Abstract: Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to macrocyclic ?-keto amide derivatives and their use as therapeutic agents.

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Abstract: A process for the production of a carbodiimide, comprising the steps of: (1) reacting an amine represented by the following formula (A) with carbon disulfide in the presence of a catalyst at a reaction temperature of 50 to 150° C. to obtain a thiourea represented by the following formula (B): (In the above formula (A), R is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.) (In the above formula (B), R is as defined in the above formula (A); (2) desulfurizing the obtained thiourea with a hypochlorite in the presence of a basic compound to obtain a carbodiimide represented by the following formula (C): (In the above formula (C), R is as defined in the above formula (A)); and (3) purifying the obtained carbodiimide.

Abstract: The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.

Abstract: The disclosure provides rifamycin and rifamycin derivative compositions, including rifabutin and rifabutin derivative compositions able to cause drug-sensitization in a cancer cell or inhibition of a cancer cell. The disclosure also provides methods of administering such compositions to cancer cells to sensitize them to drugs, such as chemotherapeutics, or directly inhibit them. The disclosure also provides methods of administering such compositions to increase reactive oxygen species (ROS), particularly superoxides, in cancer cells. The disclosure further provides methods of determining whether a cancer will respond to chemotherapeutics and whether to administer rifamycin or a rifamycin derivative based on ROS levels in cancer cells of a patient.

Abstract: The present invention discloses a class of novel macro-heterocyclic compounds represented by the formula Ia or Ib, and their intermediates, preparation methods and the uses. The macro-heterocyclic compounds of the present invention have good inhibitory activities against hepatitis C virus (HCV), and can be used to treat HCV infection effectively by its excellent inhibition against HCV, low toxicity and side effects.

Abstract: Diazonamide analogs having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders, and related pharmaceutical compositions are provided.

Abstract: Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Abstract: The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.

Abstract: A process for producing an intermediate for a cyclic carbodiimide compound. The process includes a process for producing an amine compound represented by the following formula (B), comprising the step of reducing a nitro compound represented by the following formula (A) and containing a compound having a haloarene skeleton in the presence of a metal catalyst and a basic compound. The process also includes a process for producing a thiourea compound, comprising the step of reacting an amine compound represented by the formula (B) with carbon disulfide in the presence of imidazole. (R is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.) (R is as defined in the above formula (A).

Abstract: The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.

Abstract: The present invention is directed to compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

Abstract: There are provided inter alia compounds of formula (I) useful as cyclophilin inhibitors.

Abstract: Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y1, as modulators of the serotonin receptor of subtype 5-HT2B, as blockers of the voltage-gated potassium channel Kv1.3 and as inhibitors of the ?-catenin-dependent “canonical” Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.

Abstract: The present invention relates to a compound represented by the following formula (1): wherein W, X, Y, R1, R2, R33, R34, m and n are as defined in the claims, or a pharmacologically acceptable salt thereof.

Abstract: Diazonamide analogs having anti-mitotic activity, useful for the treatment of cancer and other proliferative disorders, and related pharmaceutical compositions are provided.

Abstract: The embodiments provide compounds of the general Formulae I through general Formula VIII, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

Abstract: The invention relates to processes for the preparation of compound of CCI-779 having the Formula (I), which is useful as an antineoplastic agent. The invention further relates to certain novel intermediates useful in the preparation of compound of CCI-779 and processes for their preparation. The invention also relates to pharmaceutical compositions that include the compound of CCI-779, prepared according to the processes disclosed herein.

Abstract: The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B-W??(I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: Antitumor compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins. They have at the C-1 position a substituent selected from an optionally protected or derivatised aminomethylene group or an optionally protected or derivatised hydroxymethylene group.

Abstract: The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt thereof. These compounds inhibit serine protease, particularly the hepatitis C virus NS3-NS4A protease.

Abstract: The present invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease.

Abstract: The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.

Abstract: Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

Abstract: Compounds of formula I: wherein variables A1, A2, B, m, n, J, R4, G1, G2, G3 and Y are as described herein, which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The present invention is directed to compounds of Formula I: I (where A1, A2, B1, B2, B3, B4, D1, D2, J, K, T, U, V, W, X, Y, Z, R4, R5a, R5b, R5c, m and n are defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: Substituted rifamycin derivatives in which a nitroimidazole, nitrothiazole or nitrofuran pharmacophore is covalently bonded to a rifamycin, methods of using the rifamycin derivatives, and pharmaceutical compositions containing the rifamycin derivatives are disclosed. Methods of synthesizing these substituted rifamycin derivatives are also disclosed. The rifamycin derivatives possess antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases.

Abstract: The present invention is directed to compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

Abstract: Compounds of formula I: (wherein variables A1, A2, A3, A4, A5, A6, A7, B1, B2, B3, B4, D1, D2, E1, E2, E3, E4, E5, G1, G2, R6, T, U, V, W, X, Y and Z are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Abstract: The present invention is directed to several newly discovered ecteinascidin (Et) species, designated herein as Et 731, Et 815, Et 808, and Et 594. The physical properties of these compounds, their preparation and therapeutic properties are also reported.

Abstract: The present invention is directed to compounds of Formula I: I (where A1, A2, B1, B2, B3, B4, D1, D2, J, K, T, U, V, W, X, Y, Z, R4, R5a, R5b, R5c, m and n are defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: Antitumor compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins.

Abstract: The present invention is directed to compounds of formula I which are inhibitors of the beta-secretase enzyme and that are useful in the treatment or prevention of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease.

Abstract: This invention provides progesterone receptor modulators having the structure: wherein R1 to R7, X, and Q are as defined in the specification; or a pharmaceutically acceptable salt thereof.

Abstract: The invention relates to a dihydrospiro-[cycloalkylamine]-pyrimidone derivative represented by formula (I) or a salt thereof: wherein X, Y, R1, R2, R3, R4, o, m, n, p and q are as defined herein. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3?, such as Alzheimer disease.

Abstract: Antitumour compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins. They have at the C-1 position a substituent selected from an optionally protected or derivatised aminomethylene group or an optionally protected or derivatised hydroxymethylene group.

Abstract: Compounds of the current invention relate to rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. More specifically, compounds of the current invention relate to a series of novel spiro rifamycin derivatives which have demonstrated potent antimicrobial activity.

Abstract: A NK1 antagonist having the formula (I), wherein Ar1 and Ar2 are optionally substituted phenyl or heteroaryl, X1 is an ether, thio or imino linkage, R4 and R5 are not both H or alkyl, and the remaining variables are as defined in the in the specification, useful for treating a number of disorders, including emesis, depression, anxiety and cough. Pharmaceuticals compositions. Methods of treatment and combinations with other agents are also disclosed.

Abstract: This invention relates to tricyclic compounds having spiro union represented by the following formula (I) or its salt which is useful as a drug, and in particular, as an inhibitor for activated blood coagulation factor X, which can be administered orally and which exhibits strong anticoagulation action. The invention also relates to a pharmacophore which was derived from the compound and is useful in molecular designing of the FXa inhibitor.

Abstract: A microorganism that is a mutant bacterial strain of the species Actinosynnema pretiosum, designated PF4-4, (ATCC PTA-3921), being capable of producing maytansinoid ansamitocins such as ansamitocin P-3 in improved yield compared to previous known strains, and capable of growth under varied culture conditions, and methods of producing maytansinoid ansamitocins by culturing PF4-4 in a suitable growth medium.

Abstract: Processes are provided for preparing compounds with a fused ring structure of formula (XIV). Such products include ecteinascidins and have a spiroamine-1,4-bridge. The process involving forming a 1,4 bridge using a 1-labile, 10-hydroxy, 18-protected hydroxy, di-6,8-en-5-one fused ring compound. After formation of the 1,4 bridge, C-18 protection is removed before spiroamine introduction.

Abstract: The invention provides compounds of formula as described in the claims, or an optical isomer, diastereomer or enantiomer thereof, or a pharmaceutically-acceptable salt, or biohydrolyzable amide, ester, or imide thereof are useful as inhibitors of metalloproteases. Also disclosed are pharmaceutical compositions and methods of treating diseases, disorders and conditions characterized by metalloprotease activity using these compounds or the pharmaceutical compositions containing them.

Abstract: This invention relates to macrocyclic molecules which inhibit metalloproteinases, including aggrecanase, and the production of tumor necrosis factor (TNF). In particular, the compounds are inhibitors of metalloproteinases involved in tissue degradation and inhibitors of the release of tumor necrosis factor. The present invention also relates to pharmaceutical compositions comprising such compounds and to methods of using these compounds for the treatment of inflammatory diseases.

Abstract: Compounds of the formula: are described which have activity as anti-inflammatory agents. Cyclic disulfide compounds are provided which inhibit of binding of cells to endothelium. Such compounds are useful for treating inflammatory diseases, such as asthma, whose symptoms and/or damage are related to the binding of cell adhesion molecules to integrin expressing cells.

Abstract: The present invention relates to novel substituted pyridines/pyrimidines of the formula I where A is CH or N; X is NH, oxygen or S(O)q where q is 0, 1 or 2; Y is a direct bond or CH2; Z is oxygen, NR7 or S(O)m is 0, 1 or 2, and the radicals R1, R2, R3, R4, R5, R6 and R7 are as defined in the description, to processes for their preparation, and to their use as pesticides, fungicides, ovicides or as veterinary medicaments.