type="equation">A.sup.1 -D-Pro.sup.2 -His.sup.3 -D.sup.4 -Phe.sup.5 -D-Trp.sup.6 -Val.sup.7 -D-Trp.sup.8 -Leu.sup.9 -Nle.sup.10 -NH.sub.2 (I)

wherein

A¹ is Asp¹ or D-Asp¹ ; and

D⁴ is Asp⁴ or D-Asp⁴,

and the pharmaceutically acceptable salts thereof.

2. The decapeptide of claim 1, wherein said decapeptide of formula (I) is:

space="preserve" listing-type="equation">Asp.sup.1 -D-Pro.sup.2 -His.sup.3 -Asp.sup.4 -Phe.sup.5 -D-Trp.sup.6 -Val.sup.7 -D-Trp.sup.8 -Leu.sup.9 -Nle.sup.10 -NH.sub.2.

3. The decapeptide of claim 1, wherein said decapeptide of formula (I) is:

space="preserve" listing-type="equation">D-Asp.sup.1 -D-Pro.sup.2 -His.sup.3 -Asp.sup.4 -Phe.sup.5 -D-Trp.sup.6 -Val.sup.7 -D-Trp.sup.8 -Leu.sup.9 -Nle.sup.10 -NH.sub.2.

4. The decapeptide of claim 1, wherein said decapeptide of formula (I) is:

space="preserve" listing-type="equation">D-Asp.sup.1 -D-Pro.sup.2 -His.sup.3 -D-Asp.sup.4 -Phe.sup.5 -D-Trp.sup.6 -Val.sup.7 -D-Trp.sup.8 -Leu.sup.9 -Nle.sup.10 -NH.sub.2.

5. The decapeptide of claim 1, wherein said decapeptide of formula (I) is:

space="preserve" listing-type="equation">Asp.sup.1 -D-Pro.sup.2 -His.sup.3 -D-Asp.sup.4 -Phe.sup.5 -D-Trp.sup.6 -Val.sup.7 -D-Trp.sup.8 -Leu.sup.9 -Nle.sup.10 -NH.sub.2.