Abstract: This invention relates to a method of preparing mesylate salts of compounds that inhibit IL-12, IL-23 and/or IL-27 production.

Abstract: Amino acid derivatives of pyrrolyl-indolinones and their amide or ester derivatives have enhanced and unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.

Abstract: The present invention relates to a novel benzamidine derivative, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The benzamidine derivative of the present invention effectively inhibits osteoclast differentiation at an extremely low concentration, and greatly increases the trabecular bone volume, and thus it can be advantageously used for the prevention and treatment of osteoporosis.

Abstract: The invention concerns compounds of Formula I, or a pharmaceutically acceptable salt thereof, where R1, Q, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.

Abstract: A compound of formula I: wherein: R1 and R2 are independently selected from hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X is CH or N; n is 1 or 2; RC1 and RC2 are independently selected from H and methyl; when X is N, RX is selected from the group consisting of H, and optionally substituted C1-7 alkyl, C3-20 heterocyclyl, C5-20 aryl, acyl, ester, amido and sulfonyl; and when X is CH, RX is selected from the group consisting of H, and optionally substituted C1-7 alkyl, C3-20 heterocyclyl, C5-20 aryl, acyl, ester, amido, sulfonyl, amino and ether.

Abstract: A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and RN1 is selected from hydrogen, an optionally substituted C1-7 alkyl group, an optionally substituted C3-20 heterocyclyl group, an optionally substituted C5-20 aryl group, an acyl group, an ester group and an amido group, and its use as a pharmaceutical.

Abstract: The invention concerns pyrimidine compounds of Formula I, or a pharmaceutically acceptable salt thereof, where A1, A2 A3, R1, n, R2, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.

Abstract: A pyridothienopyrimidine derivative of formula (I), or the pharmaceutically acceptable salts or N-oxides thereof are disclosed, as well as pharmaceutical compositions comprising said compounds and methods of treatment or prevention of a pathological condition or disease susceptible to amelioration by inhibition of phosphodiesterase 4 using said compounds are disclosed.

Abstract: A compound of formula (I) where one of A1, A2 or A3 is N, and the others are independently selected from CH or N; ring B is a fused 5 or 6-membered carbocyclic or heterocyclic which is optionally substituted as defined in the specification, and R1, R2, R3, R4, and n are as defined in the specification. The compounds are inhibitors of EphB4 or EphA2 and therefore may be useful in pharmaceutical compositions for the treatment of conditions such as cancer.

Abstract: Heterocyclic compounds represented by the formula I and anti-malignant-tumor agents containing the heterocyclic compounds as effective components: wherein X represents nitrogen atom or CH; Y represents C1-C6 alkyl; R1 represents morpholino (which may be substituted with one to four C1-C6 alkyl); and R2 and R3 each represent hydrogen atom or C1-C6 alkyl.

Abstract: Fused pyrimidines of formula (I): wherein R1-R3, A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof; have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behavior associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

Abstract: There is provided a compound of formula I: wherein: one or two of X5, X6 and X8 is N, and the others are CH; R7 is selected from halo, ORO1, SRS1, NRN1RN2, NRN7aC(?O)RC1, NRN7bSO2RS2a, an optionally substituted C5-20 heteroaryl group, or an optionally substituted C5-20 aryl group, where RO1 and RS1 are selected from H, an optionally substituted C5-20 aryl group, an optionally substituted C5-20 heteroaryl group, or an optionally substituted C1-7 alkyl group; RN1 and RN2 are independently selected from H, an optionally substituted C1-7 alkyl group, an optionally substituted C5-20 heteroaryl group, an optionally substituted C5-20 aryl group or RN1 and RN2 together with the nitrogen to which they are bound form a heterocyclic ring containing between 3 and 8 ring atoms; RC1 is selected from H, an optionally substituted C5-20 aryl group, an optionally substituted C5-20 heteroaryl group, an optionally substituted C1-7 alkyl group or NRN8RN9, where RN8 and RN9 are independently selected from H, an optionally subs

Abstract: The present invention provides a compound having the following general formula (I) which is useful as a neurokinin receptor antagonist: (wherein, R1, R2: optionally substituted (hetero)aryl, R3: —CO—R4, —CO—O—R4, etc., R4: alkyl, cycloalkyl, etc., A: CH2, CO, SO2, B: a single bond, etc., D: oxygen, CH2, E: alkylene, alkenylene, n: 1 to 3).

Abstract: Compounds of the formula (I), wherein the symbol aa means a residue of an ?-amino acid. The invention is also directed to a method for the preparation of the compounds of formula (I), as well as their use as prolyl oligopeptide inhibitors, for example for the treatment of Alzheimer's disease.

Abstract: The present invention describes novel compounds of Formula I which inhibit HIV integrase.

Abstract: The invention relates to compounds of formula I, in which R1, R2, R3 and R4 have the meanings given in the claims. Said compounds are valuable active ingredients for the treatment and prophylaxis of diseases, for example of cardiovascular diseases such as hypertension, angina pectoris, heart failure, thrombosis or atherosclerosis. The compounds of the formula I are able to modulate the body's production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the treatment and prophylaxis of disorders associated with impaired cGMP balance. The invention furthermore relates to methods for producing compounds of the formula I, their use in the treatment and prophylaxis of the above diseases and in the preparation of medicaments for such diseases, and pharmaceutical preparations containing the compounds of formula I.

Abstract: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention.

Abstract: The present invention relates to novel substituted pyrazole derivatives of the general formula (I) in which the substituents R1, R2, R3, A, X and Y are each as defined, and to processes for their preparation and to their use as medicaments, in particular as medicaments for the treatment of cardiovascular disorders.

Abstract: A class of substituted or 6,7-ring fused [1, 2, 3]triazolo[1,5-&agr;]-pyrimidine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and an amino moiety at the 5-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

Abstract: Disclosed are novel cathepsin S, K, F, L and B reversible inhibitory compounds of the formula (Ia) and (Ib) where R2, R3, R4, R5, R6, R7, R8, Het and X are defined herein. The compounds are useful for treating autoimmune and other diseases. Also disclosed are processes for making such novel compounds.

Abstract: The present invention provides a compound of formula I which is useful as antiviral agents, in particular, as agents against viruses of the herpes family.

Abstract: The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus, coronavirus, and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds are substantially uncharged oligomers having a targeting base sequence that is substantially complementary to a viral target sequence which spans the AUG start site of the first open reading frame of the viral genome.

Abstract: The application is related to the field of nucleic acids with identified utility, and more particularly, to genes, related nucleic acids, their complements, polypeptides, and methods of using the same for blood vessel, cartilage, and bone formation, as well as inhibition thereof. The application describes discoveries made using the zebrafish embryo technique, as well as other techniques that are described herein. The discoveries include genes, related nucleic acids, and their complements, as well as sequences, polypeptides, other molecules, and methods for using them, e.g., TDE1, PTV, MOESIN, and HKE4. Also described are polypeptide products, inhibition of expression, administration of materials and products, screening procedures, and techniques for making drugs. Moreover, uses of these discoveries in appropriate contexts are set forth.

Abstract: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention.

Abstract: Disclosed are novel aromatic compounds of the formula(I) wherein G, E, W, Ar, X, Y and Z. The compounds are useful for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are pharmaceutical compositions containing and processes of making such compounds.

Abstract: The present invention relates to pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein X, Y, Ar1, Z, R1, R2 and R3 are as defined in the specification, and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

Abstract: A new series of derivatives of 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid and their synthesis have been discovered. Surprisingly, by modifying the substituent of the 3-carboxylic acid group, new compounds were produced with high activity as PAF receptor antagonists. These compounds were shown to protect neurons from brain damage that normally occurs in response to stroke and other cerebrovascular diseases. These compounds are also protective against edema generation resulting from traumatic breakdown of the blood-brain barrier. Moreover, these compounds were found to be non-toxic and cytoprotective of cells undergoing oxidative stress that would normally trigger apoptotic cell death; and to have activity as (a) antagonists of an intracellular platelet activating factor (“PAF”)-binding site, (b) inhibitors of PAF- and cytokine-mediated c-aminoterminal jun kinase (JNK) and extracellular regulated kinase (ERK), and (c) transcriptional inhibitors of COX-2 expression.

Abstract: The present invention provides a compound of formula I which is useful as antiviral agents, in particular, as agents against viruses of the herpes family.

Abstract: Ultraviolet absorbents and photostabilizers have an excellent absorption ability in a wide range of ultraviolet rays, and also have high stability and high safety. The ultraviolet absorbent and photostabilizer include a pyridazine derivative of the formula (1): or salts thereof. Also, described are methods for manufacturing said pyridazine derivative and/or this salts thereof comprising the process of reacting at least 10 wt % of 4,5-dichloro-3-hydroxypyridazine or 4,5-dibromo-3-hydroxypyridazine or mixtures thereof with at least 20 vol % of morpholine in reaction solution at 70° C. or higher. The ultraviolet absorbents photostabilizers include said pyridazine derivative and/or salts thereof as effective ingredient. An ultraviolet ray absorption composition and an external preparation for skin are also included.

Abstract: A compound shown by the formula II, wherein Het is a mono- or polycyclic heterocyclic group comprising one or more hetero atoms selected from the group consisting of N, O and S which may be the same or different from each other; R1 is hydrogen, an optionally substituted lower alkyl or an optionally substituted lower alkenyl; A is an optionally substituted lower alkylene, an optionally substituted lower alkenylene or a single bond; B is an optionally substituted imino or a single bond; or A and B taken together may form a single bond; and D is a single bond or a group of the formula (a):

Abstract: The invention concerns amide derivatives of formula (I) wherein R3 is (1-6C)alkyl or halogeno; m is 0-3, p is 0-2 and q is 0-4; each of R1 and R2 is a group such as hydroxy, halogeno, trifluoromethyl and cyano; R4 is a basic group such as amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, di-[(1-6C)alkyl]amino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, heteroaryl, heteroaryloxy, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy; and Q2 is a group such as heteroaryl, heteroaryloxy or heteroaryl-(1-6C)alkoxy which is optionally substituted; or pharmaceutically-acceptable salts or in-vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

Abstract: The invention concerns amide derivatives of formula (I) wherein R3 is (1-6C)alkyl or halogeno; Q1 is heteroaryl which is optionally substituted with 1, 2, 3, or 4 substituents such as hydroxy, halogeno, trifluoromethyl, (1-6C)alkyl, (1-6C)alkoxy, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, hydroxy-(2-6C)alkoxy, amino-(2-6C)alkylamino, N-(1-6C)alkyl-(1-6C)alkylamino-(2-6C)alkylamino, aryl, heteroaryl and heterocyclyl; p is 0-2 and R2 is a substituent such as hydroxy and halogeno; q is 0-4; and Q2 includes optionally substituted aryl, cycloalkyl, heteroaryl and heterocyclyl; or pharmaceutically-acceptable salts or in vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

Abstract: Ultraviolet absorbents and photostabilizers have an excellent absorption ability in a wide range of ultraviolet rays, and also have high stability and high safety. The ultraviolet absorbent and photostabilizer include a pyridazine derivative of the formula (1): or salts thereof. Also, described are methods for manufacturing said pyridazine derivative and/or this salts thereof comprising the process of reacting at least 10 wt % of 4,5-dichloro-3-hydroxypyridazine or 4,5-dibromo-3-hydroxypyridazine or mixtures thereof with at least 20 vol % of morpholine in reaction solution at 70° C. or higher. The ultraviolet absorbents photostabilizers include said pyridazine derivative and/or salts thereof as effective ingredient. An ultraviolet ray absorption composition and an external preparation for skin are also included.

Abstract: Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of Activating Protein 1 (AP-1) expression are provided. In accordance with various embodiments of the present invention, oligonucleotides are provided which are specifically hybridizable with c-fos or c-jun, the genes encoding c-Fos or c-Jun, respectively. In a preferred embodiment, a method of modulating the metastasis of malignant tumors via modulation of one or more of the AP-1 subunits is provided; this method can be effected using the oligonucleotides of the invention or any other agent which modulates AP-1 or AP-1 mediated transcription.

Abstract: A pyrimidine nucleus-containing compound represented by the formula (I): wherein ring A represents the ring of the formula (a): in which R1 is a nitro group, an amino group, a substituted amino group or a halogen atom, or the ring of the formula (b): in which R1′ is the group such as an alkyl group or an alkenyl group; R2 to R5 independently represent the group such as an alkyl group or an alkenyl group; with the proviso that at least one of R2 to R5 is an alkenyl group, or acid addition salts thereof.

Abstract: Corticotropin releasing factor (CRF) antagonists of Formula (I) ##STR1## and their use in treating psychiatric disorders and neurological diseases including major depression, anxiety-related disorders, post-traumatic stress disorders, supranuclear palsy and eating disorders.

Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains.

Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formulaM.sup.1 --L--M.sup.2where M.sup.1 and M.sup.2 are independently moieties of the formula: ##STR1## in which B.sup.1, B.sup.2, B.sup.3, R.sup.1, R.sup.2, n, W, X and Y are as defined.

Abstract: The present invention provides novel compounds, compounds and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsy, irritable bowel syndrome, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula: ##STR1## wherein R.sup.1, R.sup.3, R.sup.4, R.sup.5, Z, Y, V, X, X', J, K, L, and M are as defined herein.

Abstract: The invention relates to compounds of the formula ##STR1## in which: A is a divalent radical selected from:A.sub.1) --O--CO--A.sub.2) --CH.sub.2 --O--CO--A.sub.3) --O--CH.sub.2 --CO--A.sub.4) --O--CH.sub.2 --CH.sub.2 --A.sub.5) --N(R.sub.1)--CO--A.sub.6) --N(R.sub.1)--CO--CO--A.sub.7) --N(R.sub.1)--CH.sub.2 --CH.sub.2 --A.sub.8) --O--CH.sub.2 --in which:R.sub.1 is a hydrogen or a (C.sub.1 -C.sub.4)-alkyl; andAm is a nitrogen-containing heterocycle.

Abstract: Compounds of the formula: ##STR1## where A, B, R.sup.1 -R.sup.8 are as described herein are endothelin inhibitors that can be used in treating diseases associated with endothelin, such as high blood pressure. Chemical synthesis of these compounds and pharmaceutical compositions containing these compounds are also useful.

Abstract: The invention relates to novel pyrrolidine derivatives represented by formula (1): ##STR1## wherein: R1 represents (1) a lower alkyl group having 1 to 6 carbon atoms, or (2) a 3- to 15-membered mono- or fused cyclic hydrocarbon group which may contain a hetero atom on the ring, or which may be substituted with a substituent(s); each of n and m represents an integer and the sum of n and m is an integer of 0 to 2; each of X and E represents oxygen, NR' (wherein R' is hydrogen or a lower alkyl group having 1 to 6 carbon atoms), sulfur, phenylene, CH.dbd.CH or CH.sub.2 ; A represents an amino acid residue or an imino acid residue, which functional group may be optionally protected, or a glycine residue which may be substituted at the amino moiety thereof; and, Y1 represents a cycloalkyl group having 3 to 8 carbon atoms; or a salt thereof. The pyrrolidine derivatives inhibit a prolyl endopeptidase and are expected to be effective for the treatment of amnesia.

Abstract: This invention relates to novel statone antiviral analogs, to the processes and intermediates useful for their preparation and to their use as antiviral agents.

Abstract: Compounds of formula I: ##STR1## are disclosed. The compounds inhibit the binding of endothelin to its receptors.

Abstract: Sulfur-substituted phenylsulfonylureas; processes for their preparation and their use as herbicides and plant growth regulatorsCompounds of the formula (I) and salts thereof ##STR1## in which R*, R.sup.1, R.sup.2, R.sup.3, X, Y, Z, W, n and m are defined as in claim 1, and specifically R* is a formyl equivalent of the formula CHO, --CH.dbd.NR or CH(X.sup.1 R')(X.sup.2 R"), are suitable as herbicides and plant growth regulators. They are prepared analogously to known methods, in some cases using novel intermediate products of the formula (XVII) ##STR2## in which U*.dbd.NH.sub.2, Cl or (substituted) amino.

Abstract: Compounds of the formula ##STR1## wherein the variables are hereinbelow defined. The compounds of formula I are inhibitors for endothelin receptors. They can be used for the treatment of disorders which are associated with endothelin activities, especially circulatory disorders such as hypertension, ischaemia, vasospasms and angina pectoris.

Abstract: The present invention relates to difluorostatone derivatives useful as antiviral agents.

Abstract: The invention relates to compounds of the formula ##STR1## in which: A is a divalent radical selected from:A.sub.1) --O--CO--A.sub.2) --CH.sub.2 --O--CO--A.sub.3) --O--CH.sub.2 --CO--A.sub.4) --O--CH.sub.2 --CH.sub.2 --A.sub.5) --N(R.sub.1)--CO--A.sub.6) --N(R.sub.1)--CO--CO--A.sub.7) --N(R.sub.1)--CH.sub.2 --CH.sub.2 --A.sub.8) --O--CH.sub.2 --in which:R.sub.1 is a hydrogen or a (C.sub.1 -C.sub.4)-alkyl; andAm is a nitrogen-containing heterocycle.

Abstract: Bicyclic imides of formulae (I) and (II) and their agriculturally-suitable salts, are disclosed which are useful for controlling undesirable vegatation, wherein G is O or S; n and m are each independently 0; 1; 2; or 3; provided that m+n is 2 or 3; q is 1 or 2; X is CH.sub.2 ; CH(halogen); CF.sub.2 ; CHOCH.sub.2 F; CHOCF.sub.3 ; CHOCH.sub.2 CF.sub.3 ; O; S(O).sub.0-2 ; NH; N(C.sub.1 -C.sub.4 alkyl); or N(C.sub.1 -C.sub.4 haloalkyl); and R.sup.1. R.sup.2, and Q are as defined in the disclosure. Also disclosed are compositions containing the bicyclic imides of formulae (I) and (II) and a method for controlling growth of undesired vegetation comprising applying to the locus to be protected an effective amount, of the bicyclic imides formulae (I) and (II).

Abstract: This invention describes 2,4-diamino-5-iodopyrimidines II where R, R1, R2, and R3 are independently selected from hydrogen, alkyl, cycloalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, and arylalkyl; or, R1 and R2, and R3 and R, each independently, when taken together with pentylene or 3-oxapentylene, form piperidine and morpholine ring systems respectively; and R4 is hydrogen or lower alkyl. These compounds are useful intermediates in the preparation of insecticides I where U is an optionally substituted alkenylene.