Patents Represented by Attorney, Agent or Law Firm Arnold S. Milowsky
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Patent number: 5385909Abstract: A compound of the structure ##STR1## wherein R and R.sup.1 are each, independently, ##STR2## or hydrogen, R.sup.2 is a heterocyclic radical which may be optionally substituted;n=0-6;with the proviso that R and R.sup.1 are both not hydrogen, or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.Type: GrantFiled: November 22, 1993Date of Patent: January 31, 1995Assignee: American Home Products CorporationInventors: Frances C. Nelson, Guy A. Schiehser
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Patent number: 5378836Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, --CONH.sub.a --{{(CR.sup.3 R.sup.4).sub.m (--A--(CR.sup.5 R.sup.6).sub.n).sub.p }.sub.q --B}.sub.r ; --SO.sub.2 R.sup.7 ; --SO.sub.3 H; --CHR.sup.8 O(CH.sub.2).sub.t R.sup.9 ; or ##STR2## R.sup.3, R.sup.4, R.sup.5, R.sup.6, and B are each, independently, hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylalkyl, cycloalkyl, --OR.sup.10, --SR.sup.10, halogen, --CN, --NO.sub.2, --CF.sub.3, --COR.sup.10, --CO.sub.2 R.sup.10, --CONHR.sup.10, --SO.sub.2 R.sup.10, --OSO.sub.3 R.sup.10, --NR.sup.10 R.sup.11, --NHCOR.sup.10, --NHSO.sub.2 R.sup.10, or Ar;X is .dbd.NOR.sup.12 or .dbd.NNR.sup.12 R.sup.13 ;Y is O, .dbd.NOR.sup.12, or .dbd.NNR.sup.12 R.sup.13 ;R.sup.7, R.sup.12, and R.sup.13 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, arylalkyl;R.sup.8, R.sup.9, R.sup.10, and R.sup.Type: GrantFiled: October 8, 1993Date of Patent: January 3, 1995Assignee: American Home Products CorporationInventors: Wenling Kao, Robert L. Vogel, Magid A. Abou-Gharbia, Craig E. Caufield
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Patent number: 5378696Abstract: A compound of the structure ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1, R.sup.2, and R.sup.3 are not all hydrogen; R.sup.4 is --(CH.sub.2).sub.m X(CH.sub.2).sub.n CO.sub.2 R.sup.5 or ##STR3## R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, (CH.sub.2).sub.p NR.sup.9 R.sup.10, mono-, di-, or tri-hydroxyalkyl, aralkyl, or aryl; ##STR4## R.sup.7, R.sup.8, R.sup.9, and R.sup.10 are each, independently, hydrogen or alkyl;Y is CH or N:m is 0-4; n is 0-4; p is 0-4;with the proviso that m and n are not both 0 when X is O or S;or a pharmaceutically acceptable salt thereof, which is by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases, and diseases of inflammation, by virtue of its antitumor activity useful in treating tumors, and by virtue of its antifungal activity is useful in treating fungal infections.Type: GrantFiled: June 8, 1993Date of Patent: January 3, 1995Assignee: American Home Products CorporationInventor: Craig E. Caufield
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Patent number: 5373014Abstract: A compound of the structure ##STR1## wherein R.sup.1 is ##STR2## R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or --CO.sub.2 R.sup.8 ;R.sup.4 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, Ar, aminoalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, or --CO.sub.2 R.sup.8 ;R.sup.5 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, At, or --CO.sub.2 R.sup.8 ;R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.7 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.8 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, fluorenylmethyl, orAr;Y is O or S;X is .dbd.N--O--(CH.sub.2).sub.f --Z or .dbd.N--O--Ar;Z is hydrogen, alkenyl, alkynyl, alkoxy, cyano, fluoro, trifluoromethyl, --NR.sup.5 R.sup.Type: GrantFiled: October 8, 1993Date of Patent: December 13, 1994Assignee: American Home Products CorporationInventors: Amedeo A. Failli, Robert J. Steffan, Craig E. Caufield, David C. Hu, Alexander A. Grinfeld
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Patent number: 5362734Abstract: Compounds of formula ##STR1## wherein R.sup.1 is hydrogen or one or more specified substituents,X is --O-- or --NR.sup.2 -- where R.sup.2 is lower alkyl, lower alkenyl, lower alkynyl, aryl or specified substituted lower alkyl orR.sup.2 represents a group --Z-- which is connected to the 8-position of the aromatic ring so as to form a heterocyclic ring of 5 to 7 ring members,Y is O or NR.sup.3 where R.sup.3 is hydrogen or lower alkyl,andB is a saturated azabicyclic ring (e.g. tropanyl or quinuclidinyl) or a N-oxide thereofand their acid addition salts are 5-HT.sub.3 antagonists which may be used in, for example, the treatment of neuro-psychiatric disorders.Type: GrantFiled: February 18, 1993Date of Patent: November 8, 1994Assignee: American Home Products CorporationInventors: Terence J. Ward, Janet C. White
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Patent number: 5362718Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3 R.sup.4).sub.b (CR.sup.5 R.sup.6).sub.d CR.sup.7 R.sup.8 R.sup.9 ;R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, or --F;R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3 R.sup.4).sub.f OR.sup.10, --CF.sub.3, --F, or --CO.sub.2 R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with --(CR.sup.3 R.sup.4).sub.f 0R.sup.10 ;R.sup.7 is hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3 R.sup.4).sub.f OR.sup.10, --CF.sub.3, --F, or --CO.sub.2 R.sup.11 ;R.sup.8 and R.sup.9 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3 R.sup.4).sub.f OR.sup.10, --CF.sub.3, --F, or --CO.sub.2 R.sup.11, or R.sup.8 and R.sup.Type: GrantFiled: April 18, 1994Date of Patent: November 8, 1994Assignee: American Home Products CorporationInventors: Jerauld S. Skotnicki, Christina L. Leone, Guy A. Schiehser
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Patent number: 5358944Abstract: A compound of the structure ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1, R.sup.2, and R.sup.3 are not all hydrogen; R.sup.4 is --(CH.sub.2).sub.m X(CH.sub.2).sub.n CO.sub.2 R.sup.5 or ##STR3## R.sup.5 and R.sup.6 are each, independently, alkyl, aralkyl, or phenyl which is optionally mono-, di-, or tri-substituted with a substituent selected from alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, amino, or a carboxylic acid;X is ##STR4## O, or S; R.sup.7 and R.sup.8 are each, independently, hydrogen or alkyl;Y is CH or N;m is 0-4; n is 0-4;with the proviso that m and n are not both 0 when X is O or S;or a pharmaceutically acceptable salt thereof, which is by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs.Type: GrantFiled: April 7, 1993Date of Patent: October 25, 1994Assignee: American Home Products CorporationInventor: Craig E. Caufield
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Patent number: 5321009Abstract: This invention provides a method of prophylactically preventing the onset, preventing the development, and arresting the progression of insulin dependent diabetes mellitus in a mammal by administering an effective amount of rapamycin either alone or in combination with insulin.Type: GrantFiled: November 14, 1991Date of Patent: June 14, 1994Assignee: American Home Products CorporationInventors: William L. Baeder, Surendra N. Sehgal, Laurel M. Adams, Thomas J. Caggiano
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Patent number: 5302584Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, --CONH--[(CR.sup.3 R.sup.4).sub.m (--A--(CR.sup.5 R.sup.6).sub.n).sub.p ].sub.q --B; ##STR2## R.sup.3, R.sup.4, R.sup.5, R.sup.6, and B are each, independently, hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylalkyl, cycloalkyl, --OR.sup.7, --SR.sup.7, halogen, --CN, --NO.sub.2, --CF.sub.3, --COR.sup.7, --CO.sub.2 R.sup.7, --CONHR.sup.7, --SO.sub.2 R.sup.7, --OSO.sub.3 R.sup.7, --NR.sup.7 R.sup.8, --NHCOR.sup.7, --NHSO.sub.2 R.sup.7, or Ar;R.sup.7 and R.sup.8 are each, independently, hydrogen, alkyl, arylalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl;R.sup.9 and R.sup.10 are each, independently, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylalkyl, --CF.sub.3, --COR.sup.7, --CO.sub.2 R.sup.7, --CONHR.sup.7, --SO.sub.Type: GrantFiled: April 23, 1993Date of Patent: April 12, 1994Assignee: American Home Products CorporationInventors: Wenling Kao, Magid A. Abou-Gharbia, Robert L. Vogel
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Patent number: 5302600Abstract: This invention provides a compound of formula I, ##STR1## and 27-substituted derivatives thereof which are useful as immunosuppressive, anti-inflammatory, antifungal, antitumor, and antiproliferative agents. The compound depicted by formula I is named 27-hydroxyrapamycin, and may also be referred to as 27-deoxo-27-hydroxyrapamycin.Type: GrantFiled: July 22, 1993Date of Patent: April 12, 1994Assignee: American Home Products CorporationInventor: Frances C. Nelson
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Patent number: 5288711Abstract: This invention provides a method of preventing or treating hyperproliferative vascular disease in a mammal by administering an antiproliferative effective amount of a combination of rapamycin and heparin.Type: GrantFiled: April 28, 1992Date of Patent: February 22, 1994Assignee: American Home Products CorporationInventors: Robert D. Mitchell, Stephen Skwish
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Patent number: 5286730Abstract: This invention provides a method of treating immunionflammatory skin disease in a mammal in need thereof which comprises administering an antiimmunoinflammatory amount of rapamycin, alone or in combination with cyclosporin A, orally, parenterally, intranasally, intrabronchially, topically, transdermally, or rectally. As such, rapamycin, alone or in combination with cyclosporin A, is useful in treating skin diseases such as psoriasis, atopic dermatitis, contact dermatitis, eczematous dermatitis, seborrheic dermatitis, Lichen planus, Pemphigus, bulus pemphigoid, Epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eosinphilias, and the like.Type: GrantFiled: August 17, 1992Date of Patent: February 15, 1994Assignee: American Home Products CorporationInventors: Craig E. Caufield, John H. Musser, Surendra N. Sehgal
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Patent number: 5286731Abstract: This invention provides a method of treating immunoinflammatory bowel disease in a mammal in need thereof which comprises administering an antiimmunoinflammatory amount of rapamycin, alone or in combination with cyclosporin A. As such, rapamycin, alone or in combination with cyclosporin A, is useful in treating bowel diseases such as ulcerative colitis, Crohn's disease, ulcerative proctitis, and the like.Type: GrantFiled: August 17, 1992Date of Patent: February 15, 1994Assignee: American Home Products CorporationInventors: Craig E. Caufield, John H. Musser, Surendra N. Sehgal
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Patent number: 5256790Abstract: This invention provides a compound of formula I, ##STR1## and 27-substituted derivatives thereof which are useful as immunosuppressive, antiinflammatory, antifungal, antitumor, and antiproliferative agents. The compound depicted by formula I is named 27-hydroxyrapamycin, and may also be referred to as 27-deoxo-27-hydroxyrapamycin.Type: GrantFiled: January 27, 1993Date of Patent: October 26, 1993Assignee: American Home Products CorporationInventor: Frances C. Nelson
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Patent number: 5252579Abstract: This invention provides a compound of the structure ##STR1## wherein X is selected from the group consisting of --NR.sup.1 CR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m S--, --NR.sup.1 CR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m O--, --OCR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m O--, --NR.sup.1 CR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.p --, --OCR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.p --, --NR.sup.1 CR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m NR.sup.6 --, --OCR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m NR.sup.6 --, --SCR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m NR.sup.6 --, --SCR.sup.2 R.sup.3 (CR.sup.4 R.sup.5).sub.m S--, --NOR.sup.1 --, and --NR.sup.1 --;R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are each, independently, hydrogen, alkyl, fluorine, trifluoromethyl, aryl, arylalkyl, or any pair taken together to form a 3-6 membered ring;m=1-6; andp=0-6or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflamatory, antifungal, antiproliferative, and antitumor agent.Type: GrantFiled: February 16, 1993Date of Patent: October 12, 1993Assignee: American Home Products CorporationInventors: Jerauld S. Skotnicki, Amedeo A. Failli, Robert J. Steffan, Robert M. Kearney
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Patent number: 5233036Abstract: A compound of the structure ##STR1## wherein R.sup.1 is ##STR2## R.sup.2 is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms which is optionally unsaturated, aralkyl of 7-10 carbon atoms, or phenyl which is optionally mono-, di-, or tri-substituted with a substituent selected from alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, amino, or a carboxylic acid;or a pharmaceutically acceptable salt thereof when R.sup.2 is hydrogen, which are useful in the treatment of transplantation rejection, host vs. graft disease, autoimmune diseases, diseases of inflammation, or fungal infections.Type: GrantFiled: February 20, 1992Date of Patent: August 3, 1993Assignee: American Home Products CorporationInventor: Philip F. Hughes
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Patent number: 5225419Abstract: Compounds of formula ##STR1## wherein R.sup.1 is hydrogen or one or more specified substituents,X is --O--or --NR.sup.2 -- where R.sup.2 is lower alkyl, lower alkenyl, lower alkynyl, aryl or specified substituted lower alkyl or R.sup.2 represents a group --Z-- which is connected to the 8-position of the aromatic ring so as to form a heterocyclic ring of 5 to 7 ring members,Y is O or NR.sup.3 where R.sup.3 is hydrogen or lower alkyl,andB is a saturated azabicyclic ring (eg tropanyl or quinuclidinyl) or a N-oxide thereofand their acid addition salts are 5-HT.sub.3 antagonists which may be used in, for example, the treatment of neuro-psychiatric disorders.Type: GrantFiled: September 16, 1991Date of Patent: July 6, 1993Assignee: John Wyeth & Brother, LimitedInventors: Terence J. Ward, Janet C. White
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Patent number: 5221670Abstract: A compound of the structure ##STR1## where R.sup.1, R.sup.2, and R.sup.3 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1, R.sup.2, and R.sup.3 are not all hydrogen; R.sup.4 is --(CH.sub.2).sub.m X(CH.sub.2).sub.n CO.sub.2 R.sup.5 or ##STR3## R.sup.5 and R.sup.6 are each, independently, alkyl, aralkyl, or phenyl which is optionally mono-, di-, or tri-substituted with a substituent selected from alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, amino, or a carboxylic acid;X is ##STR4## R.sup.7 and R.sup.8 are each, independently, hydrogen or alkyl; Y is CH or N;m is 0-4; n is 0-4;with the proviso that m and n are not both 0 when X is O or S;or a pharmaceutically acceptable salt thereof, which is by virtue of its immunosuppresive activity is useful in treating transplantation rejection, host vs.Type: GrantFiled: October 17, 1991Date of Patent: June 22, 1993Assignee: American Home Products CorporationInventor: Craig E. Caufield
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Patent number: 5210088Abstract: The invention concerns a method for treating pain and/or CNS disorders characterized in that the method uses a compound which acts selectively as an antagonist of gamma aminobutyric acid (GABA) at GABA autoreceptors relative to GABA.sub.A receptors.Type: GrantFiled: May 27, 1992Date of Patent: May 11, 1993Assignee: John Wyeth & Brother, LimitedInventors: Michael C. W. Minchin, Alan C. White, John F. White
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Patent number: 5206018Abstract: This invention provides a method of treating, inhibiting the proliferation of, reducing the size of, or eradicating malignant neoplasms in a mammal in need thereof which comprises administering an antineoplastic amount of rapamycin to said mammal. In particular, rapamycin is useful in treating, inhibiting the proliferation of, reducing the size of, or eradicating malignant mammary and skin carcinomas, and central nervous system neoplasms.Type: GrantFiled: October 29, 1991Date of Patent: April 27, 1993Assignee: Ayerst, McKenna & Harrison, Inc.Inventors: Surendra N. Sehgal, Claude Vezina