Abstract: Process for the preparation of substituted thiazolines of the formula (I) in which Ar is a phenyl, naphthyl, thienyl, pyridyl or quinolinyl radical which can optionally be substituted by one or more substituents from the group consisting of halogen, OH, benzyloxy, C1-C4-alkyl, C1-C4-alkoxy, COOR1 where R1 is H or C1-C4-alkyl, by coupling of (S)-?-methylcysteine hydrochloride of the formula (II) with a nitrile of the formula (III) Ar—CN in which Ar is as defined above, or a corresponding C1-C4-alkyl imidate, in which (S)-?-methylcysteine hydrochloride of the formula (II) is reacted in a suitable solvent with a nitrile of the formula (III) or a corresponding C1-C4-alkyl imidate in the presence of a tertiary base at a pH of 6.5 to 10 at 50° C. up to the reflux temperature to give the corresponding thiazoline of the formula (I), and processes for the preparation of (S)-?-methylcysteine hydrochloride and its use for the preparation of thiazolines of the formula (I).

Abstract: Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. In one embodiment, the present invention relates to a method of preparing a 2-alkylcysteine comprising condensing cysteine with an aryl nitrile to form a 2-arylthiazoline-4-carboxylic acid, esterifying the 2-arylthiazoline-4-carboxylic acid using a substituted or unsubstituted alcohol group comprising one or more chiral carbons, and alkylating at the 4-position of the thiazoline ring to form a 2-aryl-4-alkyl-thiazoline-4-carboxylic acid ester. The chiral templates present in the thiazoline carboxylic acid ester can provide face selectivity, and consequently desired stereochemistry, during the delivery of an alkyl group to the 4-position of the thiazoline ring. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring.

Abstract: A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof Wherein R1 and R2 are independently H or C1-3 alkyl or R1 and R2 which are bonded to the same carbon atom may together with the carbon atom to which they are bonded form a 3-5 membered cycloalkyl ring; X1 represents O or S; Each R3, R4, R8 and R9 independently represents H, halogen, —CH3 and —OCH3; R5 represents H or C1-6 alkyl or R4 and R5 together form a 3-6 membered cycloalkyl ring. X2 represents NH, NCH3 or O; One of Y and Z is N, and the other is O or S; R6 represents phenyl or pyridyl (wherein the N is in position 2 or 3) and is optionally substituted by one or more halogen, CF3, C1-6 straight or branched alkyl (optionally substituted by halogen), with the provision that when R6 is pyridyl, the N is unsubstituted.

Abstract: The invention relates to thiophene carboxanmides of formula (I). wherein A, R1, R2, R3, n and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.

Abstract: The present invention is directed to a compound of Formula I: wherein A, R1, and R2 are defined herein. The present invention is also directed to compositions comprising compounds of Formula I, methods of using compounds of Formula I, and methods of making compounds of Formula I.

Abstract: Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. In one embodiment, the present invention relates to a method of preparing 2-alkylcysteine comprising condensing cysteine with an aryl nitrile to form a 2-arylthiazoline-4-carboxylic acid, forming a 2-arylthiazoline-4-amide using an amine group comprising at least one substituted or unsubstituted alkyl group that comprises one or more chiral carbon atoms, and alkylating at the 4-position of the thiazoline ring to form a 2-aryl-4-alkyl-thiazoline-4-amide. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In one embodiment, an aryl nitrile or imidate is condensed with cysteine or a 2-alkyl cysteine.

Abstract: A series of activated iodo-benzamide derivatives are described as antineoplastic and antiviral drug compounds. The compounds generally possess a chelating group, a thiol trapping group and an activating group. The presumptive mechanism of action in preventing cancer cell and virus replication is through inhibition of the binding of transcription factors to zinc finger binding domains. The compounds are effective in inhibiting growth of a variety of human and animal tumor and leukemia cell lines at low concentrations.

Abstract: There is disclosed an advantageous mixed acid anhydride production method of formula (1): R1C(O)OY(O)n(R2)p  (1) wherein R1, R2 and Y denote the same as defined below, n and p denote an integer of 1 or 2, which is characterized by adding a carboxylic acid of formula (2); R1COOH  (2) wherein R1 denotes a hydrogen atom, an optionally substituted alkyl group or the like, an organic base to a solution of a carboxylic acid activating agent of formula (3); (R2)pY(O)nX  (3) wherein R2 denotes an optionally substituted aliphatic hydrocarbyl group or the like, Y denotes a carbon atom, a phosphorus atom, or a sulfur atom, and X denotes a chlorine atom or the like.

Abstract: A useful and efficient method of preparing an alkylated thiazoline carboxylic acid, or a derivative thereof, comprises coupling a substituted aryl nitrile such as, for example, 2,4-dimethoxybenzonitrile or 4-methoxybenzonitrile, with a cysteine ester to form a substituted thiazoline carboxylic acid ester; optionally hydrolyzing the substituted thiazoline carboxylic acid ester to form a substituted thiazoline carboxylic acid; optionally, protecting the carboxyl group; alkylating the thiazoline ring at the 4-carbon position, as indicated in Structural Formula (I), with a compound of the formula R1—L, wherein R1 is as defined above and L is a leaving group, in the presence of a phase transfer catalyst; and, optionally, deprotecting the carboxyl group.

Abstract: This invention is related to novel di-substituted aminomethyl chroman derivatives which are useful in the treatment of beta-3 receptor-mediated conditions.

Abstract: The present invention relates to novel thiazoline acids and derivatives thereof useful as chelators of trivalent metals in therapeutic applications. For example, the thiazoline acid derivatives are useful in diagnosing and treating pathological conditions associated with an excess of trivalent metals in humans and animals.

Abstract: The present invention relates to a process for preparing stereoisomerically enriched 3-heteroaryl-3-hydroxycarboxylic esters by reducing 3-heteroaryl-3-oxocarboxylic esters in the presence of ruthenium-containing catalysts.

Abstract: Diarylanines, such as 5-amide substituted diarylamines of formula (I) or formula (II) wherein A is hydroxy, C1-6 alkoxy, or NR6OR7; X is OR12, NR13R12, or NR14; inhibitors of MEK and are useful in the treatment of a variety of proliferative disease states, such as conditions related to the hyperactivity of MEK, as well as diseases modulated by the MEK cascade.

Abstract: Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. A method of preparing a 2-alkyl amino acid involves reacting cysteine (or a salt or an ester thereof) and an aryl carboxylic acid to form a thiazoline ring, stereospecifically alkylating the thiazoline ring, and hydrolyzing the thiazoline ring to obtain a 2-alkylcysteine (or related compound). The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, an aryl nitrile or imidate is condensed with cysteine, a 2-alkyl cysteine, or a cysteine ester.

Abstract: There is a significant demand for organic nitriles, based on their versatility in reactions. Compounds prepared from nitriles have properties including superoxide inhibition, ferrielectric liquid crystal dopant, antipicornaviral agents, anti-inflammatory agents, anti-asthma agents, and fibringoen antagonists. The present invention discloses a facile synthesis for 2,4-dihydroxybenzonitrile, and ethers and diethers thereof, from 2,4-dihydroxybenzaldehyde or 2,4-dimethoxybenzaldehyde. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, 2,4-dihydroxybenzonitrile is condensed with (S)-2-methylcysteine.

Abstract: The invention relates to processes for preparing 2-aminomethyl-4-cyanothiazole and its salts of the formulae Ia and Ib in which n=1 or 2 and, for n=1, X is chloride, bromide, triflate and hydrogen sulfate and for n=2, X is sulfate, comprising the process step where the thioamide of the formula IV is stirred with a bromopyruvate of the formula V, in which R1 is branched or linear C1-4-alkyl in an alcohol R2OH in which R2 is branched or linear C1-8-alkyl, HO—CH2—CH2—, HO—CH2—CH2—CH2— or C1-4-alkyl- O—CH2—CH2— at from −5° C. to 40° C. until the conversion of the thioamide IV has essentially gone to completion, and to the compounds of the formulae Ia and Ib.

Abstract: The invention relates to processes for preparing 2-aminomethyl-4-cyanothiazole and its salts of the formulae Ia and Ib in which n=1 or 2 and for n=1, X is chloride, bromide, triflate and hydrogen sulfate and for n=2, X is sulfate, which comprises the process step where the aminonitrile of the formula II is stirred with a cysteine ester of the formula III, in which R1 is branched or linear C1-10-alkyl or where n=0, 1 or 2 and R2 is branched or linear C1-C10C10-alkyl or C1-C4-alkoxy or C1-C4-dialkylamino in an inert solvent in the presence of a base at from 0° C. to 80° C. until the reaction has essentially proceeded to completion, and to the compounds of the formulae Ia and Ib.

Abstract: The present invention provides novel compounds represented by formula I: 1

Abstract: Compounds of the formula: wherein R1, Y, W, A and R2 are as defined above are inhibitors of rotamase enzymes in particular FKBP-12 and FKBP-52. The compounds therefore moderate neuronal regeneration and outgrowth and can be used for treating neurological disorders arising from neurodegenerative diseases and nerve damage.

Abstract: The present invention relates to the compounds of the formula (I) and salts thereof (all the symbols are the same meanings as described in the specification). The compounds of the formula (I) possess inhibitory activity of N-type calcium channel, so they are useful as drug for prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis, epilepsy, asthma and pollakiuria etc. or agent for the treatment of pain.

Abstract: Provided are processes for synthesizing structurally diverse pyruvate-derived compounds using a parallel approach on a solid phase support. Examples of such a solid phase support include resins which have also been used in solid phase peptide synthesis.

Abstract: Process for the preparation of substituted thiazolines of the formula (I) 1

Abstract: Phenyl- and pyridyl-substituted thiazoline acid derivatives useful in diagnosing and treating pathological conditions associated with an excess of trivalent metals in humans and animals.

Abstract: Matrix metalloproteinase inhibitors are tricyclic substituted cyclic sulfonamides of the formula or a pharmaceutically acceptable salt thereof wherein R1 and R2 include hydrogen, alkyl, and substituted alkyl; R3 and R4 include hydrogen, halo, and alkyl; X is OH or NHOH, V is O, S, SO2, NR5, or CH2, R5 is a hydrogen or alkyl, and Z is (CH2)n, wherein n is an integer from 0 to 2.

Abstract: Matrix metalloproteinase inhibitors are tricyclic sulfonamides of the Formula I or a pharmaceutically acceptable salt thereof, wherein R1 and R2 include hydrogen, alkyl, and substituted alkyl; R3 is OH or NHOH; X is O or S(O)n; n is 0, 1, or 2; p is 0, 1, 2, or 3; — is absent or a bond; and the sulfur atom bearing (O)q is bonded to the benzo ring at position a or position b.

Abstract: Compounds of the formula: wherein R1 to R7 and Y are as defined in the specification, and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof, are useful for treating diseases associated with cystein proteases, such as osteoporosis, osteoarthritis, rheumatoid arthritis, tumor metastasis, glomerulonephritis, atherosclerosis, myocardial infarction, angina pectoris, instable angina pectoris, stroke, plaque rupture, transient ischemic attacks, amaurosis fugax, peripheral arterial occlusive disease, restenosis after angioplasty and stent placement, abdominal aortic aneurysm formation, inflammation, autoimmune disease, malaria, ocular fundus tissue cytopathy and respiratory disease.

Abstract: The present invention provides certain N-substituted sulfonamide derivatives useful for potentiating glutamate receptor function in a mammal and therefore, useful for treating a wide variety of conditions, such as psychiatric and neurological disorders.

Abstract: A series of activated iodo-benzamide derivatives are described as antineoplastic and antiviral drug compounds. The compounds generally possess a chelating group, a thiol trapping group and an activating group. The presumptive mechanism of action in preventing cancer cell and virus replication is through inhibition of the binding of transcription factors to zinc finger binding domains. The compounds are effective in inhibiting growth of a variety of human and animal tumor and leukemia cell lines at low concentrations.

Abstract: Compounds of the formula and the salts, esters and amides thereof wherein Z is S, SO, SO2 or O; each of R1, R2 and R3 is independently H or substituted or unsubstituted alkyl (1-10C), substituted or unsubstituted alkenyl, substituted or unsubstituted acyl (2-11C), substituted or unsubstituted aryl (6-14C), substituted or unsubstituted arylcarbonyl (7-15C), substituted or unsubstituted arylalkyl (7-15C), substituted or unsubstituted pyridyl wherein substituents on any alkyl, alkenyl, or acyl moiety are selected from the group consisting of halo, and RO, wherein R is H or alkyl (1-6C), and substituents on any aryl or pyridyl moiety are selected from the group consisting of halo, and RO, where R is H or alkyl (1-6C), —CN and —CF3; with the proviso that R1 is not H and R1 and R3 are not identical and with the proviso that in formula (1), the B ring may contain one double bond that is located between positions 2 and 3, and in formula (2), the B ring may contain one double bond tha

Abstract: A sulfur-containing unsaturated carboxylate compound comprising a sulfur-containing substituent and at least two &agr;,&bgr;-unsaturated carboxylic acid residues, which are each attached to a secondary or tertiary carbon atom via an oxygen atom; a polymerizable composition comprising the sulfur-containing unsaturated carboxylate compound; a cured product prepared by polymerizing the polymerizable composition; an optical component consisting of the cured product; and novel intermediate compounds for preparation of the above carboxylate.

Abstract: This invention relates to neurotrophic, low molecular weight, small molecule heterocyclic ketone and thioester compounds, compositions containing the same, and the use of such compounds for treating neurological disorders, including physically damaged nerves and neurodegenerative diseases.

Abstract: 3-(Substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds are useful as insecticides and acaricides. New synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds are also provided.

Abstract: This invention relates to novel N-linked sulfonamides of N-heterocyclic carboxylic acid and carboxylic acid isosteres, their preparation, and use for treating neurological disorders including physically damaged nerves and neurodegenerative diseases, and for treating alopecia and promoting hair growth.

Abstract: Process for the hydrolytic ring cleavage of thiazolidine derivatives to give 2-aminomercaptan derivatives and carbonyl compounds, which comprises bringing an aqueous solution of the thiazolidine derivative into contact with an acidic cation exchanger in the H+ form, giving a solution L1 which contains the carbonyl compound and eluting the cation exchanger with a suitable eluent, giving a solution L2 which contains the 2-aminomercaptan derivative.

Abstract: Compounds having Formula 8 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.

Abstract: The present invention relates to a method for the preparation of citalopram or any of its enantiomers and acid addition salts thereof comprising treatment of a compound of formula (IV), wherein X is O or S; R1-R2 are each independently selected from hydrogen and C1-6 alkyl, or R1 and R2 together form a C2-5 alkylene chain thereby forming a spiro-ring; R3 is selected from hydrogen and C1-6 alkyl, R4 is selected from hydrogen, C1-6 alkyl, a carboxy group or a precursor group therefore, or R3 and R4 together form a C2-5 alkylene chain thereby forming a spiro-ring, with a dehydration agent or alternatively where X is S, thermally cleavage of the thiazoline ring, or treatment in presence of a radical initiator, to form citalopram. The invention also relates to intermediates used in the new process for the preparation of citalopram, as well as citalopram prepared according to the new process.

Abstract: This invention relates to novel N-heteorocyclic carboxylic acids and carboxylic acid isosteres, their preparation and use for treating neurological disorders including physically damaged nerves and neurodengenerative diseases, for treating alopecia and promoting hair growth, for treating vision disorders and/or improving vision, and for treating memory impairment and/or enhancing memory performance by administering such compounds.

Abstract: A compound of the formula where: n, and X are as defined in the specification, and the compound possesses selectivity for inhibition of cyclooxygenase-2.

Abstract: A series of activated iodo-benzamide derivatives are described as antineoplastic and antiviral drug compounds. The compounds generally possess a chelating group, a thiol trapping group and an activating group. The presumptive mechanism of action in preventing cancer cell and virus replication is through inhibition of the binding of transcription factors to zinc finger binding domains. The compounds are effective in inhibiting growth of a variety of human and animal tumor and leukemia cell lines at low concentrations.

Abstract: A pharamceutical composition comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein A is C1-6alkyl, C2-6alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, arylC1-6alkyl, aryl, S(O)pR1.

Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

Abstract: The present invention provides a technique of selectively producing a desired polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid. The present invention also provides a method of producing various polymorphs of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, which comprises crystallizing under the conditions defined by a specific temperature and a composition of a mixed solvent of methanol and water, and polymorphs obtained by the method. The present invention further provides a method of producing the other polymorphs or amorphous compounds by drying a specific polymorph under a reduced pressure with heating, and the other polymorphs or amorphous compounds obtained by the method.

Abstract: This invention relates to neurotrophic low molecular weight, small molecule heterocyclic esters and amides having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.

Abstract: A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a &bgr;-lactam antibiotic, a therapeutically effective amount of an amino acid derivative or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof.

Abstract: A composition in unit dosage form for the inhibition, prevention or treatment of inflammatory bowel disease comprising an effective amount of a compound having the formula: ##STR1## and a pharmaceutically acceptable carrier therefor.

Abstract: Disclosed is a novel class of thiazole, thiadiazole, and oxadiazole compounds which are substituted at their nuclear carbons by aromatic moieties. These compounds exhibit antifungal activity against a variety of fungi including strains which have proven to be resistant to treatment with known antifungal agents such as Fluconazole.

Abstract: One pot synthesis of 1,2,4-triazoles uses thioimidate intermediate and 1,2-dichloroethane solvent.

Abstract: Tyrosine derivatives of formula (1) are described: ##STR1## in which R is (1) a group R.sup.1 X.sup.1 -- where R.sup.1 is an optionally substituted alkyl or aromatic group, and X.sup.1 is a covalent bond or a --(CH.sub.2).sub.n -- [where n is an integer 1 or 2], --C(O)--, --CH.sub.2 C(O)--, --NHC(O)--, --CH.sub.2 NHC(O)--, or --SO.sub.2 -- group, or (2) a group (Hal.sup.1).sub.3 CSO.sub.2 --, where Hal.sup.1 is a fluorine or chlorine atom;R.sup.2 and R.sup.3, which may be the same or different, is each a hydrogen or halogen atom or an alkyl, alkoxy, hydroxyl or nitro group;Alk is an alkylene chain;m is zero or an integer 1;R.sup.4 is a hydrogen atom or a methyl group;R.sup.5 is a group --(CH.sub.2).sub.p CO.sub.2 R.sup.8 where p is zero or an integer 1 and R.sup.8 is a hydrogen atom or an alkyl group;R.sup.6 is a hydrogen atom or an alkyl group;Y is a sulphur atom or a --S(O).sub.q -- group where q is an integer 1 or 2;X.sup.2 is a --C(O)--, --C(O)O--, --CONH-- or --S(O).sub.2 -- group;R.sup.

Abstract: Phenyl- and pyridyl-substituted thiazoline acid derivatives useful in diagnosing and treating pathological conditions associated with an excess of trivalent metals in humans and animals.

Abstract: The object amide compounds of the present invention are novel and can be represented by the following general formula (I): whereinR.sup.1 is indolyl or benzofuranyl;R.sup.2 is hydrogen, lower alkylthio(lower)alkyl or a group of the formula: ##STR1## in which R.sup.5 is hydrogen, lower alkoxy or halogen; R.sup.3 is hydrogen, quinolyl or phenyl which may have a suitable substituent selected from the group consisting of lower alkyl, lower alkoxy, lower alkylthio and halogen;R.sup.4 is hydrogen or optionally esterified carboxy; andX is S or NR.sup.6in which R.sup.6 is hydrogen, lower alkyl or a group of the formula: ##STR2## in which R.sup.7 is lower alkyl or lower alkoxy.