Patents Assigned to Ayerst McKenna & Harrison Ltd.
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Patent number: 4066780Abstract: Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of a pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9.Type: GrantFiled: October 28, 1976Date of Patent: January 3, 1978Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Christopher A. Demerson, Leslie G. Humber, Andre A. Asselin, Ivo Jirkovsky, Thomas A. Dobson
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Patent number: 4066779Abstract: Pyranolindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9.Type: GrantFiled: October 28, 1976Date of Patent: January 3, 1978Assignee: Ayerst, McKenna and Harrison Ltd.Inventors: Christopher A. Demerson, Leslie G. Humber, Andre A. Asselin, Ivo Jirkovsky, Thomas A. Dobson
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Patent number: 4062851Abstract: An efficient, commercially feasible process for the resolution of the organic bases, (.+-.)-(4a,13b-trans)-(3-hydroxy,13b-trans)-3-isopropyl-2,3,4,4a,8,9,13b,1 4-octahydro-1H-benzo[6,7]cyclohepta[1,2,-3-de)pyrido[2,1-a]isoquinolin-3-ol and (.+-.)-(4a,13b-trans)-(3-hydroxy,13b-trans)-3-tert-butyl-2,3,4,4a,8,9,13b, 14-octahydro-1H-benzo[6,7]cyclohepta[1,2,3-de]pyrido[2,1-a]isoquinolin-3-ol , known neuroleptic agents, is disclosed. The process comprises resolving the racemic organic bases with L-(+)-tartaric acid to obtain directly the pure L-(+) tartrate of the (+)-enantiomer and converting the latter salt to the corresponding (+)-enantiomer free base.Type: GrantFiled: November 26, 1975Date of Patent: December 13, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Karel Pelz, Francois T. Bruderlein, Leslie G. Humber
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Patent number: 4060613Abstract: Disclosed herein are compounds of the formula ##STR1## in which Ar is phenyl or 1-naphthyl; R.sup.1 is hydrogen or lower alkyl; and R.sup.2 and R.sup.3 together with the nitrogen atom to which they are joined form a hyterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino and 4-(lower alkyl)-1-piperazinyl. The compounds are antidepressant agents and methods for their preparation and use also are disclosed.Type: GrantFiled: May 19, 1976Date of Patent: November 29, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Jean-Marie Ferland, Real Laliberte, Wilbur Lippmann, Thomas A. Pugsley
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Patent number: 4060619Abstract: Compounds of formula 1 ##STR1## in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different selected from the group consisting of hydrogen, halogen, nitro, trifluoromethyl, lower alkyl and lower alkoxy, or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3, or R.sup.3 and R.sup.4 together form a CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 chain and R.sup.3 and R.sup.4, R.sup.1 and R.sup.4 and R.sup.1 and R.sup.2, respectively, are as defined above, R.sup.5 is hydrogen, lower alkyl or a radical of formula -Alk-OR.sup.6 wherein Alk is an alkylene selected from the group consisting of CR.sup.7 R.sup.8, CR.sup.7 R.sup.8 CR.sup.9 R.sup.10, CR.sup.7 R.sup.8 CR.sup.9 R.sup.10 CR.sup.11 R.sup.12 and CR.sup.7 R.sup.8 CR.sup.9 R.sup.10 CR.sup.11 R.sup.12 CR.sup.13 R.sup.14 wherein each of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 is hydrogen or lower alkyl and R.sup.6 is hydrogen or lower alkyl; R.sup.15 is hydrogen or lower alkyl; X is O, S, SO or SO.sub.2 ; and Y is O or NR.sup.Type: GrantFiled: January 14, 1976Date of Patent: November 29, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Adolf H. Philipp, Ivo L. Jirkovsky
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Patent number: 4059585Abstract: Disclosed is a process for preparing (4a,13b-trans)-1,2,4,4a,8,9,13b,14-octahydro-3H-benzo[6,7]cyclohepta[1,2,3 -de]-pyrido[2,1-a]isoquinolin-3-one involving a 1,3-cycloaddition of a 4-halo-1-butene to 1,7,8,12b-tetrahydrobenzo[1,2]cyclohepta-[3,4,5-de]isoquinoline N-oxide.Type: GrantFiled: July 27, 1976Date of Patent: November 22, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventor: Francois T. Bruderlein
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Patent number: 4057556Abstract: Tropone derivatives characterized by having a derivative of oxamic acid at positions 2 and/or 5 are disclosed. In addition, the tropone nucleus can be optionally further substituted. The foregoing compounds are useful for preventing or treating allergic conditions in a mammal. Methods for the preparation and use of said compounds are disclosed.Type: GrantFiled: June 17, 1976Date of Patent: November 8, 1977Assignee: Ayerst, McKenna & Harrison Ltd.Inventors: Jehan F. Bagli, Tibor Bogri
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Patent number: 4056537Abstract: Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3, 4, 5, 6, 7, 8, and 9. The derivatives having the amino(lower)alkyl radical only at position 9 possess two substituents at position 1 and may be optionally substituted at position 3, 4, 5, 6, 7, and 8. The derivatives having an amino(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3, 4, 5, 6, 7 and 8.Type: GrantFiled: October 18, 1976Date of Patent: November 1, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Christopher A. Demerson, Leslie G. Humber, Andre A. Asselin, Ivo Jirkovsky, Thomas A. Dobson
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Patent number: 4054741Abstract: Process for preparing prostanoic acid derivatives, in particular derivatives of 9,15-dioxygenated prostanoic acid and prost-13-enoic acid, related additionally unsaturated derivatives, homologs thereof and intermediates therefor, in which a lower alkyl ester of 2-(.omega.-carboxy-Y)cyclopent-2-en-1-one in which Y is CH.sub.2 --(a)--(CH.sub.2).sub.m wherein (a) is CH.sub.2 CH.sub.2, CH.dbd.CH or C.tbd.C and m is an integer from 2 - 4 is treated with nitromethane to yield 2-(.omega.-carboxy-Y)-3-nitromethyl-cyclopentan-1-one and the latter compound or its corresponding 1-hydroxy analog are converted to the corresponding aldehyde, 2-(.omega.-carboxy-Y)cyclopentan-1-on-3-al or 1-hydroxy-2-(.omega.-carboxy-Y)cyclopentan-3-al, respectively. Treatment of the aldehyde with the ylid prepared from the appropriate Wittig reagent, preferably a dimethyl 2-oxoalkylphosphonate of the formula (AlkO).sub.2 P(O)CH.sub.2 CO(CH.sub.2).sub.n CH.sub.Type: GrantFiled: June 21, 1976Date of Patent: October 18, 1977Assignee: Ayerst McKenna & Harrison Ltd.Inventors: Jehan F. Bagli, Tibor Bogri
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Patent number: 4054569Abstract: Octahydrobenzo[6,7]-(or [5,6]-)cyclohepta-[1,2,3-de]pyrido-(or pyrrolo-)[2,1-a]isoquinolines, and decahydrobenzo[6,7]-(or[5,6]-)cyclohepta[1,2,3-de]-azepino[2,1-a]isoquinol ines and derivatives thereof, optionally substituted on the pyrrolidine, piperidine or azepine ring. The compounds are useful CNS depressants, anticonvulsant and antiinflammatory agents, and methods for their preparation and use are also disclosed.Type: GrantFiled: May 17, 1976Date of Patent: October 18, 1977Assignee: Ayerst McKenna & Harrison Ltd.Inventors: Francois T. Bruderlein, Leslie G. Humber
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Patent number: 4041169Abstract: Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of a pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9.Type: GrantFiled: October 28, 1976Date of Patent: August 9, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Christopher A. Demerson, Leslie G. Humber, Andre A. Asselin, Ivo Jirkovsky, Thomas A. Dobson
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Patent number: 4036856Abstract: A process for preparing 11-deoxyprostaglandin E.sub.1, E.sub.2 and E.sub.3 and analogs thereof is realized by treating an appropriate di(lower)alkyl 3-(optionally substituted)-2-formylcyclopropane-1,1-dicarboxylate with an ylid prepared from a Wittig reagent of formula (AlkO).sub.2 POCH.sub.2 CO-(c)-CH.sub.3 in which Alk is an alkyl containing one to three carbon atoms and (c) is either (CH.sub.2).sub.q wherein q is an integer from 1 to 6 or cis CH.sub.2 CH=CH(CH.sub.2).sub.r wherein r is an integer from 0 to 3 to obtain the corresponding compound of formula: ##STR1## in which R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl, R.sup.4 is lower alkyl and (c) is as defined herein. The latter compound is reduced with an alkali metal borohydride to yield the corresponding alcohol derivative. Condensation of this alcohol derivative or preferably its corresponding tetrahydropyran-2-yl ether derivative with a triester of formula CH(COOR.sup.6).sub.2 --(a)-(CH.sub.Type: GrantFiled: November 11, 1976Date of Patent: July 19, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Nedumparambil A. Abraham, Jehan F. Bagli, Tibor Bogri
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Patent number: 4035495Abstract: 4H-Pyrrolo[2,1-c][1,4]benzoxazines and 4H-pyrrolo[2,1-c]-[1,4]benzothiazines characterized by having an alkylamine substituent at position 4 are disclosed. The compounds are characterized further by having an alkyl substituent on the same carbon atom bearing the alkylamine substituent. In addition the compounds may be optionally substituted at positions 1 and 6 to 9. Also disclosed are 4H-pyrrolo-[2,1-c][1,4]benzoxazines and 4H-pyrrolo[2,1-c][1,4]benzothiazines which are dialkylated at position 4 and have a methylamino substituent at position 1. The foregoing compounds possess antihypertensive and central nervous system depressant activity and methods for their preparation and use are described.Type: GrantFiled: February 10, 1975Date of Patent: July 12, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Ivo Jirkovsky, Leslie G. Humber
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Patent number: 4020157Abstract: Compounds of the formula 1 or 1a ##STR1##HSCH.sub.2 CH(R)CO--Lys--Asn--Phe--Phe--Trp--Lys--Thr--Phe--Thr--Ser--NHCH.sub.2 CH.sub.2 SH (1a)In which R is hydrogen or NHR.sup.1 in which R.sup.1 is lower aliphatic acyl containing from 1 - 6 carbon atoms or benzoyl, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formulae 1 and 1a are useful for the management of diabetes and the treatment of acromegaly in mammals. Methods for their use also are disclosed.Type: GrantFiled: July 8, 1975Date of Patent: April 26, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Nedumparambil A. Abraham, Hans U. Immer, Verner R. Nelson, Kazimir Sestanj
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Patent number: 4018912Abstract: The tripeptide derivatives of formula 1H--L--Pro--N(R.sup.1)CH(R.sup.2)CO--Y--R.sup.3 (1)in which R.sup.1 is hydrogen, lower alkyl or NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 each are lower alkyl, R.sup.2 is hydrogen or lower alkyl, R.sup.3 is amino, lower alkylamino, di(lower)alkylamino or amino(lower)alkylamino and Y is one of the amino acid residues Gly or D-Ala with the proviso that when R.sup.1 is NR.sup.4 R.sup.5 wherein R.sup.4 and R.sup.5 are as defined herein and R.sup.2 and Y are as defined herein, R.sup.3 is lower alkylamino, di(lower)alkylamino or amino(lower)alkylamino, and a method for their preparation are disclosed. The tripeptide derivatives of formula 1 possess central nervous system activity and methods for their use are given.Type: GrantFiled: July 28, 1975Date of Patent: April 19, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Amedeo Failli, Hans U. Immer, Manfred Gotz
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Patent number: 4012511Abstract: Oxazinoindole derivatives characterized by having an amino(lower)alkyl radical attached to the 1 position of a 1H-1,4-oxazino[4,3-a]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated in a heterocyclic amine radical. The derivatives are substituted further at positions 1 and 10 and may be optionally substituted at positions 3, 4, 6, 7, 8 and 9. The oxazinoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the use of these derivatives and compositions containing them are also disclosed.Type: GrantFiled: July 7, 1975Date of Patent: March 15, 1977Assignee: Ayerst McKenna & Harrison Ltd.Inventors: Christopher A. Demerson, Leslie G. Humber, George Santroch, Thomas A. Dobson, Ivo Jirkovsky
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Patent number: 4010260Abstract: Compounds of the formula 1 or 1a ##STR1## IN WHICH R is hydrogen or CONHCH.sub.2 CONHCH.sub.2 CH.sub.3 are disclosed. The compounds are obtained by a process which comprises the following step: preparing peptide fragments II, III, V and VII see below, by a series of condensations involving the reaction of an appropriately protected peptide having an activated ester group with an appropriately protected peptide having a free amino group; condensing ##STR2## by means of the azide method with ##STR3## followed by hydrogenolysis of the reaction product to obtain ##STR4## condensing the latter by means of the azide method with ##STR5## followed by treating the resulting compound with hydrazine hydrate to obtain ##STR6## condensing the latter by means of the azide method with ##STR7## in which R is hydrogen or CONHCH.sub.2 CONHCH.sub.2 CH.sub.Type: GrantFiled: July 28, 1975Date of Patent: March 1, 1977Assignee: Ayerst McKenna & Harrison Ltd.Inventors: Hans U. Immer, Nedumparambil A. Abraham, Verner R. Nelson
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Patent number: 4006136Abstract: A process for preparing 11-deoxyprostaglandin E.sub.1, E.sub.2 and E.sub.3 and analogs thereof is realized by treating an appropriate di(lower)alkyl 3-(optionally substituted)-2-formylcyclopropane-1,1-dicarboxylate with an ylid prepared from a Wittig reagent of formula (AlkO).sub.2 PCCH.sub.2 CO-(c)-CH.sub.3 in which Alk is an alkyl containing one to three carbon atoms and (c) is either (CH.sub.2).sub.q wherein q is an integer from 1 to 6 or cis CH.sub.2 CH=CH(CH.sub.2).sub.r wherein r is an integer from 0 to 3 to obtain the corresponding compound of formula: ##STR1## in which R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl, R.sup.4 is lower alkyl and (c) is as defined herein. The latter compound is reduced with an alkali metal borehydride to yield the corresponding alcohol derivative. Condensation of this alcohol derivative or preferably its corresponding tetrahydropyran-2-yl ether derivative with a triester of formula CH(COOR.sup.6).sub.2 -(a)-(CH.sub.Type: GrantFiled: July 19, 1974Date of Patent: February 1, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Nedumparambil A. Abraham, Jehan F. Bagli, Tibor Bogri
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Patent number: 4003902Abstract: Naphthyridinomycin complex, a major component thereof called naphthyridinomycin A and a minor component thereof called naphthyridinomycin B are disclosed. These antibiotic substances exhibit antibacterial activity. The substances are producible by culturing a microorganism of the species Streptomyces in an aqueous nutrient medium under submerged aerobic fermentation conditions. Methods for their preparation and use are included.Type: GrantFiled: June 20, 1974Date of Patent: January 18, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Dieter Kluepfel, Surendra N. Sehgal, Claude Vezina
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Patent number: 4004027Abstract: 2-(1-Hydroxy-2-octynyl)- and 2-(3-hydroxy-1-octynyl)-5-oxocyclopentaneheptanoic acids, their salts and their corresponding lower alkyl esters are disclosed. The compounds inhibit the actions of prostaglandins. Methods for their preparation and use are given.Type: GrantFiled: January 28, 1975Date of Patent: January 18, 1977Assignee: Ayerst McKenna and Harrison Ltd.Inventors: Wilbur Lippmann, Jehan F. Bagli