Abstract: The invention relates to acyloxymethyl esters of bisphosphonic acids, halo-bisphosphonic acids and hydroxy-bisphosphonic acids which exhibit oral bioavailability and are useful in the treatment of disturbances involving calcium or phosphate metabolism, in particular, the treatment and prevention of diseases involving bone resorption, especially osteoporosis, Paget's disease, malignant hypercalcemia, and metastatic bone disease.

Abstract: Described is a process for producing a new FK-506 antagonist agent, a C-21 hydroxylated analog of FR-900520 under novel fermentation conditions utilizing the novel microorganism, Streptomyces hygroscopicus (Merck Culture Collection MA 6832) ATCC No. 55166. The macrolide antagonist is useful in preventing and/or counteracting accidental or inadvertent FK-506 overdosage in an FK-506 therapeutic program designed to prevent autoimmune diseases or human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

Abstract: Described is a process for producing a new immunosuppressant, a C-19/C-22 cyclic hemiketal (Compound I) biotransformation analog of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces sp. (Merck Culture Collection MA6963) ATCC No. 55230. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

Abstract: A class of pyrazine, pyrimidine and pyridazine derivatives, substituted by a non-aromatic azabicyclic ring system and optionally by up to two further substituents, is of use in the preparation of medicaments, especially formulations adapted for topical administration to the eye, suitable for the treatment of glaucoma and/or for reducing intraocular pressure.

Abstract: A class of spirocyclic piperidine derivatives are selective ligands at sigma recognition sites and are therefore useful in the treatment and/or prevention of psychiatric disorders.

Abstract: The present invention is concerned with a novel biotransformation process for producing 17.beta.-N-monosubstituted carbamoyl-11-oxo-4-aza-5-.alpha.-androst-3-ones of the formula: ##STR1## These compounds are testosterone 5-.alpha. reductase inhibitors and are produced via a claimed novel biotransformation process using the green algae, Selenastrum capricornutum.

Abstract: A class of indazole-substituted five-membered heteroaromatic compounds are specific agonists of 5-HT.sub.1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.

Abstract: Atrial natriuretic factor analogs containing N-alkylated amino acids and showing enhanced potency and increased metabolic stability. These analogs have natriuretic, diuretic and vasorelaxant activity, making them suitable for treating congestive heart failure and renal hypertension.

Abstract: Described is a new microorganism, Actinoplanacete sp., (Merck Culture Collection MA 6559) ATCC No. 53771. The microorganism acts as a demethylating agent and can produce the new immunosuppressants, "demethomycin" (L-682,993) a C-31 demethylated analog of L-679,934, and "demethimmunomycin" (L-683,742) a C-31 demethylated analog of L-683,590, under novel fermentation conditions. These macrolide immunosuppressants are useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Abstract: Described is a process for producing a new immunosuppressant, a C-31 desmethyl, C-19/C-22 cyclic hemiketal biotransformation analog (Compound I) of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces, lavendulae ATCC No. 55209. Also disclosed is the C-31 methylated derivative (Compound II) of Compound I produced by enzymatic methylation using 31-O-desmethylimmunomycin O-methyl transferase, (DIMT), a methyl transferase enzyme. The macrolide immunosuppressants are useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

Abstract: A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 .mu.g FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H.sub.2 N G y V l G n V l G u T r I e S r P o G y A p G y A g T r P e P o L s A g-Gly-Gln-Thr-X-Val-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Fly-Lys-Phe-AS p (wherein X is undefined). The HCBV protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g. Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyses the cis-trans isomerization of proline-containing peptide bonds.

Abstract: A method for the modification of treatment of an immuno regulatory disorder or disease with an FK-506-type immunosuppressive macrolide comprising the administration to a mammalian species in need of such modification of an effective amount of a compound of the formula I.

Abstract: Fluoromacrolides and derivatives of the general structural Formula I: ##STR1## have been prepared from suitable precursors by oxidation and fluorination at C-20. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses. Also, these macrolides are useful in the treatment of reversible obstructive airways disease, particularly asthma. Furthermore, these macrolides are useful as hair revitalizing agents, especially in the treatment of male pattern alopecia or alopecia senilis.

Abstract: 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.

Abstract: Described are new agents for treating bone disorders associated with a reduction in bone mass and abnormalities in bone resportion or bone formation including osteoporosis. Paget's disease, bone metastases and malignant hypercalcemia. The agents are hydroxyl containing steroidal hormones, having bone resportion antagonist or bone formation stimulatory activity, covalently linked through the hydroxyl group via a bond hydrolyzable in the human body, e.g. carbamate or carbonate, which is further covalently linked to an amino, or hydroxy substituted alkylidene-1,1-bisphosphonate, through the respective amino or hydroxy group. The alkyl bisphosphonate moiety confers bone affinity. The agent acts by delivering the steroidal hormone directly to the bone target site where it is released for bone resorption antagonist or bone formation stimulatory action by hydrolysis of the hydrolyzable covalent bond.

Abstract: A process for the conversion of FK-506 (I,R=allyl;1) to FK-525 (XV) and analogous 23-membered ring macrolides differing in the C.1-N.7 segment of the molecule (e.g. XVI) and is also applicable to the analogs FK-523 (XVII) and FK-520 (XVIII). The overall process consists of three stages: (a) initial degradation of the primary macrolide to an acyclic fragment containing a selectively protected C.10-C.34 framework with a protected aldehyde function at C.10 and a free hydroxyl function at C.26, (b) reacylation of the C.26 hydroxyl function with an appropriately N-protected alpha-amino acid moiety, and (c) reintroduction of the C.8 and C.9 carbons followed by regeneration of the FK-macrolide system.

Abstract: Amino O-alkyl, O-alkenyl and O-alkynylmacrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and amination at C-3"/C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses. Also, these macrolides are useful in the treatment of reversible obstructive airways disease, particularly asthma.

Abstract: Described is 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.

Abstract: 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.

Abstract: Described is a process for producing a new immunosuppressant, a C-31 desmethyl, C-19/C-22 cyclic hemiketal biotransformation analog (Compound I) of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces, lavendulae ATCC No. 55209. Also disclosed is the C-31 methylated devivative (Compound II) of Compound I produced by enzymatic methylation using 31-O-desmethylimmunomycin O-methyl transferase, (DIMT), a methyl transferase enzyme. The macrolide immunosuppressants are useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.