Analogs of substance P and eledoisin

• US 4,680,283 A
• Filed: 08/20/1986
• Issued: 07/14/1987
• Est. Priority Date: 09/26/1984
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Veber, Daniel F., Freidinger, Roger
• Primary Examiner(s): Phillips, Delbert R.
• Application Number:
  US06/898,274
• Time in Patent Office: 328 Days
• Field of Search: 530/329, 530/800, 530/330, 530/331, 530/332, 514/17, 514/18
• US Class Current: 514/17.7
• 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: C07K 7/22 Tachykinins, e.g. Eledoisins , Substance P; Related peptides

Abstract

Analogs of substance P and eledoisin which are conformationally constrained by the presence of a lactam in the peptide chain demonstrate greater selectivity and increased protease stability and are useful as analgesic, anti-inflammatory, antihypertensive, central nervous system agents, and stimulants of lachrymal secretion. The compounds are prepared by standard peptide synthetic procedures.

Claims

1. A compound of structural formula:

##STR25## wherein X is <

Glu, <

Glu-Gln, Ac-Ala, Ac-Phe, or Ac; and

Y is Phe, N-Me-Phe, Ile, Val or Tyr.

2. The compound of claim 1 wherein X is <

Glu.

3. The compound of claim 1 wherein Y is Phe, Ile or Val.

4. The compound of claim 3 which is:

##STR26##

5. An ophthalmic composition for stimulating lachrymal secretion which comprises an ophthalmologically acceptable carrier and an effective lachrymal secretion stimulatory amount of a compound of structural formula:

##STR27## wherein X is <

Glu, <

Glu-Gln, Ac-Ala, or Ac-Phe, or Ac; and

Y is Phe, N-Me-Phe, Ile, Val or Tyr.

6. The formulation of claim 5 wherein X is Glu.

7. The formulation of claim 5 wherein Y is Phe, Ile, or Val.

8. The formulation of claim 7 wherein the compound is:

##STR28##

9. A method of stimulating lachrymal secretion in a patient in need of such treatment which comprises the administration of an effective amount of a compound of structural formula:

##STR29## wherein X is <

Glu, <

Glu-Gln, Ac-Ala, or Ac-Phe, or Ac; and

Y is Phe, N-Me-Phe, Ile, Val or Tyr.

10. The method of claim 9 wherein X is Glu.

11. The method of claim 9 wherein Y is Phe, Ile or Val.

12. The method of claim 11 wherein the compound is:

##STR30##