Claims
- 1. A method of treating a mammal to produce coronary dilation in the mammal, wherein the mammal is in need of such treatment and the method comprises administering to the mammal an adenosine compound which is selected from the group consisting of N-ethyladenosine-5'-uronamide, 2-chloroadenosine, N.sup.6 -methyladenosine, N.sup.6 -R-1-phenyl-2-propyladenosine, N.sup.6 -cyclohexyladenosine, N.sup.6 -phenyl-adenosine, and N.sup.6 -p-tolyladenosine.
- 2. The method according to claim 1, wherein the adenosine compound is N-ethyladenosine-5'-uronamide.
- 3. The method according to claim 1, wherein the adenosine compound is N.sup.6 -methyladenosine.
- 4. The method according to claim 1, wherein the adenosine compound is N.sup.6 -cyclohexyladenosine.
- 5. A compound of the formula: ##STR11## wherein, R is ##STR12## and R' is
- --OCH.sub.3, --NHCH.sub.3, --NHNH.sub.2,
- --NH(CH.sub.2).sub.2 NH.sub.2, ##STR13## --NH(CH.sub.2).sub.2 NHC(O) biotin, or --NH(CH.sub.2 ).sub.2 NHC(O)--(CH.sub.2).sub.5 --NHC(O) biotin.
- 6. A pharmaceutical composition comprising a compound of claim 5 in a pharmaceutical carrier.
- 7. A method of producing coronary vasodilation in a mammal in need of such vasodilation by administering to the mammal a vasodilating effective amount of a pharmaceutical composition of claim 6.
- 8. A compound having the formula ##STR14## wherein, R is --CH.sub.2 --C(O)--R', and
- R' is hydroxyl, lower alkylamino wherein the alkyl group thereof is unsubstituted or substituted by methyl, halo-lower alkyl, lower alkyl, an ester group or an amino group; monoarylamino wherein the aryl group thereof is unsubstituted or substituted by methyl, halo-lower alkyl, lower alkyl, an ester group, or an amino group; or an oligopeptide of up to five amino acids in length in which the point of attachment is through an amide bond at the p-position of phenylalanine; or
- R is ##STR15## wherein R" is alkoxy, lower alkylamino, wherein the alkyl group thereof is unsubstituted or substituted by an amino or acylamino group; or
- R is NH--(CH.sub.2).sub.2 NHR"' wherein R"' is an acyl moiety selected from the group consisting of acetyl, p-hydroxyphenylpropionyl, d-biotinyl, .alpha.-bromoacetyl, methyl fumaryl, d-biotinyl-.epsilon.-aminocaproyl, an amino acid of the L-configuration and an amino of the D-configuration; or
- R"' is a monoaryl group; or
- R"' is NH(CH).sub.2 N.dbd.C.dbd.S.
- 9. A compound, as recited in claim 8, having the formula: ##STR16## wherein: R is --CH.sub.2 --C(O)--R' and
- R' is
- --OH,
- --NHCH.sub.3,
- --NH--CH.sub.2 CO.sub.2 C.sub.2 H.sub.5, ##STR17## R is ##STR18## and R" is
- --OCH.sub.3,
- --NHCH.sub.3,
- --NHNH.sub.2,
- NHCH.sub.2 CH.sub.2 --NH.sub.2,
- NHCH.sub.2 CH.sub.2 --NHCOCH.sub.3, ##STR19## --NH(CH.sub.2).sub.2 NH--CO--CH.dbd.CH--CO--OCH.sub.3 (trans), --NH(CH.sub.2).sub.2 N.dbd.C.dbd.S, ##STR20##
- 10. The compound of claim 9, which is N.sup.6 -(4'-carboxymethyl)phenyladenosine.
- 11. The compound of claim 9, wherein R is --CH.sub.2 C(O)--NHCH.sub.3.
- 12. The compound of claim 9, wherein R is --CH.sub.2 C(O)--NH--CH.sub.2 CO.sub.2 C.sub.2 H.sub.5.
- 13. The compound of claim 9, wherein R is ##STR21##
- 14. The compound of claim 9, which is N.sup.6 -(4'-carboxymethyl)phenyladenosine-p-toluide.
- 15. The compound of claim 9, wherein R is ##STR22##
- 16. The compound of claim 9, wherein R is ##STR23##
- 17. The compound of claim 9, which is adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-aminophenylacetic acid methyl ester.
- 18. The compound of claim 9, which is adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-aminophenylacetyl-N-methyl-amide.
- 19. The compound of claim 9, wherein R is ##STR24##
- 20. The compound of claim 9, which is adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-aminophenylacetyl-1,2-diaminoethane.
- 21. The compound of claim 9, wherein R is ##STR25##
- 22. The compound of claim 9, wherein R is ##STR26##
- 23. The compound of claim 9, which is adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-aminophenylacetyl-1,2-diaminoethane-d-biotin.
- 24. A pharmaceutical composition, comprising: an effective amount of a compound having the formula ##STR27## wherein R is --CH.sub.2 C--R'; and
- R' is hydroxyl, substituted or unsubstituted lower alkylamino wherein the alkyl group thereof may be substituted by methyl, halo-lower alkyl, lower alkyl, an ester group or an amino group; substituted or unsubstituted monoarylamino wherein the aryl group thereof may be substituted by methyl, halo-lower alkyl, lower alkyl, an ester group, or amino group; or an oligopeptide of up to five amino acids in length in which the point of attachment is five amino acids in length in which the point of attachment is alkyl, an ester group, or amino group; or an oligopeptide of up to five amino acids in length in which the point of attachment is through an amide bond at the p-position of phenyl-alanine; or
- R is ##STR28## wherein R" is alkoxy, lower alkylamino wherein the alkyl group thereof is unsubstituted or substituted by an amino or an acylamino group; or
- R" is NH--(CH.sub.2).sub.2 NHR"' wherein R"' is an acyl moiety selected from the group consisting of acetyl, p-hydroxyphenylpropionyl, d-biotinyl, .alpha.-bromoacetyl, methyl fumaryl, d-biotinyl-.epsilon.-aminocaproyl, an amino acid of the L-configuration and an amino acid of the D-configuration; or
- R"' is a monoaryl group; or
- R"' is NH(CH).sub.2 N.dbd.C.dbd.S and a pharmaceutical carrier therefor.
- 25. A pharmaceutical composition as recited in claim 24, which comprises an effective amount of a compound having the formula: ##STR29## wherein: R is --CH.sub.2 --C(O)--R', and
- R' is
- --OH,
- --NHCH.sub.3,
- --NH--CH.sub.2 CO.sub.2 C.sub.2 H.sub.5, ##STR30## R is ##STR31## and R" is
- --OCH.sub.3,
- --NHCH.sub.3,
- --NHNH.sub.2,
- --NHCH.sub.2 CH.sub.2 --NH.sub.2
- --NHCH.sub.2 CH.sub.2 --NHCOCH.sub.3, ##STR32## --NH--(CH.sub.2).sub.2 NHCOCH.sub.2 Br, --NH(CH.sub.2).sub.2 NH--CO--CH.dbd.CH--CO--OCH.sub.3 (trans),
- --NH(CH.sub.2).sub.2 N.dbd.C.dbd.S, ##STR33## and a pharmaceutical carrier therefor.
- 26. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound N.sup.6 -(4'-carboxymethyl)-phenyladenosine.
- 27. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is --CH.sub.2 C(O)--NHCH.sub.3.
- 28. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is --CH.sub.2 C(O)--NH--CH.sub.2 CO.sub.2 C.sub.2 H.sub.5.
- 29. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is ##STR34##
- 30. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound N.sup.6 -(4'-carboxymethyl phenyl-adenosine-p-toluide.
- 31. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is ##STR35##
- 32. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is ##STR36##
- 33. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound adenosine-N.sup.6 -(4'-carboxymethyl)-phenyl-p-aminophenylacetic acid methyl ester.
- 34. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-amino-phenylacetyl-N-methylamide.
- 35. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is ##STR37##
- 36. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-amino-phenylacetyl-1,2-diaminoethane.
- 37. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is ##STR38##
- 38. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound wherein R is ##STR39##
- 39. The pharmaceutical composition of claim 25, which comprises an effective amount of the compound adenosine-N.sup.6 -(4'-carboxymethyl)phenyl-p-amino-phenylacetyl-1,2-diaminoethane-d-biotin.
- 40. A compound as recited in claim 8, wherein R' is an oligopeptide which is protected at is .alpha.-amino and .alpha.-carboxylate functionalities by conventional peptide blocking groups.
- 41. The pharmaceutical composition of claim 24, wherein R' is an oligopeptide which is protected at its .alpha.-amino and .alpha.-carboxylate functionalities by conventional peptide blocking groups.
- 42. A method of producing coronary vasodilation in a mammal in need thereof, by administering to the mammal a vasodilating effective amount of a pharmaceutical composition as recited in claim 24.
- 43. A method of producing coronary vasodilation in a mammal in need thereof, by administering to the mammal a vasodilating effective amount of a pharmaceutical composition as recited in claim 25.
Parent Case Info
This is a continuation of copending patent application Ser. No. 07/346,257, filed on May 1, 1989, now abandoned, which is a continuation of copending patent application Ser. No. 06/833,035, filed on Feb. 26, 1986, now abandoned, which is a continuation-in-part of copending patent application Ser. No. 06/717,624, filed on Mar. 29, 1985, now abandoned.
US Referenced Citations (10)
Continuations (2)
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Number |
Date |
Country |
Parent |
346257 |
May 1989 |
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Parent |
833035 |
Feb 1986 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
717624 |
Mar 1985 |
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