Heavy Metal, Aluminum, Boron Or Silicon Containing Patents (Class 540/452)
-
Patent number: 5563127Abstract: Novel boronic acid and ester and carboxyl-modified amino acid compounds of the Formula I, which are inhibitors of trypsin-like enzymes, are disclosed :R.sup.1 --Z--CHR.sup.2 --A,where R.sup.1, Z, R.sup.2 and A are defined within.Type: GrantFiled: December 27, 1994Date of Patent: October 8, 1996Assignee: The DuPont Merck Pharmaceutical CompanyInventors: Eugene C. Amparo, William H. Miller, Gregory J. Pacofsky, John Wityak, Patricia C. Weber, John J. V. Duncia, Joseph B. Santella, III
-
Patent number: 5561139Abstract: Compounds having the formula ##STR1## and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof, wherein one of R.sup.104 and R.sup.105 is hydrogen, and the other of R.sup.104 and R.sup.105 is a radical having the formula ##STR2## as well as pharmaceutically compositions containing such compounds and methods of immunomodulative therapy utilizing the same.Type: GrantFiled: April 11, 1995Date of Patent: October 1, 1996Assignee: Abbott LaboratoriesInventors: Jay R. Luly, Megumi Kawai
-
Patent number: 5554749Abstract: The present invention provides new and structurally diverse compositions comprising compounds of the general formula: ##STR1## Wherein U is --(CH.sub.2).sub.n X or --(CH.sub.2).sub.n NR.sub.1 (CH.sub.2)X; R.sub.1 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl or C.sub.1 -C.sub.8 alkoxyalkyl; V is --(CH.sub.2).sub.n X, --(CH.sub.2).sub.n NR.sub.1 (CH.sub.2)X, hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl or C.sub.1 -C.sub.8 alkoxyalkyl; V and R.sub.1 may jointly be --(CH.sub.2).sub.m -- to form a heterocyclic ring; X is --CO.sub.2 H, --PO.sub.3 H.sub.2, --SO.sub.3 H or --CONHOH; a, b, c, d, n and m may be the same or different and are from one to about ten, preferably from one to about three.Methods for imaging using compositions of the invention are also provided.Type: GrantFiled: January 14, 1994Date of Patent: September 10, 1996Assignee: Mallinckrodt Medical, Inc.Inventors: Rebacca A. Wallace, Dennis A. Moore
-
Patent number: 5532248Abstract: O-Aryl, O-alkyl, O-alkenyl and O-alkynyl-macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and/or arylation at C-3" and/or C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.Type: GrantFiled: May 12, 1995Date of Patent: July 2, 1996Assignee: Merck Co., Inc.Inventors: Mark Goulet, William H. Parsons, Helen M. Organ, Peter J. Sinclair, Frederick Wong, Matthew J. Wyvratt
-
Patent number: 5530120Abstract: Compounds having the formula ##STR1## and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof, wherein one of R.sup.104 and R.sup.105 is hydrogen, and the other of R.sup.104 and R.sup.105 is a radical having the formula ##STR2## as well as pharmaceutically compositions containing such compounds and methods of immunomodulative therapy utilizing the same.Type: GrantFiled: November 21, 1994Date of Patent: June 25, 1996Assignee: Abbott LaboratoriesInventors: Jay R. Luly, Megumi Kawai
-
Patent number: 5508397Abstract: Activated macrolactam compounds having the formula ##STR1## wherein n is zero or one, R.sup.101 is selected from the group consisting of methyl, ethyl, allyl, propyl and cyclopropylmethyl;R.sup.102 is hydrogen, and R.sup.103 is selected from the group consisting of hydrogen, hydroxy and a protected hydroxy group or, taken together, R.sup.102 and R.sup.103 form a bond;R.sup.104 and R.sup.105 are chosen such that one is hydrogen while the other is -OS(O).sub.2 F; andR.sup.106 is selected from the group consisting of hydrogen, a protected hydroxy group, loweralkyl, alkenyl, cycloalkyl, aryl and arylalkyl,as well as processes for making such compounds and methods for their use in the preparation of C-32-modified derivatives of ascomycin or the congeners or analogs thereof.Type: GrantFiled: December 16, 1994Date of Patent: April 16, 1996Assignee: Abbott LaboratoriesInventors: Yat S. Or, Jay R. Luly
-
Patent number: 5493019Abstract: The invention concerns the compounds of formula I ##STR1## wherein the substituents have various significances, in free form and, where such forms exist, in salt form.They can be prepared by various processes, e.g. by irradiation; oxidation; elimination; reduction; conversion by e.g. halogenation or acylation; deprotection of protected hydroxy groups; protection of free hydroxy groups; and separation of stereoisomeric mixtures into individual isomers.They are useful as pharmaceuticals, especially as antiinflammatory, and as antiproliferative and antiinflammatory agents.Type: GrantFiled: May 26, 1994Date of Patent: February 20, 1996Assignee: Sandoz Ltd.Inventor: A. R. C. Murty Bulusu
-
Patent number: 5484685Abstract: A naphthalocyanine derivative of the formula: ##STR1## wherein M, Y, R.sup.1, k, l, m, n are as defined in the specification, is an effective substance for forming a recording layer on a substrate of an optical recording medium having high sensitivity with good properties.Type: GrantFiled: May 30, 1991Date of Patent: January 16, 1996Assignees: Hitachi, Ltd., Hitachi Chemical Co., Ltd.Inventors: Seiji Tai, Nobuyuki Hayashi, Koichi Kamijima, Mitsuo Katayose, Takayuki Akimoto, Shigeru Hayashida, Hideo Hagiwara, Susumu Era, Setsuo Kobayashi, Akio Mukoh
-
Patent number: 5462964Abstract: The present invention relates to the discovery of new C-terminal boronic acid dipeptide inhibitors of trypsin-like enzymes such as thrombin and pharmaceutical compositions thereof.Type: GrantFiled: October 20, 1993Date of Patent: October 31, 1995Assignee: The Du Pont Merck Pharmaceutical CompanyInventors: John M. Fevig, Matthew M. Abelman, Eugene C. Amparo, Joseph Cacciola, Charles A. Kettner, Gregory J. Pacofsky, Chia-Lin Wang
-
Patent number: 5446158Abstract: A process is described for the total synthesis of the macrolide immunosuppressant, FK-506, and important tricarbonyl process intermediates thereof. The tricarbonyl intermediates can be produced by the mild oxidation of 2,3-dihydroxy carboxylate compounds containing olefin moieties.Type: GrantFiled: October 12, 1990Date of Patent: August 29, 1995Assignee: Merck & Co., Inc.Inventors: Todd K. Jones, Sander G. Mills, David Askin, Robert A. Reamer, Richard Desmond, David M. Tschaen, Ralph P. Volante, Ichiro Shinkai
-
Patent number: 5434260Abstract: A compound of the structure ##STR1## wherein R and R.sup.1 are each, independently, hydrogen, ##STR2## R.sup.2 and R.sup.3 are each, independently, hydrogen, alkyl, alkenyl, alkynyl. --CO.sub.2 R.sup.5, --COR.sup.5, --CN, --NO.sub.2, --SO.sub.2 R.sup.5, --SO.sub.3 R.sup.5, --OR.sup.5, --SR.sup.5, or Ar;R.sup.4 is hydrogen, alkyl, alkenyl, alkynyl, --CF3, --NR.sup.5 R.sup.6, --CO.sub.2 R.sup.5, --COR.sup.5, CONR.sup.5 R.sup.6, --NO.sub.2, halogen, --OR.sup.5, --SR.sup.5, --CN, --SO.sub.2 R.sup.5, --SO.sub.3 R.sup.5, --SO.sub.2 NR.sup.5 R.sup.6, or Ar;R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, or Ar; ##STR3## are each, independently, a 5-7 membered saturated, unsaturated, or partially unsaturated heterocyclic radical, that is optionally fused to a phenyl ring or a cycloalkane or cycloalkene ring, wherein the heterocyclic ring may optionally contain O, S, or NR.sup.8 in the heterocyclic ring, and may be optionally substituted by R.sup.7 ;R.sup.Type: GrantFiled: June 14, 1994Date of Patent: July 18, 1995Assignee: American Home Products CorporationInventors: Jerauld S. Skotnicki, Yvette L. Palmer, Wenling Kao, Magid A. Abou-Gharbia
-
Patent number: 5431896Abstract: Described is a new immunosuppressant, L-687,819, a C-31 demethylated derivative of L-683,795 (FK-523), produced under fermentation conditions utilizing the new mutant microorganism, Streptomyces hygroscopicus subsp. ascomyceticus (Merck Culture Collection MA 6646) ATCC No. 53855, being a blocked mutant of Streptomyces hygroscopicus subsp. ascomyceticus (MA 6475) ATCC No. 14891. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.Type: GrantFiled: July 30, 1992Date of Patent: July 11, 1995Assignee: Merck & Co., Inc.Inventors: Louis Kaplan, Robert P. Borris, Kevin M. Byrne, Linda S. Wicker, Deborah L. Zink
-
Patent number: 5428154Abstract: The invention is a chelate of formula I: ##STR1## wherein R.sub.1-4 is --CH.sub.2 COOH;n is 1 to 5;X is a member selected from the group consisting of--NO.sub.2,--NH.sub.2,--NCS,--NHCOCH.sub.2 --Z, with Z being a member selected from the group consisting of Br and I,--COOH; and--OCH.sub.2 OOCH;and M is a metal ion selected from the group of elements consisting ofBi, Pb, Y, Cd, Hg, Al, Th, Sr, and Lanthanides.The invention also includes a chelate, wherein M is a copper ion and n is an integer from 2 to 5. The invention includes chelate conjugates of formula I and ligand conjugates of formula II: ##STR2## The invention also includes methods to use these compounds for treatment of cellular disorders and for diagnostic tests.Type: GrantFiled: October 22, 1993Date of Patent: June 27, 1995Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Otto A. Gansow, Martin W. Brechbiel, Michael A. Magerstadt
-
Patent number: 5420279Abstract: Microporous crystallized gallium phosphate and its substituted derivatives, characterized by:a) the following approximate general formula:R.sub.r Ga.sub.g P.sub.p X.sub.x O.sub.2 F.sub.f hH.sub.2 Owhere the sum of g, p and x is equal to 1, and whereg is a number from 0.3 to 0.5,p is a number from 0.3 to 0.52,x is a number from 0 to 0.4,r is a number from 0.01 to 0.2,f is a number from 0.01 to 0.2,h varies according to the degree of hydration of the solid, from 0 to 0.5.R is an organic compound selected from the group formed by cyclic amines,X is a heteroatom selected from the group formed by the elements: Li, Be, Co, Mg, Mn, Zn, Al, B, Cr, Fe, Ge, Si, Ti, As and Vb) an X-ray diffraction diagram shown in Table 1 of the description,and a method of preparing them.Type: GrantFiled: September 9, 1993Date of Patent: May 30, 1995Assignee: Institut Francais du PetroleInventors: Jean-Francois Joly, Adballah Merrouche, Henri Kessler, Jean-Louis Guth
-
Patent number: 5411967Abstract: A compound of the structure ##STR1## where the substituents are defined in the main body of the specification which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.Type: GrantFiled: April 8, 1994Date of Patent: May 2, 1995Assignee: American Home Products CorporationInventors: Wenling Kao, Jerauld S. Skotnicki, Magid A. Abou-Gharbia, Yvette L. Palmer
-
Patent number: 5403843Abstract: A condensed pyrimidine derivative of the formula (I): ##STR1## wherein the ring A stands for an optionally substituted 5-membered ring; B stands for an optionally substituted divalent 5- or 6-membered homo- or hetero-cyclic group; X stands for, among others, amino group; Y stands for, among others, hydrogen atom, halogen atom or amino group; Z stands for a divalent aliphatic group having five or less atoms forming straight chain, optionally having nitrogen, whose chain portion may optionally have a hetero-atom; W stands for, among others, --NH--CO-- or --CO--NH--; R.sup.1 stands for an optionally substituted cyclic or chain-like group; COOR.sup.2 stands for an optionally esterified carboxyl group; and p denotes an integer of 1 to 4, provided that when --W--R.sup.1 denotes a moiety represented by the formula: ##STR2## wherein COOR.sup.16 and COOR.sup.Type: GrantFiled: August 7, 1992Date of Patent: April 4, 1995Assignee: Takeda Chemical Industries, Ltd.Inventors: Hiroshi Akimoto, Koichiro Ootsu, Fumio Itoh
-
Patent number: 5387680Abstract: This invention provides C-22 substituted rapamycin derivatives of the following formulas: ##STR1## and pharmaceutically acceptable salts thereof which are useful for inducing immunosuppression and treating transplantation rejection, host vs. graft disease, autoimmune diseases, diseases of inflammation, solid tumors, fungal infections, adult T-cell leukemia/lymphomas and hyperproliferative vascular disorders.Type: GrantFiled: August 10, 1993Date of Patent: February 7, 1995Assignee: American Home Products CorporationInventor: Frances C. Nelson
-
Patent number: 5386028Abstract: A process for the production of N-.beta.-hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecane and N-.beta.-hydroxyalkyl-tri-N-carboxyalkyl-1,4,8,11-tetraazacyclotetrade cane derivatives and their metal complexes is described.Type: GrantFiled: February 11, 1993Date of Patent: January 31, 1995Assignee: Schering AktiengesellschaftInventors: Ulf Tilstam, Helmut Borner, Klaus Nickisch, Heinz Gries, Johannes Platzek
-
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
-
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
-
Patent number: 5352671Abstract: The invention concerns the compounds of formula I ##STR1## wherein the substituents have various significances. They are prepared by several processes including epimerizing replacement, treatment with cyanogen bromide or thiophosgene, treatment with an acid having a non-nucleophilic anion, treatment with dimethylsulfoxide and acetic anhydride, acylation, treatment with an oxalyl derivative and ammonia, methylation, oxidation, deprotection and protection.They possess interesting pharmacological activity as antiinflammatory, immunosuppressant, antiproliferative and chemotherapeutic drug resistance reversing agents.Type: GrantFiled: May 9, 1991Date of Patent: October 4, 1994Assignee: Sandoz Ltd.Inventors: Karl Baumann, Gerhart Emmer
-
Patent number: 5329046Abstract: The invention relates to biscationic acid amide and acid imide derivatives with an anion of formula (BR.sub.9 R.sub.10 R.sub.11 R.sub.12)--, where R.sub.9 to R.sub.12 are aliphatic, iso- or heterocyclic aromatic residues or aralkyl residues, which may be substituted by C.sub.1 -C.sub.4 -alkyl residues, C.sub.1 -C.sub.4 -alkoxy residues, aryl residues or halogen atoms (e.g. fluorine atoms), and mixtures of these compounds and mixed crystals with mixed anions and/or cations. The invention also relates to a process for preparing them. The new compounds are excellent colorless charge controllers in toners and developers for electrophotographic recording and as charge-enhancers in powders and paints for surface coating, in particular in triboelectrically or electrokinetically sprayed powder paints.Type: GrantFiled: June 25, 1992Date of Patent: July 12, 1994Assignee: Hoechst AktiengesellschaftInventors: Hans-Tobias Macholdt, Siegfried Schiessler, Jorg Gitzel, Erwin Dietz
-
Patent number: 5274090Abstract: Disclosed is a metalloporphyrin-ligand complex which includes (a) a meso-tetraphenylporphyrin, (b) a crown ether rigidly attached to the meso-tetraphenylporphyrin by covalent attachment on one side of the porphyrin to two diagonally opposing phenyl groups, (c) a metal bound to the pyrrole nitrogens of the porphyrin, (d) a bridge covalently linking two diagonally opposing phenyl groups on the other side of the porphyrin, effective to hinder .mu.-oxo diner formation, and (e) a ligand having (i) a primary amine which is held noncovalently by the crown ether and (ii) a metal-coordinating atom which is coordinately bound to the metal.In another aspect, the invention includes a water-soluble oxygen carrier. The oxygen carrier includes a meso-.alpha.,.alpha.,.alpha.,.alpha.-tetrakis(o-propanoylamino)phenylporph yrin, in which the 3-carbons of the propanoyl groups are each covalently bound to a quaternary amine, and iron or cobalt is bound to the pyrrole nitrogens of the porphyrin.Type: GrantFiled: November 9, 1992Date of Patent: December 28, 1993Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Xumu Zhang, Erich S. Uffelman, James P. Collman
-
Patent number: 5266692Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: ##STR1## to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.Type: GrantFiled: June 18, 1992Date of Patent: November 30, 1993Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Masakuni Okuhara, Hirokazu Tanaka, Toshio Goto, Tohru Kino, Hiroshi Hatanaka
-
Patent number: 5260300Abstract: Carbonate esters with rapamycin at position 42 or positions 31 and 42 have been shown to have immunosuppressant properties and are useful in the treatment of transplant rejections and autoimmune diseases. These esters are represented by the formula below: ##STR1## wherein: R.sup.1 and R.sup.2 are independently H or --COOR.sup.3 but both R.sup.1 and R.sup.2 cannot be H, andR.sup.3 is C.sub.1 -C.sub.6 alkyl where 1 to 3 hydrogens may be replaced by fluorine, chlorine, bromine or iodine, C.sub.3 -C.sub.8 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, or Ar--(CH.sub.2).sub.n -- where n is 0 to 6 and Ar is phenyl, phenyl substituted by fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, cyano, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy; pyridinyl, indolyl, quinolyl or furanyl;or a pharmaceutically acceptable salt thereof.Type: GrantFiled: November 19, 1992Date of Patent: November 9, 1993Assignee: American Home Products CorporationInventor: David C. Hu
-
Patent number: 5254562Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: ##STR1## to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.Type: GrantFiled: June 18, 1992Date of Patent: October 19, 1993Assignee: Fujisawa Pharmaceutical Company, Ltd.Inventors: Masakuni Okuhara, Hirokazu Tanaka, Toshio Goto, Tohru Kino, Hiroshi Hatanaka
-
Patent number: 5250678Abstract: O-Aryl, O-alkyl, O-alkenyl and O-alkynyl-macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and/or arylation at C-3" and/or C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses.Type: GrantFiled: May 1, 1992Date of Patent: October 5, 1993Assignee: Merck & Co., Inc.Inventors: Mark Goulet, Frederick Wong, Peter J. Sinclair, Matthew J. Wyvratt
-
Patent number: 5248683Abstract: Compounds of the formula ##STR1## in which A.sub.1 and A.sub.2 independently of one another are CO--C.sub.1 -C.sub.4 alkyl, COO--C.sub.1 -C.sub.4 alkyl, CO--CF.sub.3, CO--N(R).sub.2 or cyano;A.sub.1 and A.sub.2 together are CO(X).sub.n --C.sub.1 -C.sub.3 alkylene-(X).sub.n CO, CO(X).sub.n --C.sub.1 -C.sub.3 alkylene-(X).sub.n CO which is substituted by C.sub.1 -C.sub.4 alkyl, COOR, CON(R).sub.2, cyano or phenyl, it being possible for the phenyl ring, in turn, to be substituted by halogen, methyl, trifluoromethyl, methoxy, nitro or cyano; CO--N(R)--CO--N(R)--CO;R is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl or C.sub.3 -C.sub.6 alkynyl;X is oxygen, sulfur or N(CH.sub.3);X.sub.1, X.sub.2 and X.sub.3 independently of one another are hydrogen, halogen, methyl, methylthio, methoxy or nitro;n is 0 or 1;including the salts of the compounds of the formula I with agriculturally acceptable organic or inorganic bases, and including the metal complexes; have valuable microbicidal properties.Type: GrantFiled: June 4, 1992Date of Patent: September 28, 1993Assignee: Ciba-Geigy CorporationInventors: Hans-Georg Brunner, Walter Kunz, Rolf Schurter
-
Patent number: 5240919Abstract: Compounds of general formula (I): ##STR1## where R, X, A, B and p are defined in the description. Medicinal products useful for treating sleep disorders comprising the same.Type: GrantFiled: March 9, 1992Date of Patent: August 31, 1993Assignee: Adir et CompagnieInventors: Said Yous, Isabelle Lesieur, Patrick Depreux, Daniel H. Caignard, Beatrice Guardiola, Gerard Adam, Pierre Renard
-
Patent number: 5225403Abstract: Described is a process for producing a new FK-506 antagonist agent, a C-21 hydroxylated analog of FR-900520 under novel fermentation conditions utilizing the novel microorganism, Streptomyces hygroscopicus (Merck Culture Collection MA 6832) ATCC No. 55166. The macrolide antagonist is useful in preventing and/or counteracting accidental or inadvertent FK-506 overdosage in an FK-506 therapeutic program designed to prevent autoimmune diseases or human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.Type: GrantFiled: June 25, 1991Date of Patent: July 6, 1993Assignee: Merck & Co., Inc.Inventors: Laszlo R. Treiber, Georgette Dezeny, Lawrence F. Colwell, Jr., Byron H. Arison, Francis Dumont
-
Patent number: 5200411Abstract: The compounds of formula I ##STR1## wherein the substituents have various significances, possess pharmacological, particularly antiinflammatory and immunosuppressant activity.They can be prepared by one or more of the following process variants: reduction, deprotection, acylation, reaction with N,N'-carbonyl- or N,N'-thiocarbonyldiimidazole, halogenation, splitting off of hydrogen halide, reaction with a hydrogen carbonate, radical deoxygenation, dehydration or reaction with diazomethane of -ethane, optionally under transient protection of reactive groups which it is not desired to react.Type: GrantFiled: June 13, 1991Date of Patent: April 6, 1993Assignee: Sandoz, Ltd.Inventors: Andrew J. F. Edmunds, Maximilian Grassberger
-
Patent number: 5162334Abstract: Amino O-alkyl, O-alkenyl and O-alkynylmacrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and amination at C-3"/C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses. Also, these macrolides are useful in the treatment of reversible obstructive airways disease, particularly asthma.Type: GrantFiled: May 13, 1991Date of Patent: November 10, 1992Assignee: Merck & Co., Inc.Inventors: Mark Goulet, Matthew J. Wyvratt
-
Patent number: 5151413Abstract: Derivatives of Rapamycin where the hydroxy group at position 31 and/or 42 are reacted with acetal forming reagents have been shown to have immunosuppressant and antifungal properties. These derivatives are represented by the formula: ##STR1## wherein R.sup.1 and R.sup.2 independently are hydrogen, --CH.sub.2 YX, --C(CH.sub.3).sub.2 YX, --CH.sub.2 (CH.sub.3)YX, or L;Y is O or S; X is --CH.sub.3, --(CH.sub.2).sub.n CH.sub.3, --CH.sub.2 C.sub.6 H.sub.6, --(CH.sub.2).sub.2 OCH.sub.3, --CH.sub.2 Cl.sub.3 or --CH.sub.2 CH.sub.2 Si(CH.sub.3).sub.3 and L is selected from tetrahydrofuran-2-yl, tetrahydrothiophen-2-yl, tetrahydrothiopyran-2-yl, tetrahydropyran-2-yl, 4-methoxytetrahydropyran-2-yl, 4-methoxytetrahydrothiopyran-2-yl, or 4-methoxytetrahydrothiopyran-S, S-dioxide-2-yl with a proviso that R.sup.1 and R.sup.2 cannot simultaneously be hydrogen and n is 1-5.Type: GrantFiled: November 6, 1991Date of Patent: September 29, 1992Assignee: American Home Products CorporationInventors: Craig E. Caufield, Guy A. Schiehser
-
Patent number: 5138052Abstract: Described is a new L-679,934 (FK-506) antagonist, L-686,292, a C-15, C-31 bisdemethylated, derivative of L-683,590, produced under fermentation conditions utilizing the microorganism, Actinoplanacete sp. (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide reverses the immunosuppressant action of L-679,934 (FK-506), and can be used diagnostically as a tool to determine the presence of FK-506 macrolide type immunosuppressants in natural product broths, distinguishing such immunosuppressants from other chemical families such as the cycloporins.Type: GrantFiled: March 5, 1991Date of Patent: August 11, 1992Assignee: Merck & Co., Inc.Inventors: Shieh-Shung T. Chen, Linda S. Wicker, Byron H. Arison
-
Patent number: 5132409Abstract: Macrocyclic derivatives of 1,4,7,10-tetraazacyclododecane of general formula (I) hereinbelow, wherein A is a group of formula (II) hereinbelow, in which R is H or alkyl or optionally substituted benzyl or a H(OCH.sub.2 CH.sub.2).sub.1-4-, Me(OCH.sub.2 CH.sub.2).sub.1-4-, or Et(OCH.sub.2 CH.sub.2).sub.1-4- group, X or O--R.sub.1, in which R.sub.1 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group or X is --NR.sub.2 R.sub.3, in which R.sub.2 and R.sub.3 are H or alkyl, hydroxyalkyl, alkoxyalkyl or alkoxyhydroxyalkyl, and B.sub.1, B.sub.2 and B.sub.3 have the same meanings as A or are H or a group of formula (III) hereinbelow, in which R.sub.4 is H or alkyl, Y is a O--R.sub.5 group, wherein R.sub.5 is H or alkyl, hydroxyalkyl, alkoxyalkyl, alkoxyhydroxyalkyl or a polyoxaalkyl group, or Y is a --NR.sub.6 R.sub.7 group, wherein R.sub.6 and R.sub.Type: GrantFiled: November 27, 1989Date of Patent: July 21, 1992Assignee: Bracco Industria Chimica S.p.A.Inventors: Ernst Felder, Carlo Musu, Luciano Fumagalli, Fulvio Uggeri
-
Patent number: 5128466Abstract: Cyclic molecules having oriented groups are capable of forming stable complexes with cations.Type: GrantFiled: October 18, 1989Date of Patent: July 7, 1992Assignee: The Research Foundation of State University of New YorkInventor: Thomas W. Bell
-
Patent number: 5120842Abstract: A compound of the structure ##STR1## wherein R.sup.1 is --SiR.sup.3 R.sup.4 R.sup.5 ;R.sup.2 is hydrogen or --SiR.sup.3 R.sup.4 R.sup.5 ; andR.sup.3, R.sup.4, and R.sup.5 are each, independently, alkyl, alkenyl, aralkyl, triphenylmethyl, or phenyl which 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 is useful in treating solid tumors; and by virtue of its antifungal activity is useful in treating fungal infections. This invention also provides a method of using rapamycin 42-[O-[(1,1-dimethylethyl)-dimethylsilyl] ether for the preparation of 31-substituted rapamycin derivatives.Type: GrantFiled: April 1, 1991Date of Patent: June 9, 1992Assignee: American Home Products CorporationInventors: Amedeo A. Failli, Robert J. Steffan
-
Patent number: 5118678Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CONH(CR.sup.3 R.sup.4).sub.n --X;R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl, aralkyl, cycloalkyl, halogen, or trifluoromethyl;X ix hydrogen, lower alkyl, cycloalkyl, trifluoromethyl, nitro, alkoxy, carboalkoxy, aralkyl, halo, dialkylamino, thioalkyl, or Y;Y is a phenyl group which may be optionally mono-, di-, or tri- substituted with a group selected from alkyl, aralkyl, alkoxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, dialkylamino, or alkylthio;n=0-5;with the proviso that R.sup.1 and R.sup.2 are not both hydrogen and when n=0, X is lower alkyl, cycloalkyl, aralkyl, or Y;or a pharmaceutically acceptable salt thereof when X is dialkylamino, which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs.Type: GrantFiled: April 17, 1991Date of Patent: June 2, 1992Assignee: American Home Products CorporationInventors: Wenling Kao, Robert L. Vogel, John H. Musser
-
Patent number: 5093338Abstract: Disclosed is a novel lipophilic macrolide of Formula I: ##STR1## The compound of assigned Formula I is an analog of rapamycin which has activity as an antifungal agent and as an immunosuppressant.Type: GrantFiled: April 23, 1991Date of Patent: March 3, 1992Assignee: Merck & Co., Inc.Inventors: Kevin Byrne, Robert T. Goegelman, Otto Hensens, Louis Kaplan, Jerrold M. Liesch
-
Patent number: 5091389Abstract: Disclosed is a novel lipophilic macrolide of assigned Formula I: ##STR1## The compound of assigned Formula I is an analog of rapamycin which has activity as an antifungal agent and as an immunosuppressant.Type: GrantFiled: April 23, 1991Date of Patent: February 25, 1992Assignee: Merck & Co., Inc.Inventors: John Ondeyka, Otto Hensens, Jerrold Liesch
-
Patent number: 5064835Abstract: Novel hydroxymacrolide derivatives of the general structural Formula I: ##STR1## have been prepared from (a) suitable precursor(s) by selective reduction of the ketone at C-2. These macrolide immunosuppressants are useful in a human host for the treatment of autoimmune diseases (such as juvenile-onset diabetes melitus, multiple sclerosis and rheumatoid arthritis), infectious diseases and/or the prevention of rejection of foreign organ transplants, e.g. bone marrow and heart transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses such as: psoriasis, atopical dermatitiis, contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis, Lichen planus, Pemphigus, bullous Pemphigoid, Epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eospinphilias, Lupus erythematosus or Alopecia areata.Type: GrantFiled: March 1, 1990Date of Patent: November 12, 1991Assignee: Merck & Co., Inc.Inventors: Richard J. Bochis, Huyn O. Ok, Matthew J. Wyvratt
-
Patent number: 5059687Abstract: A process for the condensation of imides and alcohols or amines to ester acyl lactams, ester amide acyl lactams or amide acyl lactams by reacting a polyol or polyamine in the liquid phase with an acyl lactam compound is disclosed.Type: GrantFiled: April 12, 1990Date of Patent: October 22, 1991Assignee: Stamicarbon B.V.Inventors: Christiaan Schroder, Albert A. Van Geenen, Josefina M. A. Schiffer
-
Patent number: 5003065Abstract: New compounds are described of the formula: ##STR1## wherein Z is selected from ##STR2## each x is selected from ##STR3## n is an integer from 1-10; each Y is selected from hydrogen, --NH.sub.2, --COQ, --COOQ, --COONHQ, --COOH, --OH, W, halogen and Q; wherein each Q is independently selected from substituted and unsubstituted lower alkenyl and lower alkyl and wherein the substitutuents are selected from --NH.sub.2 halogen, --OH, and --COOH; D is selected from hydroxy, hydrogen and --NH.sub.2 ; and W is selected from ##STR4## wherein each R is independently selected from hydrogen and lower alkyl; R' is selected from ethylene, propylene, isopropylene and phenylene; M is selected from chlorine and hydroxy; A is selected from hydrogen, lower alkyl, lower alkenyl, cycloalkyl, and phenyl; (B) is selected from ##STR5## --CO--, --NHCO--, --O--, --COO--, --N.dbd.N--, or represents a confugate bond; L.sub.1 and L.sub.Type: GrantFiled: June 14, 1988Date of Patent: March 26, 1991Inventors: Carey Merritt, James Winkelman, Ruth Silberman-Hazony
-
Patent number: 4987227Abstract: A 13 or 14 member macrocyclic compound having the following ring nucleus: ##STR1##This work was supported by grants from the National Institutes of Health (GM-34841) and the National Science Foundation (CHE-8706616).Type: GrantFiled: February 23, 1990Date of Patent: January 22, 1991Assignee: The Research Foundation of State University of New YorkInventors: Cynthia Burrows, Heungsik Yoon, Thomas R. Wagler
-
Patent number: 4977291Abstract: A process of producing a silanic or siloxanic compound containing at least one cycloalkyl ring by the hydrogenation of a corresponding compound containing at least one aromatic ring, in the presence of a Raney nickel catalyst having a granulometry comprised essentially between 10 and 150 micrometers and a surface area of at least 80 m.sup.2 /g.Type: GrantFiled: September 15, 1989Date of Patent: December 11, 1990Assignee: Istituto Guido Donegani S.p.A.Inventors: Francesco Gementi, Loris Sogli, Raffaele Ungarelli
-
Patent number: 4956352Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: ##STR1## to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.Type: GrantFiled: August 17, 1989Date of Patent: September 11, 1990Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Masakuni Okuhara, Hirokazu Tanaka, Toshio Goto, Tohru Kino, Hiroshi Hatanaka
-
Patent number: 4939254Abstract: A method is provided for a high yield template synthesis of macrocyclic catecholamide ligands.Type: GrantFiled: October 30, 1989Date of Patent: July 3, 1990Assignee: The Regents of the University of CaliforniaInventors: Thomas J. McMurry, Kenneth N. Raymond
-
Patent number: 4929611Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: ##STR1## to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.Type: GrantFiled: May 30, 1986Date of Patent: May 29, 1990Assignee: Fujisawa Pharmaceutical Company, Ltd.Inventors: Masakuni Okuhara, Hirokazu Tanaka, Toshio Goto, Tohru Kino, Hiroshi Hatanaka
-
Patent number: 4920218Abstract: A process is described involving an alkaline rearrangement of FK-506 producing a new decarbonylated 22-membered macrocycle rearrangement derivative of FK-506, i.e. C.9, nor-keto FK-506.Type: GrantFiled: September 5, 1989Date of Patent: April 24, 1990Assignee: Merck & Co., Inc.Inventors: David Askin, Todd K. Jones, Robert A. Reamer, Ralph P. Volante, Ichiro Shinkai
-
Patent number: 4894366Abstract: This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplantation, graft-versus-host diseases by medulla ossium transplantation, autoimmune diseases, infectious diseases, and the like, which can be represented by the following formula: ##STR1## to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.Type: GrantFiled: November 20, 1985Date of Patent: January 16, 1990Assignee: Fujisawa Pharmaceutical Company, Ltd.Inventors: Masakuni Okuhara, Hirokazu Tanaka, Toshio Goto, Tohru Kino, Hiroshi Hatanaka