Paul D Gesellchen

US Patent:

43093434, Jan 5, 1982

Filed:

Nov 25, 1980

Appl. No.:

6/210210

Inventors:

Paul D. Gesellchen - Indianapolis IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352

US Classification:

2601125E

Abstract:

Compounds of the formula [R-Tyr-A-Gly-(N-R. sub. 1)Phe(p-Y)-X]. sub. 2 -(CH. sub. 2). sub. n in which R is hydrogen or methyl; A is the residue of a D-amino acid selected from the group consisting of Ala, Abu, Ser, Thr, and Met; R. sub. 1 is hydrogen, C. sub. 1 -C. sub. 3 primary alkyl, cyclopropylmethyl, or allyl; Y is hydrogen or fluoro; n is an integer from 1 to 10; and X is --NH-- or a group of the formula ##STR1## in which R. sub. 2 is hydrogen or C. sub. 1 -C. sub. 3 primary alkyl; R. sub. 3 is phenyl, 2-methylthioethyl, or isobutyl; or R. sub. 2 and R. sub. 3 taken together are --CH. sub. 2 --CH. sub. 2 --CH. sub. 2 --; subject to the limitation that, when R. sub. 2 is other than hydrogen, R. sub. 1 is hydrogen; are useful analgesic agents.

US Patent:

42514398, Feb 17, 1981

Filed:

Dec 17, 1979

Appl. No.:

6/104345

Inventors:

Paul D. Gesellchen - Indianapolis IN
David L. Smiley - Greenfield IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352

US Classification:

2601125R

Abstract:

Compound of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality; R. sub. 1 is hydrogen or C. sub. 1 --C. sub. 3 primary alkyl; R. sub. 2 is C. sub. 1 --C. sub. 4 primary or secondary alkyl, allyl, cyclopropylmethyl, C. sub. 1 --C. sub. 2 hydroxyalkyl, or --(CH. sub. 2). sub. m --U--CH. sub. 3 in which U is --S-- or >S--O and m is 1 or 2; R. sub. 3 is hydrogen, C. sub. 1 --C. sub. 4 primary or secondary alkyl, cyclopropylmethyl, or allyl; X is hydrogen, halo, hydroxy, C. sub. 1 --C. sub. 3 alkoxy, nitro, C. sub. 1 --C. sub. 3 alkyl, or trifluoromethyl; and Z is --CH. sub. 2 OR. sub. 4, ##STR2## in which R. sub. 4 is hydrogen or C. sub. 1 --C. sub.

US Patent:

54300231, Jul 4, 1995

Filed:

Sep 14, 1993

Appl. No.:

8/121134

Inventors:

Paul D. Gesellchen - Indianapolis IN
Robert T. Shuman - Greenwood IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

A61K 3800
C07K 508

US Classification:

514 18

Abstract:

Thrombin inhibitors represented by the formula ##STR1## as provided wherein A(C. dbd. O)-- is, inter alia, phenylglycyl, cyclohexylglycyl, cyclohexenylglycyl, thienylglycyl or naphthylglycyl, wherein the. alpha. -amino group is preferably substituted by alkyl e. g. methyl or an alkoxycarbonyl, cycloalkoxycarbonyl or arylkoxycarbonyl group e. g. t-butyloxycarbonyl. A(C. dbd. O)-- also represents an. alpha. -substituted acetyl group such as. alpha. -methoxyphenylacetyl; or a bicyclic group such as a tetrahydroisoquinolin-1- or 3-carbonyl group; a perhydroisoquinolin -1- or -3-carbonyl group; or a 1-amino or (substituted amino) cycloalkylcarbonyl group such as 1-aminocyclohexylcarbonyl. Also provided are a method for inhibiting the formation of blood clots in man and animals by administering a thrombin inhibitor of the above formula and pharmaceutical formulations useful in the method.

US Patent:

42833299, Aug 11, 1981

Filed:

Dec 17, 1979

Appl. No.:

6/104348

Inventors:

Paul D. Gesellchen - Indianapolis IN
Robert T. Shuman - Greenwood IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352
A61K 3700

US Classification:

2601125R

Abstract:

Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality; R. sub. 1 is hydrogen or C. sub. 1 -C. sub. 3 primary alkyl; R. sub. 2 is C. sub. 1 -C. sub. 4 primary or secondary alkyl, allyl, cyclopropylmethyl, C. sub. 1 -C. sub. 2 hydroxyalkyl, or --(CH. sub. 2). sub. m --U--CH. sub. 3 in which U is --S-- or >S--O and m is 1 or 2; R. sub. 3 is hydrogen, C. sub. 1 -C. sub. 4 primary or secondary alkyl, cyclopropylmethyl, or allyl; R. sub. 4 is hydrogen, C. sub. 1 -C. sub. 5 primary or secondary alkyl, --(CH. sub. 2). sub. n --X--(CH. sub. 2). sub. p --CH. sub. 3 in which X is --O--, --S--, >S--O or ##STR2## n is 1 or 2, and p is 0 or 1, phenyl, or monosubstituted phenyl in which the substituent is halo, hydroxy, C. sub. 1 -C. sub. 3 alkoxy, nitro, C. sub. 1 -C. sub. 3 alkyl, or trifluoromethyl; R. sub.

US Patent:

43223397, Mar 30, 1982

Filed:

Oct 20, 1980

Appl. No.:

6/198896

Inventors:

Paul D. Gesellchen - Indianapolis IN
Robert T. Shuman - Greenwood IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352

US Classification:

2601125E

Abstract:

Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which R is hydrogen, methyl, or ethyl; A is the residue of a D-amino acid selected from the group consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp), Met, Cys(Me), Met(O), Cys(Me) (O), Ser, Thr, and Hse; R. sub. 1 is hydrogen, C. sub. 1 -C. sub. 3 primary alkyl, cyclopropylmethyl, allyl, or propargyl; X is bromo, iodo, chloro, C. sub. 1 -C. sub. 3 alkyl, trifluoromethyl, or C. sub. 1 -C. sub. 2 alkoxy; B is the residue of a D- or L-amino acid lacking its carboxyl moiety and selected from the group consisting of Gly, Ala, Abu, Nva, Val, Nle, Leu, Ile, Pgl, Cys(Me), Cys(Me) (O), Cys(Me) (O. sub. 2), Cys(Et), Cys(Et) (O), Cys(Et) (O. sub. 2), Met, Met(O), Met(O. sub.

US Patent:

42658080, May 5, 1981

Filed:

Dec 17, 1979

Appl. No.:

6/104529

Inventors:

Paul D. Gesellchen - Indianapolis IN
Robert T. Shuman - Greenwood IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352

US Classification:

2601125R

Abstract:

Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality; R. sub. 1 is hydrogen or C. sub. 1 -C. sub. 3 primary alkyl; R. sub. 2 is C. sub. 1 -C. sub. 4 primary or secondary alkyl, allyl, cyclopropylmethyl, C. sub. 1 -C. sub. 2 hydroxyalkyl, or --(CH. sub. 2). sub. m --U--CH. sub. 3 in which U is --S-- or >S--O and m is 1 or 2; R. sub. 3 is hydrogen, C. sub. 1 -C. sub. 4 primary or secondary alkyl, cyclopropylmethyl, allyl or propargyl; and Z is --CH. sub. 2 OR. sub. 4, ##STR2## in which R. sub. 4 is hydrogen, acetyl, or acetoxymethyl and R. sub. 5 is C. sub. 1 -C. sub. 3 alkyl; are useful analgesic agents.

US Patent:

43223400, Mar 30, 1982

Filed:

Oct 20, 1980

Appl. No.:

6/198900

Inventors:

Robert T. Shuman - Greenwood IN
Paul D. Gesellchen - Indianapolis IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352

US Classification:

2601125E

Abstract:

Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which R is hydrogen, methyl, ethyl, cyclopropylmethyl, or allyl; A is a residue of a D-amino acid selected from the group consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp), Met, Cys(Me), Met(O), Cys(Me) (O), Ser, Thr, and Hse; R. sub. 1 is C. sub. 1 -C. sub. 3 primary alkyl, cyclopropylmethyl, allyl, ethylthiomethyl, 2-fluoroethyl, or propargyl; X is bromo, iodo, chloro, methyl, trifluoromethyl, or methoxy; and Z is --CH. sub. 2 OR. sub. 2, ##STR2## in which R. sub. 2 is hydrogen, acetyl, or acetoxymethyl and R. sub. 3 is C. sub. 1 -C. sub. 3 alkyl; are useful analgesic agents.

US Patent:

44734972, Sep 25, 1984

Filed:

Mar 7, 1983

Appl. No.:

6/472440

Inventors:

Paul D. Gesellchen - Indianapolis IN
Robert T. Shuman - Greenwood IN

Assignee:

Eli Lilly and Company - Indianapolis IN

International Classification:

C07C10352

US Classification:

2601125E

Abstract:

Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which R is hydrogen, methyl, ethyl, cyclopropylmethyl, or allyl; A is a residue of a D-amino acid selected from the group consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp), Met, Cys(Me), Met(O), Cys(Me)(O), Ser, Ser(Me), Thr, and Hse; R. sub. 1 is hydrogen, C. sub. 1 -C. sub. 3 primary alkyl, cyclopropylmethyl, allyl, ethylthiomethyl, 2-fluoroethyl, or propargyl; and X is hydrogen, fluoro, bromo, iodo, chloro, hydroxy, C. sub. 1 -C. sub. 3 alkyl, trifluoromethyl, or C. sub. 1 -C. sub. 2 alkoxy; are useful analgesic agents.