cas 115-08-2, THIOFORMAMIDE | Articles data

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Londergan et al.
p. 4456
(1953)
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Characterization of the Simplest Thiolimine: The Higher Energy Tautomer of Thioformamide
As sulfur-containing organic molecules thioamides and their isomers are conceivable intermediates in prebiotic chemistry, for example, in the formation of amino acids and thiazoles and resemble viable candidates for detection in interstellar media. Here, we report the characterization of parent thioformamide in the solid state via single-crystal X-ray diffraction and its photochemical interconversion to its hitherto unreported higher energy tautomer thiolimine in inert argon and dinitrogen matrices. Upon photogeneration, four conformers of thiolimine form, whose ratio depends on the employed wavelength. One of these conformers interconverts due to quantum mechanical tunneling with a half-life of 30–45 min in both matrix materials at 3 and 20 K. A spontaneous reverse reaction from thiolimine to thioformamide is not observed. To support our experimental findings, we explored the potential energy surface of the system at the AE-CCSD(T)/aug-cc-pCVTZ level of theory and computed tunneling half-lives with the CVT/SCT approach applying DFT methods.
Bernhardt, Bastian,Dressler, Friedemann,Eckhardt, André K.,Becker, Jonathan,Schreiner, Peter R.
p. 6732 - 6739
(2021)
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Structure-Based Design of a Small Molecule CD4-Antagonist with Broad Spectrum Anti-HIV-1 Activity
Earlier we reported the discovery and design of NBD-556 and their analogs which demonstrated their potential as HIV-1 entry inhibitors. However, progress in developing these inhibitors has been stymied by their CD4-agonist properties, an unfavorable trait for use as drug. Here, we demonstrate the successful conversion of a full CD4-agonist (NBD-556) through a partial CD4-agonist (NBD-09027), to a full CD4-antagonist (NBD-11021) by structure-based modification of the critical oxalamide midregion, previously thought to be intolerant of modification. NBD-11021 showed unprecedented neutralization breath for this class of inhibitors, with pan-neutralization against a panel of 56 Env-pseudotyped HIV-1 representing diverse subtypes of clinical isolates (IC50 as low as 270 nM). The cocrystal structure of NBD-11021 complexed to a monomeric HIV-1 gp120 core revealed its detail binding characteristics. The study is expected to provide a framework for further development of NBD series as HIV-1 entry inhibitors for clinical application against AIDS.
Curreli, Francesca,Kwon, Young Do,Zhang, Hongtao,Scacalossi, Daniel,Belov, Dmitry S.,Tikhonov, Artur A.,Andreev, Ivan A.,Altieri, Andrea,Kurkin, Alexander V.,Kwong, Peter D.,Debnath, Asim K.
p. 6909 - 6927
(2015)
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A convenient preparation of thioformamide. Synthesis of thiazole-4-carboxylic acid
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Rohaly,Novak,Szantay
p. 693 - 694
(1999)
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Synthesis of bis(ethylenedithio)dithiadiazafulvalenes (BEDT-DTDAF) and generation of charge-transfer complexes with tetracyanoquinodimethane
The synthesis of bis(ethylenedithio)dithiadiazafulvalenes (BEDT-DTDAFs), in four steps via 4,5-(ethylenedithio)thiazole and 3-alkyl-4,5-(ethylenedithio) thiazolium salts, and the generation of conducting charge-transfer complexes from a new type of dithiadiazafulvalene and tetracyanoquinodimethane are reported. Georg Thieme Verlag Stuttgart.
Makowiec, Slawomir,Koczan, Wioletta,Rachon, Janusz
p. 696 - 698
(2008)
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Preparation method of 4-methyl-5-(2-acetoxyethyl) thiazole
The invention relates to a preparation method of 4-methyl-5-(2-acetoxyethyl) thiazole, and discloses a preparation method of 4-methyl-5-(2-acetoxyethyl) thiazole, the 4-methyl-5-(2-acetoxyethyl) thiazole is obtained by reaction of 3-halogenated-5-acetoxy-2-pentanone and thioformamide, and the reaction takes SBA-15 molecular sieve loaded ionic liquid as a catalyst. The catalyst not only improves the reaction yield, but also improves the product purity.
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Paragraph 0032; 0035

(2021/07/14)

Thioformamide as well as preparation method and application thereof
The invention discloses thioformamide as well as a preparation method and application thereof. The preparation method disclosed by the invention comprises the following steps: taking carbon disulfide,liquid ammonia and carbon monoxide as raw materials, reacting under the catalytic action of an organic alkali under the pressure of 4-6MPa to generate thioformamide, and rectifying and collecting thioformamide after the reaction is finished. Thioformamide prepared by the method can be used as a thiabendazole intermediate, is used for synthesizing thiabendazole, and is applied to the fields of sterilization, corrosion prevention, fresh keeping and the like. Thioformamide is prepared by adopting a one-step method, and the preparation method is simple, mild in reaction condition, easy to implement, safe, controllable, low in production cost, high in yield, free of generation of wastewater and toxic gas and capable of reducing environmental pollution.
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Paragraph 0027-0029

(2020/03/09)

Thioformamide, and preparation method and application thereof
The invention discloses a thioformamide, and a preparation method and an application thereof. Carbon disulfide and formamide which are used as raw materials are reacted under a pressure of 3-5 MPa under the catalytic action of an organic alkali to generate thioformamide, and the thioformamide is rectified and collected after the reaction is finished. The thioformamide prepared in the invention canbe used as an thiabendazole intermediate to synthesize thiabendazole which is applied to the fields of sterilization, corrosion prevention, fresh keeping and the like. The preparation method has theadvantages of simplicity, mild reaction conditions, safety, controllability, low production cost, high yield, no generation of wastewater or toxic gases, and reduction of environmental pollution.
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Paragraph 0020; 0028-0030

(2020/03/13)

Evaluation of thioamides, thiolactams and thioureas as hydrogen sulfide (H2S)donors for lowering blood pressure
Hydrogen sulfide (H2S)is a biologically important gaseous molecule that exhibits promising protective effects against a variety of pathological processes. For example, it was recognized as a blood pressure lowering agent. Aligned with the need for easily modifiable platforms for the H2S supply, we report here the preparation and the H2S release kinetics from a series of structurally diversified thioamides, thiolactams and thioureas. Three different thionation methods based on the usage of a phosphorus pentasulfide and Lawesson reagent were applied to prepare the target thioamides and thiolactams. Furthermore, obtained H2S donors were evaluated both in in vivo and in vitro studies. The kinetic parameters of the liberating H2S was determined and compared with NaHS and GYY4137 using two different detection technics i.e.; fluorescence labeling 7-azido-4-methyl-2H-chromen-2-one and 5,5‘-dithiobis (2-nitrobenzoic acid), sulfhydryl probe, also known as the Ellman's reagent. We have proved that the amount of releasing H2S from these compounds is controllable through structural modifications. Finally, the present study shows a hypotensive response to an intravenous administration of the developed donors in the anesthetized rats.
Zaorska, Ewelina,Hutsch, Tomasz,Gawry?-Kopczyńska, Marta,Ostaszewski, Ryszard,Ufnal, Marcin,Koszelewski, Dominik
supporting information

(2019/04/29)

Tetrahydrobenzothiazol-2-acetone oxime derivative and preparation method and application thereof
The invention discloses a tetrahydrobenzothiazole-2-acetone oxime derivative, and a preparation method and application thereof. A structural formula is shown in the description. R is any one of the following radical groups: 4-methylphenyl, phenyl, 2-methylphenyl, 3-methylphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 4-n-propylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 3,4,5-trimethoxyphenyl, 3-biphenyl, 4-trifluoromethoxyphenyl, 3-fluorophenyl, 4-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 3,5-bis(trifluoromethyl)phenyl, 3-chloro-4-methylphenyl, 3-furyl, 3-thienyl, 2-pyridyl, 4-pyridyl, 2-quinolyl, and 6-quinolyl. The tetrahydrobenzothiazol-2-acetone oxime derivative has relatively high antitumor activity and is suitable for preparing antitumor drugs. The preparationmethod of the derivative has the characteristics of cheap and readily available raw materials, short steps, and high reaction efficiency.
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Paragraph 0037; 0039

(2018/04/21)

5 - (3 - Phenyl-acryloyl) thiazole derivative and its preparation method and application (by machine translation)
The present invention is shown in formula I 5 - (3 - phenyl-acryloyl) thiazole derivatives and their pharmaceutically acceptable salt, pharmaceutical composition and thereof in the preparation of influenza virus neuraminidase inhibitors in the application. Wherein R is selected from: methyl, ethyl, C3 - C4 Straight-chain or C3 - C4 Branched alkyl; R1 Is selected from: hydrogen, 2 - nitro, 3 - nitro, 4 - nitro, 2 - amino, 3 - amino, 4 - amino, 2 - methylamino, 3 - methylamino, 4 - methylamino, 2 - dimethylamino, 3 - dimethylamino, 4 - dimethylamino, 2 - methoxy, 3 - methoxy, 4 - methoxy, 2 - ethoxy, 3 - ethoxy, 4 - ethoxy, 2 - hydroxy, 3 - hydroxy, 4 - hydroxy, 2, 3 - dihydroxy, 2, 4 - dihydroxy, 2, 5 - dihydroxy, 3, 4 - dihydroxy, 3, 5 - dihydroxy, 2 - hydroxy - 3 - methoxy, 3 - hydroxy - 4 - methoxy, 4 - hydroxy - 3 - methoxy, 4 - hydroxy - 3 - ethoxy, 3, 4, 5 - trimethoxy or 4 - hydroxy - 3, 5 - dimethoxy; R2 Is selected from: hydrogen, C1 - C2 Alkyl, C3 - C4 Straight-chain or C3 - C4 Branched alkyl, trifluoromethyl or chloro C1 - C4 Straight-chain alkyl. (by machine translation)
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Paragraph 0043; 0045-0047

(2018/10/02)

Method for preparing 4-methylthiazole-5-ethyl formate
The invention discloses a preparation method of 4-methylthiazole-5-ethyl formate. The preparation method comprises the following steps: taking tetrahydrofuran as a solvent and formamide and phosphorus sulfide as raw materials, dissolving the phosphorus sulfide in the tetrahydrofuran firstly, dropwise adding the formamide, carrying out reaction for 1-2h, concentrating to dry, dissolving a dried product with a low-concentration sodium hydroxide solution, carrying out extraction with ethyl acetate, drying an organic layer, and filtering and concentrating to obtain thioformamide; and taking absolute ethyl alcohol as a solvent and the thioformamide and 2-chloracetyl acetidin as raw materials, carrying out reflux reaction, concentrating a reactant to dry, dissolving the dried reactant with water, extracting with the ethyl acetate, drying an organic layer, filtering, concentrating and carrying out rectification under vacuum to obtain the 4-methylthiazole-5-ethyl formate. The preparation method provided by the invention is low in cost and convenient to operate.
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Paragraph 0006; 0017; 0021

(2017/08/29)

Thiophosphate - A Versatile Prebiotic Reagent?
Described are our preliminary studies on the reactivity of thiophosphate in a setting which correlates with the cyanosulfidic systems chemistry we have previously reported. Thiophosphate adds to various nitrile groups giving the corresponding thioamides in a highly efficient manner and the mechanistic implications are briefly discussed. Thiophosphate can also act as a phosphorylating agent, which was demonstrated with adenosine. The prebiotic availability of thiophosphate must be questioned, but if a plausible synthesis can be found, the advantages it would bring to the field of prebiotic chemistry appear to be highly beneficial.
Ritson, Dougal J.,Xu, Jiangfeng,Sutherland, John D.
p. 64 - 67
(2016/12/27)

NOVEL COMPOUND, ORGANIC CATION TRANSPORTER 3 DETECTION AGENT, AND ORGANIC CATION TRANSPORTER 3 ACTIVITY INHIBITOR
[Problem] The present invention addresses the problem of providing a novel compound. The present invention also addresses the problem of providing an OCT3 detection agent or an OCT3 activity inhibitor, which comprises the novel compound. [Solution] A compound represented by formula (A), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. ????????R1-R2-R3-R4?????(A)
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Paragraph 0831-0833

(2016/08/17)

Simple method for the preparation of dialkyl (2,3-dihydro-1,3-thiazol-2-YL) -phosphonates
A simple synthesis of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates from thiazolium salts and trialkyl phosphites is described. The series of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates with various substituents in positions 3, 4, and 5 of the thiazole ring were prepared. However, only phosphonates with an aryl on the nitrogen atom were stable enough for chromatographic purification, although all the new phosphonates are very sensitive to oxidation. We made efforts to apply dialkyl (2,3-dihydro-1,3- thiazol-2-yl)-phosphonates in a Horner-Wadsworth-Emmons reaction, but the generated antiaromatic anion of phosphonate decomposed quickly, even at -70°C. Copyright Taylor & Francis Group, LLC.
Janikowska, Karolina,Makowiec, Slawomir
experimental part
p. 12 - 20
(2011/03/20)

PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS
Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.
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Page/Page column 8

(2011/10/04)

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS
Compounds of structural formulas I-1 and I-2 are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders.
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Page/Page column 51-52

(2012/01/05)

Photochromic properties of terarylene derivatives having a π-conjugation unit on central aromatic ring
A series of terarylenes based on 4,5-bisbenzothienylthiazole have been synthesized, and their photochromic properties are studied both in solution and in the crystalline state. The substitution effect of the central aromatic ring on the photochromic reactivity were also studied. The introduction and expansion of the π-conjugated system at the 2-position of the thiazole ring led to a red-shift of the absorption peaks for both open- and closed-ring isomers of terarylenes. 2-Hydro and 2-phenyl derivatives of 4,5-bisbenzothienylthiazoles displayed a photochromic reaction, even in the single-crystal state. X-Ray crystal analysis showed their molecular structure to have quasi-C2 symmetry, suggesting significant CH...N and CH...S interactions. Although the 2-hydro and 2-phenyl derivatives exhibited high photocyclization reaction quantum yields over 0.5, the 2-phenylthienyl derivative showed a considerably smaller reactivity, even though it is supposed to have a similar conformation to those of the other two derivatives. Meanwhile, these molecules showed similar photocycloreversion quantum yields as high as 0.3. The relationship between their electronic structures and photochromic reactivity is also discussed by means of quantum chemical calculations. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009.
Kutsunugi, Yuichiro,Kawai, Shigekazu,Nakashima, Takuya,Kawai, Tsuyoshi
experimental part
p. 1368 - 1373
(2009/09/24)

Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents
Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles to replace the saturated cyclic amine derivatives appended to the benzimidazole core. Not only did a variety of these new generation compounds maintain high enzymatic potency, many of them also displayed robust cellular activity. For example, the enzymatic IC50 and cellular EC50 values were as low as 1 nM or below. Compounds 24 (EC50 = 3.7 nM) and 44 (EC50 = 7.8 nM), featuring an oxadiazole and a pyridine moiety, respectively, demonstrated balanced potency and PK profiles. In addition, these two molecules exhibited potent oral in vivo efficacy in potentiating the cytotoxic agent temozolomide in a B16F10 murine melanoma model.
Tong, Yunsong,Bouska, Jennifer J.,Ellis, Paul A.,Johnson, Eric F.,Leverson, Joel,Liu, Xuesong,Marcotte, Patrick A.,Olson, Amanda M.,Osterling, Donald J.,Przytulinska, Magdalena,Rodriguez, Luis E.,Shi, Yan,Soni, Nirupama,Stavropoulos, Jason,Thomas, Sheela,Donawho, Cherrie K.,Frost, David J.,Luo, Yan,Giranda, Vincent L.,Penning, Thomas D.
experimental part
p. 6803 - 6813
(2010/04/06)

Thiazolymethyl and Oxazolylmethyl Heteroaryl Derivatives
Compounds of Formula I are provided, as are methods for their preparation. The variables in the above formula are defined herein. Such compounds may be used to modulate ligand binding to GABAA receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals and livestock animals. Compounds provided herein may be administered alone or in combination with one or more other CNS agents to potentiate the effects of the other CNS agents(s). Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting GABAA receptors (e.g., receptor localization studies).
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Page/Page column 26

(2008/12/06)

Synthesis of some new 5-(2-substituted-1,3-thiazol-5-yl)-2-hydroxy benzamides and their 2-alkoxy derivatives as possible antifungal agents
The 2-hydroxy-5-(1,3-thiazol-5-yl) benzamide (4a), 5-(2-amino-1, 3-thiazol-5-yl)-2-hydroxy benzamide (4b), 2-hydroxy-5-(2-alkyl-1,3-Thiazol-5-yl) benzamide (4c and 4d), 5-{2-[(N-substituted aryl)amino]-1,3-thiazol-5-yl}2- hydroxy benzamides (6a-j) were prepared by reacting 5-(bromoacetyl) salicylamide (2) with thiourea, thioformamide, thioalkylamide (3c-d) and substituted thioureas (5a-j) in absolute ethanol. These compounds were converted to 5-(2-substituted-1,3-thiazol-5-yl)-2-alkoxybenzamides and 5-(2-N-(substituted aryl)-1,3-thiazol-5-yl)-2-alkoxy benzamides (8a-g) by reacting with n-alkylbromides (7a-b) in presence of a base. The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral data. Compounds were also screened for their antifungal activity.
Narayana,Vijaya Raj,Ashalatha,Kumari, N. Suchetha,Sarojini
p. 867 - 872
(2007/10/03)

Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element
Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl) sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c] pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.
Haginoya, Noriyasu,Kobayashi, Syozo,Komoriya, Satoshi,Yoshino, Toshiharu,Suzuki, Makoto,Shimada, Takashi,Watanabe, Kengo,Hirokawa, Yumiko,Furugori, Taketoshi,Nagahara, Takayasu
p. 5167 - 5182
(2007/10/03)

LTA4 Hydrolase inhibitors
The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB4 production, such as proriasis, ulcerative colitis, IBD and asthma.
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Page 55

(2010/01/31)

Thiazolium compounds and treatments of disorders associated with protein aging
A method and compositions are disclosed for, among other things, in an animal, (i) improving the elasticity or reducing wrinkles of the skin, treating (ii) diabetes or treating or preventing (iii) adverse sequelae of diabetes, (iv) kidney damage, (v) damage to blood vasculature, (vi) hypertension, (vii) retinopathy, (viii) damage to lens proteins, (ix) cataracts, (x) peripheral neuropathy, or (xi) osteoarthritis.
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(2008/06/13)

Method for treating fibrotic diseases or other indications IC
Provided, among other things, is a method of treating or ameliorating or preventing an indication of the invention in an animal, including a human comprising administering an effective amount of a compound of the formula I:
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(2011/07/06)

Design, synthesis, and evaluation of α-ketoheterocycles as class C β-lactamase inhibitors
A series of specific α-ketoheterocycles (benzoxazole, thiazole, imidazole, tetrazole, and thiazole-4-carboxylate) has been synthesized in order to assess their potential as β-lactamase inhibitors. The syntheses were achieved either by construction of the heterocycle (benzoxazole) from an appropriate α-hydroxyimidate, followed by oxidation of the alcohol, or by direct reaction of methyl phenaceturate with a lithiated heterocycle. The properties of these compounds in aqueous solution are described and their inhibitory activity against β-lactamases assessed. They did inhibit the class C β-lactamase of Enterobacter cloacae P99 but not the TEM β-lactamase. The most effective inhibitor of the former enzyme (Ki = 0.11 mM) was 5-(phenylacetylglycyl) tetrazole, probably because it is an anion at neutral pH. Interpretation of the results was aided by computational models of the tetrahedral adducts. Most of the compounds also inhibited α-chymotrypsin but not porcine pancreatic elastase.
Kumar, Sanjai,Pearson, Andre L.,Pratt
p. 2035 - 2044
(2007/10/03)

Compounds for inhibiting β-amyloid peptide release and/or its synthesis
Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis.
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(2008/06/13)

Methods and compounds for inhibiting β-amyloid peptide release and/or its synthesis
Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
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(2008/06/13)

Compounds for inhibiting β-amyloid peptide release and/or its synthesis
Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis.
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(2008/06/13)

Inhibitors of protein isoprenyl transferases
Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (d) —C(O)NH—CH(R14)—C(O)NHSO2R16, (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, and —P(W)RR3RR3′; R4is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4—L6—C(W)—N(R5)—L5—, (e) —L4—L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7—L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) and (m) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
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(2008/06/13)

Structure-activity relationship studies on 1-[2-(4- phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A4 (LTA4) hydrolase
Leukotriene B4 (LTB4) is a pro-inflammatory mediator that has been implicated in the pathogenesis of a number of diseases including inflammatory bowel disease (IBD) and psoriasis. Since the action of LTA4 hydrolase is the rate-limiting step for LTB4 production, this enzyme represents an attractive pharmacological target for the suppression of LTB4 production. From an in- house screening program, SC-22716 (1, 1-[2-(4- phenylphenoxy)ethyl]pyrrolidine) was identified as a potent inhibitor of LTA4 hydrolase. Structure-activity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA4 hydrolase, several of which demonstrated good oral activity in a mouse ex vivo whole blood assay.
Penning, Thomas D.,Chandrakumar, Nizal S.,Chen, Barbara B.,Chen, Helen Y.,Desai, Bipin N.,Djuric, Stevan W.,Docter, Stephen H.,Gasiecki, Alan F.,Haack, Richard A.,Miyashiro, Julie M.,Russell, Mark A.,Yu, Stella S.,Corley, David G.,Durley, Richard C.,Kilpatrick, Brian F.,Parnas, Barry L.,Askonas, Leslie J.,Gierse, James K.,Harding, Elizabeth I.,Highkin, Maureen K.,Kachur, James F.,Kim, Suzanne H.,Krivi, Gwen G.,Villani-Price, Doreen,Pyla, E. Yvonne,Smith, Walter G.,Ghoreishi-Haack, Nayereh S.
p. 721 - 735
(2007/10/03)

Compound with platelet aggregation inhibitor activity
A compound represented by the general formula (I) and a pharmaceutically acceptable salt and solvate thereof having an effect for inhibiting the agglutination of platelets is disclosed: STR1 wherein R1 represents a group --W--(CH2)i --COOR3, R2 represents a hydrogen atom or a group --W--(CH2)i --COOR3 or --OR4, X represents --CH= or --N=, Y represents (i) a group --(CO)k --N(R5)--Z--, wherein Z represents a bond or a group --(CH2)m --CO-- or a group --(CH2)m --CHR6 --, (ii) a group --(CH2)m --N(R5)--(CO)k --, or (iii) a group --(CO)k -Het, wherein Het represents a five- or six-membered heterocyclic ring comprising a nitrogen atom, A represents (i) the following groups (III) or (IV) STR2 B represents a bond, C1-6 alkylene or C2-6 alkenylen.
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(2008/06/13)

Pharmaceutical composition
A solid pharmaceutical composition is disclosed which comprises a pharmaceutically acceptable adsorbent or a mixture of pharmaceutically acceptable adsorbents to which is adsorbed a mixture of (1) a pharmaceutically acceptable organic solvent or a mixture of pharmaceutically acceptable organic solvents, (2) an HIV protease inhibiting compound and (3) one or more pharmaceutically acceptable acids. The solid composition can optionally be encapsulated in a hard gelatin capsule.
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(2008/06/13)

Pharmaceutical composition for inhibiting HIV protease
A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a mixture of (1) (a) a solvent selected from propylene glycol and polyethylene glycol or (b) a solvent selected from polyoxyethyleneglycerol triricinoleate, polyethylene glycol 40 hydrogenated castor oil, fractionated coconut oil, polyoxyethylene (20) sorbitan monooleate and 2-(2-ethoxyethoxy)ethanol or (c) a mixture thereof and (2) ethanol or propylene glycol.
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(2008/06/13)

Second-Generation Leukotriene B4 Receptor Antagonists Related to SC-41930: Heterocyclic Replacement of the Methyl Ketone Pharmacophore
Our previous reports have highlighted the first-generation leukotriene B4 (LTB4) receptor antagonist SC-41930 (7--3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid) which has potent oral, topical, and intracolonic activity in various animal models of inflammation.Extensive structure-activity relationship studies, in which series of heterocyclic replacements for the methyl ketone functional group of SC-41930 was explored, identified SC-50605 (7-propoxy>-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid) as an optimized analog within a series of thiazoles.SC-50605 was found to be significantly more potent than SC-41930 in LTB4 receptor binding, chemotaxis, and degranulation assays.It also displayed very good activity in animal models of colitis and epidermal inflammation by oral, topical, intravenous, and intracolonic routes of administration.The resolved enantiomers of SC-50605 were obtained by chiral chromatography and both demonstrated good in vitro and in vivo activity.The (+)-isomer (SC-52798) is currently being evaluated as a potential clinical candidate for psoriasis and ulcerative colitis therapy.
Penning, Thomas D.,Djuric, Stevan W.,Miyashiro, Julie M.,Yu, Stella,Snyder, James P.,et al.
p. 858 - 868
(2007/10/02)

N-substituted acylamino acid compounds, process for their production and their use
The present invention provides an N-substituted acylamino acid compound of the formula: STR1 a process for their production and pharmaceutical uses, and intermediates useful for their production.
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(2008/06/13)

RETROVIRAL PROTEASE INHIBITING PIPERAZINE COMPOUNDS
Retroviral protease inhibiting compounds of the formula: STR1 are disclosed.
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(2008/06/13)

RETROVIRAL PROTEASE INHIBITING COMPOUNDS
A retroviral protease inhibiting compound of the formula: STR1 is disclosed wherein R 1, R 2, R 5, R 6, Y m and Y' n are herein defined.
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(2008/06/13)

INDOLE CARBOXYLATE DERIVATIVES WHICH INHIBIT LEUKOTRIENE BIOSYNTHESIS
Compounds of the structure where A is straight or branched divalent alkylene or divalent cycloalkylene, R1 is selected from hydrogen; alkylthio; optionally substituted phenylthio; optionally substituted phenylalkylthio; optionally substituted 2-, 3-, and 4-pyridyl; optionally substituted 2-, and 3-thienylthio; and optionally substituted 2-thiazolythio, R2 is selected from -COOB; -COOalkyl; -COOalkyl(carbocyclic aryl); -CONR5R6 ; -COR6 ; and -OH, R3 is selected from phenylalkyl and heteroarylalkyl, and R4 is selected from optionally substituted alkoxy(carbocyclic aryl); optionally substituted carbocyclic aryloxy; optionally substituted heteroarylalkoxy; and optionally substituted heteroaryloxy are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states
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(2008/06/13)

ENCAPSULATED RENIN INHIBITOR COMPOSITION
A pharmaceutical composition comprising a solution of a tenin inhibitor of the formula: STR1 wherein R 1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl or 1-methyl-4-homopiperazinyl; R 2 is benzyl, p-methoxybenzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl;R 3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 1-imidazolyl, n-propyl, isopropyl, CH 3 S--or CH 3 SCH 2--;R 4 is loweralkyl or cyclopropyl;R 5 is hydrogen or loweralkyl; andX is CH 2 or NH; or a pharmaceutically acceptable salt, ester or prodrug thereof in a pharmaceutically acceptable solvent, said solution being encapsulated in a soft elastic gelatin capsule.
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(2008/06/13)

Psoriasis treatment
The present invention relates to the use of renin inhibitors and to renin inhibitor compositions for treatment of psoriasis.
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(2008/06/13)

Method for enhancement of chemiluminescence
A method for enhancing chemiluminescence which uses a heterocyclic compound of the formula: STR1 wherein R1 is an oxygen or sulfur atom or an imino group optionally substituted by 4-hydroxyphenyl, and R2, R3 and R4 are a hydrogen or halogen atom, an optionally substituted hydrocarbon residue, a heterocyclic group or the like in a luminescence system.
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(2008/06/13)

A new synthesis of 3-chloro-2-(thiazol-4-yl)propenoic acid and its application to cephalosporins
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Nishide,Yamamura,Yamazaki,Kobori,Tunemoto,Kondo,Sato
p. 2346 - 2353
(2007/10/02)

Synthesis and Platelet Aggregation Inhibitory Activity of 4,5-Bis(aryl)-2-substituted-thiazoles
In our continuing effort to discover compounds which inhibit collagen-induced platelet aggregation, we have screened compounds in a mouse pulmonary thromboembolism screen.Methyl 4,5-bis(4-methoxyphenyl)-2-thiazoleacetate (3) was very active in the above screen.However, 3 was active for less than 5 min when given orally to guinea pigs.As a result, our synthetic goal was to prepare 2-substituted thiazoles with a much longer duration of activity.This paper describes the preparation of a number 4,5-bis(aryl)-2-substituted-thiazoles and their in vitro and ex vivo activity against collagen-induced platelet aggregation.It was determined that 4,5-bis(4-methoxyphenyl)-2-(trifluoromethyl)thiazole (16) is the most promising compound.
Rynbrandt, Ronald H.,Nishizawa, Edward E.,Balogoyen, Doris P.,Mendoza, A. Rene,Annis, Kathleen A.
p. 1507 - 1510
(2007/10/02)

N-substituted 1,2,4-triazoles
Antiviral 1-(G)-1,2,4-triazole carboxamides, thiocarboxamides and carboxamidines wherein G is an acid labile hydrocarbon moiety, e.g., 1-(α-alkoxyalkyl), are prepared by, e.g., the acid-catalyzed addition reaction of appropriately substituted 1,2,4-triazole and an α,β-unsaturated ether.
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(2008/06/13)

Thioformamide improved process
Thioformamide is prepared from hydrogen cyanide and hydrogen sulfide in an improved process employing a tertiary amino ion exchange resin as the catalyst. The process provides for nearly quantitative yields, and affords a purer, more stable product, and the elimination of polluting by-products.
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(2008/06/13)