US 5,399,587 AGranted

Biologically active compounds

AssigneeMerck & Co., Inc.

InventorsMaria L. Garcia, Robert A. Giacobbe, Otto D. Hensens, Gregory J. Kaczorowski, Seok H. Lee, Owen B. McManus, Deborah L. Zink

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Abstract

The present invention relates to novel potassium channel agonists which are useful in activating the calcium activated Maxi-K potassium channel in mammalian neuronal and smooth muscle tissue. The claimed compounds are of the general formula: ##STR1## In addition, a novel microbiological process for producing the claimed compounds is described.

Claims8

Dependent claims

A compound of the formula:

##STR14## and its pharmaceutically acceptable salts, wherein:
R.sup.1 is:
(a) H,
(b) C.sub.1-5 alkyl,
(c) C.sub.2-5 alkenyl
(d) C.sub.1-30 alkylcarbonyl,
(e) C.sub.2-30 alkenylcarbonyl,
(f) R.sup.4 --O--R.sup.4 --,
(e) substituted R.sup.4 --O--R.sup.4 -- wherein the substituent is phenyl or methoxy,
(f) tetrahydropyran, or
(g) (R.sup.4).sub.3 Si--R.sup.4 -- wherein R.sup.4 is independently C.sub.1-5 alkyl or C.sub.2-5 alkenyl at each occurrence,
R.sup.3 is:
(a) H,
(b) C.sub.1-5 alkyl,
(c) C.sub.2-5 alkenyl
(d) C.sub.1-30 alkylcarbonyl,
(e) C.sub.2-30 alkenylcarbonyl,
(e) R.sup.4 --O--R.sup.4 --,
(f) substituted R.sup.4 --O--R.sup.4 -- wherein the substituent is phenyl or methoxy,
(g) tetrahydropyran, or
(h) (R.sup.4).sub.3 SiR.sup.4,
or R.sup.1 and R.sup.3 together with the adjacent oxygen and ring carbon atoms, form a five-membered ting wherein R.sup.1 and R.sup.3 together are a single substituted or unsubstituted carbon or boron atom, wherein the carbon atom is substituted with two substituents independently selected from:
(a) H,
(b) C.sub.1-4 alkyl,
(c) C.sub.2-5 alkenyl,
(d) C.sub.1-6 alkoxy,
(e) C.sub.2-6 alkenyloxy, and
(f) phenyl, and
wherein the boron atom is substituted with one substituent selected from:
(a) H,
(b) C.sub.1-4 alkyl,
(c) C.sub.2-5 alkenyl,
(d) C.sub.1-6 alkoxy,
(e) C.sub.2-6 alkenyloxy, and
(f) phenyl;
R.sup.2 is:
(a) H,
(b) OH,
(c) C.sub.1-5 alkyloxy,
(d) C.sub.2-5 alkenyloxy,
(e) C.sub.1-30 alkylcarbonyloxy,
(f) C.sub.2-30 alkenylcarbonyloxy,
(g) R.sup.4 --O--R.sup.4 --O--,
(h) substituted R.sup.4 --O--R.sup.4 --O-- wherein the substituent is phenyl or methoxy,
(i) tetrahydropyran-oxy, or
(j) (R.sup.4).sub.3 Si--R.sup.4 --,
provided that when R.sup.2 is H and R.sup.3 is H, R.sup.1 is not H or CH.sub.3 CO;
R.sup.4 is independently C.sub.1-5 alkyl or C.sub.2-5 alkenyl at each occurrence, and the dashed line indicates the optional presence of a double bond.

45 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of the formula:

##STR14## and its pharmaceutically acceptable salts, wherein:
R.sup.1 is:
(a) H,
(b) C.sub.1-5 alkyl,
(c) C.sub.2-5 alkenyl
(d) C.sub.1-30 alkylcarbonyl,
(e) C.sub.2-30 alkenylcarbonyl,
(f) R.sup.4 --O--R.sup.4 --,
(e) substituted R.sup.4 --O--R.sup.4 -- wherein the substituent is phenyl or methoxy,
(f) tetrahydropyran, or
(g) (R.sup.4).sub.3 Si--R.sup.4 -- wherein R.sup.4 is independently C.sub.1-5 alkyl or C.sub.2-5 alkenyl at each occurrence,
R.sup.3 is:
(a) H,
(b) C.sub.1-5 alkyl,
(c) C.sub.2-5 alkenyl
(d) C.sub.1-30 alkylcarbonyl,
(e) C.sub.2-30 alkenylcarbonyl,
(e) R.sup.4 --O--R.sup.4 --,
(f) substituted R.sup.4 --O--R.sup.4 -- wherein the substituent is phenyl or methoxy,
(g) tetrahydropyran, or
(h) (R.sup.4).sub.3 SiR.sup.4,
or R.sup.1 and R.sup.3 together with the adjacent oxygen and ring carbon atoms, form a five-membered ting wherein R.sup.1 and R.sup.3 together are a single substituted or unsubstituted carbon or boron atom, wherein the carbon atom is substituted with two substituents independently selected from:
(a) H,
(b) C.sub.1-4 alkyl,
(c) C.sub.2-5 alkenyl,
(d) C.sub.1-6 alkoxy,
(e) C.sub.2-6 alkenyloxy, and
(f) phenyl, and
wherein the boron atom is substituted with one substituent selected from:
(a) H,
(b) C.sub.1-4 alkyl,
(c) C.sub.2-5 alkenyl,
(d) C.sub.1-6 alkoxy,
(e) C.sub.2-6 alkenyloxy, and
(f) phenyl;
R.sup.2 is:
(a) H,
(b) OH,
(c) C.sub.1-5 alkyloxy,
(d) C.sub.2-5 alkenyloxy,
(e) C.sub.1-30 alkylcarbonyloxy,
(f) C.sub.2-30 alkenylcarbonyloxy,
(g) R.sup.4 --O--R.sup.4 --O--,
(h) substituted R.sup.4 --O--R.sup.4 --O-- wherein the substituent is phenyl or methoxy,
(i) tetrahydropyran-oxy, or
(j) (R.sup.4).sub.3 Si--R.sup.4 --,
provided that when R.sup.2 is H and R.sup.3 is H, R.sup.1 is not H or CH.sub.3 CO;
R.sup.4 is independently C.sub.1-5 alkyl or C.sub.2-5 alkenyl at each occurrence, and the dashed line indicates the optional presence of a double bond.

45 more elements