Patents by Inventor Ivo Monkovic
Ivo Monkovic has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Patent number: 5635503Abstract: A series of non-peptidergic antagonists of NPY have been synthesized and are comprised of piperazine and homopiperazine derivatives of 4-phenyl-1,4-dihydropyridines of Formula (I). ##STR1## As antagonists of NPY-induced feeding behavior, these compounds are expected to act as effective anorexiant agents in promoting weight loss and treating eating disorders.Type: GrantFiled: June 7, 1995Date of Patent: June 3, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Graham S. Poindexter, Marc Bruce, Graham Johnson, Michael Kozlowski, Karen LeBoulluec, Ivo Monkovic, Ramakrishna Seethala, Charles P. Sloan
-
Patent number: 5349066Abstract: The present invention provides novel N-substituted hydrazine bifunctional compounds, novel N-substituted hydrazone derivatives of a cytotoxic reagent incorporating the bifunctional compounds, novel conjugates containing at least one cytotoxic reagent molecule reacted with the bifunctional compound and bound to a molecule reactive with a target cell population, methods for their production, and pharmaceutical compositions and methods for delivering cytotoxic reagents to a target population of cells. The hydrazone bonds of the conjugates of the invention permit the release of free cytotoxic reagent from the conjugates in the acidic external or internal environment of the target cells. The bifunctional compounds, derivatives, conjugates and methods of the invention are useful in antibody-or ligand-mediated drug delivery systems for the preferential killing of a target cell population to treat diseases such as cancers, infections and autoimmune disorders.Type: GrantFiled: April 8, 1992Date of Patent: September 20, 1994Assignee: Bristol-Myers Squibb CompanyInventors: Takushi Kaneko, David Willner, Ivo Monkovic, Robert S. Greenfield, Gary R. Braslawsky
-
Patent number: 5173486Abstract: This invention relates to a compound of formula I ##STR1## wherein p is 1 to 3;R.sup.1 and R.sup.2 each are independently hydrogen or an acyl group R.sup.6 CO--, in which R.sup.6 is C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-7 alkenyl, aryl or radical of the formula ##STR2## R.sup.3 is hydrogen or chloro; R.sup.4 and R.sup.5 each are independently C.sub.1-6 alkyl.Compounds of formula I are useful for the reversal of multidrug resistance of cancer drugs.Type: GrantFiled: August 26, 1991Date of Patent: December 22, 1992Assignee: Bristol-Myers Squibb CompanyInventors: Ivo Monkovic, Lotte Wang
-
Patent number: 5137877Abstract: The present invention provides novel N-substituted hydrazine bifunctional compounds, novel N-subhstituted hydrazone derivatives of a cytotoxic reagent incorporating the bifunctional compounds, novel conjugates containing at least one cytotoxic reagent molecule reacted with the bifunctional compound and bound to a molecule reactive with a target cell population, methods for their production, and pharmaceutical compositions and methods for delivering cytotoxic reagents to a target population of cells. The hydrazone bonds of the conjugates of the invention permit the release of free cytotoxic reagent from the conjugates in the acidic external or internal environment of the target cells. The bifunctional compounds, derivatives, conjugates and methods of the invention are useful in antibody-or ligand-mediated drug delivery systems for the perferential killing of a target cell population to treat diseases such as cancers, infections and autoimmune disorders.Type: GrantFiled: May 14, 1990Date of Patent: August 11, 1992Assignee: Bristol-Myers SquibbInventors: Takushi Kaneko, David Willner, Ivo Monkovic, Robert S. Greenfield, Gary R. Braslawsky
-
Patent number: 5011992Abstract: Novel substituted benzamides of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and A are as defined herein are useful in the treatment of emesis, and particularly chemotherapy-induced emesis in cancer patients. Some of the compounds are also useful in disorders relating to impaired gastric motility.Type: GrantFiled: August 22, 1989Date of Patent: April 30, 1991Assignee: Bristol-Myers Squibb CompanyInventors: Ivo Monkovic, David Willner
-
Patent number: 4829073Abstract: The present invention provides a method for treating gastrointestinal motility disorders and thiadiazole oxide compounds for use in the method.Type: GrantFiled: May 12, 1988Date of Patent: May 9, 1989Assignee: Bristol-Myers CompanyInventors: Jaswant S. Gidda, Ivo Monkovic
-
Patent number: 4820715Abstract: Novel substituted benzamides of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and A are as defined herein are useful in the treatment of emesis, and particularly chemotherapy-induced emesis in cancer patients. Some of the compounds are also useful in disorders relating to impaired gastric motility.Type: GrantFiled: May 18, 1987Date of Patent: April 11, 1989Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, David Willner
-
Patent number: 4808624Abstract: Novel substituted benzamides of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and A are as defined herein are useful in the treatment of emesis, and particularly chemotherapy-induced emesis in cancer patients. Some of the compounds are also useful in disorders relating to impaired gastric motility.Type: GrantFiled: May 6, 1985Date of Patent: February 28, 1989Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, David Willner
-
Patent number: 4507485Abstract: Histamine H.sub.2 -antagonists of the formula: ##STR1## wherein m is an integer of from 0 to 2 inclusive;n is an integer of from 2 to 5 inclusive;Z is oxygen, sulfur or methylene; andA is ##STR2## in which R.sup.1 is hydrogen, (lower)alkyl, or (lower)alkoxy, and R.sup.2 is ##STR3## in which q is an integer of from 1 to 4 inclusive, and R.sup.3 and R.sup.4 each are independently, (lower)alkyl, (lower)-alkoxy(lower)alkyl in which the (lower)alkoxy moiety is at least two carbon atoms removed from the nitrogen atom, cyclo(lower)alkyl, or phenyl(lower)alkyl; provided that R.sup.3 and R.sup.4 may not both be cyclo(lower)alkyl; or R.sup.3 and R.sup.4, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, N-methylpiperazino, 1,2,3,6-tetrahydropyridyl, homopiperidino, heptamethyleneimino, octamethyleneimino, or 3-azabicyclo[3.2.Type: GrantFiled: January 23, 1984Date of Patent: March 26, 1985Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Ronnie R. Crenshaw
-
Patent number: 4202982Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclobutylmethyl-3,14-dihydroxymorphinan has been found to possess potent agonist/antagonist activity as a non-narcotic analgesic. A new and efficient total synthesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline.Type: GrantFiled: March 22, 1979Date of Patent: May 13, 1980Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Carol Bachand, Henry Wong
-
(.+-.)-2-Cyclobutylmethyl-9.alpha.,10.beta.-dihydroxy-1.beta.-(p-alkox y-benzyl)perhydroisoquinoline
Patent number: 4153603Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclobutylmethyl-3,14-dihydroxymorphinan has been found to possess potent agonist/antagonist activity as a non-narcotic analgesic. A new and efficient total synthesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline.Type: GrantFiled: September 28, 1977Date of Patent: May 8, 1979Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Carol Bachand, Henry Wong -
Patent number: 4139534Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclobutylmethyl-3,14-dihydroxymorpinan has been found to posess potent agonist/antagonist activity as a non-narcotic analgesic. An improved total snythesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline. A preferred feature of the process involves borane reduction of 2-cyclobutylcarbonyl-9,10-dihydroxy-1-(p-methoxybenzyl)perhydroisoquinolin e (Va) to provide the corresponding cyclobutylmethyl derivative complexed with borane which is converted directly to N-cyclobutylmethyl-14.beta.-hydroxy-3-methoxymorphinan (LVa) by treating with acid.Type: GrantFiled: February 17, 1977Date of Patent: February 13, 1979Assignee: Bristol-Myers CompanyInventors: Gary Lim, Ivo Monkovic
-
Patent number: 4115389Abstract: N-Alkyl allylic tertiary amines are dealkylated as illustrated by treatment of (-)-1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline in cold methylene chloride with m-chloroperbenzoic acid followed by the addition of aqueous ferrous chloride to provide a good yield of (+)-1-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline with substantial if not complete retention of optical activity. The product is an intermediate in a synthesis of the analgesic known as butorphanol.Type: GrantFiled: May 2, 1977Date of Patent: September 19, 1978Assignee: Bristol-Myers CompanyInventor: Ivo Monkovic
-
Patent number: 4058531Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclobutylmethyl-3,14-dihydroxymorphinan has been found to possess potent agonist/antagonist activity as a non-narcotic analgesic. A new and efficient total synthesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline.Type: GrantFiled: March 23, 1976Date of Patent: November 15, 1977Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Carol Bachand, Henry Wong
-
Patent number: 4052389Abstract: The disclosed invention is to a compound of the formula: ##STR1## in which R.sup.2 is lower alkyl. These compounds are useful in the preparation of N-substituted-14-hydroxy-3-substituted morphinan derivatives which have been found to possess potent narcotic agonist or antagonist activity.Type: GrantFiled: March 23, 1976Date of Patent: October 4, 1977Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Carol Bachand, Henry Wong
-
Patent number: 3980641Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound 3,14-dihydroxy-N-cyclopropylmethylmorphinan has been found to possess potent agonist-antagonist activity.Type: GrantFiled: July 31, 1975Date of Patent: September 14, 1976Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Henry Wong, Gary Lim
-
Patent number: 3966747Abstract: N-substituted-9-hydroxy-6,7-benzomorphans have been found to possess potent narcotic agonist and/or antagonist activity. In particular, the compound 2'-hydroxy-2-cyclobutylmethyl-5-allyl-9.beta.-hydroxy-9.alpha.-methyl-6,7- benzomorphan has been found to possess potent narcotic agonist and antagonist activity. These compounds are prepared by total synthesis and are not derived from opium alkaloids.Type: GrantFiled: July 9, 1974Date of Patent: June 29, 1976Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Michel Saucier, Yvon Lambert, Thomas Alfred Montzka
-
Patent number: 3959290Abstract: N-Substituted-3-hydroxy-8-oxamorphinans have been found to possess potent narcotic agonist and/or antagonist activity. In particular, the compound l-N-cyclopropylmethyl-3-hydroxy-14.beta.-methyl-8-oxamorphinan has been found to possess potent narcotic antagonist and agonist activity. These compounds are prepared by total synthesis and are not derived from opium alkaloids.Type: GrantFiled: November 27, 1974Date of Patent: May 25, 1976Assignee: Bristol-Myers CompanyInventors: Ivo Monkovic, Yvon Lambert