The Six-membered Hetero Ring Shares Ring Members With One Other Cyclo Only Patents (Class 546/77)
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Patent number: 5324734Abstract: The compounds of formula (I) ##STR1## wherein R is selected from the group hydroxymethyl and carboxy, have been identified as metabolites of 5.alpha.-23-methyl-4-aza-21-nor-chol-1-ene-3,20-dione and are believed to be active as testosterone 5.alpha.-reductase inhibitors and would thus be useful for treatment of acne, seborrhea, female hirsutism or benign prostatic hypertrophy.Type: GrantFiled: September 15, 1992Date of Patent: June 28, 1994Assignee: Merck & Co., Inc.Inventors: John D. Gilbert, Timothy V. Olah
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Patent number: 5304562Abstract: Compounds of the formula ##STR1## wherein carbon atoms 1 and 2 are linked by a single bond or a double bond, R.sub.1 is hydrogen, methyl or ethyl, and A is a group of the formula --N(--R.sub.2)--X-- wherein R.sub.2 is hydrogen or C.sub.1 -C.sub.4 alkyl and X is C.sub.1 -C.sub.12 alkylene or C.sub.3 -C.sub.6 cycloalkylidene; a group of the formula --N(--R.sub.2)--Y--Phe-- wherein R.sub.2 is as defined above, Y is a direct bond or C.sub.1 -C.sub.6 -alkylene and Phe is an unsubstituted or substituted phenylene radical; a group of the formula --O--X-- wherein X is as defined above, or a group --O--Y--Phe-- wherein Y and Phe are as defined above, are inhibitors of 5.alpha.-reductase and can be used for the therapeutic treatment of the human and animal body.Type: GrantFiled: September 30, 1992Date of Patent: April 19, 1994Assignee: Ciba-Geigy CorporationInventor: Michel Biollaz
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Patent number: 5302621Abstract: Compounds of formula (I): ##STR1## (in which: R.sup.1 is a hydrogen atom, an unsubstituted alkyl group, an aryl-substituted alkyl group or a heterocyclic-substituted alkyl group; R.sup.2 is an aryl-substituted alkyl group, a heterocyclic-substituted alkyl group or a diarylamino group; R.sup.3 is a hydrogen atom, an unsubstituted alkyl group, an aryl-substituted alkyl group or an alkenyl group having from 3 to 6 carbon atoms; and each of the bonds represented by .alpha.-.beta. and .gamma.-.delta. is a carbon-carbon single bond or a carbon-carbon double bond;) and pharmaceutically acceptable salts and esters thereof are useful for the treatment and prophylaxis of prostatic hypertrophy. We also provide processes for their preparation.Type: GrantFiled: February 26, 1993Date of Patent: April 12, 1994Assignee: Sankyo Company, LimitedInventors: Koichi Kojima, Hitoshi Kurata, Hiroyoshi Horikoshi, Takakazu Hamada
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Patent number: 5302589Abstract: The present invention relates to certain substituted 17 .beta.-substituted carbonyl-6-azaandrost-4-en-3-ones of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 arei) independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, orii) taken together are a --CH.sub.2 -- group to form a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond;X is ##STR2## wherein R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are independently hydrogen or lower alkyl,p and q are independently either 0 or 1;R.sup.3 is lower alkyl, lower alkenyl, lower cycloalkyl, lower alkoxy, thiopyridyl, adamantyl, --NR.sup.9 R.sup.10 or --Ar--NR.sup.9 R.sup.10whereinR.sup.9 and R.sup.Type: GrantFiled: August 7, 1992Date of Patent: April 12, 1994Assignee: Glaxo, Inc.Inventors: Stephen V. Frye, David Middlemiss, Francis G. Fang
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Patent number: 5294701Abstract: This invention provides novel anti-tumour compounds of the formula ##STR1## wherein R.sub.1 and R.sub.2 are hydrogen or together form an alkyl-, alkoxy- or OH-substituted aromatic group, which optionally contains an N atom as a hetero-atom; R is --COCH.sub.3 or --C.tbd.C--R.sub.4 and R.sub.4 is H or trimethylsilyl; and R.sub.3 is H or --COCF.sub.3 ; and acid addition salts thereof; as well as compositions containing these compounds.Type: GrantFiled: May 6, 1992Date of Patent: March 15, 1994Assignee: Pharmachemie B.V.Inventors: Johan W. Scheeren, Joannes F. M. de Bie, Dirk de Vos
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Patent number: 5278159Abstract: Described are new 17.beta.-aryl ester carboxylates of 4-aza-5.alpha.-androstan-3-ones and related compounds and the use of such compounds as 5.alpha.-reductase inhibitors for treatment of benign prostatic hyperplasia and other hyperandrogenetic related disorders.Type: GrantFiled: October 6, 1992Date of Patent: January 11, 1994Assignee: Merck & Co., Inc.Inventors: Raman K. Bakshi, Gool F. Patel, Gary H. Rasmusson
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Patent number: 5276053Abstract: A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.Type: GrantFiled: October 6, 1992Date of Patent: January 4, 1994Assignee: Warner-Lambert CompanyInventor: Graham Johnson
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Patent number: 5236929Abstract: Disclosed is UCA1064-B, a compound represented by formula (I): ##STR1## and having an antibacterial, antifungal and anti-tumor activity. UCA1064-B is produced by culturing a microorganism belonging to the genus Wallemia.Type: GrantFiled: March 10, 1992Date of Patent: August 17, 1993Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Tatsuya Tamaoki, Isami Takahashi, Katsuhiko Ando, Mayumi Yoshida, Toshiaki Iwazaki
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Patent number: 5237064Abstract: Described is a new process for producing 7.beta.-substituted-4-aza-5.alpha.-androstan-3-ones and related compounds which are 5.alpha.-reductase inhibitors.Type: GrantFiled: May 20, 1992Date of Patent: August 17, 1993Assignee: Merck & Co., Inc.Inventors: Raman K. Bakshi, Gary H. Rasmusson
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Patent number: 5237061Abstract: A process for preparing compounds of the formula ##STR1## which comprises reacting an imidazolide of the formula ##STR2## with an amine of the formula NHR.sub.4 R.sub.5 in the presence of a Grignard reagent to form a compound of formula I or reacting an imidazolide of formula II with a compound of the formula R.sub.6 Mgx to form a compound of formula I.Type: GrantFiled: October 31, 1988Date of Patent: August 17, 1993Assignee: Merck & Co., Inc.Inventors: Apurba Bhattacharya, Ulf H. Dolling, Joseph S. Amato, John M. Williams
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Patent number: 5237065Abstract: Invented are 4-aza-5-alpha-8(14)-17 substituted-androsten-3-ones having an 8(14), 7(8), or 16(17) double bond, optionally also having a 1(2) double bond, pharmaceutical compositions containing the compounds, and methods of using these compounds to inhibit steroid 5-alpha-reductase.Type: GrantFiled: February 4, 1992Date of Patent: August 17, 1993Assignee: SmithKline Beecham CorporationInventors: Dennis A. Holt, Mark A. Levy, Brian W. Metcalf
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Patent number: 5229511Abstract: This invention pertains to novel 3-substituted-aminomethyl-3-substituted-oxy-17a-methyl-17a-lower-alkyl-17a -aza-D-homo-5-alpha-androstane compounds useful as muscle relaxants, methods for preparing such compounds, and method for administering muscle relaxation, wherein the novel compounds are represented the general formula: ##STR1## including optical active isomeric forms, and pharmaceutically acceptable acid addition salts thereof, wherein:R is a selected from the group consisting of hydrogen, lower-alkyl, lower-alkyl carbonyl, and di(lower-alkyl)amino carbonyl:R.sup.1 is selected from the group consisting of: di(lower-alkyl)substituted amino; lower-cycloalkyl lower-alkyl, lower-alkyl substituted amino;, -piperidinyl; 1-pyrrolidinyl; 1-hexamethyleneimino; 4-morpholinyl; 1-piperazinyl, 1-(4-methylpiperazinyl), tri(lower-alkyl)substituted amino, 1-(1-methylpiperidinyl); 1-(1-methylpyrrolidinyl); and 1-(4,4-dimethylpiperazinyl), each lower-alkyl group having from 1 to 6 carbon atoms;R.sub.Type: GrantFiled: June 8, 1992Date of Patent: July 20, 1993Assignee: Anaquest, Inc.Inventor: Roger S. Chen
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Patent number: 5219879Abstract: The present invention relates to novel substituted 15-oxa-, 15-thia-, and 15-aza- dihydrolanosterols, to pharmaceutical compositions containing such compounds, and to methods of using these compounds to suppress the activity of 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMGR), an enzyme which is important in cholesterol biosynthesis. The overall effect of these heterocyclic lanosterol analogs is to decrease cholesterol formation, thereby resulting in lower serum cholesterol levels in mammals, and impaired ergosterol synthesis in fungi.Type: GrantFiled: March 1, 1991Date of Patent: June 15, 1993Assignee: Du Pont Merck Pharmaceutical CompanyInventors: Soo S. Ko, James M. Trzaskos
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Patent number: 5187278Abstract: A novel single-pot trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si-OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the .alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the .alpha.-methylene carbon, of .DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase.Type: GrantFiled: November 1, 1991Date of Patent: February 16, 1993Assignee: Merck & Co., Inc.Inventors: Anthony O. King, Kevin Anderson, Sandor Karady, Alan W. Douglas, Newton L. Abramson, Richard F. Shuman
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Patent number: 5180736Abstract: A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.Type: GrantFiled: May 17, 1991Date of Patent: January 19, 1993Assignee: Warner-Lambert CompanyInventor: Graham Johnson
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Patent number: 5162332Abstract: Selected 17.beta.-Polyaroyl-4-aza-5.alpha.-androst-1-en-3-ones as steroidal reductase inhibitors of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethylR.sup.2 is polycyclic aromatic radical which can be substituted with one or more of: --OH, protected --OH, --OC.sub.1 --C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyl, or nitro, wherein the doted line represents a double bond which can be present, and pharmaceutically acceptable salts or esters thereof, and a pharmaceutical formulation. The above compounds are active as steroidal reductase inhibitors and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.Type: GrantFiled: October 9, 1991Date of Patent: November 10, 1992Assignee: Merck & Co., Inc.Inventors: Nathan G. Steinberg, Gary H. Rasmusson, Thomas N. Salzmann
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Patent number: 5155107Abstract: The present invention concerns steroidic 5.alpha.-reductase inhibitors having the formula: ##STR1## As a result of their 5.alpha.-reductase inhibiting activity, these compounds are useful in the treatment of androgen dependent conditions and diseases.Type: GrantFiled: February 5, 1991Date of Patent: October 13, 1992Assignee: Farmitalia Carlo ErbaInventors: Achille Panzeri, Enrico Di Salle, Marcella Nesi
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Patent number: 5151429Abstract: 17.beta.-Acyl-4-aza-5.alpha.-androst-1-en-3-ones of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.2 is a monovalent radical selected from straight and branched chain alkyl of from 1-12 carbons, or monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents, aralkyl selected from benzyl and phenethyl and heterocyclic selected from 2- or 4-pyridyl, 2-pyrrolyl, 2-furyl or thiophenyl;and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.Type: GrantFiled: September 23, 1991Date of Patent: September 29, 1992Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 5151430Abstract: Specific 17.beta.-thiobenzoyl-4-aza-5.alpha.-androst-1-en-3-ones as antiandrogenic agents of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.2 is phenyl substituted with one or more of: --SH, --SC.sub.1 --C.sub.4 alkyl, --SO--C.sub.1 --C.sub.4 alkyl, --SO.sub.2 --C.sub.1 --C.sub.4 alkyl, --SO.sub.2 N--(C.sub.1 -C.sub.4 alkyl).sub.2, C.sub.1 -C.sub.4 alkyl, --(CH.sub.2).sub.m SH, --S(CH.sub.2).sub.n OCOCH.sub.3, where m is 1-4, n is 1-3, and providing C.sub.1 -C.sub.4 alkyl is only present when one of the above sulfur-containing radicals is present, wherein the dotted line can represent a double bond, and pharmaceutically acceptable esters and salts thereof. Also included is a pharmaceutical formulation thereof. The above compounds are active as antiandrogenic agents and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.Type: GrantFiled: August 16, 1991Date of Patent: September 29, 1992Assignee: Merck & Co., Inc.Inventors: Nathan G. Steinberg, Gary H. Rasmusson, Thomas N. Salzmann
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Patent number: 5140022Abstract: This invention pertains to novel 3-substituted-aminomethyl-3-substituted-oxy-17a-methyl-17a-lower-alkyl-17a -aza-D-homo-5-alpha-androstane compounds useful as muscle relaxants, methods for preparing such compounds, and methods for administering muscle relaxation, wherein the novel compounds are represented the general Formula: ##STR1## including optically active isomeric forms, and pharmaceutically acceptable acid addition salts thereof, wherein:R is selected from the group consisting of hydrogen, lower-alkyl, lower-alkyl carbonyl, and di(lower-alkyl)amino carbonyl;R.sub.1 is selected from the group consisting of: di(lower-alkyl)substituted amino; lower-cycloalkyl lower-alkyl, lower-alkyl substituted amino;, 1-piperidinyl; 1-pyrrolidinyl; 1-hexamethyleneimino; 4-morpholinyl; 1-piperazinyl, 1-(4-methylpiperazinyl), tri(lower-alkyl)substituted amino, 1-(1-methylpiperidinyl); 1-(1-methylpyrrolidinyl); and 1-(4,4-dimethylpiperazinyl), each lower-alkyl group having from 1 to 6 carbon atoms;R.sub.Type: GrantFiled: March 21, 1991Date of Patent: August 18, 1992Assignee: Anaquest, Inc.Inventor: Roger S. Chen
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Patent number: 5138063Abstract: 17.beta.-Acyl-4-aza-5.alpha.-androst-1-in-3-ones of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl R.sup.2 is methoxy, a monovalent radical selected from straight and branched chain alkyl of from 1-12 carbons, or monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents, aralkyl selected from benzyl and phenethyl and heterocyclic selected from 2- or 4-pyridyl, 2-pyrrolyl, 2-furyl or thiophenyl; and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulations of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, and benign prostatic hypertrophy.Type: GrantFiled: May 9, 1991Date of Patent: August 11, 1992Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 5120847Abstract: A novel, facile, and specific process for .alpha.-iodinating or .alpha.-brominating the .alpha.-methylenic carbon of a straight chain, branched chain, or cyclic secondary amide, such as a lactam or an azasteroid, comprises reacting the amide with trialkylsilyl-X (R.sub.3 Si--X), where X is Br, I, or Cl, and R is methyl, ethyl, or n-propyl, in the presence of I.sub.2 or Br.sub.2. The .alpha.-iodo- or .alpha.-bromo-amide is useful for making the .alpha.,.beta.-unsaturated amide through dehydrohalogenation.Type: GrantFiled: August 27, 1990Date of Patent: June 9, 1992Assignee: Merck & Co., Inc.Inventors: Anthony O. King, Sandor Karady, Kevin Anderson, Newton L. Abramson, Richard F. Shuman
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Patent number: 5120742Abstract: 17.beta.-Acyl-4-aza-5.alpha.-Androst-1-end-3-ones of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.3 is cycloalkyl of from 4-8 carbons;and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, androgenic alopecia, prostatic carcinoma and benign prostatic hypertrophy.Type: GrantFiled: April 9, 1991Date of Patent: June 9, 1992Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 5116983Abstract: A process for dehydrogenating a compound of the formula ##STR1## which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a .DELTA..sup.1 double bond.Type: GrantFiled: May 8, 1990Date of Patent: May 26, 1992Assignee: Merck & Co., Inc.Inventors: Apurba Bhattacharya, Alan W. Douglas, Edward J. Grabowski, Ulf H. Dolling
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Patent number: 5098908Abstract: Novel 17.beta.-hydroxybenzoyl-4-aza-5.alpha.-androst-1-en-3-ones as tetosterone reductase inhibitors of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethy andR.sup.2 is phenyl substituted with one or more of: --OH, --OFC.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyl, --(CH.sub.2).sub.m H, --(CH.sub.2).sub.n COOH, including protected --OH, where m is 1-4, n is 1-3, and providing C.sub.1 -C.sub.4 alkyl is only present when one of the above oxygen containing radicals is present, wherein the dotted line represents a double bond which can be present, pharmaceutically acceptable salts and esters thereof, and a pharmaceutical formulation thereof. The above compounds are active as testosterone reductase inhibitors and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.Type: GrantFiled: June 20, 1990Date of Patent: March 24, 1992Assignee: Merck & Co., Inc.Inventors: Nathan G. Steinberg, Gary H. Rasmusson, Thomas N. Salzmann
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Patent number: 5091534Abstract: A novel single-pot trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si--OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the .alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the .alpha.-methylene carbon, of .DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase.Type: GrantFiled: August 27, 1990Date of Patent: February 25, 1992Assignee: Merck & Co., Inc.Inventors: Anthony O. P. King, Sandor Karady, Kevin Anderson, Alan W. Douglas, Newton L. Abramson, Richard F. Shuman
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Patent number: 5089496Abstract: Derivatives of benzo[5,6]cyclohepta pyridine, and pharmaceutically acceptable salts and solvates thereof are disclosed, which possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.Type: GrantFiled: May 1, 1989Date of Patent: February 18, 1992Assignee: Schering CorporationInventors: John J. Piwinski, Ashit K. Ganguly, Michael J. Green, Frank J. Villani, Jesse Wong
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Patent number: 5086059Abstract: There are provided novel bis-napthalimide compounds useful as antitumor agents, pharmaceutical compositions containing them and processes for preparing intermediates to such compounds.Type: GrantFiled: June 7, 1990Date of Patent: February 4, 1992Assignee: Du Pont Merck Pharmaceutical CompanyInventors: Robert J. Ardecky, Arthur D. Patten, Jung-Hui Sun
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Patent number: 5084574Abstract: A process for dehydrogenating a compound of the formula ##STR1## which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a .DELTA..sup.1 double bond.Type: GrantFiled: February 7, 1990Date of Patent: January 28, 1992Assignee: Merck & Co., Inc.Inventors: Apurba Bhattacharya, Alan W. Douglas, Edward J. Grabowski, Ulf H. Dolling
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Patent number: 5071853Abstract: A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.Type: GrantFiled: February 27, 1990Date of Patent: December 10, 1991Inventors: Christopher F. Bigge, Sheryl J. Hays, Graham Johnson, Perry M. Novak, Daniel F. Ortwine
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Patent number: 5061802Abstract: New 17.beta.-aminobenzoyl-4-aza-5.alpha.-androst-1-en-3-ones as benign prostatic hypertrophy agents of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.2 is phenyl substituted with --N(R.sup.3).sub.2, which can be protected, where R.sub.3 is independently H or C.sub.1 -C.sub.4 alkyl, wherein the phenyl ring can also be further substituted by C.sub.1 -C.sub.4 alkyl, wherein the dotted line can represent a double bond, and pharmaceutically acceptable salts thereof, and a pharmaceutical formulation thereof. The above compounds are active as benign prostatic hypertrophy therapy agents and are useful topically for the treatment of acne, seborrhea, female hirsutism, and particularly effective systemically in the treatment of benign prostatic hypertrophy.Type: GrantFiled: June 20, 1990Date of Patent: October 29, 1991Assignee: Merck & Co. Inc.Inventors: Nathan G. Steinberg, Gary H. Rasmusson, Thomas N. Salzmann
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Patent number: 5061801Abstract: Described is a new intermediate and new process for preparing 3-oxo-4-aza-androst-1-ene 17.beta.-ketones. The process involves converting the corresponding 17.beta.-alkyl carboxylate to the N-methoxy-N-methyl carboxamide and reacting this with an appropriate Grignard reagent to form the desired ketone. The reaction can be conducted in "one pot", thus eliminating isolation of intermediates and avoiding the use of less stable intermediates, e.g., acid chlorides, acyl imidazolides and the like. The intermediate has the formula: ##STR1## wherein R.sup.1 is hydrogen.Type: GrantFiled: September 24, 1990Date of Patent: October 29, 1991Assignee: Merck & Co., Inc.Inventors: John M. Williams, Ulf H. Dolling
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Patent number: 5061803Abstract: Disclosed is a new process for making 17-beta branched alkanoyl-3-oxo-4-aza-5-.alpha.-androst-1-enes, agents for treating benign prostatic hypertrophy (BPH), by reacting methyl 3-oxo-4-aza-5-.alpha.-androst-1-ene-17-beta carboxylate with isobutylmagnesium bromide in the novel presence of the hexamethyldisilazane (HMDS). Use of the HMDS results in higher yield and less by-products as opposed to the standard Grignard reaction in the absence of HMDS.Type: GrantFiled: September 24, 1990Date of Patent: October 29, 1991Assignee: Merck & Co., Inc.Inventor: John M. Williams
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Patent number: 5049562Abstract: 17.beta.-Acyl-4-aza-5.alpha.-androst-1-ene-3-ones of the formula ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.2 is monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents;and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, androgenic alopecia, prostatic carcinoma and benign prostatic hypertrophy.Type: GrantFiled: August 21, 1989Date of Patent: September 17, 1991Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 5021575Abstract: A process for introducing a 1,2 double bond into a compound of the formula ##STR1## which comprises the process of (a) treating the compound of formula I with oxalyl chloride; (b) brominating the product of step (a) followed by in situ dehydrobromination; (c) deprotecting the product of step (b) to yield the .alpha. and .beta. isomers; (d) dehydrobrominating the product of step (c), which results in the introduction of a double bond at the 1,2 position.Type: GrantFiled: November 13, 1989Date of Patent: June 4, 1991Assignee: Merck & Co., Inc.Inventors: Anthony O. King, Robert K. Anderson, Richard E. Shuman, Leonard M. Weinstock
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Patent number: 4966971Abstract: To prepare the compound (I), a lithiation of the compound (II) is performed, an aldehyde (IV) is reacted with the compound (III) formed, leading to the secondary alcohol (V) which is subjected to a reduction leading to the compound (VI), which is then subjected to a hydrolysis (of the dioxolane group)/cyclization/dehydration reaction. The procedure may be followed by a nucleophilic substitution reaction of the chlorine. The compounds (a) below exhibit antitumor activity. ##STR1## R=C.sub.1 -C.sub.3 alkyl; Ar=aromatic or polycyclic aromatic group; R.sub.1 and r.sub.2 =H or C.sub.1 -C.sub.3 alkyl; and n=2 to 4. No drawing.Type: GrantFiled: November 14, 1988Date of Patent: October 30, 1990Assignee: Centre National de la Recherche Scientifique (C.N.R.S.)Inventors: Emile R. B. Bisagni, Marilys Greletepouse Rautureau
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Patent number: 4888336Abstract: Invented are 4-aza-5-alpha-8(14)-17 substituted-androsten-3-ones having an 8(14), 7(8), or 16(17) double bond, optionally also having a 1(2) double bond, pharmaceutical compositions containing the compounds, and methods of using these compounds to inhibit steroid 5-alpha-reductase.Type: GrantFiled: July 28, 1987Date of Patent: December 19, 1989Assignee: SmithKline Beckman CorporationInventors: Dennis A. Holt, Mark A. Levy, Brian W. Metcalf
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Patent number: 4874803Abstract: The present invention comprises reaction products resulting from the reaction of hydrazido-substituted or certain amino-substituted polymer stabilizers and cyclic dianhydrides, as well as the use of such products. The polymer stabilizers of the invention are useful for protecting a large variety of synthetic polymeric organic materials from the degradative effects of heat, light and oxygen. Some of the modifiers are flame retardants and many are metal deactivators in addition to their primary activity.Type: GrantFiled: September 21, 1987Date of Patent: October 17, 1989Assignee: Pennwalt CorporationInventors: Arthur L. Baron, Terry N. Myers, Jerome Wicher
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Patent number: 4859681Abstract: 17.beta.-Acyl-4-aza-5.alpha.-androst-1-en-3-ones of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.2 is a monovalent radical selected from straight carbons, or monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents, aralkyl selected from benzyl and phenethyl and heterocyclic selected from 2- or 4-pyridyl, 2-pyrrolyl, 2-furyl or thiophenyl;and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.Type: GrantFiled: December 3, 1987Date of Patent: August 22, 1989Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 4845104Abstract: The compounds of formula (I) ##STR1## wherein R is selected from hydrogen, methyl or ethyl, and R.sup.1 is C.sub.1-12 straight or branched chain alkyl wherein one of the hydrogens is substituted by hydroxy, carboxylic acid or C.sub.1-4 alkyl ester, and A is --CH.sub.2 --CH.sub.2 or --CH.dbd.CH--, and pharmaceutical formulations of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism or benign prostatic hypertrophy.Type: GrantFiled: November 20, 1986Date of Patent: July 4, 1989Assignee: Merck & Co., Inc.Inventors: Josephine R. Carlin, Gary H. Rasmusson, W. J. A. VandenHeuvel
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Patent number: 4785103Abstract: A compound represented by the following formula ##STR1## wherein A represents a hydrogen atom or a lower alkanoyl group, Z represents an oxygen atom or the group ##STR2## in which R represents a hydrogen atom or a lower alkyl group, and X represents a halogen atom, the compound being useful for controlling androgen-dependent diseases, particularly for preventing prostatic hypertrophy.Type: GrantFiled: February 27, 1986Date of Patent: November 15, 1988Assignee: Teikoku Hormone Mfg. Co., Ltd.Inventors: Kenyu Shibata, Nobuaki Yamakoshi, Naoyuki Koizumi, Shigehiro Takegawa, Eiichiro Shimazawa, Mamoru Mieda
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Patent number: 4760071Abstract: This invention is for the compound 17.beta.-(N-t-butylcarbamoyl)-4-aza-5.alpha.-androst-1-en-3-one, pharmaceutical compositions containing the compound, methods of inhibiting testosterone 5.alpha.-reductase with the compound and methods of treating hyperandrogenic conditions with the compound, particularly benign prostatic hypertrophy.Type: GrantFiled: November 21, 1985Date of Patent: July 26, 1988Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 4739062Abstract: A new widely-applicable method has been found for synthesis of 9,10-anthraquinones and similar chemical compounds of wide use in industry and pharmacology, by reacting suitable aromatic substrates with activated dicarboxylic acids (more particularly dichlorides) in the presence of metal halides. The special characteristics of the reaction are the good yields, high selectivity, the possibility of operating in a single reactor and the use of starting compounds which are cheap and easily available on the market.Type: GrantFiled: June 27, 1986Date of Patent: April 19, 1988Assignee: Consiglio Nazionale Delle RicercheInventors: Franca Bigi, Giovanni Casiraghi, Giuseppe Casnati, Giovanni Sartori
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Patent number: 4732897Abstract: The present invention relates to new 4-aza-17.beta.-substituted 5.alpha.-androstan-3-ones, to a process for their preparation, to pharmacological compostions containing them, and to the use of said compounds as inhibitors of androgen action by means of testosterone 5-reductase inhibition.Type: GrantFiled: February 3, 1986Date of Patent: March 22, 1988Assignees: Farmitalia Carlo Erba, S.p.A., Consiglio Nazionale Delle RicercheInventors: Gianfranco Cainelli, Giorgio Martelli, Mauro Panunzio, Giuseppe Spunta, Giuliano Nannini, Enrico di Salle
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Patent number: 4539326Abstract: The present invention relates to novel 5-oxo-5H-[1]benzopyrano[2,3-b]pyridine derivatives useful for effective medicines for the treatment of various connective tissue diseases such as chronic rheumatoid arthritis and varieties of inflammatory diseases caused by immunoreaction, which have the following formula: ##STR1## wherein R is the same or different and represents hydrogen, alkyl, alkoxy, nitro, hydroxyl, acyl, hydroxyalkyl, halogen with the proviso that m is 1,2 or 3, or a tetramethylene (--(CH.sub.2).sub.4 --) or butadienylene (--CH.dbd.CH--CH.dbd.CH--) group which, in conjunction with two adjacent carbon atoms on the ring, forms a six-membered ring with the proviso that m is 1; n is 1 or 2, or a physiologically acceptable salt or ester thereof.Type: GrantFiled: July 5, 1983Date of Patent: September 3, 1985Assignee: Takeda Chemical Industries, Ltd.Inventors: Akira Nohara, Seiji Kuzuna
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Patent number: 4467091Abstract: Novel N-(4-pyridyl)acetamide derivatives having the formula ##STR1## [where R.sup.1 and R.sup.2 are aryl or heteroarly (optionally linked together by a lower alkylene bridge) or one of R.sup.1 and R.sup.2 is aryl or heteroaryl and the other of R.sup.1 and R.sup.2 is lower alkyl or ar(lower)alkyl, R.sup.3 and R.sup.4 are each hydrogen or lower alkyl] and their nontoxic acid addition salts are described. They are chemical intermediates for the preparation of 4-pyridinamine derivatives having the formula ##STR2## which show CNS activity and may be used as antidepressant drugs.Type: GrantFiled: January 28, 1983Date of Patent: August 21, 1984Assignee: John Wyeth & Brother LimitedInventors: Edwin T. Edington, Alan C. White
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Patent number: 4377584Abstract: 4-Aza-17.beta.-substituted-5.alpha.-androstan-3-ones and their A-homo analogs of the formula: ##STR1## where Formula (I) may also have the structure of partial Formulas (II) and/or (III);and pharmaceutically acceptable salts of the above compounds are active as testosterone 5.alpha.-reductase inhibitors, and thus useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.Type: GrantFiled: September 23, 1980Date of Patent: March 22, 1983Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, David B. R. Johnston, Glen E. Arth, deceased
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Patent number: 4220775Abstract: A method of preparing a compound of the formula: ##STR1## where Formula (I) may also have the structure of partial Formula (III); wherein, ##STR2## R' is hydrogen or methyl; R" is hydrogen or .beta.-methyl;R'" is .beta.-methyl or hydroxy;Z is (1) oxo;(2) .beta.-hydrogen and .alpha.-hydroxy; or .alpha.-hydrogen or .alpha.-hydroxyl and(3) (Y).sub.n Q where n=0 or 1, Y is a straight or branched hydrocarbon chain of 1 to 12 carbon atoms andQ is ##STR3## where R.sup.8 is, ##STR4## where the dashed bond replaces the 17.alpha. hydrogen; (6) cyano; or(7) tetrazolyl;and pharmaceutically acceptable salts of the above compounds;CHARACTERIZED IN THAT(I.) a compound of the formula: ##STR5## , where A has the meanings above except --CH.dbd.CH--, is (1) treated with an oxidizing agent at reduced temperatures to form the corresponding 5-oxo-3,5-seco-androstan-3-oic acid compound;(2) treating the product of step (1) with an amine of formula: R.sup.1 NH.sub.Type: GrantFiled: March 15, 1979Date of Patent: September 2, 1980Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, David B. R. Johnston, Donald F. Reinhold, Torleif Utne, Ronald B. Jobson
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Patent number: 4200636Abstract: The invention relates to new 3-amino-17a-aza-D-homo-5.alpha.-androstane derivatives of the general formula I ##STR1## wherein R.sub.1 represents a methylene or an >N--CH.sub.3 group, and n stands for 1 or 2, and the acid addition salts and the quaternary salts of the general formula ##STR2## thereof, wherein R.sub.2 stands for an alkyl or alkenyl group having from 1 to 4 carbon atoms, and A represents a halogen atom, provided that if R.sub.1 stands for an >N--CH.sub.3 group, R.sub.2 is attached to the nitrogen of that >N--CH.sub.3 group. The new compound possess a non-polarizing neuromuscular blocking activity and have a short activity period.Type: GrantFiled: August 17, 1978Date of Patent: April 29, 1980Assignee: Richter Gedeon Vegyeszeti Gyar Rt.Inventors: Zoltan Tuba, Maria Marsai, Sandor Gorog, Katalin Biro, Egon Karpati, Laszlo Szporny
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Patent number: 4158059Abstract: The invention relates to novel dibenzo[1,2;5,6] cyclohepta pyridine or -pyrrole derivatives, dibenzo[2,3;6,7] oxepino pyridine or pyrrole derivatives, dibenzo[2,3;6,7] thiepino pyridine or pyrrole derivatives and dibenzo[b,f] pyrido or pyrrolo azepine derivatives of general formula: ##STR1## as well as the pharmaceutically acceptable salts and nitrogen oxides thereof, whereinR.sub.1, r.sub.2, r.sub.3 and R.sub.4 each represent hydrogen, hydroxy, halogen, an alkyl (1-6 C) group, an alkoxy or alkylthio group in which the alkyl group contains 1-6 C-atoms, or a trifluoromethyl group,R.sub.5 represents hydrogen, an alkyl group with 1-6 carbon atoms or an aralkyl group with 7-10 carbon atoms,M is the number 1 or 2,X represents oxygen, sulphur, the group ##STR2## or the group --CH.sub.2 -- and R.sub.6 represents hydrogen or a lower alkyl group (1-4 C),having CNS-depressant activity and excellent antihistamine and antiserotonin activities.Type: GrantFiled: June 23, 1978Date of Patent: June 12, 1979Assignee: Akzona IncorporatedInventor: Willem J. van der Burg