- A new route for the synthesis of the repaglinide key intermediate 3-ethoxy-4-ethoxycarbonylphenylacetic acid
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A new method is described for manufacturing 3-ethoxy-4-ethoxycarbonylphenylacetic acid, which is a key intermediate of the antidiabetic drug repaglinide, starting from 3-hydroxyphenylacetic acid and involving esterification, formylation, oxidation, etherification and selective hydrolysis. The effect of reaction temperature, time, solvent and substrate ratios on the yield were studied in detail and the optimal conditions are presented in the paper. The new method makes the scale-up operation easier and the environmental problems are fewer. The impurities in the intermediate of the new route were also determined. Characterisation of the product and intermediates involved was achieved by FTIR, 1H NMR, 13C NMR, HRMS and DSC.
- Zhang, Yue,Liu, Tingting,Niu, Zhaohuan,Fu, Yajing,Yang, Jixia,Song, Yongxing,Zhao, Shuchun
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Read Online
- Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists
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A series of A-region analogues of 2-(3-fluoro-4-methylsufonamidophenyl) propanamide 1 were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that a fluoro group at the 3- (or/and) 5-position and a methylsulfonamido group at the 4-position were optimal for antagonism of TRPV1 activation by capsaicin. The most potent antagonist 6 not only exhibited potent antagonism of activation of hTRPV1 by capsaicin, low pH and elevated temperature but also displayed highly potent antagonism of activation of rTRPV1 by capsaicin. Further studies demonstrated that antagonist 6 blocked the hypothermic effect of capsaicin in vivo, consistent with its in vitro mechanism, and it showed promising analgesic activity in the formalin animal model.
- Kim, Changhoon,Ann, Jihyae,Lee, Sunho,Sun, Wei,Blumberg, Peter M.,Frank-Foltyn, Robert,Bahrenberg, Gregor,Stockhausen, Hannelore,Christoph, Thomas,Lee, Jeewoo
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p. 2539 - 2542
(2018/06/07)
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- Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity
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γ-Glutamyl transpeptidase (GGT, EC 2.3.2.2) that catalyzes the hydrolysis and transpeptidation of glutathione and its S-conjugates is involved in a number of physiological and pathological processes through glutathione metabolism and is an attractive phar
- Kamiyama, Akane,Nakajima, Mado,Han, Liyou,Wada, Kei,Mizutani, Masaharu,Tabuchi, Yukiko,Kojima-Yuasa, Akiko,Matsui-Yuasa, Isao,Suzuki, Hideyuki,Fukuyama, Keiichi,Watanabe, Bunta,Hiratake, Jun
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supporting information
p. 5340 - 5352
(2016/10/24)
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- 1,2,3-Triazole-containing uracil derivatives with excellent pharmacokinetics as a novel class of potent human deoxyuridine triphosphatase inhibitors
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Deoxyuridine triphosphatase (dUTPase) has emerged as a potential target for drug development as a 5-fluorouracil-based combination chemotherapy. We describe the design and synthesis of a novel class of human dUTPase inhibitors, 1,2,3-triazole-containing u
- Miyakoshi, Hitoshi,Miyahara, Seiji,Yokogawa, Tatsushi,Endoh, Kanji,Muto, Toshiharu,Yano, Wakako,Wakasa, Takeshi,Ueno, Hiroyuki,Chong, Khoon Tee,Taguchi, Junko,Nomura, Makoto,Takao, Yayoi,Fujioka, Akio,Hashimoto, Akihiro,Itou, Kenjirou,Yamamura, Keisuke,Shuto, Satoshi,Nagasawa, Hideko,Fukuoka, Masayoshi
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supporting information; experimental part
p. 6427 - 6437
(2012/09/22)
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- PURINE DERIVATIVES USEFUL AS HSP90 INHIBITORS
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The present application provides substituted purine derivatives and related compounds of the formulas shown. These com ounds are useful as inhibitors of HSP90, and hence in the treatment of related diseases. (Formulae) Z1-Z3, Xa-Xc, X2, X4, Y and R are as defined in the specification.
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Page/Page column 127-128
(2011/04/26)
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- Receptor activity and conformational analysis of 5′-halogenated resiniferatoxin analogs as TRPV1 ligands
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A series of 5′-halogenated resiniferatoxin analogs have been investigated in order to examine the effect of halogenation in the A-region on their binding and the functional pattern of agonism/antagonism for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Halogenation at the 5-position in the A-region of RTX and of 4-amino RTX shifted the agonism of parent compounds toward antagonism. The extent of antagonism was greater as the size of the halogen increased (I > Br > Cl > F) while the binding affinities were similar, as previously observed for our potent agonists. In this series, 5-bromo-4-amino RTX (39) showed very potent antagonism with K i (ant) = 2.81 nM, which was thus 4.5-fold more potent than 5′-iodo RTX, previously reported as a potent TRPV1 antagonist. Molecular modeling analyses with selected agonists and the corresponding halogenated antagonists revealed a striking conformational difference. The 3-methoxy of the A-region in the agonists remained free to interact with the receptor whereas in the case of the antagonists, the compounds assumed a bent conformation, permitting the 3-methoxy to instead form an internal hydrogen bond with the C4-hydroxyl of the diterpene.
- Lim, Kwang Su,Kang, Dong Wook,Kim, Yong Soo,Kim, Myeong Seop,Park, Seul-Gi,Choi, Sun,Pearce, Larry V.,Blumberg, Peter M.,Lee, Jeewoo
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scheme or table
p. 299 - 302
(2011/02/27)
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- Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin
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As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3- methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with Ki (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6′-iodononivamide.
- Kang, Dong Wook,Kim, Yong Soo,Lim, Kwang Su,Kim, Myeong Seop,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Tao, Andy K.,Lang-Kuhs, Krystle A.,Blumberg, Peter M.,Lee, Jeewoo
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experimental part
p. 8092 - 8105
(2011/01/13)
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- Vanilloid Receptor Ligands, Pharmaceutical Compositions Containing Them, Process for Making Them, and Use Thereof for Treating Pain and Other Conditions
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Vanilloid receptor ligand compounds corresponding to formula I: pharmaceutical compositions containing such compounds, a process for producing such compounds, and methods of using such compounds for treating or inhibiting pain and various other disorders or conditions.
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Page/Page column 40; 49; 52-53
(2009/07/03)
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- CYCLIC DIARYL ETHER COMPOUNDS AS ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
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Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the antagonists of PGD2 receptors described herein, as well as methods of using such antagonists of PGD2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.
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Page/Page column 95
(2009/10/09)
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- AMINOALKYLPHENYL ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
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Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the compounds described herein that are antagonists of PGD2 receptors. Also described herein are methods of using such antagonists of PGD2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.
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Page/Page column 104
(2009/12/27)
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- COMPOUNDS AND METHOD FOR REDUCING URIC ACID
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Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In Formula (I) m is 0, 1, 2, 3 or 4; n is 0 or 1; m + n is not more than 4; t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R6 is hydrogen, methyl or ethyl and R12 is hydrogen or methyl, or R6 is hydroxy and R12 is hydrogen, or R6 is O and R12 is absent, or R6 and R12 together are -CH2CH2-. R7 is hydrogen or alkyl having from 1 to 3 carbon atoms. One of R8 and R9 is alkyl having from 1 to 3 carbon atoms, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms. R10 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms or alkoxy having from 1 to 3 carbon atoms. X is C(O) and r is 0 and t is 0; or X is NH(R11) wherein R11 is hydrogen or alkyl having from 1 to 3 carbon atoms. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula (I) by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl. The uric acid-lowering effects of the Compounds of Formula (I) are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, and cognitive impairment.
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Page/Page column 71-72
(2010/01/07)
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- PYRAZOLOPYRIMIDINONE KINASE INHIBITOR
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The present invention provides a novel pyrazolo[3,4-d]pyrimidin-4-one, specifically a derivative of 1-(pyridin-4-yl)-pyrazolo[3,4-d]pyrimidin-4-one. This compound is a kinase inhibitor that shows unexpected anti-proliferative activity against cells, inclu
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Page/Page column 41-42
(2009/01/20)
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- COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS
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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families.
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Page/Page column 26
(2008/06/13)
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- COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS
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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families.
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Page/Page column 22
(2010/11/27)
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- Identification and synthesis of a novel selective partial PPARδ agonist with full efficacy on lipid metabolism in vitro and in vivo
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The aim was to identify a novel selective PPARδ agonist with full efficacy on free fatty acid (FFA) oxidation in vitro and plasma lipid correction in vivo. Using the triple PPARα,γ,δ agonist 1 as the structural starting point, we wanted to investigate the
- Sauerberg, Per,Olsen, Grith S.,Jeppesen, Lone,Mogensen, John P.,Pettersson, Ingrid,Jeppesen, Claus B.,Daugaard, Jens R.,Galsgaard, Elisabeth D.,Ynddal, Lars,Fleckner, Jan,Panajotova, Vladimira,Polivka, Zdenek,Pihera, Pavel,Havranek, Miroslav,Wulff, Erik M.
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p. 1495 - 1503
(2008/02/03)
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- COMPOUNDS FOR THE TREATMENT OF METABOLIC DISORDERS
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Agents useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, polycystic ovary syndrome, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis are disclosed. (Formula
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Page/Page column 37; 39
(2008/06/13)
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- COMPOUNDS FOR THE TREATMENT OF METABOLIC DISORDERS
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3-(2,4-Bis(trifluoromethyl)benzyloxy)phenylacetic acid, 4-(2,6-Dimethylbenzyloxy)- phenylacetic acid, and their pharmaceutically acceptable salts are useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, polycystic ovary syndrome, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis.
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Page/Page column 10
(2008/06/13)
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- COMPOUNDS FOR THE TREATMENT OF METABOLIC DISORDERS
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Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis are disclosed. wherein n is 1 or 2; m is 0, 1, 2
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Page/Page column 44
(2008/06/13)
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- Two classes of p38α MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes
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Two new classes of diphenylether inhibitors of p38α MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38α ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38α inhibitors are discussed.
- Michelotti, Enrique L.,Moffett, Kristofer K.,Nguyen, Duyan,Kelly, Martha J.,Shetty, Rupa,Chai, Xiaomei,Northrop, Katrina,Namboodiri, Variketta,Campbell, Brandon,Flynn, Gary A.,Fujimoto, Ted,Hollinger, Frank P.,Bukhtiyarova, Marina,Springman, Eric B.,Karpusas, Michael
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p. 5274 - 5279
(2007/10/03)
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- Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. Design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activity
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Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures of HIV-1 RT pro
- Fattorusso, Caterina,Gemma, Sandra,Butini, Stefania,Huleatt, Paul,Catalanotti, Bruno,Persico, Marco,De Angelis, Meri,Fiorini, Isabella,Nacci, Vito,Ramunno, Anna,Rodriquez, Manuela,Greco, Giovanni,Novellino, Ettore,Bergamini, Alberto,Marini, Stefano,Coletta, Massimo,Maga, Giovanni,Spadari, Silvio,Campiani, Giuseppe
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p. 7153 - 7165
(2007/10/03)
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- DITHIAZOLE COMPOUNDS, MATRIX METALLOPROTEASE INHIBITORS AND EXTERNAL PREPARATIONS FOR THE SKIN
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A dithiazole compound or a salt thereof expressed by formula (I): wherein R1, is hydrogen atom, alkyl, etc.; R2 is hydrogen atom, hydroxy, alkyl, aryl, arylalkoxy, arylalkyl, etc.; R3 is one group of formulae (II), (III) and (IV): This compound has an excellent inhibiting action on matrix metalloprotease (MMPs) activity, and is useful for pharmaceutical, cosmetic and skin external compositions.
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- A novel tandem [2 + 2] cycloaddition-Dieckmann condensation with ynolate anions. Efficient synthesis of substituted cycloalkenones and naphthalenes via formal [n + 1] cycloaddition
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A novel tandem [2 + 2] cycloaddition-Dieckmann condensation via ynolate anions is described. Ynolate anions are useful for the formation of reactive β-lactone enolates via a pathway not involving the enolization of the corresponding β-lactones. The [2 + 2] cycloaddition of ynolate anions with δ- or σ-keto esters, followed by Dieckmann condensation, gives bicyclic β-lactones, which are easily decarboxylated to produce synthetically useful 2,3-disubstituted cyclopentenones and cyclohexenones in one pot. This tandem reaction was applied to a novel, one-pot synthesis of highly substituted naphthalenes.
- Shindo,Sato,Shishido
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p. 7818 - 7824
(2007/10/03)
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- 4-substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists
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PCT No. PCT/US96/20872 Sec. 371 Date Sep. 16, 1998 Sec. 102(e) Date Sep. 16, 1998 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/23216 PCT Pub. Date Jul. 3, 1997Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs are selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described.
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- Barbituric acid derivatives, processes for their production and pharmaceutical agents containing these compounds
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PCT No. PCT/EP96/05766 Sec. 371 Date Aug. 26, 1998 Sec. 102(e) Date Aug. 26, 1998 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/23465 PCT Pub. Date Jul. 3, 1997Compounds of formula I, useful as matrix metalloprotease inhibitors, wherein X, Y and Z are each oxygen; R1 is selected from the group consisting of (a) n-octyl, (b) n-decyl, (c) biphenyl and (d) (4-phenoxy)phenyl, wherein the terminal monocycle for moieties (c)-(d) is unsubstituted or substituted by a substituent selected from the group consisting of -NH2, -NO2, -SO2NH2, -SO2CH3, acetyl, hydroxy, methoxy, ethoxy, cyano and halogen; R2 and R3 are each hydrogen; and R4 and R5, together with the nitrogen atom to which they are bound, form a piperazinyl or piperidyl ring, wherein the piperazinyl ring is substituted in the 4-position with a substituent selected from the group consisting of (a) a 6-membered aromatic monocycle having 0, 1 or 2 nitrogen atoms and the remainder of the atoms in the monocycle being carbon and (b) hydroxy-C1-C6 alkyl, wherein the monocycle is unsubstituted or substituted by a substituent selected from the group consisting of halogen, -NH2, -NO2, -SO2NH2, -SO2CH3, acetyl and cyano.
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- THROMBIN INHIBITORS
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A compound which inhibits human thrombin and which has the general structure STR1
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- Structure-activity studies for a novel series of N-(arylethyl)-N- (1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamines possessing dual 5- HT uptake inhibiting and α2-antagonistic activities
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In search of an α2-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the α2-receptor (K(i) = 6.71 nM) and
- Meyer, Michael D.,Hancock, Arthur A.,Tietje, Karin,Sippy, Kevin B.,Prasad, Rajnandan,Stout, David M.,Arendsen, David L.,Donner, B. Greg,Carroll, William A.
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p. 1049 - 1062
(2007/10/03)
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- 1-AZONIABICYCLO[2.2.1]HEPTANES, METHODS OF PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS IN WHICH THEY ARE PRESENT
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The invention relates to quaternary basic amides of the formula STR1 in which Ar is an optionally substituted mono-, di-or tricyclic aromatic or heteroaromatic group;T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C 1-C. sub.4, or a C 1-C 5-alkylene group; Ar' is an unsubstituted or mono-or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C 1-C. sub.4-alkyl, or a C 1-C 4-ω-alkoxy(C 2-C 4) alkyl, or a C 2-C 4-ω-alkanoyloxy (C 1-C 4)alkyl;.Q is hydrogen;or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group;Am ⊕ is the radical STR2 in which X 1, X 2 and X 3, together with the nitrogen atom to which they are bonded, form a 1-AZONIABICYCLO[2.2.1] HEPTANE optionally substituted by a phenyl or benzyl group; and A . crclbar. is a pharmaceutically acceptable anion. These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.
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- Quaternary ammonium salts of aromatic amine compounds, their preparation and pharmaceutical compositions in which they are present
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The present invention relates to quaternary ammonium salts of the formula STR1 in which: J is either a group Ar--CXX''--CX"" or a group Ar--(CH 2) x CH 1, in which:Ar is a substituted or unsubstituted phenyl, a cycloalkyl, a pyridyl or a thienyl;X is hydrogen;X'' is hydrogen or is combined with X"" below to form a carbon-carbon bond, or else X and X'' together form an oxo group;X"" is hydrogen or forms a carbon-carbon bond with X'';X is zero or one; andX 1 is hydrogen (n=0), a hydroxyl, an alkoxy, an acyloxy, a carboxyl, a carbalkoxy, a cyano or an alkoxyamino group;Q is an alkyl group or a benzyl group;A is an anion;m is 2 or 3;Ar'', R, T and Z are as defined in the specification, are neurokinin receptor antagonists.
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- 6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof
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6-Substituted pyrazolo[3,4 -d]pyrimidin-4-one derivatives, pharmaceutical compositions containing them and methods for effecting c-GMP-phosphodiesterase inhibition and for treating heart failure and/or hypertension.
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- Enantio- and diastereoselective synthesis of the AB ring system of aklavinone by coupling a chemoenzymatic procedure with organometal chemistry
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Two different approaches were investigated in order to prepare the title compound 2; best results were obtained when the tandem reduction/intramolecular hydroxyalkylation of the appropriate 5-alkoxy-(3-hydroxyphenyl)pentanoate was performed on an ester of chemoenzymatic origin, already bearing the two chiral centers present in 2 with the correct relative and absolute stereochemistry.
- Banfi, Luca,Guanti, Giuseppe,Riva, Renata
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p. 13493 - 13512
(2007/10/03)
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- 1-AZONIABICYCLO[2.2.1] HEPTANES AND PHARMACEUTICAL COMPOSITIONS IN WHICH THEY ARE PRESENT
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The invention relates to quaternary basic amides of the formula STR1 in which Ar is an optionally substituted mono-, di-or tri-cyclic aromatic or heteroaromatic group;T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C 1-C. sub.4, or a C 1-C 5-alkylene group; Ar' is an unsubstituted or mono-or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C 1-C 4-alkyl, or a ω-C 1-C. sub.4-alkoxy(C 2-C 4) alkyl, or a ω-C 2-C. sub.4-alkanoyloxy (C 1-C 4)alkyl;.Q is hydrogen;or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group;Am ⊕ is the radical STR2 in which X 1, X 2 and X 3, together with the nitrogen atom to which they are bonded, form an azabicyclic or azatricyclic system optionally substituted by a phenyl or benzyl group; andA ? is a pharmaceutically acceptable anion.These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.
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- BENZOPYRAN AND RELATED LTB4 ANTAGONISTS
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The invention relates to benzopyran leukotriene B 4 (LTB. sub.4) antagonists and pharmaceutical compositions containing the compounds. The compounds inhibit the action of LTB 4 and are therefore useful in the treatment of LTB 4 induced illnesses such as inflammatory disorders.
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- On the optimization of pig pancreatic lipase catalyzed monoacetylation of prochiral diols
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The effect of various experimental variables (solvent, methodology of supportation on celite, presence of water, conversion and so on) on the rate and on the enantioselectivity of monoacetylation of some prochiral 2-substituted-1,3-propanediols with vinyl acetate catalyzed by crude PPL (pig pancreatic lipase) was analyzed. This study allowed to assess the best conditions for performing these transformations, providing an efficient methodology for the synthesis of valuable chiral building blocks with moderate amounts of inexpensive PPL, which can also be easily recycled.
- Banfi,Guanti,Riva
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p. 1345 - 1356
(2007/10/02)
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- Regioselective synthesis of 1,8-dihydroxytetralins through a tandem reduction/intramolecular hydroxyalkylation of 4-(3-hydroxyphenyl)alkanoates
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A series of 4-(3-hydroxyphenyl)butanoates 3 has been prepared and transformed into 1,8-dihydroxytetralins of general formula 2 by treatment with 2 equivalents of DIBALH followed by quenching with aqueous NH4Cl. A possible mechanism for this novel totally regioselective intramolecular hydroxyalkylation is suggested and the factors affecting the stability of 1,8-dihydroxytetralins 2 are also discussed.
- Guanti, Giuseppe,Banfi, Luca,Riva, Renata
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p. 11945 - 11966
(2007/10/02)
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- Chemoenzymatic approach to the AB ring system of Aklavinone
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Both enantiomers of compound 3, a possible intermediate for the AB ring system 2 of Aklavinone 1, were obtained in optically active form from diol 7. Key steps were the preparation of both enantiomers of monoacetate 8d, via enzymatic reactions that utiliz
- Guanti, Giuseppe,Banfi, Luca,Brusco, Stefano,Riva, Renata
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p. 8549 - 8552
(2007/10/02)
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- PYRAN DERIVATIVES AND THEIR USE AS INHIBITORS OF 5-LIPOXYGENASE
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The invention concerns a cyclic ether derivative of the formula I, wherein Ar1 is optionally substituted phenyl, naphthyl or a 9-or 10-membered bicyclic heterocyclic moiety; A1 is a direct link to X1 or (l-3C)alkylene; X1 is oxy, thio, sulphinyl, sulphony
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- Tandem Reduction / Intramolecular Hydroxyalkylation of (3-Hydroxyphenyl)alkanoates: a New Regioselective Approach to 1,8-Dihydroxytetralins
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4-(3-hydroxyphenyl)-butanoates 4, on treatment with DIBALH, followed by hydrolytic work-up, undergo a novel completely regioselective intramolecular hydroxyalkylation reaction to give 1,8-dihydroxytetralins.The yield of the reaction depends heavily on the structure of starting material, best results being achieved with 3,3-disubstituted butanoates.
- Guanti, Giuseppe,Banfi, Luca,Narisano, Enrica,Riva, Renata,Thea, Sergio
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p. 3919 - 3922
(2007/10/02)
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