Abstract: The embodiments described herein concern 5-substituted pyrimidine derivatives of conformationally locked nucleoside analogues and to the use of these derivatives as anti-viral and anti-cancer agents. The compounds are of the formula: wherein B is uracil-1-yl or cytosin-1-yl having a 5-substituent selected from halogen, alkyl, alkenyl, and alkynyl, with the proviso that where B is uracil-1-yl, the 5-substituent is not methyl. The compounds are useful in the treatment of Herpes simplex virus (HSV).

Abstract: This invention describes novel pyrazole compounds of formula IV: wherein Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are independently selected from T-R3, or taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 1-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen; and R2, R2?, T, and R3 are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of aurora-2 and GSK-3, for treating diseases such as cancer, diabetes and Alzheimer's disease.

Abstract: There is provided a process for the production a compound of general formula I: wherein A, R1, R2, R3 and R4 have meanings given in the description, which process comprises the reaction of a compound of formula II, wherein Rx is a group substitutable by an aminopyrazole, with a compound of general formula III

Abstract: Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein R1 is a halogen, or an oxygen linked leaving group including an aromatic ether, an alkyl sulfonate, an aryl sulfonate, an alkyl phosphonate, an aryl phosphonate, an alkyl phosphate or aryl phosphate; R2 is COOR5, C(?O)NH(CHR5)m—COOR5, NH(CHR5)mCON(R5)R6, C(?O)N(R5)R6 or NH(CHR5)mOH; R3 is H or alkyl; R4 is H, substituted or unsubstituted aryl, heteroaryl or alkyl; R5 and R6 are independently H, lower alkyl, aryl, hydroxy alkyl, amino alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycloalkyl; and m=0–6; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1? protease activity in a mammal utilizing the compounds and compositions.

Abstract: Methods of treating certain neurological diseases using exogenous uridine or a uridine source alone as a precursor of endogenous cytidine, particularly in the human brain, are disclosed. Methods are also disclosed wherein exogenous uridine or a uridine source is combined either with drugs increasing uridine availability or with compounds that serve as a source of choline in phospholipid synthesis.

Abstract: In one embodiment, the present invention relates to a new class of ammonium salts of N?-acyl derivatives of N?-(4-amino-4-deoxypteroyl)-L-ornithine compounds having a structure according to formula II-IV. Formula II has the structure of: wherein: R2 represents up to four groups independently selected at each occurrence of R2 from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C1-6 alkoxy, chloro, fluoro, hydroxy, and —COOH; R3, R4, and R5 are each independently selected from hydrogen and C1-6 alkyl; or NR3R4 taken combination can form a 5 to 7 member heterocycle having at least one nitrogen ring atom; and x is a real number greater than 0 and less than about 4. The ammonium salts provided by the invention exhibit high inhibitory activity against the growth o methotrexate-resistant cells, and also exhibit superior chemical stability than corresponding acidic N?-acyl derivatives of N?-acyl derivatives of N?(4-amino-4-deoxypteroyl)-L-ornithine compounds.

Abstract: Compounds of Formula (I): wherein Ar1 is aryl; Ar2 is hydrogen, cycloalkyl, aryl or heteroaryl; Z is —C(?O) or a single bond; R1, R2, R3, R4 and R5 are independently hydrogen or alkyl optionally substituted with hydroxy; alk is an alkylene chain of one to six carbon atoms; X is —O—, —NRh (where Rh is hydrogen or alkyl), (CR6R7)m(where R6 and R7 are independently in each occurrence hydrogen or alkyl and m is an integer from 0 to 3), or —S(O)n (wherein n is an integer from 0 to 2); or prodrugs thereof, and pharmaceutically acceptable salts thereof, are inhibitors of CCR3 useful for treating eosinophil induced diseases such as asthma.

Abstract: Compounds exhibiting CNS activity in mammalian species, having the structure wherein A is an optionally heterocyclic 5 or 6 membered aromatic ring system; R2 is an organyl group substituent or two R2 together may form a fused ring system, o is an integer from 0 to 4, the upper limit of o bounded by the num er of available substitutent sites on said optionally heterocyclic 5 or 6 membered aromatic ring structure; n is an integer from 0 to 2; R1 is an organyl group; p is 1 to 4; wherein one (CH2)n group may be replaced by O or S; or a pharmaceutically acceptable derivative thereof; The compounds exhibit activity in dopamine transporter systems, and in p rticular a high differential activity between the D3 and D2 receptors.

Abstract: Disclosed are novel nitrile compounds of formula (I) further defined herein, which compounds are useful as reversible inhibitors of cysteine proteases such as cathepsin K, S, F, L and B. These compounds are useful for treating diseases and pathological conditions exacerbated by these proteases such as, but not limited to, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and other autoimmune diseases, Alzheimer's disease, atherosclerosis. Also disclosed are processes for making such novel compounds.

Abstract: A diphosphonic acid ester of formula [VII] or [VII?] and a diphosphonium salt of formula [VIII] or [VIII?] are provided: wherein R75, R76, R75? and R76? may be the same or different and independently represent an alkyl or alkenyl group having from 1 to 4 carbon atoms, a cyclohexyl group or a phenyl group, R77, R78, R79 and R80 may be the same or different provided that at least three thereof are cyano groups and the others independently represent a hydrogen atom, a cyano group, a nitro group or a halogen atom, R77?, R78?, R79? and R80? may be the same or different and independently represent a group selected from a hydrogen atom and a halogen atom provided that at least three thereof are fluorine atoms and X represents a halogen atom. These compounds are useful as synthetic intermediates for the preparation of luminescent bis(aminostyryl)benzene compounds.

Abstract: The invention pertains to theophylline (1-methyl, 3-methyl xanthine) and IBMX (1-methyl, 3-isobutyl xanthine) derivatives of formulas I and II: where R1 is —CH3 or —CH2CH(CH3)2, and R2 is where R3 and R4 are independently selected from the group consisting of OCH3, CH3, NO2, F, Cl, Br and I.

Abstract: Imidazo[1,2-?]pyrimidinones and pyrimido[1,2-?]pyrimidinones useful for preventive and/or therapeutic treatment of neurodegenerative diseases, such as Alzheimer's disease, caused by abnormal GSK3? activity.

Abstract: A compound of formula: (wherein X is O or S and R1, R3, R4, and R5 are disclosed herein) or a pharmaceutically acceptable salt thereof (a “Thiadiazolylpiperazine Compound”), pharmaceutical compositions comprising a Thiadiazolylpiperazine Compound, and methods for treating or preventing pain in a patient comprising administering to a patient in need thereof an effective amount of a Thiadiazolylpiperazine Compound are disclosed.

Abstract: The invention provides piperidine and piperazine derivatives of general formula (I), processes for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy

Abstract: This invention relates to the compounds represented by a general formula [I]: [in which A1 and A2 represent optionally fluorine-substituted methine or the like; B represents halogen, cyano, lower alkyl or the like; D represents optionally substituted heterocyclic group or the like; and G represents C3-C20 aliphatic group such as alicyclic group]. These compounds inhibit nociceptin activities due to their high affinity to nociceptin receptor, and are useful as analgesic, antiobestic, corebral function improver, drugs for treatment of alzheimer's disease and dementia, remedies for schizophrenia and neurodegenerative diseases, antidepressant, remedies for diabetes insipidus, polyuria, hypotension and so on.

Abstract: A polycyclic guanine phosphodiesterase V inhibitor having the formula (I.1) or (II.

Abstract: The present invention offers novel cyclic diamine compounds and a pharmaceutical composition containing the same. The present invention relates to a compound represented by the formula (I) or salt(s) or solvate(s) thereof. (In the formula, is an optionally substituted divalent residue of benzene, pyridine, cyclohexane or naphthalene or is a vinylene group where Ar is an optionally substituted aryl group; X is —NH—, oxygen atom or sulfur atom; Y is —NR1—, oxygen atom, sulfur atom, sulfoxide or sulfone; Z is a single bond or —NR2—; R1 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group; R2 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group; l is an integer of from 0 to 15; m is an integer of 2 or 3; and n is an integer of from 0 to 3).

Abstract: The invention relates to the new crystalline forms II, III and V of meloxicam; to the processes for obtaining the crystalline forms I, II, III and V; and, finally, to the interconversion processes of the forms II, III, IV and V into the form I.

Abstract: Pyrazole compounds represented by the formula: are described. The pyrazole compounds and pharmaceutical compositions containing them may be used in inhibiting ERAB or HADH2 activity and in treating ERAB, HADH2 or amyloid-? mediated diseases and conditions.

Abstract: The invention provides compounds of formula (I) wherein R is as defined in the description, and the preparation thereof. The compounds of formula (I) are useful as pharmaceuticals, for use in the treatment of any state associated with high levels of activeted PARP.