Biologically active carboxylic acid esters

• US 5,200,553 A
• Filed: 07/25/1988
• Issued: 04/06/1993
• Est. Priority Date: 07/30/1987
• Status: Expired due to Term

• Current Assignee: BAR ILAN University, Kupat Holim Health Insurance Institution
• Original Assignee: Kupat Holim Health Insurance Institution of The General Federation of Labor
• Inventors: Rephaeli, Ada, Shaklai, Matitiahu, Nudelman, Abraham
• Primary Examiner(s): PRESCOTT, ARTHUR
• Assistant Examiner(s): Garner, Vivian
• Application Number:
  US07/223,595
• Time in Patent Office: 1,716 Days
• Field of Search: 560/263, 560/174, 560/178, 560/254, 560/105, 560/112, 560/189, 260/410.6, 549/62, 549/71, 549/479, 514/512, 514/547, 514/548, 514/533, 558/270, 558/271, 558/276, 558/273
• US Class Current: 560/263
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07D 307/89 with two oxygen atoms directly attached in positions 1 and 3

Abstract

Biologically active carboxylic acid esters which promote antitumor or immune response are selected from the group consisting of compounds having formulas (I), (II) and (III):

XCH.sub.2 --CHX--CHX--C(═O)--O--Z                      (I)

CH.sub.3 --CO--CH.sub.2 --C(═O)--O--Z                  (II)

CH.sub.3 --CH.sub.2 --CO--C(═O)--O--Z                  (III)

wherein X is H, or one X only may be OH; Z is --CHR--O--(O═)C--R'"'"', R represents a member selected from the group consisting of hydrogen and alkyl, and R'"'"' represents a member of the group consisting of alkyl, aminoalkyl, aralkyl, aryl, alkoxy, aralkoxy and aryloxy, in which aryl by itself, and aryl in aralkyl, aralkoxy and aryloxy, are each selected from the group consisting of sub-groups (a) and (b), wherein (a) is unsubstituted phenyl, napthyl, furyl or thienyl, and (b) is phenyl, napthyl, furyl or thienyl, each of which is substituted by at least one substituent selected from the group consisting of alkyl, alkoxy or halogen, provided that in (I) when X is H and R'"'"' is propyl, then R is alkyl which contains at least three carbon atoms.

Claims

1. Compounds selected from the group consisting of compounds having formulas (I), (II) and (III):

space="preserve" listing-type="equation">XCH.sub.2 --CHX--CHX--C(═

O)--O--Z (I),

space="preserve" listing-type="equation">CH.sub.3 --CO--CH.sub.2 --C(═

O)--O--Z (II) and

space="preserve" listing-type="equation">CH.sub.3 --CH.sub.2 --CO--C(═

O)--O--Z (III)

wherein X is H, or one X only may be OH;

Z is --CHR--O--(O═

)C--R¹, R represents a member selected from the group consisting of hydrogen and alkyl, and R'"'"' represents a member selected from the group consisting of alkyl, aminoalkyl, aralkyl, aryl, alkoxy, aralkoxy and aryloxy, in which aryl by itself, and aryl in aralkyl, aralkoxy and aryloxy, are each selected from the group consisting of sub-groups (a) and (b), wherein (a) is unsubstituted phenyl, naphthyl, furyl or thienyl, and (b) is phenyl, naphthyl, furyl or thienyl, each of which is substituted by at least one substituent selected from the group consisting of alkyl, alkoxy or halogen, provided that in (I) when X is H and R'"'"' is propyl, then R is alkyl which contains at least three carbon atoms.

2. Compounds of any of the formulae depicted in claim 1, wherein R represents a member selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl and tertiary butyl.

3. Compounds according to claim 1, wherein R'"'"' represents a member selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, tertiary butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, secondary butoxy and tertiary butoxy, provided that in formula (I) when X is H and R'"'"' is propyl, then R is a member selected from the group consisting of propyl, isopropyl, butyl, isobutyl, secondary butyl and tertiary butyl.

4. Pharmaceutical compositions for producing at least one effect selected from an antitumor effect and an immune response modulating effect, and which contain at least one compound selected from the group consisting of compounds having formulae (I), (II), and (III) as defined in claim 1, together with at least one pharmaceutically acceptable adjuvant, diluent or carrier.

5. Pharmaceutical compositions according to claim 4, wherein R represents a member selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl and tertiary butyl.

6. Pharmaceutical compositions according to claim 4, wherein R'"'"' represents a member selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, tertiary butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, secondary butoxy and tertiary butoxy.

7. Pharmaceutical compositions according to claim 4, and which are adapted for oral, parenteral or rectal administration.

8. Pharmaceutical compositions according to claim 4, and which are in unit dosage form.

9. A method of treating tumors in animals, which comprises administering to an animal an antitumorogenic effective dose of at least one compound selected from the group consisting of compounds having any of the formulae (I), (II) and (III), as defined in claim 1.

10. A method according to claim 9, wherein at least one compound is administered in the form of a pharmaceutical composition which comprises at least one pharmaceutically acceptable adjuvant, diluent or carrier.

11. A method to claim 9, wherein the manner of administration is intermittent injection.

12. Pivaloyloxymethyl butyrate.