Abstract: A method of suppressing immune responses, comprising administering to a patient in need thereof an effective amount of a composition comprising a substance capable of reducing the content of reductive glutathione in macrophages.

Abstract: This invention is directed to novel oxamyl dipeptide ICE/ced-3 family inhibitor compounds. The invention is also directed to pharmaceutical compositions containing these compounds, as well as to the use of such compositions in the treatment of patients suffering inflammatory, autoimmune and neurodegenerative diseases, for the prevention of ischemic injury, and for the preservation of organs that are to undergo a transplantation procedure.

Abstract: The present invention relates to methods for promoting tissue repair, angiogenesis and cell migration. The method of the invention utilizes thymosin a1 (T&agr;1) peptide to promote tissue repair, angiogenesis and cell migration. The invention further relates to modulating T&agr;1 activity in tissues.

Abstract: The invention relates to novel mimetics of the tetrasaccharides sialyl- Lewis-X (SLeX) and sialyl- Lewis-A (SLeA) having an improved action as inhibitors of cell adhesion, specifically a compound of the formula I in which R1 is —H, —CH3 or —CH2OH, R2 is —H or —OH, R3, R4 and R5 independently of one another are —H, C1-C4-alkyl or —OH, R6, R7, R8, R9 and R10 independently of one another are —H or C1-C4-alkyl D is —O—C(O)—, —C(O)—or —NR6—C(O)—, E is —CR7R8—, —NR7—, or a nitrogen heterocycle of the formula n is 1 or 2, m is 0 or 1, p is an integer from 0 to 10, q is 1 or 2 and X1 and X2 independently of one another are —H, —COOR9, —NR9R10, —OH, —OSO3H, —CH2COOR9 or —CH2OSO3H or together are ═O, to a process for preparing these compounds and to their use as pharmacological active compounds and diagnostic

Abstract: Pyranoside derivatives of the formula I wherein 1, m and n independently of one another denote an integer chosen from 0, 1, 2, 3 and 4 and 1+m+n≦4. These are are LTB4-antagonists. Also disclosed are processes for making these compounds.

Abstract: The present invention provides methods and compositions for the suppression of oncogenic transformation, tumorigenesis and metastasis. The present invention discloses functional domains of E1A responsible for the suppression of transformation, and provides mini-E1A constructs that can be used for tumor suppression. The invention also discloses methods for the novel use of mini-E1A in combination with chemotherapeutic drugs and/or tyrosine kinase inhibitors.

Abstract: Methods of introducing genetic material into cells of an individual and compositions and kits for practicing the same are disclosed. The methods comprise the steps of contacting cells of an individual with a genetic vaccine facilitator and administering to the cells, a nucleic acid molecule that is free of retroviral particles. The nucleic acid molecule comprises a nucleotide sequence that encodes a protein that comprises at least one epitope that is identical or substantially similar to an epitope of a pathogen antigen or an antigen associated with a hyperproliferative or autoimmune disease, a protein otherwise missing from the individual due to a missing, non-functional or partially functioning gene, or a protein that produce a therapeutic effect on an individual. Methods of prophylactically and therapeutically immunizing an individual against HIV are disclosed. Pharmaceutical compositions and kits for practicing methods of the present invention are disclosed.

Abstract: Methods for induction of E2F-1 related vascular smooth muscle cell (VSMC) death to limit vascular stenosis or restenosis, to regress atherosclerotic plaque and to prevent atherogenesis are disclosed. Also disclosed is an adenovirus vector containing the E2F-1 gene, and a method of transferring the gene to a vessel or graft. A method of limiting cell proliferation and/or reducing cell numbers includes transferring the E2F-1 gene into VSMC to achieve overexpression of E2F-1 gene product, which drives vascular cells into S-phase and thereby causes their subsequent death.

Abstract: Particles comprising an outer wall formed of one or more saccharide components selected from the group consisting of monosaccharides and oligosaccharides crosslinked by interfacial crosslinking in emulsion, preferably at room temperature, with a polyfunctional acylating crosslinking agent to produce ester linkages between the acylatable hydroxyl group(s) of the primary alcohol(s) of the saccharide component and the acyl groups of the polyfunctional acylating agent. These particles can be used for the manufacture of cosmetic, pharmaceutical and food compositions.

Abstract: An objective of the present invention is to provide compositions for supplying minerals to patients who underwent gastrectomy to thereby treat or prevent postgastrectomic syndrome. The composition for postgastrectomic mineral supply according to the present invention comprises an indigestible oligosaccharide and/or an indigestible sugar alcohol and a mineral.

Abstract: Osteoblast-specific mitogens and drugs containing such compounds can be used for treating metabolic bone diseases. These compounds include lysophosphatidylic acid derivatives selected from the group consisting of compounds of formula: wherein R1=alkenyl or alkynyl having from 6 to 24 carbon atoms; n=0-12; X=oxygen or NH; the compounds (all-cis-5,8,11,14)-eicosatetraenoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9, cis-12-octadecadienoic acid 2-hydroxy-3-phosphonooxypropyl ester; (all-cis-9,12,15)-octadecatrienoic acid 2-hydroxy-3-phosphonooxypropyl ester; cis-9-octadecenoic acid 2-hydroxy-3-phosphonooxypropyl ester; and erucic acid 2-hydroxy-3-phosphonooxypropylester being excluded, and the physiologically tolerable salts, esters, optically active forms, and racemates of said compounds, and derivatives of said compounds, salts, esters, optically active forms and racemates which can be metabolized in vivo to yield the corresponding compound of formula (I).

Abstract: Isophosphoramide mustard analogs useful for treating cancer are provided.

Abstract: Compounds of the androstane series are described having general formula and solvates thereof, in which R1 represents O, S or NH; R2 individually represents OC(═O)C1-6 alkyl; R3 individually represents hydrogen, methyl (which may be in either the &agr; or &bgr; configuration) or methylene; or R2 and R3 together represent where R6 and R7 are the same or different and each represents hydrogen or C1-6 alkyl; R4 and R5 are the same or different and each represents hydrogen or halogen and represents a single or a double bond. These compounds and their solvates have use in medicine as anti-inflammatory or anti-allergic agents.

Abstract: Disclosed are (i) compounds of a steroid, a &bgr;-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, &bgr;-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO•) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.

Abstract: Novel dietary complexes for gastrointestinal symptoms and gastrointestinal microbes are provided. They comprise a dietary metal and a dietary ligand wherein the dietary metal is selected from zinc, copper, cobalt, manganese and iron and the dietary ligand is lawsone or tropolone.

Abstract: The invention provides compositions that include conjugates of a fatty acid molecule, preferably cis-docosahexaenoic acid, and clozapine. The conjugates are useful in treating psychological disorders such as schizophrenia.

Abstract: The present invention discloses a treatment for syndrome-X, and resulting complications, that include hyperlipidemia, hypertension, central obesity, hyperinsulinemia and impaired glucose intolerance. Diabetic complications include excess proinsulin levels.

Abstract: Insecticidal dihydrooxadiazine compounds having the formula: wherein X is O, N or S; R is a substituted or unsubstituted phenyl or C4-C5 heterocyclic group; R2, R3, R4, and R5 are one of the following: a) R2, R3, and R4 are, independently, hydrogen, alkyl, alkoxy, or furanyl; and R5 is nitro, cyano, alkyl, dialkylamino, alkylthio, alkoxy, haloalkoxy, phenoxy, phenylthio, or alkoxycarbonyl, wherein R3 and R5 together can form a ring; or b) R3, R4, and R5 are hydrogen; and R2 is alkylthio, alkylsulfinyl, alkylsulfonyl, nitroalkoxy, hydroxy, dialkoxyphosphinyl, cyano, acyloxy, alkoxy, haloalkoxy, cycloalkyl, or alkenyl; or R2 is a substituted or unsubstituted phenyl, phenylthio, phenylsulfinyl, phenylsulfonyl, pyrazolyl, furanyl, thienyl, phenylalkoxy, or benzoyloxy; and R6 is hydrogen, alkyl, alkylthio, alkoxyalkyl, acyl, benzyl, or alkoxycarbonyl.

Abstract: The invention provides various derivatives of arglabin, a sesquiterpene lactone isolated from Artemisia glabella. These compounds are effective for suppressing tumor growth in mammals. A method of suppressing tumor growth in humans is also described.

Abstract: The invention relates to novel pyridocarbazole derivatives having highly selective action in inhibiting cyclic GMP-phosphodiesterase (hereinafter abbreviated as cGMP-PDE), processes for producing such derivatives, agents containing at least one of such derivatives as an active ingredient for preventing and/or treating pulmonary hypertension, ischemic heart diseases or diseases against which the cGMP-PDE inhibitory action is effective, and intermediates useful for the production of pyridocarbazole derivatives.

Abstract: A compound having general formula (I) wherein R1, R2, R′3, R4, and R6 have the meanings stated in the description, acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids an pharmaceutically acceptable quaternary salts thereof.

Abstract: Disclosed are compounds which are inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the compounds have a structure according to the following Formula (I): where X, W, Z, A, G, R1, R2, R3, R4, R5, R5′ and k have the meanings described in the specification. This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof Also described are pharmaceutical compositions comprising these compounds, and methods of treating or preventing metalloprotease-related maladies using the compounds or the pharmaceutical compositions.

Abstract: Novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones represented by the formula: or a pharmaceutically acceptable salt thereof, are disclosed, wherein the formula variables R1, R2, X, Y, m and n are as defined herein. Also disclosed are methods of treatment using the same and intermediate compounds useful in the preparation thereof.

Abstract: This invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, as substance-P antagonists; their preparation, compositions containing them and their use as a medicine.

Abstract: A compound of the formula wherein m, R1, R2, R3, R4, R5 and X are as defined above, useful in treating or preventing migraine, depression and other disorders for which a 5-HT1 agonist or antagonist is indicated.

Abstract: The present invention provides a novel pyrimidine derivative represented by the general formula (1): (wherein R, R4 and R8 are the same as defined in the specification) or pharmaceutically acceptable salt thereof, which possesses an excellent activity for inhibiting the formation of NO (nitrogen oxide) in vivo.

Abstract: A compound represented by the following general formula (I) which has an antiviral activity: wherein R1 represents hydrogen atom, C1-C6 alkyl group, or C7-C10 aralkyl group; R2 represents C1-C6 alkyl group, C7-C10 aralkyl group, or phenyl group; R3 and R4 independently represent hydrogen atom, C1-C6 alkyl group, acyloxymethyl group, acylthioethyl group, or ethyl gorup substituted with at least one halogen atom; R5 represents hydrogen atom, C1-C4 alkyl gorup, C1-C4 hydroxyalkyl group, C1-C4 alkyl group substituted with at least one halogen atom; and X represents carbon atom or nitrogen atom.

Abstract: An improved method for treatment of conditions in human beings associated with either or both reactive arthritis or bursitis comprising administration of a combination of acyclovir, L-lysine, minocycline hydrochloride, and metronidazole. An alternate method comprises administration of isonicotinic acid hydrazide.

Abstract: A method and composition for the treatment of HIV infection, HBV infection, or abnormal cellular proliferation in humans and other host animals is disclosed that includes the administration of an effective amount of a 1,3-oxaselenolane nucleoside or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

Abstract: Disclosed are nitrosated and/or nitrosylated phosphodiesterase inhibitors having the formula NOn-PDE inhibitor where n is 1 or 2. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides a composition comprising a therapeutically effective amount of an phosphodiesterase inhibitor (PDE inhibitor), which can optionally be substituted with at least one NO or NO2 moiety, and one to ten fold molar excess of a compound that donates, transfers or releases nitrogen monoxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO•) or which stimulates endogenous EDRF production. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides methods for treating sexual dysfunctions in males and females.

Abstract: This invention concerns the use of the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein A is CH, CR4 or N; n is 0 to 4; Q is hydrogen or —NR1R2; R1 and R2 are selected from hydrogen, hydroxy, C1-12alkyl, C1-12alkyloxy, C1-12alkylcarbonyl, C1-12alkyloxycarbonyl, aryl, amino, mono- or di(C1-12alkyl)amino, mono- or di(C1-12alkyl)aminocarbonyl wherein each C1-12alkyl may optionally be substituted; or R1 and R2 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido or mono- or di(C1-12alkyl)aminoC1-4alkylidene; R3 is hydrogen, aryl, C1-6alkylcarbonyl, optionally substituted C1-6alkyl, C1-6alkyloxycarbonyl,; and R4 is hydroxy, halo, optionally substituted C1-6alkyl, C1-6alkyloxy, cyano, aminocarbonyl, nitro, amino, trihalomethyl, trihalomethyloxy; R5 is hydrogen or C1-4alkyl; L is optionally substituted C1-10alkyl, C3-10alkenyl, C3-10alkynyl, C3-7cycloalkyl; or L is —X1—R6 or

Abstract: Diseases caused by obesity are treated with endothelin receptor antagonists. Diseases treated include those frequently associated with obesity such as hypertension, type 2 diabetes, hyperlipidemia, chronic kidney failure, arteriosclerosis and gout.

Abstract: A pharmaceutical composition in the form of a solid dispersion comprising a macrolide, e.g. a rapamycin or an ascomycin, and a carrier medium.

Abstract: Disclosed are nitrosated and/or nitrosylated phosphodiesterase inhibitors having the formula NOn-PDE inhibitor where n is 1 or 2. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides a composition comprising a therapeutically effective amount of an phosphodiesterase inhibitor (PDE inhibitor), which can optionally be substituted with at least one NO or NO2 moiety, and one to ten fold molar excess of a compound that donates, transfers or releases nitrogen monoxide as a charged species, i. e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO.) or which stimulates endogenous EDRF production. The invention also provides compositions comprising such compounds in a pharmaceutically acceptable carrier. The invention also provides methods for treating sexual dysfunctions in males and females.

Abstract: Tetrahydropyrido compounds of formula (I) in which the substituents have the meanings mentioned in the description, are suitable for the prevention or treatment of gastrointestinal diseases.

Abstract: Small creatures from the group of insects and worms which are pathogenic to humans, animals and plants can be controlled effectively by applying or introducing an aqueous percarboxylic acid solution containing one or more percarboxylic acids with 1 to 6 carbon atoms to surfaces and/or into water. A solution which contains peracetic acid and/or performic acid is preferably used. In the case of insects, the larvae of these are controlled in water using an application concentration of 1 to 5000 ppm of percarboxylic acid.

Abstract: A compound, compositions, methods of use, and processes of making formula I: or a pharmaceutically acceptable salt, hydrate, ester, solvate, prodrug, metabolite, stereoisomer, or mixtures thereof, wherein: R1, when present, is hydrogen or lower alkyl; R2 is lower alkyl, aryl, aralkyl, lower alkanoyl, or —(CH2)n—(CHOH)y(CH2)mA, wherein n is 1-4, y is 0 or 1, m is 0-5, and A is cycloalkyl, cycloalkenyl, lower alkanoyl, aryl, aralkyl, —NH2, —NH—(lower alkyl), Y represents the atoms necessary to form a fused 5- to 6-membered ring that is aromatic or nonaromatic and carbocyclic or heterocyclic; Z is (i) —CHR2CHR3— where R2 and R3 are independently hydrogen, alkyl, aryl or aralkyl; (ii) —R6C═CR3— where R6 and R3 are independently hydrogen, lower alkyl, aryl, aralkyl, chlorine, bromine or —NR7R8, where R7 and R8 are independently hydrogen or lower alkyl, or, R6 and R3, taken together, form a fused 5- to 6-membere

Abstract: Cholesteryl ester transfer protein inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

Abstract: A method for preparing pharmaceutical formulations of poorly soluble drug substances in the form of concentrated solutions for filling soft gelatin capsules and solid dispersions and suspensions for filling hard gelatin capsules and compressing into tablets is provided. Pharmaceutical formulations of poorly soluble drug substances are also disclosed. The formulations include the sodium salt of the poorly soluble drug substance, a conversion aid such as PEG, polysorbate, a sugar alcohol (e.g. mannitol or xylitol), propylene glycol or transcutol, and, in some cases an excipient, such as dicalcium phosphate dihydrate, lactose monohydrate, or microcrystalline cellulose.

Abstract: The present invention relates to the use of (±)-R*,S*)-alpha-2-piperidnyl-2,8-bis(trifluoromethyl)-4-quinolinemthanol and in particular (−)-(11S,2′R)-alpha-2-piperidnyl-2,8-bis(trifluoromethyl)-4-quinolinemthanol in the treatment of disorders in which the reduction of purinergic neurotransmission could be beneficial. The invention relates in particular to adenosine receptors, and particularly adenosine A2a receptors and to the treatment of movement disorders such as Parkinson's disease.

Abstract: A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): wherein Z is C═O or a covalent bond; Y is H or O(C1-C4)alkyl, R1 and R2 are individually (C1-C4)alkyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H, R5 is I, O(C1-C4)alkyl or H and R6 is I, O(C1-C4)alkyl or H with the proviso that when R4, R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to elevate the level of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene, toremifene or salts thereof. Further provided is a method for identifying an agent that elevates the level of TGF-beta. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro.

Abstract: A method for alleviating the symptoms of post-menopausal syndrome comprising administering to a woman in need thereof an effective amount of a compound of formula I wherein R1a is —H or —OR7a in which R7a is —H or a hydroxy protecting group; R2a is —H, halo, or —OR8a in which R8a is —H or a hydroxy protecting group; R3 is 1-piperidinyl, 1-pyrrolidino, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and Z is —O— or —S—; or a pharmaceutically acceptable salt thereof.

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states.

Abstract: Compounds of the general formula (1) wherein: ═W— is ═N—; Y is halogen or an alkyl or —XRa group; X is —O—, —S(O)m— or —N(Ra)—, where m is zero or an integer 1 or 2; Ra is hydrogen or an optionally substituted alkyl group; R2 is an optionally substituted cycloalkyl or cycloalkenyl group; R3 is R13 or —L1R13, where R13 is a halogen atom, an optionally substituted straight or branched chain C2-6alkenyl group or an optionally substituted C6-12 monocyclic or bicyclic aryl group and L1 is an optionally substituted straight or branched chain C1-6alkylene, C2-6alkenylene or C2-6alkynylene group; R4 is a hydrogen atom or a group —(CH2)nAr where Ar is an optionally substituted monocyclic aryl group and n is zero or an integer 1, 2 or 3; R5 is hydrogen; R6 is an optionally substituted 2-, 3- or 4-pyridyl group; and each of R7 and R8 is independently hydrogen or an optionally substituted straight or branched alkyl group.

Abstract: Novel compounds of general formula (I) which have homoregulatory activities and can be used to stimulate haematopoiesis and for the treatment of viral, fungal and bacterial infectious diseases.

Abstract: Phenylalanine derivatives of formula (1) are described: in which L1 is a linker atom or group; A is a chain —[C(R7)(R8)]pY[C(R9)(R10)]q— in which Y is a sulphur atom or a —S(O)— or —S(O)2— group, R7, R8, R9 and R10, which may be the same or different, is each a hydrogen atom or a straight or branched alkyl or optionally substituted aromatic group, or R7 and R8 together with the carbon atom to which they are attached, or R9 and R10 together with the carbon atom to which they are attached, each forms a C3-7cycloalkyl group, and p and q, which may be the same or different, is each zero or an integer 1 or 2, provided that when one of p or q is zero the other is an integer 1 or 2; L2 is a linker group selected from —C(O)—, —C(O)O—, —C(S)—, —S(O)2—, —CON(R11)—, [where R11 is a hydrogen atom or a straight or branched alkyl group], —CSN(R11)—, —SON(R11)&m

Abstract: The present invention relates to the discovery of novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (e.g.

Abstract: An anticancer composition comprising a diaminotrifluoromethylpyridine derivative of the formula (I) or its pharmaceutically acceptable salt, as an active ingredient: wherein X is a cycloalkylcarbonyl group, a furancarbonyl group or a benzoyl group which may be substituted by a halogen atom, and Y is an alkylsulfonyl group.

Abstract: The present invention relates to hitherto unknown compounds of formula (I) or their tautomeric forms, the attachment to the pyridine being in the 3- or 4-position, in which formula R1 stands for one or more substituents which can be the same or different and are selected from the group consisting of: hydrogen, halogen, trifluoromethyl nitro, amino, cyano, carboxy, or alkyl, alkoxy, or alkoxycarbonyl, the C-content of which can be from 1 to 4; X stands for a straight or branched C9-C20 carbon chain, saturated or unsaturated or Q—Ar—R; in which formula Ar stands for phenyl, Q stands for a C5-C20 divalent hydrocarbon radical which can be straight, branched, saturated or unsaturated and R stands for hydrogen or for one or more substituents which can be the same or different and are selected from the group consisting of: hydroxy, amino, halogen, trifluoromethyl, cyano, nitro, carboxy, carbamoyl, or alkyl, alkoxy, alkylthio, alkylamino, or alkoxycarbonyl, the C-content of which can be from 1 to 4; and p

Abstract: Compounds of the formula I wherein R2—C, R3—C, R4—C or R5—C may be replaced by N; and wherein n is 1, 2 or 3; R1 is aryl, cycloalkyl or heterocyclyl; R2, R3, R4 and R5 are independently hydrogen, optionally substituted alkyl, halo, amino, substituted amino, trifluoromethyl, cyano, carboxyl, alkoxycarbonyl, aralkoxycarbonyl, (alkyl, aryl or aralkyl)-thio, (alkyl, aryl or aralkyl)-oxy, acyloxy, (alkyl, aryl or aralkyl)-aminocarbonyloxy; or any two of R2, R3, R4 and R5 at adjacent positions are alkylenedioxy; R6 is hydrogen, optionally substituted alkyl, amino, substituted amino, acylamino, wherein Ra is hydrogen or optionally substituted alkyl, Rb and Rc are independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; or Rb and Rc together represent lower alkylene or lower alkylene interrupted by O, S, or N—(H, alkyl or aralkyl); Rd is optionally substituted alkyl, cycloalkyl, aryl or heterocyclyl; and Re is op