The Six-membered Hetero Ring Shares Ring Members With One Other Cyclo Only Patents (Class 546/77)
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Patent number: 5886184Abstract: Disclosed is a new process for producing finasteride which involves reacting the magnesium halide salt of 17.beta.-carboalkoxy-4-aza-5.alpha.-androst-1-en-3-one with t-butylamino magnesium halide, present in at least a 2:1 molar ratio to the ester, formed from t-butyl amine and an aliphatic/aryl magnesium halide at ambient temperature in an inert organic solvent under an inert atmosphere followed by heating and recovering the product finasteride.Also disclosed are two polymorphic crystalline Forms I and II of finasteride, and methods of their production.Type: GrantFiled: March 26, 1997Date of Patent: March 23, 1999Assignee: Merck & Co., Inc.Inventors: Ulf H. Dolling, James A. McCauley, Richard J. Varsolona
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Patent number: 5843682Abstract: Novel derivatives of LSD having the formula ##STR1## wherein R.sub.1 is an alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 carbon atom;R.sub.2 is a bond or ##STR2## wherein R.sub.3 is alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms, preferably an alkyl group having 2 or 5 carbon atoms; Z is an immunogenic carrier substance, an enzyme donor polypeptide or a label selected from the group consisting of an enzyme, a substance having fluorescent or luminescent properties and a radioactive substance; and n is 1 to p where p equals MW of Z/1000. The derivatives include maleimide conjugates of an immunogenic poly(amino acid), an enzyme donor polypeptide or a labeling substance such as an enzyme, a fluorescent substance or a radioactive substance. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and their conjugate derivatives are also disclosed.Type: GrantFiled: November 20, 1995Date of Patent: December 1, 1998Assignee: Boehringer Mannheim CorporationInventors: Gerald F. Sigler, Riaz Rouhani, David Davoudzaheh
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Patent number: 5843953Abstract: Compounds of formula (I) wherein: the dotted line indicates that a double bond may be present or absent; R.sup.1 is H, methyl or ethyl; R.sup.2 is .alpha.- or .beta.-C.sub.1-10 straight or branched alkyl; R.sup.3 is CO.sub.2 H, CN, CO.sub.2 R.sup.4, COHNR.sup.4, or CON(R.sup.4).sub.2 ; R.sup.4 is H, C.sub.1-10 straight or branched alky, aryl, heteroaryl, or aralkyl; Aryl is phenyl, substituted phenyl, naphthyl, or biphenyl; Heteroaryl is pyridil, pyrrolyl, thienyl, furanyl or quinolinyl; and Aralkyl is C.sub.1-10 alkyl substituted with one to three phenyl or substituted phenyl moieties; and their pharmaceutically acceptable salts are described. These compounds are 5.alpha.-reductase type 1 inhibitors. They may be used for treating conditions associated with an excess of DHT, either alone or in combination with other 5.alpha.-reductase inhibitors.Type: GrantFiled: March 24, 1997Date of Patent: December 1, 1998Assignee: Merck & Co., Inc.Inventors: Donald W. Graham, Josephine R. Carlin, Richard L. Tolman, Shuet-Hing Lee Chiu
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Patent number: 5817818Abstract: The present invention relates to compounds of formula (I), wherein carbons 1 and 2 are joined by either a single or a double bond; R.sup.1 is hydrogen or methyl; R.sup.2 is hydrogen or methyl; R.sup.3 is (A) or (B) wherein X, W, Z, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are various groups, and pharmaceutically acceptable solvates thereof and their use in the treatment of androgen responsive and mediated diseases.Type: GrantFiled: March 14, 1996Date of Patent: October 6, 1998Assignee: Glaxo Wellcome Inc.Inventors: Kenneth William Batchelor, Stephen Vernon Frye
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Patent number: 5763361Abstract: The novel compounds of the present invention are those of structural formula I: ##STR1## or a pharmaceutically acceptable salt, or stereoisomer thereof, which are inhibitors of 5.alpha.-reductase, particularly 5.alpha.-reductase type 1. The compounds of formula I are useful in the systemic, including oral, or parenteral or topical treatment of hyperandrogenic conditions such as acne vulgaris, seborrhea, androgenic alopecia which includes female and male pattern baldness, female hirsutism, benign prostafic hyperplasia, and the prevention and treatment of prostatic carcinoma, as well as in the treatment of prostatitis. Methods of using the compounds of formula I for the treatment of hyperandrogenic conditions such as acne vulgaris, seborrhea, androgenic alopecia, male pattern baldness, female hirsutism, benign prostatic hyperplasia, and the prevention and treatment of prostatic carcinoma, as well as the treatment of prostatitis are provided, as well as pharmaceutical compositions for the compounds of formula I.Type: GrantFiled: October 21, 1996Date of Patent: June 9, 1998Assignee: Merck & Co., Inc.Inventors: Georgianna Harris, Richard L. Tolman, Soumya P. Sahoo
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Patent number: 5760045Abstract: Described are new delta-17 and delta-20 olefic and saturated 17.beta.-substituted 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 hyperandrogenic related disorders.Type: GrantFiled: February 6, 1996Date of Patent: June 2, 1998Assignee: Merck & Co., Inc.Inventors: Donald W. Graham, Susan D. Aster, Richard L. Tolman
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Patent number: 5739137Abstract: Compounds of formula (I) are inhibitors of the 5.alpha.-reductase 1 isozyme, and are useful alone, or in combination with a 5.alpha.-reductase 2 inhibitor, for the treatment of androgenic sensitive disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.Type: GrantFiled: February 28, 1996Date of Patent: April 14, 1998Assignee: Merck & Co., Inc.Inventors: Philippe L. Durette, William K. Hagmann, Thomas J. Lanza, Jr., Soumya P. Sahoo, Gary H. Rasmusson, Richard L. Tolman, Derek Von Langen
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Patent number: 5719159Abstract: The present invention provides compounds of formula (D wherein the symbol - - - represents a single or a double bond; R is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group; A is a single bond or a straight or branched C.sub.1 -C.sub.6 alkylene chain; B is a straight or branched C.sub.1 -C.sub.12 alkylene group optionally substituted by one or more aryl groups or fluorine atoms; W is a group R.sub.1 or (a) wherein R.sub.1 is a straight or branched C.sub. -C.sub.6 alkyl group unsubstituted or substituted by one or more fluorine atoms, provided that at least a fluorine atom is present in B or W. The compounds of the invention are useful as testosterone 5.alpha.-reductase inhibitors.Type: GrantFiled: May 31, 1996Date of Patent: February 17, 1998Assignee: Pharmacia S.p.A.Inventors: Achille Panzeri, Marcella Nesi, Enrico Di Salle
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Patent number: 5719158Abstract: Compounds of the Formula I ##STR1## are inhibitors of the 5.alpha.-reductase 1 isozyme, and are useful alone, or in combination with a 5.alpha.-reductase 2 inhibitor, for the treatment of androgenic sensitive disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.Type: GrantFiled: June 5, 1995Date of Patent: February 17, 1998Assignee: Merck & Co., Inc.Inventors: Philippe L. Durette, William K. Hagmann, Thomas J. Lanza, Jr., Soumya P. Sahoo, Gary H. Rasmusson, Richard L. Tolman, Derek von Langen
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Patent number: 5710275Abstract: Described are new 7.beta.-substituted 4-aza-5.alpha.-androstan-3-ones and related compounds as 5.alpha.-reductase inhibitors.Type: GrantFiled: April 3, 1995Date of Patent: January 20, 1998Assignee: Merck & Co., Inc.Inventors: Raman K. Bakshi, Gary H. Rasmusson, Richard L. Tolman, Gool F. Patel, Georgianna S. Harris, Donald W. Graham, Bruce E. Witzel
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Patent number: 5696266Abstract: The novel process of this invention involves the reduction of certain .DELTA.-5 steroidal alkenes to selectively produce either the 5.alpha. or 5.beta. reduction products. Particularly, this invention involves reduction of .DELTA.-5 steroidal alkenes using a rhodium based catalyst in the presence of hydrogen to selectively yield 5.alpha. steroids or alternatively reduction of .DELTA.-5 steroidal alkenes in an ionizing medium with a trialkylsilane to selectively yield 5.beta. steroids.Type: GrantFiled: July 28, 1995Date of Patent: December 9, 1997Assignee: Merck & Co., Inc.Inventors: Guy R. Humphrey, Ross A. Miller
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Patent number: 5693647Abstract: Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.Type: GrantFiled: June 5, 1995Date of Patent: December 2, 1997Assignee: Ligand Pharmaceuticals IncorporatedInventors: Todd K. Jones, Lin Zhi, Christopher M. Tegley, David T. Winn, Lawrence G. Hamann, James P. Edwards, Sarah J. West
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Patent number: 5693810Abstract: Described are new 17.beta.-carboxanilides of 4-aza-5.alpha.-androstan-3-ones and related compounds of structural formula I: ##STR1## and the use of such compounds as 5.alpha.-reductase inhibitors for treatment of benign prostatic hyperplasia acne, seborrhea, female hirsutism, prostatitis, and prostatic carcinoma and other hyperandrogenetic related disorders.Type: GrantFiled: March 21, 1995Date of Patent: December 2, 1997Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Raman K. Bakshi, Gool F. Patel
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Patent number: 5693809Abstract: Described are new 16-substituted and 7,16-disubstituted 4-aza-5.alpha.-androstan-3-ones and related compounds as 5.alpha.-reductase inhibitors.Type: GrantFiled: May 12, 1995Date of Patent: December 2, 1997Assignee: Merck & Co., Inc.Inventors: Philippe L. Durette, William Hagmann, Gary H. Rasmusson, Richard L. Tolman, Ihor E. Kopka, Soumya P. Sahoo, Craig K. Esser, Nathan G. Steinberg, Donald W. Graham, Bruce E. Witzel
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Patent number: 5688808Abstract: Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.Type: GrantFiled: June 5, 1995Date of Patent: November 18, 1997Assignee: Ligand Pharmaceuticals IncorporatedInventors: Todd K. Jones, David T. Winn, Lin Zhi, Lawrence G. Hamann, Christopher M. Tegley, Charlotte L. F. Pooley
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Patent number: 5670643Abstract: The present invention relates to a process for the preparation of finasteride, the compound of formula (I), comprising the reaction of the compound of formula (II) with t-butylamine.Type: GrantFiled: March 16, 1995Date of Patent: September 23, 1997Assignee: Glaxo Wellcome Inc.Inventors: Roman Davis, Alan Millar
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Patent number: 5665726Abstract: 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 3, 1995Date of Patent: September 9, 1997Assignee: Schering CorporationInventors: John J. Piwinski, Ashit K. Ganguly, Michael J. Green, Jesse Wong
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Patent number: 5658922Abstract: Compounds of formula (I), wherein: R.sup.1 is selected from the group consisting of hydrogen and methyl; R.sup.2 is selected from the group consisting of methyl and ethyl; R.sup.3 is selected from the group consisting of hydrogen and methyl; and the C1-C2 carbon-carbon bond may be a single or double bond. Such compounds are useful in the treatment of pathologic conditions that benefit from blockade of isozymes of 5.alpha.-reductase.Type: GrantFiled: October 31, 1995Date of Patent: August 19, 1997Assignee: Merck & Co., Inc.Inventors: Philippe L. Durette, Soumya P. Sahoo
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Patent number: 5652365Abstract: A process for producing polymorphic Form I of finasteride, 17B-(N-tert-butyl carbamoyl)-4-aza-5.alpha.-androst-1-en-3-one, in substantially pure form comprising the steps of: (1) crystallization from a solution of finasteride in a water immiscible organic solvent and 0% or more by weight of water, producing solvated and non-solvated finasteride in solution, such that the amount of organic solvent and water in the solution is sufficient to cause the solubility of the non-solvated form of finasteride to be exceeded and the non-solvated form of finasteride to be less soluble than any other form of finasteride in the organic solvent and water solution: (2) recovering the resultant solid phase; and (3) removing the solvent therefrom; wherein the water immiscible organic solvent is ethyl acetate or isopropyl acetate and the amount of water in the solvent mixture is below 4 mg./ml.Type: GrantFiled: March 30, 1995Date of Patent: July 29, 1997Assignee: Merck & Co., Inc.Inventors: James A. McCauley, Richard J. Varsolona
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Patent number: 5639741Abstract: Novel amino substituted 4-azasteroid 5.alpha.-reductase inhibitors of formula (I). ##STR1## wherein A is (a), (b) or (c), are claimed as well as pharmaceutically acceptable salts and formulations thereof. These compounds are effective in inhibiting testosterone 5.alpha.-reductase(s) and are thus useful in the treatment of a number of hyperandrogenic conditions including benign prostatic hypertrophy, acne, seborrhea, female hirsutism, and male and female pattern baldness (alopecia).Type: GrantFiled: March 20, 1995Date of Patent: June 17, 1997Assignee: Merck & Co., Inc.Inventors: Bruce E. Witzel, Jeffrey P. Bergman, Richard L. Tolman
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Patent number: 5620993Abstract: This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha-1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral fining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.Type: GrantFiled: June 7, 1995Date of Patent: April 15, 1997Assignee: Merck & Co., Inc.Inventors: Michael A. Patane, Mark G. Bock, Roger M. Friedinger
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Patent number: 5620986Abstract: Novel substituted 4-azasteroid 5-.alpha.-reductase inhibitors of formula (I), wherein A is (a), (b) or (c), are claimed as well as pharmaceutically acceptable salts and formulations thereof. These compounds are effective inhibitors of testosterone 5.alpha.-reductase(s) and are thus useful in the treatment of a number of hyperandrogenic conditions including benign prostatic hypertrophy, acne, seborrhea, female hirsutism, and male and female pattern baldness (alopecia).Type: GrantFiled: March 1, 1995Date of Patent: April 15, 1997Assignee: Merck & Co., Inc.Inventors: Bruce E. Witzel, Richard L. Tolman
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Patent number: 5612356Abstract: A heterocycle-containing carbonic acid derivative represented by the following general formula (I): ##STR1## or a physiologically acceptable salt thereof which exhibits an excellent preventive and therapeutic effect against various diseases, and an intermediate which is useful for the production of the heterocycle-containing carbonic acid derivative.Type: GrantFiled: April 25, 1995Date of Patent: March 18, 1997Assignee: Eisai Co., Ltd.Inventors: Hiroyuki Yoshimura, Mitsuo Nagai, Shigeki Hibi, Koichi Kikuchi, Ieharu Hishinuma, Junichi Nagakawa, Makoto Asada, Norimasa Miyamoto, Takayuki Hida, Aichi Ogasawara, Isao Yamatsu
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Patent number: 5610162Abstract: Compounds of Formula (I), ##STR1## wherein X is sulfur or oxygen are inhibitors of the 5.alpha.-reductase enzyme and isozymes thereof. The compounds are useful for the treatment of hyperandrogenic disease conditions and diseases of the skin and scalp.Type: GrantFiled: November 17, 1994Date of Patent: March 11, 1997Assignee: Merck & Co., Inc.Inventors: Bruce E. Witzel, Gary H. Rasmusson, Richard L. Tolman, Shu Shu Yang
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Patent number: 5597832Abstract: A tetracyclic compound of the formula: ##STR1## wherein A and the atoms to which it is attached and the optional double bond represent a mono- or di-heterocyclic ring selected from: ##STR2## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X are specifically defined, which compounds are useful in the treatment of dopamine-related neurological, psychological and cardiovascular disorders as well as in the treatment of substance abuse and other addictive behavior disorders, cognitive impairment and attention deficit disorder.Type: GrantFiled: November 10, 1994Date of Patent: January 28, 1997Assignee: Abbott LaboratoriesInventors: Michael R. Michaelides, Yufeng Hong
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Patent number: 5595996Abstract: Compounds of the Formula I ##STR1## wherein: the dotted line indicates that a double bond may be present or absent; R.sup.1 is H, methyl or ethyl; R.sup.2 is .alpha.- or .beta.-C.sub.1-10 straight or branched alkyl; R.sup.3 is CO.sub.2 H, CN, CO.sub.2 R.sup.4, COHNR.sup.4, or CON(R.sup.4).sub.2 ; R.sup.4 is H, C.sub.1-10 straight or branched alkyl, aryl, heteroaryl, or aralkyl; Aryl is phenyl, substituted phenyl, naphthyl, or biphenyl; Heteroaryl is pyridyl, pyrrolyl, thienyl, furanyl or quinolinyl; and Aralkyl is C.sub.1-10 alkyl substituted with one to three phenyl or substituted phenyl moieties; and their pharmaceutically acceptable salts are described. These compounds are 5.alpha.-reductase type 1 inhibitors. They may be used for treating conditions associated with an excess of DHT, either alone or in combination with other 5.alpha.-reductase inhibitors.Type: GrantFiled: October 25, 1994Date of Patent: January 21, 1997Assignee: Merck & Co., Inc.Inventors: Donald W. Graham, Josephine R. Carlin, Shuet-Hing L. Chiu, Richard L. Tolman
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Patent number: 5585383Abstract: By this invention, there is provided a process for producing crystalline 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one of structural formula (I) from 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one oil. ##STR1## This crystallization process of the present invention comprises crystallization of the oil optionally containing residual solvent with vigorous but controlled agitation. Preferably, this crystallization process is carried out at select and controlled temperatures. Further, 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one has been found to exist in at least two novel polymorphic nonsolvated forms, herein referred to as Form I and Form II. Form I can be prepared pure by careful control of the crystallization process.Type: GrantFiled: May 3, 1995Date of Patent: December 17, 1996Assignee: Merck & Co., Inc.Inventors: Andrew L. Forman, Sean R. Holihan, Guy R. Humphrey, David M. Lashen, James A. McCauley, Paul F. McKenzie, Ross A. Miller, Pascal H. Toma
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Patent number: 5583138Abstract: The invention relates to novel 17.beta.-substituted 4-azaandrostane derivatives of general formula (I), ##STR1## wherein R means hydrogen or a C.sub.1-3 alkyl group;R.sup.1 and R.sup.2 are the same or different and stand for hydrogen or a C.sub.1-4 alkyl group with the proviso that both can mean hydrogen only in the case when n is higher than 5; orR.sup.1 and R.sup.2 together means an .alpha.,.omega.-alkylene group containing 5 to 7 carbon atoms, the terminal carbon atoms of said alkylene group being bound to the same ring carbon atom;n is 4, 5, 6 or 7; and--- bond line represents a single or double bond.Furthermore, the invention relates to pharmaceutical composition containing these compounds as well as a process for the preparation of the compounds of general formula (I).The compounds of general formula (I) exert a 5.alpha.Type: GrantFiled: March 23, 1995Date of Patent: December 10, 1996Assignee: Richter Gedeon Vegyeszeti Gyar Rt.Inventors: Zolt an Tuba, Judit Horv ath, L aszl o Koll ar, M aria Lovas n ee Marsai, G abor Balogh, Attila Csehi, Andr as J avor, Gy orgy Hajo os, L aszl o Szporny
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Patent number: 5583228Abstract: The invention relates to novel 4-azaandrostene intermediates of formula (I), ##STR1## wherein R is hydrogen or a C.sub.1-3 alkyl group;X is chlorine, bromine or iodine; and the---- bond line is a single or double bond.Type: GrantFiled: December 6, 1995Date of Patent: December 10, 1996Assignee: Richter Gedeon Vegyeszeti Gyar Rt.Inventors: Zolt an Tuba, Judit Horv ath, J anos Sz eles, M aria Lovas n ee Marsai, G abor Balogh
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Patent number: 5578726Abstract: 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, consisting of reducing the corresponding androsteneone with lithium and liquid ammonia, contacting the product with an isomerizing agent, oxidizing the product to a seco acid and reacting that seco acid with an amine to cyclize to form 4-aza-5.alpha.-androstan-3-ones.Type: GrantFiled: November 10, 1994Date of Patent: November 26, 1996Assignee: Merck & Co., Inc.Inventors: Raman K. Bakshi, Gary H. Rasmusson
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Patent number: 5571817Abstract: 17.beta.-N-monosubstituted-carbamoyl-4-5.alpha.-androst-1-en-3-ones of the formula ##STR1## wherein R.sup.1 is selected from hydrogen, methyl and ethyl and R.sup.2 is a branched chain alkyl of from 3-12 carbons, and R', R", R'" are hydrogen or methyl are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of androgenic alopecia.Type: GrantFiled: July 20, 1993Date of Patent: November 5, 1996Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 5567708Abstract: 17.beta.-N-monosubstituted-carbamoyl-4-5.alpha.-androst-1-en-3-ones of the formula ##STR1## wherein R.sup.1 is selected from hydrogen, methyl and ethyl and R.sup.2 is a branched chain alkyl of from 3-12 carbons, and R', R", R"' are hydrogen or methyl are active as testosterone 5.alpha.-reductase inhibitors and thus are useful topically for treatment of androgenic alopecia.Type: GrantFiled: May 31, 1995Date of Patent: October 22, 1996Assignee: Merck & Co., Inc.Inventors: Gary H. Rasmusson, Glenn F. Reynolds
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Patent number: 5565467Abstract: The present invention relates to the compound of formula (I), ##STR1## also known as 17.beta.-N-(2,5-bis(Trifluoromethyl))phenylcarbamoyl-4-aza-5.alpha.-andros t-1-en-3-one, solvates thereof, its preparation, intermediates used in its preparation, pharmaceutical formulations thereof and its use in the treatment of androgen responsive and mediated diseases.Type: GrantFiled: March 16, 1995Date of Patent: October 15, 1996Assignee: Glaxo Wellcome Inc.Inventors: Kenneth W. Batchelor, Stephen V. Frye, George F. Dorsey, Jr., Robert A. Mook, Jr.
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Patent number: 5561124Abstract: The invention relates to substituted 17.alpha.-acyl steroidal 5.alpha.-reductase inhibiting compounds. The invention also relates to pharmaceutical compositions containing these compounds and their use for reducing prostate size and treating prostate adenocarcinoma. Further, the invention describes a process for making these compounds by heating the corresponding substituted 17.beta.-acyl steroid in a solvent, such as ethylene glycol or dimethyl sulfoxide (DMSO), in a base, such as sodium or potassium hydroxide.Type: GrantFiled: May 17, 1995Date of Patent: October 1, 1996Inventor: Robert L. Webb
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Patent number: 5536727Abstract: Compounds of Formula I ##STR1## wherein Z contains an ether or thioether moeity, are inhibitors of the 5.alpha.-reductase enzyme and isozymes thereof. The compounds are useful for the treatment of hyperandrogenic disease conditions and diseases of the skin and scalp.Type: GrantFiled: November 17, 1994Date of Patent: July 16, 1996Assignee: Merck & Co., Inc.Inventors: Bruce E. Witzel, Richard L. Tolman, Gary H. Rasmusson, Raman K. Bakshi, Shu Shu Yang
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Patent number: 5527807Abstract: Described are new 7.beta.-substituted 4-aza-5.alpha.-cholestan-3-ones and related compounds as 5.alpha.-reductase inhibitors.Type: GrantFiled: November 15, 1994Date of Patent: June 18, 1996Assignee: Merck & Co., Inc.Inventors: Raman K. Bakshi, Gary H. Rasmusson, Richard L. Tolman, Gool F. Patel, Georgianna Harris
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Patent number: 5527806Abstract: Invented are 17.beta.-substituted acyl-4-aza analogues of steroidal synthetic compounds, pharmaceutical compositions containing these compounds, and methods for using these compounds to inhibit steroid 5-.alpha.-reductase. Also invented are intermediates and processes used in preparing these compounds.Type: GrantFiled: November 21, 1994Date of Patent: June 18, 1996Assignee: SmithKline Beecham CorporationInventors: Dennis A. Holt, Mark A. Levy, Hye-Ja Oh
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Patent number: 5525608Abstract: Compounds of the formula ##STR1## are inhibitors of 5.alpha.-reductase and are useful alone or in combination with other active agents for the treatment of hyperandrogenic disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.Type: GrantFiled: April 20, 1994Date of Patent: June 11, 1996Assignee: Merck & Co., Inc.Inventors: Alan D. Adams, Gary H. Rasmusson, Nathan G. Steinberg
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Patent number: 5516779Abstract: Compounds of the formula ##STR1## are inhibitors of 5 .alpha.-reductase and are useful alone or in combination with other active agents for the treatment of hyperandrogenic disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.Type: GrantFiled: June 8, 1994Date of Patent: May 14, 1996Assignee: Merck & Co., Inc.Inventors: Derek Von Langen, Donald W. Graham, Richard L. Tolman
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Patent number: 5510485Abstract: Described are new 17.beta.-ester, amide and ketone 4-aza-5a-androstan-3-ones and related compounds and their use as 5a-reductase inhibitors for treatment of benign prostatic hyperplasia and other hyperandrogenetic related disorders.Type: GrantFiled: November 10, 1994Date of Patent: April 23, 1996Assignee: Merck & Co., Inc.Inventors: Donald W. Graham, Susan D. Aster, William Hagmann, Richard L. Tolman
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Patent number: 5510351Abstract: Described are delta 17 and delta 20 olefinic and saturated 17 Beta-substituted 4-aza-5 alpha-androstan-3-ones and related compounds having 5 alpha reductase inhibitors for treatment of benign prostatic hyperplasia and other hyperandrogenic related disorders.Type: GrantFiled: November 14, 1994Date of Patent: April 23, 1996Assignee: Merck & Co., Inc.Inventors: Donald W. Graham, Susan D. Aster, Richard L. Tolman
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Patent number: 5470976Abstract: The novel process of this invention involves the reduction of certain .DELTA.-5 steroidal alkenes to selectively produce either the 5.alpha. or 5.beta. reduction products. Particularly, this invention involves reduction of .DELTA.-5 steroidal alkenes using a rhodium based catalyst in the presence of hydrogen to selectively yield 5.alpha. steroids or alternatively reduction of .DELTA.-5 steroidal alkenes in an ionizing medium with a trialkylsilane to selectively yield 5.beta. steroids.Type: GrantFiled: September 7, 1994Date of Patent: November 28, 1995Assignee: Merck & Co., Inc.Inventors: Guy R. Humphrey, Ross A. Miller
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Patent number: 5468860Abstract: Disclosed is a new process for producing finasteride which involves reacting the magnesium halide salt of 17.beta.B-carboalkoxy-4-aza-5.alpha.-androst-1-en-3-one with t-butylamino magnesium halide, present in at least a 2:1 molar ratio to the ester, formed from t-butyl amine and an aliphatic/aryl magnesium halide at ambient temperature in an inert organic solvent under an inert atmosphere followed by heating and recovering said product finasteride.Also disclosed are two polymorphic crystalline Forms I and II of finasteride, and methods of their production.Type: GrantFiled: January 29, 1993Date of Patent: November 21, 1995Assignee: Merck & Co., Inc.Inventors: Ulf H. Dolling, James A. McCauley, Richard J. Varsolona
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Patent number: 5420136Abstract: A class of predominantly hydrophobic non-azo N-substituted 1,8-naphthalimide compounds, each bearing, at its 3-position, a nucleofuge and, at its 4-position, a heteroatomic electron-releasing group. The heteroatomic electron-releasing group is being characterized as having a heteroatom directly linked to the 4-position of the ring, and having at least one hydrogen directly attached to the heteroatom. Upon activation by an activating agent in an environment independent of the presence or absence of oxygen, these compounds generate activated species. The activated species initiate chemical changes in lipid bilayer membranes of viruses and other target cells. These changes can eradicate viruses and other target cells. The activated species can also cause structural changes in lipid and any associated proteins and polypeptides at a level beneath the surface of the membrane, leading to polymerization and crosslinking.Type: GrantFiled: August 9, 1993Date of Patent: May 30, 1995Assignee: MicroBioMed CorporationInventors: David E. Lewis, Ronald E. Utecht, Millard M. Judy, J. Lester Matthews
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Patent number: 5418238Abstract: A compound of formula (I): ##STR1## wherein R is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group;A is a single bond or a straight or branched C.sub.1 -C.sub.6 alkylene chain;R.sub.1 is a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group;R.sub.2 is a C.sub.1 -C.sub.6 alkyl group, a C.sub.5 -C.sub.7 cycloalkyl or a C.sub.6 -C.sub.10 cycloalkylalkyl group, aryl or a C.sub.7 -C.sub.10 arylalkyl group, or a C.sub.6 -C.sub.10 heterocyclylalkyl group;R.sub.3 is hydrogen, a C.sub.1 -C.sub.4 alkyl group or an aryl or a C.sub.7 -C.sub.10 arylalkyl group;Z is a C.sub.1 -C.sub.6 alkyl group, an --OR.sub.5 group wherein R.sub.5 is a C.sub.1 -C.sub.6 alkyl group, ##STR2## group wherein each of R.sub.6 and R.sub.7 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.5 -C.sub.7 cycloalkyl, phenyl or R.sub.6 and R.sub.7 taken together with the nitrogen to which they are linked form a pentatomic or hexatomic saturated heteromonocyclic ring; and the symbol represents a single or a double bond, is a testosterone 68 5.alpha.Type: GrantFiled: July 29, 1993Date of Patent: May 23, 1995Assignee: Farmitalia Carlo Erba S.R.L.Inventors: Achille Panzeri, Marcella Nesi, Enrico di Salle
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Patent number: 5407939Abstract: Compounds of formula (I) ##STR1## wherein: the symbol represents a single or a double bond;B is a bond or a straight or branched C.sub.1 -C.sub.6 alkylene chain;R is hydrogen or C.sub.1 -C.sub.4 alkyl;R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or benzyl;R.sub.2 isa) hydrogen, fluorine, C.sub.1 -C.sub.6 alkyl, C.sub.5 -C.sub.7 cycloalkyl or C.sub.6 -C.sub.9 cycloalkylalkyl; orb) aryl or C.sub.7 -C.sub.10 arylalkyl;R.sub.3 isa) hydrogen, fluorine or C.sub.1 -C.sub.4 alkyl; orb) aryl or C.sub.7 -C.sub.10 arylalkyl;R.sub.4 is hydrogen, fluorine, or is absent when Y is a double bond;R.sub.5 is hydrogen, fluorine or C.sub.1 -C.sub.6 alkyl; and when Y is a single bond, A is hydrogen, fluorine or ##STR2## wherein each of R.sub.6, R.sub.7 and R.sub.8 independently is hydrogen, fluorine or C.sub.1 -C.sub.6 alkyl; and when Y is a double bond, A is a ##STR3## wherein each of R.sub.6 and R.sub.7 is independently hydrogen, fluorine or C.sub.1 -C.sub.6 alkyl; with the proviso that at least one of the groups R, R.sub.1, R.Type: GrantFiled: July 29, 1993Date of Patent: April 18, 1995Assignee: Farmitalia Carlo Erba S.R.L.Inventors: Achille Panzeri, Marcella Nesi, Enrico Di Salle
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Patent number: 5380728Abstract: 17.beta.-N-monosubstituted-carbamoyl-4-aza-5.alpha.-androst-1-en-3-ones of the formula: ##STR1## wherein the dotted line can represent a double bond when present,R.sup.1 is selected from hydrogen, methyl and ethyl andR.sup.2 is CONHC(CH.sub.3).sub.2 CHO, andRa is methyl,are described as being useful for the treatment of benign prostatic hypertrophy.Type: GrantFiled: February 10, 1993Date of Patent: January 10, 1995Assignee: Merck & Co., Inc.Inventor: Gary H. Rasmusson
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Patent number: 5378710Abstract: 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: October 6, 1993Date of Patent: January 3, 1995Assignee: Ciba-Geigy Corp.Inventor: Michel Biollaz
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Patent number: 5359071Abstract: Compounds of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.1 is selected from the group consisting of hydrogen and C.sub.1-10 alkyl;R.sup.2 is selected from the group consisting of hydrogen and C.sub.1-10 alkyl;R.sup.3 is selected from the group consisting of C.sub.1-10 alkoxyl, C.sub.1-10 alkyl and cyano;R.sup.4 is selected from the group consisting of C.sub.1-10 alkenyloxyl, C.sub.1-10 alkoxyl, C.sub.1-10 alkyl, C.sub.1-10 alkylcarbamic, C.sub.1-10 alkylcarbonyloxyl, carbonyl, hydroxyl, and --NHR.sup.5, andR.sup.5 is selected from the group consisting of hydrogen and C.sub.1-10 alkylcarbonyl. Such compounds are useful as selective antagonists of testosterone 5.alpha.-reductase 1.Type: GrantFiled: March 12, 1993Date of Patent: October 25, 1994Assignee: Merck & Co., Inc.Inventors: Philippe L. Durette, Craig K. Esser, William Hagmann, Ihor E. Kopka
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Patent number: 5342948Abstract: The preparation of a compound of formula (I) ##STR1## wherein X is oxygen or sulphur; R.sub.1 is hydrogen or C.sub.1 -C.sub.6 alkyl; each of R.sub.2 and R.sub.3 is, independently, hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.5 or C.sub.6 cycloalkyl or C.sub.6 -C.sub.9 cycloalkylalkyl; R.sub.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 - or C.sub.6 cycloalkyl, C.sub.6 -C.sub.9 cycloalkylalkyl or aryl; and the symbol represents a single or a double bond; by a multi-step process is disclosed.Type: GrantFiled: March 19, 1993Date of Patent: August 30, 1994Assignee: Farmitalia Carlo Erba S.R.L.Inventors: Achille Panzeri, Lucio Ceriani, Pierluigi Griggi, Marcella Nesi