Peptide-substituted heterocyclic immunostimulants

• US 4,619,915 A
• Filed: 10/19/1984
• Issued: 10/28/1986
• Est. Priority Date: 10/19/1984
• Status: Expired due to Fees

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Ives, Jeffrey L.
• Primary Examiner(s): Phillips, Delbert R.
• Application Number:
  US06/662,668
• Time in Patent Office: 739 Days
• Field of Search: 260/112.5 R, 514/17, 514/18, 514/19, 530/330, 530/331, 530/332
• US Class Current: 514/2.3
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07D 207/26 2-Pyrrolidones
• CPC Class Codes: C07D 211/62 attached in position 4
• CPC Class Codes: C07D 213/40 Acylated substituent nitrogen atom
• CPC Class Codes: C07D 233/76 with substituted hydrocarbon radicals attached to the third ring carbon atom
• CPC Class Codes: C07D 277/46 by carboxylic acids, or sulfur or nitrogen analogues thereof
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain
• CPC Class Codes: C07K 5/0215 containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu

Abstract

Peptide-substituted heterocyclic compounds having the formula below, pharmaceutically acceptable salts thereof and intermediates therefor; processes for their preparation and use as immunostimulant and antiinfective agents. ##STR1## wherein R is a 5- or 6-membered N-containing heterocyclyl moiety which can have an additional hetero atom selected from N, S or O; R¹ is hydrogen or (C_1-4)alkyl; x is 0 or an integer from 1 to 5; and y is 0 or 1; provided that when y is 0, said N-containing heterocyclyl moiety is linked to the ##STR2## group at its N atom.

Claims

1. A compound having the formula ##STR8## or a pharmaceutically acceptable salt thereof wherein R is an unsubstituted or substituted 5- or 6-membered heterocyclyl moiety selected from the group consisting of imidazolidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinyl, morpholinyl, thienyl, imidazolyl, pyrazolyl, thiomorpholinyl, thiazolyl, thiazolinyl, furyl, tetrahydrofuryl, pyrimidinyl and isoxazolyl;

and wherein the substituent is selected from the group consisting of methyl, oxo, carboxy or carbo(C_1-4 alkoxy);

R¹ is hydrogen or (C_1-2)alkyl;

x is 0 or an integer from 1 to 5; and

y is 0 or 1;

pk provided that when y is 0, said heterocyclyl moiety is linked to the --CO-- group at its N atom.

2. A compound according to claim 1 wherein y is O.

3. A compound according to claim 2 wherein said heterocyclyl moiety has one N atom and is pyridinyl, piperidinyl or pyrrolidinyl.

4. A compound according to claim 3 wherein said heterocyclyl moiety is a substituted heterocyclyl moiety.

5. A compound according to claim 4 wherein said heterocyclyl moiety is a carboxy substituted pyridinyl or piperidinyl moiety.

6. A compound according to claim 2 wherein said heterocyclyl moiety has two N atoms and is imidazolyl, imidazolidinyl, pyrazolyl, piperazinyl or pyrimidinyl.

7. A compound according to claim 6 wherein said heterocyclyl moiety is a substituted heterocyclyl moiety.

8. The compound according to claim 7 wherein said substituted heterocyclyl moiety is 4-methylpiperazin-1-yl.

9. A compound according to claim 2 wherein said heterocyclyl moiety has one N and one O hetero atom and is isoxazolyl or morpholinyl.

10. The compound according to claim 9 wherein said heterocyclyl moiety is morpholin-4-yl.

11. A compound according to claim 1 wherein y is 1.

12. A compound according to claim 11 wherein x is O and R¹ is hydrogen.

13. The compound according to claim 12 wherein R is a 5-membered heterocyclyl moiety having one N and one S atom and is thiazol-2-yl.

14. The compound according to claim 11 wherein x is 2, R¹ is methyl and R is pyrid-2-yl.

15. A compound according to claim 11 wherein R¹ is hydrogen, and R is 5-L-hydantoin.

16. The compound according to claim 15 wherein x is 4.

17. A pharmaceutical composition in unit dosage form comprising a pharmaceutically acceptable carrier and an antiinfective or immunostimulant effective amount of a compound of claim 1.

18. A method for treating an infection in a human suffering therefrom which comprises administering to said human antiinfective amount of a compound of claim 1.