- Expeditious process improvement for the synthesis of RWJ-333966
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We improved chemical processes for synthesizing RWJ-333966 1 and obtained this compound over five steps in 40% overall yield.
- Guillaume, Michel
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Read Online
- HETEROCYCLIC COMPOUND, APPLICATION THEREOF, AND COMPOSITION CONTAINING SAME
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A heterocyclic compound represented by formula XI, a pharmaceutically acceptable salt, a solvate, or a solvate of a pharmaceutically acceptable salt thereof, use thereof, and a composition containing the same. The compound is novel in structure and has good STAT5 inhibitory activity.
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- 1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to 1,3,4-oxadiazole derivative compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, a use thereof in preparation of a medicament, a pharmaceutical composition comprising the same, a therapeutic method using the composition, and a method for preparing the same, and the 1,3,4-oxadiazole derivative compounds are represented by a following chemical formula (I).
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Page/Page column 103-104
(2020/12/11)
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- [11C]Carbonyl Difluoride—a New and Highly Efficient [11C]Carbonyl Group Transfer Agent
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Herein, the synthesis and use of [11C]carbonyl difluoride for labeling heterocycles with [11C]carbonyl groups in high molar activity is described. A very mild single-pass gas-phase conversion of [11C]carbon monoxide into [
- Jakobsson, Jimmy E.,Lu, Shuiyu,Pike, Victor W.,Telu, Sanjay
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supporting information
p. 7256 - 7260
(2020/03/13)
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- Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias
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While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/βarr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.
- Kennedy, Nicole M.,Schmid, Cullen L.,Ross, Nicolette C.,Lovell, Kimberly M.,Yue, Zhizhou,Chen, Yen Ting,Cameron, Michael D.,Bohn, Laura M.,Bannister, Thomas D.
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p. 8895 - 8907
(2018/10/05)
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- The preparation method of the deuterium generation of Mauzy is special
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The invention discloses a preparation method of deuterated pimozide. The pimozide-d4 is synthesized from 4-bromopentafluorobenzene-d4 through eight steps. The provided preparation method has the advantages of reasonable technological design, simple operation, easy product separation and purification, easily-available raw materials, high yield, and high purity. The isotope abundance of the obtained target product is high. The prepared stable isotope-labeled pimozide-d4 can be well applied to clinical pharmacokinetics researches, so people can acknowledge the metabolism process and action mechanism of pimozide in human body more precisely and conveniently, and thus the deuterated pimozide has an important application value.
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Paragraph 0028; 0040-0041
(2017/07/01)
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- Effects of Pimozide Derivatives on pSTAT5 in K562 Cells
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STAT5 is a transcription factor, a member of the STAT family of signaling proteins. STAT5 is involved in many types of cancer, including chronic myelogenous leukemia (CML), in which this protein is found constitutively activated as a consequence of BCR-ABL expression. The neuroleptic drug pimozide was recently reported to act as an inhibitor of STAT5 phosphorylation and is capable of inducing apoptosis in CML cells in vitro. Our research group has synthesized simple derivatives of pimozide with cytotoxic activity and that are able to decrease the levels of phosphorylated STAT5. In this work we continued the search for novel STAT5 inhibitors, synthesizing compounds in which the benzoimidazolinone ring of pimozide is either maintained or modified, in order to obtain further structure–activity relationship information for this class of STAT5 inhibitors. Two compounds of the series showed potent cytotoxic activity against BCR-ABL-positive and pSTAT5-overexpressing K562 cells and were able to markedly decrease the levels of phosphorylated STAT5.
- Rondanin, Riccardo,Simoni, Daniele,Maccesi, Martina,Romagnoli, Romeo,Grimaudo, Stefania,Pipitone, Rosaria Maria,Meli, Maria,Cascio, Antonio,Tolomeo, Manlio
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p. 1183 - 1190
(2017/08/15)
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- RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
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Compounds of Formula (I): wherein R1, R2 and R3 are defined herein, are useful as inhibitors of RSV.
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Page/Page column 20; 21
(2015/05/19)
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- Concise and simple synthesis of M1 allosteric agonist TBPB
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A concise and simple synthesis of M1 allosteric agonist 1-(1′-(2-methylbenzyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d] imidazol-2(3H)-one (TBPB) using economical and commercially available orthophenylenediamine (O-PDA) and Boc piperidone has been described. The disclosed scheme allows synthesizing more analogs that were otherwise difficult to prepare with the original method. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Rasheed, Mohammed Abdul,Shaik, Nagul Meera,Nirogi, Ramakrishna
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supporting information
p. 1796 - 1801
(2013/05/21)
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- Non-benzimidazole containing inhibitors of respiratory syncytial virus
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Several non-benzimidazole containing inhibitors of respiratory syncytial virus are described. Core template modification, analysis of antiviral activity, physicochemistry and optimisation of properties led to the thiazole-imidazole 13, that showed a good potency and pharmacokinetic profile in the rat.
- Pryde, David C.,Tran, Thien-Duc,Gardner, Iain,Bright, Helen,Stupple, Paul,Galan, Sebastien,Alsop, Liam,Watson, Lesa,Middleton, Donald S.,Dayal, Satish,Platts, Michelle,Murray, Edward J.,Parkinson, Tanya,Webster, Robert
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supporting information
p. 827 - 833
(2013/03/13)
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- Structure-activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide
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Twelve derivatives of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide (Comp 24) were synthesized and tested in binding experiments performed on CHOsu
- Trapella, Claudio,Fischetti, Carmela,Pela', Michela,Lazzari, Ilaria,Guerrini, Remo,Calo', Girolamo,Rizzi, Anna,Camarda, Valeria,Lambert, David G.,McDonald, John,Regoli, Domenico,Salvadori, Severo
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experimental part
p. 5080 - 5095
(2009/12/24)
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- HETEROCYCLIC AMIDE COMPOUNDS AS PROTEIN KINASE INHIBITORS
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The present invention related to novel heterocyclic amide compounds of Formula 1: as disclosed herein or a pharmaceutically accept able salt, solvate, ester, prodrug or stereoisomer thereof. Also disclosedare compositions comprising said compounds, and methods for using said compounds for treating or preventing a proliferative disease, an anti-proliferative disorder, inflammation, arthritis, a neurological or neurodenerative disease, a cardiovascular disease, alopecia, a neuronal disease, an ischemic injury, a viral disease or a fungal disease
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Page/Page column 79
(2009/03/07)
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- Rearrangement of spiro-benzimidazolines: preparation of N-alkenyl- and N-alkyl-benzimidazol-2-ones
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A synthetically useful protocol has been developed for the preparation of highly functionalized N-alkenyl-benzimidazol-2-ones. Reaction of commercially available o-phenylenediamines with variously substituted cyclic ketones provides spiro-benzimidazolines. Treatment of these spiro-benzimidazolines with triphosgene in the presence of potassium carbonate results in rapid rearrangement and formation of N-alkenyl-benzimidazol-2-ones in modest to excellent yield for the two-step sequence. Extension of this methodology toward the preparation of a μ opiate receptor antagonist and droperidol, a potent antiemetic and antipsychotic agent, currently a marketed pharmaceutical is also described. Upon treatment of spiro-benzimidazolines with triphosgene in the presence of sodium triacetoxyborohydride, N-alkyl-benzimidazol-2-ones were formed.
- Kuethe, Jeffrey T.,Varon, Jack,Childers, Karla G.
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p. 11489 - 11502
(2008/03/13)
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- Cascade coupling/cyclization process to N-substituted 1,3- dihydrobenzimidazol-2-ones
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Assembly of N-substituted 1,3-dihydrobenzimidazol-2-ones is achieved starting from methyl o-haloarylcarbamates via a Cul/amino acid catalyzed coupling with amines and subsequent condensative cyclization. A number of functional groups are tolerated by thes
- Zou, Benli,Yuan, Qiliang,Ma, Dawei
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p. 4291 - 4294
(2008/02/12)
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- Synthesis and evaluation of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic and sedative properties
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A series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues have been discovered as novel NOP receptor agonists. Structure-activity relationships have been explored via N-3 substitution of the benzimidazol-2-one with a range of functionality. The
- Palin, Ronald,Bom, Anton,Clark, John K.,Evans, Louise,Feilden, Helen,Houghton, Andrea K.,Jones, Philip S.,Montgomery, Brian,Weston, Mark A.,Wishart, Grant
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p. 1828 - 1847
(2008/02/03)
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- Indol-3-yl-carbonyl-piperidin-benzoimidazol derivatives
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The present invention relates to Indol-3-yl-carbonyl-piperidin-benzoimidazol derivatives which act as V1a receptor antagonists and which are represented by Formula I: wherein the residues R1 to R7 are as defined herein. The invention
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Page/Page column 19-20
(2010/11/25)
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- MUSCARINIC RECEPTOR AGONISTS THAT ARE EFFECTIVE IN THE TREATMENT OF PAIN, ALZHEIMER'S DISEASE AND SCHIZOPHRENIA
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Compounds of Formulae I, or pharmaceutically acceptable salts thereof: wherein R1, R2, R3, R4, R5, R6, R7, m and n are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
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Page/Page column 28
(2008/06/13)
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- Method for treating allergies using substituted pyrazoles
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A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.
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- Sulfonyldihydrobenzimidazolone compounds as 5-hydroxytryptamine-6 ligands
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The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor.
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Page/Page column 11
(2008/06/13)
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- 2-CYANOPYRROLOPYRIMIDINES AND PHARMACEUTICAL USES THEREOF
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The invention relates to pyrrolo pyrimidines of formula (I), wherein Y represents -(CH2)t-O- or -(CH2)r-S-, p is 1 or 2, r is 1, 2 or 3, t is 1, 2 or 3, or Y is -(CH2)j- or -CH=CH-, j is 1 or 2; p is 1 or 2, or Y is -(CH2)f-, f is 1 or 2, p is 1, and the further radicals and symbols have the meaning as defined herein; their preparation, their use as pharmaceuticals, pharmaceutical compositions containing them, the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment of neuropathic pain and to a method for the treatment of such a disease in animals, especially in humans.
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Page/Page column 50
(2010/02/08)
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- 1-(4-PIPERIDINYL) BENZIMIDAZOLONES AS HISTAMINE H3 ANTAGONISTS
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Disclosed are histamine H3 antagonists of the formula (I) wherein R1 is benzimidazolone derivative, M1 and M2 are optionally substituted carbon or nitrogen, R2 includes optionally substituted aryl or heteroaryl, and the remaining variables are as defined
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- NOVEL SUBSTITUTED BENZIMIDAZOL-2-ONES AS VASOPRESSIN RECEPTOR ANTAGONISTS AND NEUROPEPTIDE Y MODULATORS
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The invention is directed to substituted benzimidazol-2-ones of Formula I, wherein A, X, Y, m, n, R1, R2, R 3, R4, and R5 are as described in the specification, which are useful as vasopressin receptor antagonists or Neuropeptide Y Modulators for treating
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- alpha 1a adrenergic receptor antagonists
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This invention relates to novel compounds, their synthesis and use as selective alpha 1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
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- Dipeptides which promote release of growth hormone
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Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1
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- Alpha 1a adrenergic receptor antagonists
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This invention relates to novel compounds, their synthesis and use as selective α 1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the α 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
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- Alpha IC adrenergic receptor antagonists
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This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha-1C adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hypertrophy. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha1C receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
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- Easy microwave assisted deprotection of N-Boc derivatives
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A simple and efficient method for the cleavage of tert-butoxycarbonyl amides and amines is described, which takes place on silica gel under microwave irradiation.
- Siro, Jorge G.,Martín, Justina,García-Navío, José L.,Remui?an, Modesto J.,Vaquero, Juan J.
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p. 147 - 148
(2007/10/03)
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- Synthesis of (1-substituted piperidin-4-yl)-1H-benzimidazoles and (1-substituted piperidin-4-yl)-3,4-dihydroquinazolines as possible antihypertensive agents
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Structural modifications of 4-piperidylbenzimidazolinones (I) by replacing the benzimidazolinone group with other heterocycles (2-cyanoamino, 2-ethoxy, and 2-methylbenzimidazole and 2-cyanoamino-3,4-dihydroquinazoline) has been made and a number of new pi
- Obase,Takai,Teranishi,Nakamizo
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p. 565 - 573
(2007/10/02)
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