α-ketoamide derivatives as inhibitors of thrombosis

Claim 2

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the formula ##STR58## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR59## wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to about 6 carbon atoms or alkyl of about 6 to about 15 carbon atoms; m is 2; B is selected from a group consisting of -Gly-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-; C is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5diiodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 3

A composition according to claim 1 wherein B is -Gly-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe- and C is -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH.

Claim 4

A composition according to claim 1 wherein B is -Gly-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe- and C is -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH.

Claim 5

A composition according to claim 1 wherein B is -Gly-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe- and C is -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH.

Claim 6

A composition according to claim 1 wherein B is -Gly-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe- and C is -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH.

Claim 7

A composition of claim 1 wherein said compound has the formula: ##STR60##

Claim 8

A composition of claim 1 wherein said compound has the formula: ##STR61##

Claim 9

A composition of claim 1 wherein said compound has the formula: ##STR62##

Claim 10

A composition of claim 1 wherein said compound has the formula: ##STR63##

Claim 11

A composition of claim 1 wherein said compound has the formula: ##STR64##

Claim 12

A composition of claim 1 wherein said compound has the formula: ##STR65##

Claim 13

A composition of claim 1 wherein said compound has the formula: ##STR66##

Claim 14

A composition of claim 1 wherein C is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 .

Claim 15

A composition of claim 13 wherein B is -Gly-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe- and C is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH.

Claim 16

A composition of claim 13 wherein B is -Gly-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe- and C is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH.

Claim 17

A composition of claim 13 wherein B is -Gly-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe- and C is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH.

Claim 18

A composition of claim 13 wherein B is -Gly-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe- and C is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH.

Claim 19

A composition of claim 2, 3, 4 or 5, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 20

A composition of claim 18, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl and 2-phenylethyl.

Claim 21

A composition of claim 19, wherein R 1 is 4-heptyl.

Claim 22

A composition of claim 20, wherein A is selected from a group consisting of ##STR67##

Claim 23

A composition of claim 13, 14, 15, 16 or 17, wherein R 1 is alkyl of about 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 24

A composition of claim 22, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl and 2-phenylethyl.

Claim 25

A composition of claim 23, wherein R 1 is 4-heptyl.

Claim 26

A composition of claim 24, wherein A is selected from a group consisting of ##STR68##

Claim 27

A composition of claim 25 wherein A is -CO 2 H.

Claim 28

A composition comprising a radioactive atom and a compound of the formula: ##STR69## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR70## wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms; m is 1, 2 or 3; D is selected from a group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-, wherein X has the formula: ##STR71## wherein r is an integer selected from 2 to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group; E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 29

A composition comprising a radioactive atom and a compound of the formula: ##STR69## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR70## wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms; m is 1, 2 or 3; D is selected from a group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-, wherein X has the formula: ##STR71## wherein r is an integer selected from 2 to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group; E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 30

A composition of claim 27, wherein m is 2.

Claim 31

A composition of claim 28, wherein E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH.

Claim 32

A composition of claim 29, wherein D is selected from a group consisting of -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe- and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-.

Claim 33

A composition of claim 30, wherein Y has the formula -C(=S)- and L is 1-(p-aminobenzyl)diethylene-triaminepentaacetic acid.

Claim 34

A composition of claim 31, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 35

A composition of claim 32, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl and 2-phenylethyl.

Claim 36

A composition of claim 33, wherein R 1 is 4-heptyl.

Claim 37

A composition of claim 34, wherein A is selected from a group consisting of ##STR72##

Claim 38

A composition of claim 30, wherein Y has the formula ##STR73##

Claim 39

A composition of claim 36, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 40

A composition of claim 32, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl or 2-phenylethyl.

Claim 41

A composition of claim 38, wherein R 1 is 4-heptyl.

Claim 42

A composition of claim 39, wherein A is selected from a group consisting of ##STR74##

Claim 43

A composition of any of claims 27 to 35 or 36 to 40 wherein the radioactive atom is selected from the group consisting of In-111 and TC-99m.

Claim 44

A composition comprising a paramagnetic atom and a compound of the formula ##STR75## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR76## and -C(O)NHR', wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms; m is 1, 2 or 3; D is selected from a group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe- -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-, wherein X has the formula: ##STR77## wherein r is an integer selected from 2 to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group; E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH2, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 45

A composition comprising a paramagnetic atom and a compound of the formula ##STR75## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR76## and -C(O)NHR', wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms; m is 1, 2 or 3; D is selected from a group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe- -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-, wherein X has the formula: ##STR77## wherein r is an integer selected from 2 to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group; E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH2, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 46

A composition of claim 42, wherein m is 2.

Claim 47

A composition of claim 43, wherein E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH.

Claim 48

A composition of claim 44, wherein D is selected from a group consisting of -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe- and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-.

Claim 49

A composition of claim 45, wherein Y has the formula -C(=S)- and L is 1-(p-aminobenzyl)diethylene-triaminepentaacetic acid.

Claim 50

A composition of claim 46, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 51

A composition of claim 47, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl and 2-phenylethyl.

Claim 52

A composition of claim 48, wherein R 1 is 4-heptyl.

Claim 53

A composition of claim 165, wherein A is selected from a group consisting of ##STR78##

Claim 54

A composition of claim 45, wherein Y has the formula ##STR79## and L is metallothionein.

Claim 55

A composition of claim 51, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 56

A composition of claim 52, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl or 2-phenylethyl.

Claim 57

A composition of claim 53, wherein R 1 is 4-heptyl.

Claim 58

A composition of claim 54, wherein A is selected from a group consisting of ##STR80##

Claim 59

A composition of claim 55, where A is -CO 2 H.

Claim 60

A composition of any of claims 42 to 50 or 51 to 56, wherein the paramagnetic atom is selected from a group consisting of gadolinium, copper, cobalt, nickel and manganese.

Claim 61

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of a compound having the formula: ##STR81## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR82## and -C(O)NHR', wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms; m is 1, 2 or 3; D is selected from a group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-, wherein X has the formula: ##STR83## wherein r is an integer selected from 2 to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group; E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 62

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of a compound having the formula: ##STR81## wherein R 1 is alkyl of 1 to about 12 carbon atoms, alkenyl of about 3 to about 6 carbon atoms, aryl of about 6 to about 14 carbon atoms, aralkyl of about 6 to about 15 carbon atoms, aralkenyl of about 8 to 15 carbon atoms, alkoxy of 1 to about 12 carbon atoms, alkenyloxy of about 3 to about 8 carbon atoms, aryloxy of about 6 to about 14 carbon atoms, or aralkyloxy of about 6 to about 15 carbon atoms; A is selected from a group consisting of ##STR82## and -C(O)NHR', wherein R' is H, alkyl of 1 to about 6 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms and R" is alkyl of 1 to 6 carbon atoms or aralkyl of about 6 to about 15 carbon atoms; m is 1, 2 or 3; D is selected from a group consisting of -X-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Asn-Gly-Asp-Phe-, -X-Gly-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-X-Gly-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-X-Gly-Arg-Gly-Asp-Phe-, -Gly-Gly-Gly-Gly-X-Arg-Gly-Asp-Phe-, and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-, wherein X has the formula: ##STR83## wherein r is an integer selected from 2 to 6, L is a chelating means for chelating a radioactive or paramagnetic atom, and Y is an attaching means for attaching chelating means to the amino group; E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-OH, -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3-iodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Tyr(3,5-diiodo)-Leu-NH 2 , -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3-iodo)-Leu-NH 2 , and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr(3,5-diiodo)-Leu-NH 2 ; or pharmaceutically acceptable salt thereof.

Claim 63

A composition of claim 58, wherein m is 2.

Claim 64

A composition of claim 59, wherein E is selected from a group consisting of -Glu-Glu-Ile-Pro-Glu-Tyr-Leu-OH and -Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH.

Claim 65

A composition of claim 60, wherein D is selected from a group consisting of -Gly-Gly-X-Gly-Gly-Asn-Gly-Asp-Phe-, -Gly-Gly-X-Gly-Gly-Arg-Gly-Asp-Phe- and -Gly-Gly-Gly-Gly-Gly-X-Gly-Asp-Phe-.

Claim 66

A composition of claim 61, wherein Y has the formula -C(=S)- and L is 1-(p-aminobenzyl)diethylene-triaminepentaacetic acid.

Claim 67

A composition of claim 62, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 68

A composition of claim 63, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl and 2-phenylethyl.

Claim 69

A composition of claim 64, wherein R 1 is 4-heptyl.

Claim 70

A composition of claim 65, wherein A is selected from a group consisting of ##STR84##

Claim 71

A composition of claim 61, wherein Y has the formula ##STR85##

Claim 72

A composition of claim 67, wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 73

A composition of claim 68, wherein R 1 is selected from a group consisting of cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl or 2-phenylethyl.

Claim 74

A composition of claim 69, wherein R 1 is 4-heptyl.

Claim 75

A composition of claim 70, wherein A is selected from a group consisting of ##STR86##

Claim 76

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of any of claims 27 to 35 or 36 to 40.

Claim 77

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of and of claim 41.

Claim 78

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of and of claims 42 to 50 or 51 to 56.

Claim 79

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of claim 57.

Claim 80

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of any of claims 13 to 17 wherein all iodo groups are together selected from a group consisting of I-123, I-125 and I-131.

Claim 81

A diagnostic composition comprising a pharmaceutically acceptable carrier and a diagnostically effective amount of the composition of claim 76 wherein R 1 is alkyl of 1 to about 10 carbon atoms or aralkyl of about 7 to about 12 carbon atoms.

Claim 82

A diagnostic composition comprising a pharmaceutically acceptable carrier and a diagnostically effective amount of the composition of claim 77 wherein R 1 is selected from cyclohexyl, 4-heptyl, 3-methylpentyl, 2-methylpropyl, 3-octyl and 2-phenylethyl.

Claim 83

A diagnostic composition comprising a pharmaceutically acceptable carrier and a diagnostically effective amount of the composition of claim 78 wherein R 1 is 4-heptyl.

Claim 84

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of claim 79 wherein A is selected from -CO 2 H, -CH 2 CO 2 H, -CO 2 CH 3 and -CH 2 CO 2 CH 3 .

Claim 85

A diagnostic composition comprising a phramaceutically acceptable carrier and a diagnostically effective amount of the composition of claim 80 wherein A is -CO 2 H.