Patents Represented by Attorney Frank P. Hoffman
  • Patent number: 4393221
    Abstract: There is presented a process for the manufacture of hexahydronaphthacene derivatives of the general formula ##STR1## wherein one of R.sup.1 and R.sup.2 represents a hydrogen atom and the other represents a hydrogen atom or a hydroxy group or R.sup.1 and R.sup.2 together represent a protected oxo group, R.sup.3 represents a hydrogen atom or a hydroxy or acyloxy group and R.sup.4 represents a lower alkyl or esterified carboxy group or a group of the formula ##STR2## wherein R.sup.5 and R.sup.6 together form an oxo group or a protected oxo group and X represents a hydrogen atom or a hydroxy or acyloxy groupor ##STR3## in which n stands for 1 or 2 and Y represents a hydrogen atom or an alkyl or acyl group.Also presented are certain of the novel derivatives per se and various novel intermediates in the process.
    Type: Grant
    Filed: November 4, 1981
    Date of Patent: July 12, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Michael J. Broadhurst, Cedric H. Hassall, Gareth J. Thomas
  • Patent number: 4390471
    Abstract: Novel Imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. An especially preferred genus included with the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl, preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro or halogen, most preferably, chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof; R.sub.6 is phenyl or halo, nitro, or lower alkylsubstituted phenyl, preferably, halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety; and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 12, 1981
    Date of Patent: June 28, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4388239
    Abstract: Compounds of the formula ##STR1## wherein X and Y are selected from the group consisting of hydrogen, halogen and trifluoromethyl,are disclosed.The compounds are useful as intermediates in the production of 2-benzazepines, compounds of pharmacological activity.Also disclosed are other intermediates and processes for their production.
    Type: Grant
    Filed: November 23, 1981
    Date of Patent: June 14, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventor: Eugene J. Trybulski
  • Patent number: 4386028
    Abstract: There is provided imidazodiazepines of the formula ##STR1## wherein R.sup.1 is methyl, ethyl or isopropyl, one of R.sup.4 and R.sup.5 is hydrogen and the other is nitro or cyano, and either R.sup.2 is hydrogen and R.sup.3 is hydrogen or lower alkyl or R.sup.2 and R.sup.3 together are dimethylene, trimethylene or propenylene and the carbon atom denoted as .gamma. has the (S)- or (R,S)-configuration, and X is an oxygen or sulphur atom,and their pharmaceutically acceptable acid addition salts. The compounds are useful in the antagonization of the central-depressant muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of indication, for example of schistosomicidally-active 1,4-benzodiazepines. Also provided are methods for making the compounds.
    Type: Grant
    Filed: July 30, 1982
    Date of Patent: May 31, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Walter Hunkeler, Emilio Kyburz
  • Patent number: 4383037
    Abstract: There is presented a process for producing anthracycline glycosides A by converting the sugar moiety of anthracycline glycosides B, represented by the following formula: ##STR1## into the sugar moiety of anthracycline glycosides A, represented by the following formula: ##STR2## with the aid of a microorganism belonging to the species Streptomyces galilaeus or Streptomyces melanogenes.
    Type: Grant
    Filed: October 19, 1981
    Date of Patent: May 10, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Akiko Fujiwara, Tatsuo Hoshino, Yuzuru Sekine
  • Patent number: 4382032
    Abstract: There is presented imidazodiazepines of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is the group ##STR2## R.sup.1 is hydrogen, lower alkyl, lower alkoxymethyl, halogen, nitro or a group of the formula --COOR.sup.4, R.sup.2 is hydrogen, trifluoromethyl or halogen,R.sup.3 is hydrogen, trifluoromethyl, halogen or lower alkyl, R.sup.4 is methyl, ethyl or isopropyl and X is an oxygen or sulphur atom and the carbon atom denoted as .gamma. has the (S)-- or (R,S)-- configuration,and their pharmaceutically acceptable acid addition salts.The compounds are useful in the antagonization of the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of therapy, for example, of schistosomicidally-active 1,4-benzodiazepines.
    Type: Grant
    Filed: July 30, 1982
    Date of Patent: May 3, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Walter Hunkeler, Emilio Kyburz
  • Patent number: 4379765
    Abstract: There are presented compounds of the formulas ##STR1## wherein R.sub.1 is hydrogen or lower alkyl; R.sub.2 and R.sub.3 are selected from the group consisting of hydrogen, lower alkyl, C.sub.2 to C.sub.7 carboxylic acids, hydroxy C.sub.2 to C.sub.7 alkyl, C.sub.2 to C.sub.7 carboxylic acid esters and amides and the group COR.sub.11 wherein R.sub.11 is alkoxy, amino or mono- lower alkyl amino; R.sub.6 is nitro or halo and R.sub.5 is hydrogen or halo,and the pharmaceutically acceptable salts thereof.The pyrazolobenzazepines are useful as anxiolytic and sedative agents.Also provided are processes and intermediates in the production of the above pyrazolobenzazepines.
    Type: Grant
    Filed: July 23, 1981
    Date of Patent: April 12, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: George F. Field, Rodney I. Fryer, Eugene J. Trybulski, Armin Walser
  • Patent number: 4379090
    Abstract: Compounds of the formula ##STR1## wherein X and Y are selected from the group consisting of hydrogen, halogen and trifluoromethyl, are disclosed.The compounds are useful as intermediates in the production of 2-benzazepines, compounds of pharmacological activity.Also disclosed are other intermediates and processes for their production.
    Type: Grant
    Filed: November 23, 1981
    Date of Patent: April 5, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventor: Eugene J. Trybulski
  • Patent number: 4377522
    Abstract: There are presented novel benzodiazepine derivatives of the formula ##STR1## wherein R.sup.1 is lower alkyl, lower hydroxyalkyl or lower dialkylaminoalkyl, R.sup.2 and R.sup.3 each are lower alkyl, R.sup.4 is halogen, R.sup.5, R.sup.7 and R.sup.8 each are hydrogen or halogen and R.sup.6 is nitro, amino, lower alkylamino, lower dialkylamino or a group of the formula H.sub.2 N--C(CH.sub.3).sub.2 --CO--NH--, R.sup.9 R.sup.10 N--CO--NH-- or ##STR2## and either R.sup.9 is hydrogen or lower alkyl and R.sup.10 is lower alkyl or lower hydroxyalkyl or R.sup.9 and R.sup.10 together with the nitrogen atom are a 3- to 7-membered heterocycle which, provided it is at least 5-membered, can contain as a ring member an oxygen or sulfur atom or a group of the formula >N--R in which R is hydrogen or lower alkyl,and their pharmaceutically acceptable acid addition salts.
    Type: Grant
    Filed: July 6, 1981
    Date of Patent: March 22, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Quirico Branca, Albert E. Fischli, Andre Szente
  • Patent number: 4377523
    Abstract: Novel Imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. An especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably, chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof, R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably, halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 12, 1981
    Date of Patent: March 22, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4376075
    Abstract: Novel Imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. An especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably, chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof, R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably, halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 12, 1981
    Date of Patent: March 8, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4376074
    Abstract: Novel Imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. An especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably, chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof, R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably, halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 12, 1981
    Date of Patent: March 8, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4375511
    Abstract: The present invention relates to a process for producing aclacinomycins A and B. More particularly, the present invention is concerned with a process for producing selectively aclacinomycins A and B in high yield without formation of cinerubins A and B, by means of a fermentation process, utilizing Streptomyces galilaeus OBB-731.
    Type: Grant
    Filed: October 22, 1981
    Date of Patent: March 1, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Akiko Fujiwara, Tatsuo Hoshino, Masaaki Tazoe
  • Patent number: 4374773
    Abstract: There are presented compounds of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or a lower alkyl group, R.sup.2 and R.sup.3 each are a hydrogen atom or a lower alkyl group, R.sup.4 is a halogen atom and either R.sup.5 is a hydrogen atom or a lower alkyl group and R.sup.6 is a lower alkyl or lower hydroxyalkyl group or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached are a 3-membered to 7-membered heterocycle,and pharmaceutically acceptable acid addition salts thereof.The compounds and their salts are novel and possess valuable pharmacodynamic properties.
    Type: Grant
    Filed: January 16, 1981
    Date of Patent: February 22, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Quirico Branca, Albert E. Fischli, Andre Szente
  • Patent number: 4371468
    Abstract: Novel imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. As especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl, preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof. R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 16, 1981
    Date of Patent: February 1, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4368157
    Abstract: Novel imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. As especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl, preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof. R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 12, 1981
    Date of Patent: January 11, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4368158
    Abstract: Novel imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. As especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl, preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof. R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 12, 1981
    Date of Patent: January 11, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4368265
    Abstract: Antibiotic X-14868A having the following chemical structure ##STR1## and the pharmaceutically acceptable salts thereof is presented. Also presented is a fermentative method of producing the above antibiotic.Antibiotic X-14868A exhibits anticoccidiostatic activity.
    Type: Grant
    Filed: February 23, 1981
    Date of Patent: January 11, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Chao-Min Liu, Barbara Prosser, John Westley
  • Patent number: 4368159
    Abstract: Novel imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. As especially preferred genus included within the purview of the invention encompasses a compound of the formula ##STR1## wherein R.sub.1 is hydrogen and lower alkyl, preferably methyl; R.sub.3 and R.sub.5 are hydrogen; R.sub.4 is hydrogen, nitro and halogen, most preferably chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof. R.sub.6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R.sub.2 is hydrogen and lower alkyl.
    Type: Grant
    Filed: March 13, 1981
    Date of Patent: January 11, 1983
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Armin Walser, Rodney I. Fryer
  • Patent number: 4363762
    Abstract: Imidazodiazepine derivatives of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is selected from the group consisting of: ##STR2## the dotted line represents the double bond present in groups (a) and (b), D is >C.dbd.O or >C.dbd.S, R.sup.1 is selected from the group consisting of cyano, lower alkanoyl and a group of the formula --COOR.sup.4, R.sup.4 is selected from the group consisting of methyl, ethyl, isopropyl and 2-hydroxyethyl, R.sup.5 is selected from the group consisting of hydrogen, trifluoromethyl and halogen and R.sup.6 is selected from the group consisting of hydrogen, trifluoromethyl, halogen and lower alkyl and either R.sup.2 is hydrogen and R.sup.3 is hydrogen or lower alkyl or R.sup.2 and R.sup.3 together are trimethylene or propenylene and the carbon atom denoted as .gamma.
    Type: Grant
    Filed: November 16, 1981
    Date of Patent: December 14, 1982
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Max Gerecke, Willy Haefely, Walter Hunkeler, Emilio Kyburz, Hanns Mohler, Lorenzo Pieri, Petar Polc