Abstract: A method of preventing headache in a human is disclosed which comprises the administration to a human in need thereof of an effective amount of a compound of formula I ##STR1## wherein R.sup.1 and R.sup.3 are, independently, --H, --CH.sub.3, --CO(C.sub.1 -C.sub.6 alkyl), or --COAr, where Ar is optionally substituted phenyl;R.sup.2 is selected from the group consisting of pyrrolidine, piperidine, and hexamethyleneimino; ora pharmaceutically acceptable salt or solvate thereof.
Abstract: The present invention relates to sulfonate and carbamate derivatives of 3-aroylbenzo[b]thiophenes, pharmaceutical formulations containing these compounds and methods of using such compounds for inhibiting the loss of bone, lowering serum cholesterol levels and therapeutically treating hormone dependent mammalian breast and uterine carcinoma.
Type:
Grant
Filed:
February 22, 1995
Date of Patent:
November 30, 1999
Assignee:
Eli Lilly and Company
Inventors:
Larry J. Black, Henry U. Bryant, George J. Cullinan
Abstract: The current invention provides methods for the up-regulation of trkA in a mammal, including humans, comprising the administration of an effective amount of a compound of formula I ##STR1## wherein R.sup.1 and R.sup.3 are, independently, --H, --CH.sub.3, --CO(C.sub.1 -C.sub.6 alkyl), or --COAr, where Ar is optionally substituted phenyl;R.sup.2 is selected from the group consisting of pyrrolidine, piperidine, and hexamethyleneimino; ora pharmaceutically acceptable salt or solvate thereof.In addition, the current invention provides method to increase the effect of NGF (Nerve Growth Factor), NGF-like activities or NGF agonists, whether such is from endogenous or exogenous sources.Further, the current invention provides methods for maintaining the homeostasis and health of the hippocampus, hypothalamus, and cortex, thus maintaining their biological functions.
Type:
Grant
Filed:
September 9, 1998
Date of Patent:
November 23, 1999
Assignee:
Eli Lilly and Company
Inventors:
Henry Uhlman Bryant, Robert Frank Santerre
Abstract: A method of increasing gastroesophageal sphincter competence comprising administering to a human in need of treatment 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 pyrrolidino, hexamethyleneimino, and piperidino; or a pharmaceutically acceptable salt or solvate thereof.
Abstract: This invention provides orally administerable pharmaceutical formulations comprising raloxifene, its ethers or esters, or a pharmaceutically-acceptable salt thereof, in combination with a hydrophilic carrier composition.
Type:
Grant
Filed:
June 1, 1998
Date of Patent:
October 26, 1999
Assignee:
Eli Lilly and Company
Inventors:
Lowell L. Gibson, Kerry J. Hartauer, Julian L. Stowers, Stephanie A. Sweetana, Arvind L. Thakkar
Abstract: Provided are compounds of the formula (1): ##STR1## wherein R' is hydrogen, methyl or NH.sub.2 C(O)CH.sub.2 --;R" and R'" are independently methyl or hydrogen;R and R.sup.y are independently hydroxy or hydrogen;R.sub.1 is hydroxy, hydrogen, or hydroxysulfonyloxy;R.sub.7 is hydroxy, hydrogen, hydroxysulfonyloxy or phosphonooxy;R.sub.2 is a novel acyl side chain. Also provided are novel formulations, methods of inhibiting fungal and parasitic activity, and a process for preparing dideoxy (R=H) forms of the compounds.
Type:
Grant
Filed:
May 24, 1995
Date of Patent:
October 12, 1999
Assignee:
Eli Lilly and Company
Inventors:
Frederick J. Burkhardt, Manuel Debono, Jeffrey S. Nissen, William W. Turner, Jr.
Abstract: The invention provides novel benzothiophenes of the formula (I): ##STR1## wherein R.sub.1 is N-pyrrolidinyl or N-piperidinyl;R.sub.2 and R.sub.3 are independently hydrogen, --CO--(C.sub.10 -C.sub.22 alkyl), --CO--(C.sub.10 -C.sub.22 branched alkyl), --CO--(C.sub.10 -C.sub.22 alkenyl), --CO--(C.sub.10 -C.sub.22 polyalkenyl), --CO--(C.sub.10 -C.sub.22 alkynyl), or --CO--(CH.sub.2).sub.n COR.sub.4 ; provided R.sub.2 and R.sub.3 are not both dodecanoyl, and one of R.sub.2 or R.sub.3 is not hydrogenR.sub.4 is -3-cholesteryl or --O(CH.sub.2).sub.2 (OR.sub.5)CH.sub.2 OR.sub.6 ;R.sub.5 and R.sub.6 are independently hydrogen, --CO--(C.sub.10 -C.sub.22 alkyl), --CO--(C.sub.10 -C.sub.22 branched alkyl), --CO--(C.sub.10 -C.sub.22 alkenyl), --CO--(C.sub.10 -C.sub.22 polyalkenyl), or --CO--(C.sub.10 -C.sub.22 alkynyl); provided one of R.sub.5 or R.sub.
Type:
Grant
Filed:
October 3, 1997
Date of Patent:
July 27, 1999
Assignee:
Eli Lilly and Company
Inventors:
George Joseph Cullinan, Raymond Francis Kauffman
Abstract: The present invention is directed to N.sup.LEU -carbamoyl and thiocarbamoyl derivatives of A82846B and N.sup.DISACC variations thereof. These derivatives are useful as antibacterials and also as starting materials from which further antibacterial compounds are prepared.
Abstract: The present application relates to a series of compounds, and pharmaceutical formulations thereof, of the formula ##STR1## which provide a method of inhibiting hyperlipidemia, especially hypercholesterolemia, and the pathological sequelae thereof, in mammals, including humans.
Type:
Grant
Filed:
August 4, 1998
Date of Patent:
June 1, 1999
Assignee:
Eli Lilly and Company
Inventors:
George Joseph Cullinan, Patrick Irving Eacho, Patricia Sue Foxworthy-Mason, Robert John Schmidt
Abstract: A method of inhibiting endometrial mitoses 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, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.
Abstract: Sulfated benzothiophenes of the formula I ##STR1## wherein R.sup.1 is hydrogen, hydroxy, C.sub.1 -C.sub.4 alkoxy, --OCOO(C.sub.1 -C.sub.6 alkyl), --OCO(C.sub.1 -C.sub.6 alkyl), --OCOAr wherein Ar is phenyl or optionally substituted phenyl, --OSO.sub.2 (C.sub.4 -C.sub.6 straight chain alkyl), or --OSO.sub.3 H;R.sup.2 is R.sup.1, Cl or F; with the proviso that at least one of R.sup.1 or R.sup.2 is --OSO.sub.3 H;R.sup.3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; andn is 2 or 3;or a pharmaceutically acceptable salt or solvate thereof.
Type:
Grant
Filed:
April 14, 1997
Date of Patent:
December 1, 1998
Assignee:
Eli Lilly and Company
Inventors:
Michael Paul Clay, Charles Alan Frolik, Charles David Jones, Terry Donald Lindstrom
Abstract: A method of inhibiting ovarian dysgenesis, delayed puberty, or sexual infantilism 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, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.
Abstract: A method of inhibiting melanoma 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, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino, or a pharmaceutically acceptable salt of solvate thereof; alone or in combination with one or more melanoma-inhibiting agents.
Abstract: The invention provides novel benzothiophenes of the formula (I): ##STR1## wherein R.sub.1 is N-pyrrolidinyl or N-piperidinyl; R.sub.2 and R.sub.3 are independently hydrogen, --CO--(C.sub.10 -C.sub.22 alkyl), --CO--(C.sub.10 -C.sub.22 branched alkyl), --CO--(C.sub.10 -C.sub.22 alkenyl), --CO--(C.sub.10 -C.sub.22 polyalkenyl), --CO--(C.sub.10 -C.sub.22 alkynyl), or --CO--(CH.sub.2).sub.n COR.sub.4 ; provided R.sub.2 and R.sub.3 are not both dodecanoyl, and one of R.sub.2 or R.sub.3 is not hydrogenR.sub.4 is -3-cholesteryl or --O(CH.sub.2).sub.2 (OR.sub.5)CH.sub.2 OR.sub.6 ;R.sub.5 and R.sub.6 are independently hydrogen, --CO--(C.sub.10 -C.sub.22 alkyl), --CO--(C.sub.10 -C.sub.22 branched alkyl), --CO--(C.sub.10 -C.sub.22 alkenyl), --CO--(C.sub.10 -C.sub.22 polyalkenyl), or --CO--(C.sub.10 -C.sub.22 alkynyl); provided one of R.sub.5 or R.sub.6 is not hydrogen;n is 0-4; and pharmaceutically acceptable salts and solvates thereof.
Type:
Grant
Filed:
October 3, 1997
Date of Patent:
October 27, 1998
Assignee:
Eli Lilly and Company
Inventors:
George Joseph Cullinan, Raymond Francis Kauffman
Abstract: The invention provides novel benzothiophenes of the formula (I): ##STR1## wherein R.sub.1 is N-pyrrolidinyl or N-piperidinyl; R.sub.2 and R.sub.3 are independently hydrogen, --CO--(C.sub.10 -C.sub.22 alkyl), --CO--(C.sub.10 -C.sub.22 branched alkyl), --CO--(C.sub.10 -C.sub.22 alkenyl), --CO--(C.sub.10 -C.sub.22 polyalkenyl), --CO--(C.sub.10 -C.sub.22 alkynyl), or --CO--(CH.sub.2).sub.n COR.sub.4 ; provided R.sub.2 and R.sub.3 are not both dodecanoyl, and one of R.sub.2 or R.sub.3 is not hydrogenR.sub.4 is -3-cholesteryl or --O(CH.sub.2).sub.2 (OR.sub.5)CH.sub.2 OR.sub.6 ;R.sub.5 and R.sub.6 are independently hydrogen, --CO--(C.sub.10 -C.sub.22 alkyl), --CO--(C.sub.10 -C.sub.22 branched alkyl), --CO--(C.sub.10 -C.sub.22 alkenyl), --CO--(C.sub.10 -C.sub.22 polyalkenyl), or --CO--(C.sub.10 -C.sub.22 alkynyl); provided one of R.sub.5 or R.sub.6 is not hydrogen;n is 0-4; and pharmaceutically acceptable salts and solvates thereof.
Type:
Grant
Filed:
October 3, 1997
Date of Patent:
September 22, 1998
Assignee:
Eli Lilly and Company
Inventors:
George Joseph Cullinan, Raymond Francis Kauffman
Abstract: The current invention provides methods for increasing the concentration of nitric oxide (NO) in vascular endothelial cells, comprising administering a compound of formula I ##STR1## Wherein: R is hydrogen, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCO(C.sub.1 -C.sub.4 alkyl), or --OCOAr where Ar is a phenyl or optionally substituted phenyl;R.sub.1 is R, --C.sub.1, or --F;R.sub.2 is 1-pyrrolidinyl, 1-piperidinyl, or 1-hexamethyleneimino;or a pharmaceutically acceptable salt or solvate thereof.
Abstract: This invention provides solid orally administerable pharmaceutical formulations comprising raloxifene hydrochloride, a surfactant being sorbitan fatty acid ester or a polyoxyethylene sorbitan fatty acid ester, polyvinylpyrrolidone, and a water soluble diluent which is polyol or sugar.
Type:
Grant
Filed:
March 26, 1997
Date of Patent:
September 22, 1998
Assignee:
Eli Lilly and Company
Inventors:
Lowell L. Gibson, Kerry J. Hartauer, Julian L. Stowers, Stephanie A. Sweetana, Arvind L. Thakkar
Abstract: The invention relates to an improved process for preparing cephalosporins by reaction compounds such as 7-amino-cephalosporanic acid, 7-amino-3-deacetoxy-cephalosporanic acid or their derivatives with derivatives of .alpha.-amino acids in the presence of a properly immobilized penicillin acylase enzyme under the following conditions, independently, or in combination: (1) at a temperature ranging from 0.degree. C. to +20.degree. C.; or (2) at ambient pH; with a high molar ratio of .alpha.-amino acid to a cephalosporanic nucleus.
Abstract: The present invention relates to sulfonate and carbamate derivatives of 3-aroylbenzo?b!thiophenes, pharmaceutical formulations containing these compounds and methods of using such compounds for inhibiting the loss of bone, lowering serum cholesterol levels and therapeutically treating hormone dependent mammalian breast and uterine carcinoma.
Type:
Grant
Filed:
October 27, 1997
Date of Patent:
August 25, 1998
Assignee:
Eli Lilly and Company
Inventors:
Larry J. Black, Henry U. Bryant, George J. Cullinan