Acyl-substituted phenyl esters of prostacyclin-type compounds

Claim 2

An acid ester of prostacyclin of the formula ##STR26## or its (5E) isomer, wherein R 1 is alkyl of one to 4 carbon atoms, inclusive, with the proviso that when R 1 is tert-butyl the group ##STR27## is only in the 4-position.

Claim 3

Prostacyclin, 4-acetylphenyl ester, a compound according to claim 1.

Claim 4

Prostacyclin, 3-acetylphenyl ester, a compound according to claim 1.

Claim 5

Prostacyclin, 2-acetylphenyl ester, a compound according to claim 1.

Claim 6

Prostacyclin, 4-propionylphenyl ester, a compound according to claim 1.

Claim 7

Prostacyclin, 4-butyrylphenyl ester, a compound according to claim 1.

Claim 8

Prostacyclin, 4-isobutyrylphenyl ester, a compound according to claim 1.

Claim 9

Prostacyclin, 4-valerylphenyl ester, a compound according to claim 1.

Claim 10

Prostacyclin, 4-isovalerylphenyl ester, a compound according to claim 1.

Claim 11

Prostacyclin, 4-pivalylphenyl ester, a compound according to claim 1.

Claim 12

(5E)-Prostacyclin, 4-acetylphenyl ester, a compound according to claim 1.

Claim 13

An acid ester of a prostacyclin analog of the formula ##STR28## wherein A is (1) --O--(oxa) or, when E is --CH 2 --, (2) --CH 2 --O--, with --CH 2 bonded to R 2 wherein E is --CH 2 -- or --CH 2 CH 2 --, wherein L 1 is (1) --(CH 2 ) n -- wherein n is one to 5, inclusive, (2) --(CH 2 ) p --CF 2 -- wherein p is 2, 3, or 4, or (3) --(CH 2 ) v --CH═CH-- wherein v is 1, 2, or 3, wherein M 1 is ##STR29## where ˜ indicates attachment in alpha or beta configuration, wherein Q is ##STR30## wherein R 4 is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R 1 is alkyl of one to 4 carbon atoms, inclusive, with the proviso that when R 1 is tert-butyl the --C(O)--R 1 group is in the 4-position, wherein R 2 is ##STR31## wherein R 3 is ##STR32## wherein C g H 2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR 5 R 6 -- and terminal methyl, wherein R 5 and R 6 are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R 5 and R 6 is fluoro only when the other is hydrogen or fluoro and the further proviso that neither R 5 nor R 6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C j H 2j wherein C j H 2j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between CR 5 R 6 -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms; inclusive, fluoro, chloro, trifluoromethyl, or --OR 7 -- wherein R 7 is alkyl of one to 4 carbon atoms, inclusive, and s is zero, one, 2 or 3, with the proviso that not more than two T's are other thn alkyl and when s is 2 or 3 the T's are either the same or different, and wherein X is (1) trans-CH═CH-- (2) cis-CH═CH-- (3)--C.tbd.C-- or (4) --CH 2 CH 2 -- with the proviso that said formula does not include prostacyclin or its (5E) isomer.

Claim 14

An acid ester of a prostacyclin analog of the formula ##STR28## wherein A is (1) --O--(oxa) or, when E is --CH 2 --, (2) --CH 2 --O--, with --CH 2 bonded to R 2 wherein E is --CH 2 -- or --CH 2 CH 2 --, wherein L 1 is (1) --(CH 2 ) n -- wherein n is one to 5, inclusive, (2) --(CH 2 ) p --CF 2 -- wherein p is 2, 3, or 4, or (3) --(CH 2 ) v --CH═CH-- wherein v is 1, 2, or 3, wherein M 1 is ##STR29## where ˜ indicates attachment in alpha or beta configuration, wherein Q is ##STR30## wherein R 4 is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R 1 is alkyl of one to 4 carbon atoms, inclusive, with the proviso that when R 1 is tert-butyl the --C(O)--R 1 group is in the 4-position, wherein R 2 is ##STR31## wherein R 3 is ##STR32## wherein C g H 2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR 5 R 6 -- and terminal methyl, wherein R 5 and R 6 are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R 5 and R 6 is fluoro only when the other is hydrogen or fluoro and the further proviso that neither R 5 nor R 6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C j H 2j wherein C j H 2j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between CR 5 R 6 -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms; inclusive, fluoro, chloro, trifluoromethyl, or --OR 7 -- wherein R 7 is alkyl of one to 4 carbon atoms, inclusive, and s is zero, one, 2 or 3, with the proviso that not more than two T's are other thn alkyl and when s is 2 or 3 the T's are either the same or different, and wherein X is (1) trans-CH═CH-- (2) cis-CH═CH-- (3)--C.tbd.C-- or (4) --CH 2 CH 2 -- with the proviso that said formula does not include prostacyclin or its (5E) isomer.

Claim 15

(5Z)-trans-Δ 2 -PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 16

(5Z)-2,2-Difluoro-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 17

(5Z)-11-Deoxy-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 18

(5Z)-13,14-Dihydro-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 19

(5Z)-13,14-Didehydro-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 20

(5Z)-15-Deoxy-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 21

(5Z)-(15S)-15-Methyl-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 22

(5Z)-16,16-Dimethyl-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 23

(5Z)-16,16-Difluoro-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 24

(5Z)-16-Phenoxy-17,18,19,20-tetranor-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 25

(5Z)-17,18-Didehydro-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 26

(5Z)-17-Phenyl-18,19,20-trinor-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 27

(5E)-11-Deoxy-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 28

(5E)-16,16-Dimethyl-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 29

(5E)-16,16-Difluoro-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 30

(5E)-16-Phenoxy-17,18,19,20-tetranor-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 31

(5E)-17-Phenyl-18,19,20-trinor-PGI 2 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 32

(6S and 6R)-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 33

(6S and 6R)-Trans-Δ 2 -PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 34

(6S and 6R)-2,2-Difluoro-13,14-dihydro-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 35

(6S and 6R)-2,2-Difluoro-16-phenoxy-17,18,19,20-tetranor-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 36

(6S and 6R)-2,2-Difluoro-13,14-dihydro-17-phenyl-18,19,20-trinor-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 37

(6S and 6R)-Trans-Δ 2 -16,16-dimethyl-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 38

(6S and 6R)-13,14-Dihydro-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 39

(6S and 6R)-13,14-Didehydro-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 40

(6S and 6R)-(15S)-15-methyl-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 41

(6S and 6R)-(15R)-15-methyl-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 42

(6S and 6R)-16,16-Dimethyl-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 43

(6S and 6R)-16,16-Difluoro-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 44

(6S and 6R)-16-Phenoxy-17,18,19,20-tetranor-PGI 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 45

6ε-6-Hydroxy-PGI 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 46

(4Z)-9-Deoxy-5,9α-epoxy-Δ 4 -PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 47

(4Z)-9-Deoxy-5,9α-epoxy-Δ 4 -17-phenyl-18,19,20-trinor-PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 48

(4Z)-9-Deoxy-5,9α-epoxy-Δ 4 -13,14-didehydro-PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 49

(4Z)-9-Deoxy-5,9α-epoxy-Δ 4 -(15S)-15-methyl-PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 50

(4E)-9-Deoxy-5,9α-epoxy-Δ 4 -PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 51

(5S and 5R)-9-Deoxy-5,9α-epoxy-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 52

(5S and 5R)-9-Deoxy-5,9α-epoxy-(15S)-15-methyl-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 53

(5S and 5R)-9-Deoxy-5,9α-epoxy-(15R)-15-methyl-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 54

(2E, 5R)-9-Deoxy-5,9α-epoxy-Δ 2 -PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 55

(5Z)-9-Deoxy-6,9α-epoxymethano-Δ 5 -PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 56

(5Z)-9-Deoxy-6,9α-epoxymethano-Δ 5 -13,14-didehydro-PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 57

(5E)-9-Deoxy-6,9α-epoxymethano-Δ 5 -PGF 1 , 4-acetylphenyl ester, a compound according to claim 12.

Claim 58

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 59

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-11-deoxy-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 60

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-(15S)-15-methyl-PGF 1 , 4-acetylphenyl

Claim 61

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-(15S)-15-methyl-PGF 1 , 4-acetylphenyl

Claim 62

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-16,16-dimethyl-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 63

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-16-phenoxy-17,18,19,20-tetranor-PGF.sub.1, 4-acetylphenyl ester, compounds according to claim 12.

Claim 64

(6S and 6R)-9-Deoxy-6,9α-epoxymethano-17-phenyl-18,19,20-trinor-PGF 1 , 4-acetylphenyl ester, compounds according to claim 12.

Claim 65

An acid ester of a prostacyclin analog of the formula ##STR33## wherein L 1 is (1) --(CH 2 ) n -- wherein n is one to 5, inclusive, (2) --(CH 2 ) p --CF 2 -- wherein p is 2, 3, or 4, or (3) --(CH 2 ) v --CH═CH-- wherein v is 1, 2, or 3, wherein Q is ##STR34## wherein R 4 is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R 1 is alkyl of one to 4 carbon atoms, inclusive, with the proviso that when R 1 is tert-butyl the group ##STR35## is in the 4-position, wherein R 2 is ##STR36## wherein R 3 is ##STR37## wherein C g H 2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR 5 R 6 -- and terminal methyl, wherein R 5 and R 6 are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R 5 and R 6 is fluoro only when the other is hydrogen or fluoro and the further proviso that neither R 5 nor R 6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C j H 2j wherein C j H 2j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between CR 5 R 6 -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms; inclusive, fluoro, chloro, trifluoromethyl, or --OR 7 -- wherein R 7 is alkyl of one to 4 carbon atoms, inclusive, and s is zero, one, 2 or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different, wherein R 10 is straight-chain alkyl of one to 6 carbon atoms, inclusive, wherein X is (1) trans-CH═CH-- (2) cis-CH═CH-- (3) --C═C-- or (4) --CH 2 CH 2 --, and wherein ˜ indicates attachment in cis or trans configuration.

Claim 66

An acid ester of a prostacyclin analog of the formula ##STR33## wherein L 1 is (1) --(CH 2 ) n -- wherein n is one to 5, inclusive, (2) --(CH 2 ) p --CF 2 -- wherein p is 2, 3, or 4, or (3) --(CH 2 ) v --CH═CH-- wherein v is 1, 2, or 3, wherein Q is ##STR34## wherein R 4 is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R 1 is alkyl of one to 4 carbon atoms, inclusive, with the proviso that when R 1 is tert-butyl the group ##STR35## is in the 4-position, wherein R 2 is ##STR36## wherein R 3 is ##STR37## wherein C g H 2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR 5 R 6 -- and terminal methyl, wherein R 5 and R 6 are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R 5 and R 6 is fluoro only when the other is hydrogen or fluoro and the further proviso that neither R 5 nor R 6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C j H 2j wherein C j H 2j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between CR 5 R 6 -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms; inclusive, fluoro, chloro, trifluoromethyl, or --OR 7 -- wherein R 7 is alkyl of one to 4 carbon atoms, inclusive, and s is zero, one, 2 or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different, wherein R 10 is straight-chain alkyl of one to 6 carbon atoms, inclusive, wherein X is (1) trans-CH═CH-- (2) cis-CH═CH-- (3) --C═C-- or (4) --CH 2 CH 2 --, and wherein ˜ indicates attachment in cis or trans configuration.

Claim 67

(6S and 6R)-6-Methoxy-PGI 1 , 4-acetylphenyl ester, compounds according to claim 62.