Patents Represented by Attorney Alan M. Krubiner
  • Patent number: 4347186
    Abstract: 5-Substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids of the formula ##STR1## wherein: X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of ##STR2## in which: Y is oxygen or sulfur;R is hydrogen, methyl, chloro, or bromo, the R substitution being at the 3, 4 or 5 position of the ring;R.sup.1 is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo, the R.sup.1 substitution being at any available position in the ring;R.sup.2 is hydrogen or lower alkyl;are prepared by .beta.-decarboxylation of the corresponding dialkyl-1,1-dicarboxylates. Certain substituted pyrroles are useful as intermediates for preparing the compounds of formula I.
    Type: Grant
    Filed: October 20, 1980
    Date of Patent: August 31, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Joseph M. Muchowski, Robert Greenhouse
  • Patent number: 4347187
    Abstract: 5-Substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids of the formula ##STR1## wherein: X is hydrogen, lower alkyl, chloro or bromo; Ar is a moiety selected from the group consisting of ##STR2## in which: Y is oxygen or sulfur;R is hydrogen, methyl, chloro, or bromo, the R substitution being at the 3, 4 or 5 position of the ring;R.sup.1 is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo, the R.sup.1 substitution being at any available position in the ring;R.sup.2 is hydrogen or lower alkyl; are prepared by .beta.-decarboxylation of the corresponding dialkyl-1,1-dicarboxylates. Certain substituted pyrroles are useful as intermediates for preparing the compounds of formula I.
    Type: Grant
    Filed: June 11, 1981
    Date of Patent: August 31, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Joseph M. Muchowski, Robert Greenhouse
  • Patent number: 4347185
    Abstract: 5-benzoyl-7-halo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids, represented by the formula ##STR1## and the pharmaceutically acceptable non-toxic esters and salts thereof, wherein:R is hydrogen or lower alkyl;X is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, carboxyl, lower alkylcarbonyl, sulfonic acid, sulfonic acid alkyl ester, fluoro, chloro, or bromo; and Y is chloro or bromo, which are novel, and 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids which are represented by the formula ##STR2## wherein X and R are as above defined except that X cannot be chloro or bromo, are prepared by decarboxylation of the corresponding 1,1 dicarboxylates. Intermediates in said preparation are also disclosed.
    Type: Grant
    Filed: October 20, 1980
    Date of Patent: August 31, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Joseph M. Muchowski, Robert Greenhouse
  • Patent number: 4344943
    Abstract: Novel 5-aroyl-6-chloro- or 6-bromo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-7-carboxylic acids represented by the formula ##STR1## and the pharmaceutically acceptable, non-toxic esters and salts thereof, wherein Y is chloro or bromo and Ar is an optionally substituted phenyl, 2-furyl, or 2-thienyl ring or a 3-furyl, 3-thienyl, 2-pyrrolyl or 1-alkyl-2-pyrrolyl ring. These compounds are useful as anti-inflammatory, analgesic and antipyretic agents and as smooth muscle relaxants.
    Type: Grant
    Filed: June 9, 1980
    Date of Patent: August 17, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Joseph M. Muchowski
  • Patent number: 4341767
    Abstract: Nonapeptide and decapeptide analogs of LHRH which have the formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein: X is a D-alanyl residue wherein one hydrogen on C-3 is replaced by:(a) a carbocyclic aryl-containing radical selected from the group consisting of phenyl substituted with three or more straight chain lower alkyl groups, naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl and benzhydryl; or(b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl, and adamantyl; or(c) a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: ##STR2## wherein A" and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur;A is an aminoac
    Type: Grant
    Filed: October 6, 1980
    Date of Patent: July 27, 1982
    Assignee: Syntex Inc.
    Inventors: John J. Nestor, Gordon H. Jones, Brian H. Vickery
  • Patent number: 4332804
    Abstract: Compounds useful in the prevention and/or treatment of hypertension, congestive heart failure, arrhythmia, migraine, vasospastic disorders, and asthma are represented by the formula ##STR1## wherein: R, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently hydrogen or lower alkyl of one to four carbon atoms; andR.sup.5 and R.sup.6 are independently hydrogen, lower alkyl of one to four carbon atoms or lower alkoxy of one to four carbon atoms; andthe pharmaceutically acceptable acid addition salts thereof.
    Type: Grant
    Filed: March 23, 1981
    Date of Patent: June 1, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Robin D. Clark
  • Patent number: 4328245
    Abstract: Stable compositions of PGE-type compounds are achieved by dissolving those compounds in carbonate diester solvents which may contain water up to the solubility limit of the carbonate diester.
    Type: Grant
    Filed: February 13, 1981
    Date of Patent: May 4, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Cheng-Der Yu, Ursula Bruenner
  • Patent number: 4323467
    Abstract: A solution for cleaning, storing or wetting contact lenses which comprises a poly(oxyethylene)-poly(oxypropylene) substituted ethylenediamine surfactant having a molecular weight between 1,600 and 27,000; a germicidal agent; a viscosity builder; a tonicity agent; a sequestering agent and water.
    Type: Grant
    Filed: November 24, 1980
    Date of Patent: April 6, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Cherng-Chyi Fu
  • Patent number: 4323564
    Abstract: The 17-butyrate, 17-benzoate, 17,21-methyl orthobutyrate, 17,21-methyl orthobenzoate, and 17,21-dibutyrate esters of cloprednol (6-chloro-11.beta., 17.alpha., 21-trihydroxy-pregna-1,4,6-triene-3,20-dione) are useful as topical, anti-inflammatory steroids.
    Type: Grant
    Filed: March 9, 1978
    Date of Patent: April 6, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: John H. Fried, Denis J. Kertesz, Michael Marx
  • Patent number: 4322421
    Abstract: Certain 1,4,5,6-tetrahydropyrimidine compounds which are substituted with an amino, amido or carbamate at the 2-position, with an optionally substituted phenyl at the 5-position or at the 4-position when there is no alkyl at the 1-position and optionally a lower alkyl at the 1-position when the phenyl is at the 5-position are useful as CNS agents and as antihypertensives.
    Type: Grant
    Filed: December 1, 1980
    Date of Patent: March 30, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Klaus Weinhardt, Michael Marx
  • Patent number: 4321272
    Abstract: Compounds useful as anticonvulsant agents, antifungals and antibacterials are represented by the formula ##STR1## wherein R.sup.1 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, lower alkyl of one to four carbon atoms, lower alkoxy of one to four carbon atoms and trifluoromethyl; Z is ethylene or propylene optionally substituted by one or more lower alkyl groups of one to four carbon atoms; m is 1, 2, 3 or 4 and n is 0, 1, 2 or 3 with the proviso that the sum of m and n is 2, 3 or 4; and the pharmaceutically acceptable acid addition salts thereof.The ketone intermediates useful in preparing compounds of formula (I) also have anticonvulsant activity.
    Type: Grant
    Filed: August 25, 1980
    Date of Patent: March 23, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Keith A. M. Walker
  • Patent number: 4320118
    Abstract: Novel peptides of the formula: ##STR1## wherein: A, A' and A" are each independently Gly, D-Ala, D-Leu, or D-Trp, wherein A may optionally be N-alkylated or N-acylated;B is Pro, .DELTA..sup.3 -Pro, Thz, or diMeThz;C and C' are each independently Thr, Ser, Val, or alloThr;D is Glu, Gln, Asp, or Asn;R is hydrogen, or is lower alkyl or lower acyl, substituted for one of the hydrogens on the .epsilon.-amino group of the lysyl residue;X is Cys, Ala, ABU, or Cys(Me); andY is selected from the group consisting of hydroxy, Pro, Pro-Leu, and Pro-Leu-Met, -NH.sub.2, ProNH.sub.2, Pro-LeuNH.sub.2 and Pro-leu-MetNH.sub.2 ;and the pharmaceutically acceptable salts thereof, are useful for increasing immunologic competence. Methods for preparation of the peptides are also described.
    Type: Grant
    Filed: December 22, 1980
    Date of Patent: March 16, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Abraham White, deceased, John J. Nestor, Gordon H. Jones, Pamela M. Burton
  • Patent number: 4318905
    Abstract: Nonapeptide and decapeptide analogs of LH-RH of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein: V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl;W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl;X is a D-amino acid residue of the formula: ##STR2## wherein R is a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: ##STR3## wherein A and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur;Y is leucyl, isoleucyl, nor-leucyl or N-methyl-leucyl;Z is glycinamide or --NH--R.sup.1, wherein:R.sup.1 is lower alkyl, cycloalkyl, fluoro lower alkyl or ##STR4## wherein R.sup.2 is hydrogen or lower alkyl,are disclosed. These compounds exhibit potent LH-RH agonist properties.
    Type: Grant
    Filed: June 23, 1980
    Date of Patent: March 9, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: John J. Nestor, Gordon H. Jones, Brian H. Vickery
  • Patent number: 4310466
    Abstract: Certain 16.beta.-methyl-3-oxoandrost-4-ene and 16.beta.-methyl-3-oxoandrosta-1,4-diene 17.beta.-thiocarboxylic acid esters are useful as anti-inflammatory steroids. These compounds are optionally substituted at the 6.alpha.-position with fluoro or chloro; optionally substituted at the 9.alpha. position with fluoro, chloro or bromo; substituted at the 11 position with a keto, a .beta.-hydroxy or a .beta.-chloro (the latter only when there is a 9.alpha.-chloro); and substituted with 17.alpha.-hydroxy (or an ester thereof).
    Type: Grant
    Filed: November 7, 1980
    Date of Patent: January 12, 1982
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: John A. Edwards
  • Patent number: 4302469
    Abstract: 2-(1,4-Benzodioxan-2-ylalkyl)imidazoles having the general formula: ##STR1## wherein R.sup.1, and R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, and alkyl, and wherein n is an integer equal to 0, 1 or 2, and the pharmaceutically acceptable acid addition salts thereof, are useful as antidepressants.
    Type: Grant
    Filed: September 10, 1980
    Date of Patent: November 24, 1981
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Arthur F. Kluge, Arthur M. Strosberg, Roger Whiting, George Christie
  • Patent number: 4301171
    Abstract: Compounds of the formula ##STR1## and the pharmaceutically acceptable, non-toxic salts thereof, wherein: R is hydrogen, lower alkyl, or benzyl;X is a substitution for hydrogen at any position in the benzene ring and is selected from the group consisting of lower alkyl, lower alkoxyl, benzyl and halo;m is an integer from 0 to 4; andn is an integer from 0 to 2;are novel. These compounds have been shown to be .alpha..sub.2 blockers, and are, therefore, anti-depressants.
    Type: Grant
    Filed: December 3, 1980
    Date of Patent: November 17, 1981
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Arthur F. Kluge, Arthur M. Strosberg, Roger Whiting, George A. Christie
  • Patent number: 4296042
    Abstract: This process relates to the synthesis of unsaturated aliphatic esters useful as insect sex attractants, including gossyplure, the insect sex pheromone of the pink bollworm moth, Pectinophora gossypiella, and intermediates therefor. The process utilizes a cyclic phosphonium (Wittig) reagent.
    Type: Grant
    Filed: June 18, 1980
    Date of Patent: October 20, 1981
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Joseph M. Muchowski, Michael C. Venuti
  • Patent number: 4294844
    Abstract: 4,5-Dihydro-2-lower alkoxycarbonylamino-4-phenyl imidazoles and substituted phenyl derivatives thereof lower the blood pressure in a human being when administered at low doses.
    Type: Grant
    Filed: June 4, 1979
    Date of Patent: October 13, 1981
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: George S. Harris
  • Patent number: 4293561
    Abstract: Compounds of the formula ##STR1## wherein Z is C.sub.1 and C.sub.4 alkoxymethylene, hydroxymethylene, esterified hydroxymethylene, carbonyl, or ketal-protected carbonyl, and the pharmaceutically acceptable acid addition salts thereof, are useful as anticonvulsant and anti-secretory agents.
    Type: Grant
    Filed: March 9, 1979
    Date of Patent: October 6, 1981
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Keith A. M. Walker
  • Patent number: 4278669
    Abstract: Certain 3-oxoandrost-4-ene and 3-oxoandrosta-1,4-diene 17.beta.-carboxylic acids (and esters thereof) substituted at the 4-position with a fluoro or chloro, optionally substituted at the 6- position with fluoro or chloro and at 16.beta. with methyl are useful as anti-inflammatory steroids. These compounds are optionally substituted at the 9.alpha. position with fluoro, chloro or bromo; substituted at the 11 with a keto, a beta-hydroxy or a beta-chloro (the latter only when there is a 9.alpha.-chloro); when there is a 17.alpha.-hydroxy (or an ester).
    Type: Grant
    Filed: August 29, 1979
    Date of Patent: July 14, 1981
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Francisco S. Alvarez