Abstract: Methods and pharmaceutical compositions are provided for enhancing or stimulating regeneration of a tissue in a subject. In one aspect, the invention provides a method including administering to a subject in need thereof a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration of a tissue. In another aspect, the invention provides a method including administering to a subject a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration of a tissue to treat or prevent a disease, disorder, trauma, or condition resulting from an injury of the tissue. In an additional aspect, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of an aminosterol to stimulate or enhance regeneration of a tissue.

Abstract: This application is directed to the use of aminosteroid compounds for the selective inhibition of the enzyme PTP1B in a mammal for the treatment of diabetes.

Abstract: The present invention relates to novel aminosteroid derivatives substituted in position 3 andor 6, and to the use thereof in the context of the treatment of type 2 diabetes and of insulin resistance.

Abstract: Methods and pharmaceutical compositions are provided for enhancing or stimulating regeneration of a tissue in a subject. In one aspect, the invention provides a method including administering to a subject in need thereof a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration of a tissue. In another aspect, the invention provides a method including administering to a subject a therapeutically effective amount of an aminosterol or a pharmaceutically acceptable salt thereof to stimulate or enhance regeneration of a tissue to treat or prevent a disease, disorder, trauma, or condition resulting from an injury of the tissue. In an additional aspect, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of an aminosterol to stimulate or enhance regeneration of a tissue.

Abstract: The invention relates to select squalamine salts, methods of their synthesis, their therapeutic use and their advantages relating to manufacturing, product stability and toxicity. More specifically, this application is directed to various forms of the dilactate salt of squalamine and their utility in inhibiting neovascularization and endothelial cell proliferation.

Abstract: Pregnanolone derivatives, substituted in 3 alpha-position with the cationic group, of general formula I, and a method of the production of these compounds and their utilization for treatment of neuropsychiatric disorders related to imbalance of glutamatergic neurotransmitter system, such as ischemic damage of CNS, neurodegenerative changes and disorders of CNS, affective disorders, depression, post traumatic stress disorder, and other diseases related to stress, anxiety, schizophrenia, and psychotic disorders, pain, addictions, multiple sclerosis, epilepsy, and gliomas. The compounds are also used for production of veterinary and human pharmaceutical preparation for treatment of above mentioned diseases and for production of pharmaceutical preparations containing these compounds.

Abstract: The present invention relates to SHIP inhibitor compounds and methods for using these compounds. In particular, the present invention discloses the following methods: (i) a method of treating graft versus host disease in a subject; (ii) a method of inhibiting a SHIP1 protein in a cell; (iii) a method of selectively inhibiting a SHIP1 protein in a cell; (iv) a method for treating or preventing graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant; (v) a method of modulating SHIP activity in a cell expressing SHIP1 or SHIP2; (vi) a method of ex vivo or in vitro treatment of transplants; (vii) a method of inhibiting tumor growth and metastasis in a subject; (viii) a method of treating a hematologic malignancy in a subject; (ix) a method of inducing apoptosis of multiple myeloma cells; (x) a method of treating multiple myeloma in a subject; (xi) a method of inhibiting the proliferation of a human breast cancer cell; and (xii) a method of treating breast cancer in a subject.

Abstract: A method for preparing 3?-arachidylamido-7?,12?,5?-cholan-24-carboxylic acid represented by the following formula V is disclosed, which includes the following steps: converting cholic acid to the compound of formula III by acylation reaction and azidation reaction, reducing the compound of formula III to the compound of formula IV and in the end acylating the compound of formula IV with arachidoyl chloride to get the compound of formula V. The method avoids the use of protection groups.

Abstract: The present invention relates to methods for treatment, prevention, and inhibition of progression of Alzheimer's disease, and other brain diseases characterized by amyloid plaque deposits, comprising the administration to a subject a bile acid fatty acid conjugates or bile salt fatty acid conjugate (FABAC).

Abstract: The invention relates to select squalamine salts, methods of their synthesis, their therapeutic use and their advantages relating to manufacturing, product stability and toxicity. More specifically, this application is directed to various forms of the dilactate salt of squalamine and their utility in inhibiting neovascularization and endothelial cell proliferation.

Abstract: Novel benzoic acid hydrazones of 5?-androstan-3,17-dione have been prepared on the basis of steroidal tigogenin of the plant Yucca gloriosa. The hydrazones of the General Formula (I), General Formula (II) and General Formula (III) as shown in the accompanying FIGURE of the drawing are synthesized. The hydrazones have shown promising anti-T.B., anti-cancer and anti-HIV activity revealing immense potential as more efficacious, less toxic drugs with fewer undesirable side effects. They could also prove valuable in correcting hormonal abnormalities that cause severe health problems.

Abstract: The invention relates to select squalamine salts, methods of their synthesis, their therapeutic use and their advantages relating to manufacturing, product stability and toxicity. More specifically, this application is directed to various forms of the dilactate salt of squalamine and their utility in inhibiting neovascularization and endothelial cell proliferation.

Abstract: This application is directed to the use of steroid compounds for the selective inhibition of the enzyme PTP1B in a mammal for the treatment of diabetes.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to methods for synthesizing preferred membrane-binding elements, preferably cholesterylamine derivatives, including 3?-amino-5-cholestene (3?-cholesterylamine) and related 3?-halides through i-steroid and retro-i-steroid rearrangements. The invention further relates to use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: An efficient method for the synthesis of aminosterol compounds such as squalamine and compound 1436 is described. A method of the invention provides for regioselective sulfonation of a fused ring system. The fused ring system base can be, for example, a steroid ring base. The aminosterol compounds are effective as, among others, antibiotics, antiangiogenic agents and NHE3 inhibitors.

Abstract: The invention relates to a diastereoselective method for obtaining a primary amine on a steroid, comprising the reduction of an oxime by lithium in ammonia at a low temperature in an ether/alcohol mixture.

Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

Abstract: A pharmaceutical composition includes, as an active ingredient, a compound according to formula 1436 as shown in FIG. 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Various pharmaceutical products may be produced including this pharmaceutical composition. Such pharmaceutical products may be used for the treatment of obesity or diabetes. Methods for using the pharmaceutical compositions also are described. In these methods, various diseases are treated or other body functions are activated or inhibited by administering an effective amount of the pharmaceutical composition. For example, diabetes and obesity may be treated by administering an effective amount of the pharmaceutical compositions. Weight gain, and growth factor production can be inhibited by administering an effective amount of these pharmaceutical compositions.

Abstract: A pharmaceutical composition includes, as an active ingredient, a compound according to formula 1436 as shown in FIG. 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Various pharmaceutical products may be produced including this pharmaceutical composition. Such pharmaceutical products may be used for the treatment of obesity or diabetes. Methods for using the pharmaceutical compositions also are described. In these methods, various diseases are treated or other body functions are activated or inhibited by administering an effective amount of the pharmaceutical composition. For example, diabetes and obesity may be treated by administering an effective amount of the pharmaceutical compositions. Weight gain, and growth factor production can be inhibited by administering an effective amount of these pharmaceutical compositions.

Abstract: Compositions and methods for treating mammalian disease characterized by undesirable angiogenesis by administering compounds of the general formula: wherein the variables are defined in the specification.

Abstract: The invention relates to novel crystalline forms of 3-beta-amino-17-methylene-androstane-6-alpha,7-beta-diol hydrochloride, referred to as form A, form B and form C, a method for preparing same, the use thereof as a drug, and pharmaceutical compositions containing same.

Abstract: A compound of the formula: and pharmaceutically acceptable salts, solvates, stereoisomers and prodrugs thereof, in isolation or in mixture, wherein R groups are as defined by the present specification. The compounds may be formulated into pharmaceutical compositions, and used in the treatment and/or prevention of various conditions, including inflammation, asthma, an allergic disease, chronic obstructive pulmonary disease, atopic dermatitis, solid tumors, AIDS, ischemia, and cardiac arrhythmias.

Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Abstract: The present invention relates to a novel process for the preparation of bile esters derivatives of general formula (1), in which R0 is H or OH; R1 is H, &agr;-OH or &bgr;-OH; R2 and R3 are independently hydrogen, straight or branched (C1-C20) alkyl optionally substituted with aryl; R5 is a straight or branched (C1-C4) alkyl and R6 is a straight or branched (C1-C4) alkyl or a benzyl group, via transamidation of the amine (V) with the 5-ocoproline derivative (II), wherein R4 is selected from the group consisting of tertbutoxycarbonyl, methoxycarbonyl, ethoxycarbonyl, 2-trimethylsilylethoxycarbonyl, cyclobutoxycarbonyl and 1-methylcyclobutoxy carbonyl, followed by the selective cleavage of the protecting group R4 under acidic conditions.

Abstract: A compound of the formula or pharmaceutically acceptable salts, solvates, and stereoisomers thereof, in isolation or in mixture, wherein the R groups are as defined by the present specification. The compounds may be formulated into pharmaceutical compositions, and used in the treatment and/or prevention of various conditions, including inflammation, asthma, an allergic disease, chronic obstructive pulmonary disease, atopic dermatitis, solid tumors, AIDS, ischemia, and cardiac arrhythmias.

Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.

Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Abstract: Compounds of the general formula I 1

Abstract: A process for the preparation of the compounds of general formula (I) in which R1 is H or OH; R2 is H, &agr;-OH, or &bgr;-OH; and R3 is a straight or branched C1-C4 alkyl group or a benzyl group, comprising the reduction of compounds of formula (III) wherein R1, R2 and R3 have the same meanings as in formula I, in the presence of sodium borohydride.

Abstract: A compound of the formula 1

Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.

Abstract: Newly isolated aminosterol compounds and pharmaceutical compositions based on the aminosterol compounds are described. Methods for the treatment of various disorders, for example, a microbial infection, are also described.

Abstract: A process for the preparation of the compounds of general formula (I) 1

Abstract: A process for the preparation of the compounds of general formula (I) in which R1 is H or OH; R2 is H, &agr;-OH, or &bgr;-OH; and R3 is a straight or branched C1-C4 alkyl group or a benzyl group, comprising the reduction of compounds of formula (III) wherein R1, R2 and R3 have the same meanings as in formula I, in the presence of sodium borohydride.

Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.

Abstract: Gelators gel a variety of nonpolar and polar liquids. Moreover, gelation of various monomers with subsequent polymerization of the gelled monomers forms organic zeolites and membrane materials. An ionic gelator includes salts of compounds of the formula (I):?R.sup.1 R.sup.2 R.sup.3 X-R.sup.4 !.+-.Y.-+. (I)where R.sup.1, R.sup.2 and R.sup.3 are the same or different hydrogen or organic groups including alkyl groups, alkenyl groups, alkynyl groups, aryl groups, arylalkyl groups, alkoxy groups, aryloxy groups; X is a Group IIIA or Group VA element; R.sup.4 is a steroidal group, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an arylalkyl group, an alkoxy group or an aryloxy group; and Y is a Group IA or Group VIIA element or one-half of a Group IIA or VIA element, that is, a divalent counterion. The gelling agent composition may include a single isomer or mixtures of isomers of the formula (I). A non-ionic gelator also includes compounds of the formula:R.sup.1 R.sup.2 R.sup.3 X (II)where R.

Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Abstract: This invention discloses compounds useful as steroid sulfatase inhibitors. The compounds comprise the formula (1) ##STR1## wherein (a) R is selected from the group consisting of hydrogen, a lower alkyl group, an alkoxy group, halogen, NH.sub.2, NO.sub.2, C.tbd.N and N.dbd.C.dbd.S; and (b) the ring system ABCD is a steroid nucleus selected from the group consisting of estrone, dehydroepiandrosterone, estradiols, estradiolesters, pregnenolone, substituted estrones, substituted dehydroepiandrosterones, substituted estradiols, substituted estradiolesters and substituted pregnenolone. The compounds also comprise the formula (5) ##STR2## wherein (a) R.sub.1 is hydrogen and R.sub.2 is selected from the group consisting of SO.sub.2 CF.sub.3, SO.sub.2 NH.sub.2, SO.sub.2 (C.sub.1 -C.sub.6 -alkyl), COCF.sub.3, CONH.sub.2, CO(C.sub.1 -C.sub.

Abstract: An aminosterol compound according to the following formula: ##STR1## wherein: R.sub.1 is a member selected from the group of: ##STR2## R.sub.2 is H or OH; R.sub.3 is H or OH;R.sub.4 is H or OH; andR.sub.5 is a C.sub.1 to C.sub.12 alkyl group.Preferably, R.sub.5 is a C.sub.1 to C.sub.6 alkyl group, and a methyl group is particularly preferred.

Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Abstract: Disclosed are aminosterol compounds 1360 and 1361: ##STR1## which can be obtained in isolated or purified form from the liver of the dogfish shark.

Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also disclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Abstract: The present invention relates to a bile acid derivative, which comprises a bile acid derivatized at the carboxyl group with a hydroxamic acid or hydroxamate ester. The carboxyl group in the bile acid compound can also be derivatized with an amino acid or oligopeptide, whose C-terminus is derivatized with a hydroxamic acid or a hydroxamate ester. The present invention also relates to a method of use of a bile acid or a bile acid derivative to inhibit a metalloproteinase enzyme, comprising contacting a metalloproteinase with an effective amount of a bile acid or bile acid derivative. In another embodiment, the present invention further relates to a method of use of a bile acid or bile acid derivative to therapeutically treat a disease, which is ameliorated by inhibiting a metalloproteinase enzyme. In this method, a therapeutically effective amount of a bile acid, a bile acid derivative or physiologically acceptable salts thereof, is administered to a human or other mammal.

Abstract: Compounds having a broad range of antimicrobial activity generally have a structure including asteroid nucleus with a cationic, preferably polyamine, side chain (X) and an anionic side chain (Y). The invention is also directed to compounds of the Formula III: ##STR1## preferably where the steroid ring nucleus is saturated; the steroid ring substituent Z.sub.5 is .alpha.-H; one Z.sub.7 is .beta.-H and the other is .alpha.-H or .alpha.-OH; both substituents Z.sub.12 are hydrogen; X' is a polyamine side chain of the formula --NH--(CH.sub.2).sub.p --NH--(CH.sub.2).sub.q --N(R.sup.II)(R.sup.III) where p and q are each independently 3 or 4, and R.sup.II and R.sup.III are each independently hydrogen or methyl; R' is methyl; and Y' is (C.sub.1 -C.sub.10)-alkyl substituted with a group such as --CO.sub.2 H or --SO.sub.3 H.

Abstract: New steroidal polyamines have the structure of formula I or formula II: ##STR1## wherein R.sub.1 and R.sub.2 are independently N(R').sub.3.sup.+ or H in the .alpha.- or .beta.- position except both R.sub.1 and R.sub.2 are not H;R.sub.3 is N(R').sub.3.sup.+ in the .alpha.- position or hydrogenR.sub.4 is OH, N(R').sub.3, or NHC(NH.sub.2)NH.sub.2.sup.+R' is hydrogen, alkyl of one to four carbons, aralkyl, or combinations thereof.

Abstract: This invention discloses compounds useful as steroid inhibitors. The compounds comprise the formula (5) ##STR1## wherein (a) R.sub.1 is hydrogen and R.sub.2 is selected from the group consisting of SO.sub.2 CF.sub.3, SO.sub.2 NH.sub.2, SO.sub.2 (C.sub.1 -C.sub.6 -alkyl), COCF.sub.3, CONH.sub.2, CO(C.sub.1-C.sub.6 -alkyl); and (b) the ring system ABCD is a steroid nucleus selected from the group consisting of estrone, dehydroepiandrosterone, estradiol, estradiolester, pregnenolone, substituted estrones, substituted dehydroepiandrosterone, substituted estradiols, substituted estradiolesters and substituted pregnenolone. Preferably the steroid nucleus is selected from the group consisting of estrone, dehydropeiandrosterone and pregnenolone. The invention also discloses methods of treating a patient therapeutically and prophylactically for estrogen dependent diseases with the compounds of this invention.

Abstract: 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.

Abstract: Ethylenically unsaturated bile acid derivatives of the formula IG--X--A Iin which G, X and A have the meanings indicated, are described. They are suitable for the preparation of polymeric bile acid derivatives. Bile acid derivatives of the formula IVaG--X' IVain which G and X' have the meanings indicated, are also described. They are useful synthesis components for the preparation of pharmaceuticals.

Abstract: Process for the preparation of 3.beta.-aminocholanic acid derivativesA process for the preparation of 3.beta.-aminocholanic acid derivatives of the formula II ##STR1## wherein R(1), R(2) and R(3) have the meanings given, starting from the corresponding 3.beta.-hydroxycholanic acid esters, is described.