Abstract: 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.

Abstract: A process is described for the improved synthesis of the optically pure C.sub.10 -C.sub.18 fragment of the macrolide structure of the immunosuppressant FK-506. This compound is also useful as an intermediate for preparing FK-506 derivatives.

Abstract: 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.

Abstract: Described is a new L-679,934 (FK-506) antagonist, L-686,292, a C-15, C-31 bisdemethylated, derivative of L-683,590, produced under fermentation conditions utilizing the microorganism, Actinoplanacete sp. (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide reverses the immunosuppressant action of L-679,934 (FK-506), and can be used diagnostically as a tool to determine the presence of FK-506 macrolide type immunosuppressants in natural product broths, distinguishing such immunosuppressants from other chemical families such as the cycloporins.

Abstract: There is disclosed a child resistant blister package comprising a conventional blister package having cavities containing unit doses of medication. The blister package is adapted to receive a locking member which is slidably secured to the blister package to effectively prevent children from accessing the medication therein and yet is readily, slidably removed from the blister package by an adult to access medication therefrom.

Abstract: The present invention relates to the use of peptide analogues as inhibitors of their respective naturally occurring peptides. The structure of the peptide analogues is exemplified by an internal region of the N-terminus of humoral hypercalcemic factor hHCF, and truncations thereof: hHCF(14-34)NH.sub.2, hHCF(13-34)NH.sub.2, hHCF(12-34)NH.sub.2, hHCF(11-23)NH.sub.2, hHCF(10-34)NH.sub.2, hHCF(9-34)NH.sub.2, hHCF(8-34)NH.sub.2 and various amino acid substitutions.

Abstract: There is disclosed a child resistant bottle closure assemblage comprising an outer cap member, an inner cap member and an interlocking member disposed between the inner and outer cap members. When secured to a bottle in its normal, upright position, the outer cap member can be rotated without engaging the interlocking member so that the assemblage can not be removed from the bottle. When the bottle is inverted so that the interlocking member engages the outer cap member, rotation of the outer cap member results in removal of the entire assemblage from the bottle.

Abstract: 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.

Abstract: The present invention relates to the use of peptide hormone analogues as inhibitors of their respective naturally occurring peptide hormone. The structure of the peptide hormone analogues is exemplified by parathyroid hormone (PTH), wherein Lys.sup.13 is substituted to increase the biological activity of the PTH analogues. Thus, there are disclosed peptides having the formulae:PTH(7-34)NH.sub.2 ;[Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;[D-Trp.sup.12, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;[Nle.sup.8,18, D-Trp.sup.12, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;[Nle.sup.8,18, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ;desamino[Nle.sup.8,18, D-Trp.sup.12, Tyr.sup.34 ]PTH(7-34)NH.sub.2 ; and,desamino[Nle.sup.8,18, D-Trp.sup.12, Tyr.sup.34 ]PTH(8-34)NH.sub.2wherein Lys.sup.13 is modified in the epsilon-amino acid group by N,N-diisobutyl or 3-phenylpropanoyl.

Abstract: N-monosubstituted adamantyl/norbornanyl 17.beta.-carbamides of 3-carboxy-androst-3,5-dienes as testosterone 5.alpha.-reductase inhibitors of the formula: ##STR1## wherein R is a hydrocarbon radical selected from substituted or unsubstituted 1- or 2-adamantyl or 1-, 2- or 7-norbornanyl and pharmaceutically acceptable salts or esters thereof. Also described is a pharmaceutical formulation. 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.

Abstract: The present invention relates to the use of peptide analogues as inhibitors of their respective naturally occurring peptides. The structure of the peptide hormone analogues is exemplified by human humoral hypercalcemic factor (hHCF), wherein Lys.sup.13 or Lys.sup.11 is modified on the epsilon-amino group by biotin so as to produce HCF analogues which can inhibit the action of HCF.

Abstract: The present invention relates to the use of peptide analogues as inhibitors of their respective naturally occurring peptides. The structure of the peptide hormone analogues is exemplified by human humoral hypercalcemic factor (hHCF), wherein Lys.sup.13 is modified so as to produce HCF analogues which can inhibit the action of HCF.

Abstract: Fermentation of the microorganism Streptomyces sp. MA6751 (ATCC No. 55043) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields an N2-tetrazole .beta.-glucuronide analog which is also an A II antagonist useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Abstract: A child resistant unit dose package for medications comprises a container member having concealed locking means, a plurality of cavities along its longitudinal axis for holding medication, each cavity closed with a peel-off seal, and a cover for the container member that requires two operations to open.

Abstract: New intermediates in the synthesis of 17.beta.-acyl-3-carboxy-androsta-3,5-dienes, of the formula: ##STR1## wherein R.sup.2 is 2-thiopyridyl, andR.sup.3 is C.sub.2 -C.sub.4 alkoxycarbonyl, C.sub.1 -C.sub.4, or trifluoromethylsulfonyloxy. The above compounds are useful intermediates in producing testosterone 5.alpha.-reductase inhibitors which are useful topically for treatment of acne, seborrhea, female hirsutism, and systemically in treatment of benign prostatic hypertrophy.

Abstract: Novel biotransformation compounds I, II, III and IV are prepared by fermenting 3-[(2'-tetrazol-5-yl-biphenyl-4-yl) methyl]-7-methyl-2-propyl-3H-imidzao [4,5-b]pyridine in a culture of Streptomyces sp., Accession Number ATCC 55041. ##STR1## These novel compounds are Angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Described is a new diphosphonate intermediate useful in a new process for producing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), a new antihypercalcemic agent. The process involves a 3-step sequence starting with 4-phthalimidobutanoyl chloride which can be practiced as a "one-pot" reaction sequence, without employing PCl.sub.3 or H.sub.3 PO.sub.3. The new intermediate has the structure: ##STR1## where n=1-5.