Abstract: A series of hetero-oxy alkanamines are effective pharmaceuticals for the treatment of conditions related to or affected by the reuptake of serotonin and by the serotonin 1.sub.A receptor. The compounds are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal, and for the treatment of depression and other conditions for which serotonin reuptake inhibitors are used.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
April 21, 1998
Assignee:
Eli Lilly and Company
Inventors:
David J. Hibschman, Joseph H. Krushinski, Jr., Kurt Rasmussen, Vincent P. Rocco, John M. Schaus, Dennis C. Thompson
Abstract: This invention provides novel bis-indolemaleimide macrocycle derivatives of the formula: ##STR1## wherein R1, R2, X, W, and Y are as defined in the specification. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.
Type:
Grant
Filed:
March 20, 1997
Date of Patent:
April 14, 1998
Assignee:
Eli Lilly and Company
Inventors:
William F. Heath, Jr., Michael R. Jirousek, John H. McDonald, III, Christopher J. Rito
Abstract: Disclosed herein is a method of treating a disease of the central nervous system with a compound of the formula ##STR1## in which m is 0, 1 or 2, n and q are each 0 or 1 to 5, and p is 0 or 1, X is --CO.sub.2 H or tetrazolyl,Y is --CH.dbd.CH--, andZ is(i) phenyl, naphthyl or thienyl, said phenyl, naphthyl and thienyl being optionally substituted,(ii) --CHR.sup.1 R.sup.2 where R.sup.1 and R.sup.2 are each phenyl, naphthyl or thienyl, said phenyl, naphthyl and thienyl being optionally substituted,(iii) .dbd.CR.sup.1 R.sup.2 where R.sup.1 and R.sup.2 are each phenyl, naphthyl or thienyl, said phenyl, naphthyl and thienyl being optionally substituted, or(iv) ##STR2## where r is 0 or 1 to 3 and the phenyl rings are optionally substituted; provided that when Z is phenyl and m is 1, p is 1; and salts and esters thereof.
Type:
Grant
Filed:
September 13, 1996
Date of Patent:
April 14, 1998
Assignee:
Eli Lilly and Company
Inventors:
Jesus Ezquerra Carrera, Almudena Rubio Esteban, Andre Mann, Angele Schoenfelder, Darryle Darwin Schoepp, Concepcion Pedregal Tercero, Camille-Georges Wermuth
Abstract: The present invention provides methods for binding a 5-HT.sub.2B receptor in mammals using both known and novel compounds. Further, the invention provides a method for treating or preventing 5-HT.sub.2B related conditions. Finally, the invention provides an article of manufacture.
Type:
Grant
Filed:
March 25, 1996
Date of Patent:
April 7, 1998
Assignee:
Eli Lilly and Company
Inventors:
James E. Audia, Marlene L. Cohen, Jaswant S. Gidda, David L. G. Nelson
Abstract: This invention provides a method for treating a condition resulting from the cessation or withdrawal of tobacco or nicotine, opioids, ethanol or combinations thereof comprising administering an effective amount of 4-chloro-5-(imidazoline-2-y(amino)-6-methoxy-2-methylpyrimidine.
Type:
Grant
Filed:
August 12, 1996
Date of Patent:
March 31, 1998
Assignee:
Eli Lilly and Company
Inventors:
August M. Watanabe, Thomas F. Bumol, Mitchell I. Steinberg, Mary J. Kallman, Kurt Rasmussen
Abstract: A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids for treatment of conditions such as septic shock.
Type:
Grant
Filed:
March 28, 1997
Date of Patent:
March 31, 1998
Assignee:
Eli Lilly and Company
Inventors:
Nicholas J. Bach, Robert D. Dillard, Susan E. Draheim
Abstract: The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-?4-(2-aminoethoxy)benzoyl!benzo?b!-thiophenes. The present invention is also directed to crystalline solvates and a non-solvated crystalline form of 6-hydroxy-2-(4-hydroxyphenyl)-3-?4-(2-piperidinoethoxy)benzoyl!-benzo?b!th iophene hydrochloride, as well as processes for their preparation.
Abstract: A method of inhibiting plasminogen activator inhibitor 1 comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneimino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.
Type:
Grant
Filed:
September 4, 1996
Date of Patent:
March 24, 1998
Assignee:
Eli Lilly and Company
Inventors:
David Thompson Berg, Brian William Grinnell, Mark Alan Richardson
Abstract: The present invention relates to compounds of formula I ##STR1## wherein R.sup.1 is --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl);R.sup.2 is 1-naphthyl, 2-naphthyl, 2-thienyl, 3-thienyl, benzothienyl, or --CH.sub.2 C.sub.6 H.sub.5 ; any of which may be optionally substituted with 1-3 substituents independently selected from the group halo, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl);X is --CH.sub.2 --, --CO--, or --CH(OH)--;n is 2 or 3; andR.sup.3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
August 6, 1996
Date of Patent:
March 17, 1998
Assignee:
Eli Lilly and Company
Inventors:
Henry Uhlman Bryant, Timothy Alan Grese, Stephen Sung Yong Cho
Abstract: This invention relates to thrombin inhibiting compounds having the Formula IX--Y--NH--(CH.sub.2).sub.r --G Iwhere X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.
Type:
Grant
Filed:
September 1, 1995
Date of Patent:
March 10, 1998
Assignee:
Eli Lilly and Company
Inventors:
Aaron L. Schacht, Robert T. Shuman, Gerald F. Smith, Michael R. Wiley
Abstract: A process for the preparation of (+)-2-amino-bicyclo?3.1.0!-hexane-2-6-dicarboxylic acid, or a pharmaceutically acceptable salt thereof, which comprises hydrolysing (-)-2-spiro-5'-hydantoinbicyclo?3.1.0!hexane-6-carboxylic acid or a salt thereof, and optionally forming a pharmaceutically acceptable salt. Also disclosed are intermediates useful in the process.
Abstract: A container for a liquid medicament suspension, e.g. an insulin crystal suspension, has a tube with a sealing piston, a cap, and a mixing element which moves along the tube to assist mixing the suspension. The element is guided by the inner surface of the tube and has restricted lateral movement but is free to move axially, for example, by tilting or end to end inversion of the container. Flow passages such as apertures and peripheral recesses are provided in the mixing element which can serve to promote turbulent flow.The containers are particularly suited for use as multi-dose cartridges for pen-like injection devices or for portable infusion devices which have piston-operating mechanisms to cooperate with the container piston.
Abstract: Viridin, viridiol, demethoxyviridin, demethoxyviridiol, virone, and wortmannolone, and analogs thereof, are inhibitors of phosphatidylinositol 3-kinase. The compounds are particularly useful for inhibiting phosphatidylinositol 3-kinase in vertebrates and for treating phosphatidylinositol 3-kinase-dependent conditions, especially neoplasms, restenosis and atherosclerosis, and bone disorders in vertebrates.
Type:
Grant
Filed:
February 25, 1997
Date of Patent:
March 10, 1998
Assignee:
Eli Lilly and Company
Inventors:
Jeffrey A. Dodge, Masahiko Sato, Chris J. Vlahos
Abstract: The present invention provides compounds of formula I: ##STR1## wherein X is --O-- or --S--,Y is --O--, --S--, --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, or --NR.sup.5 --;R.sup.1, R.sup.2, and R.sup.3 are each independently --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl), --OSO.sub.2 CF.sub.3, Cl, or F;n is 1 or 2;W is CH.sub.2 or C.dbd.O;R.sup.4 is 1-piperidinyl, 2-oxo-1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino;R.sup.5 is C.sub.1 -C.sub.3 alkyl, --COC.sub.6 H.sub.5, --CO(C.sub.1 -C.sub.6 alkyl), --C(O)OC.sub.6 H.sub.5, --C(O)O(C.sub.1 -C.sub.6 alkyl), --SO.sub.2 (C.sub.1 -C.sub.6 alkyl), --SO.sub.2 C.sub.6 H.sub.5, or --SO.sub.2 CF.sub.3 ;or a pharmaceutically acceptable salt or solvate thereof.