- 3-PYRROLIDINE-INDOLE DERIVATIVES AS SEROTONERGIC PSYCHEDELIC AGENTS FOR THE TREATMENT OF CNS DISORDERS
-
The present application relates to 3-cyclic amine-indole derivatives of general Formula (I), to processes for their preparation, to compositions comprising them and to their use in activation of a serotonin receptor in a cell, as well as to treating diseases, disorders or conditions by activation of a serotonin receptor in a cell. The diseases, disorders or conditions include, for example, psychosis, mental illnesses, and other neurological diseases, disorders and conditions. Formula (I)
- -
-
Paragraph 00275
(2021/08/14)
-
- Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis
-
Diazophosphonates, readily prepared from α-ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3-dipolar cycloaddition reactions to alkynes to give N-H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties into the diazo 1,3-dipole. The electron-withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]-sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product. Overall, the diazophosphonate acts as a surrogate for the much less stable diazoalkane in cycloadditions, with the phosphoryl group playing a vital, but traceless, role. The cycloaddition proceeds more readily with alkynes bearing electron-withdrawing groups, and is regiospecific with asymmetrical alkynes. The potential of diazophosphonates for use in bioorthogonal cycloadditions is demonstrated by their facile addition to strained alkynes.
- Green, Michael T.,Hayes, Christopher J.,Inman, Martyn,Lewis, William,Moody, Christopher J.,Nicolle, Simon M.,Ruffell, Katie,Smith, Frances R.
-
supporting information
p. 13703 - 13708
(2021/09/09)
-
- Preparation method of water-soluble florfenicol amino acid salt
-
The invention discloses a preparation method of a water-soluble florfenicol amino acid ester salt. The method comprises the following steps: using florfenicol and N-Cbz-amino acid as the initial raw materials, carrying out acylating chlorination, esterifi
- -
-
Paragraph 0077; 0096-0097
(2020/07/21)
-
- PROCESSES FOR THE PREPARATION OF 4-{8-AMINO-3-[(2S)-1-(BUT-2-YNOYL)-PYRROLIDIN-2-YL]IMIDAZO[1,5-A]-PYRAZIN-1-YL}N-(PYRIDIN-2-YL)-BENZAMIDE
-
The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
- -
-
Paragraph 00229
(2020/03/23)
-
- BENZIMIDAZOLE-LINKED INDOLE COMPOUND ACTING AS NOVEL DIVALENT IAP ANTAGONIST
-
The present invention discloses a benzimidazole-linked indole compound acting as novel divalent IAP antagonist, specifically disclosing the compound shown in fomulas (I) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0117; 0118
(2019/03/14)
-
- PROCESSES TO PRODUCE ACALABRUTINIB
-
The present invention relates to a method for preparing the compound of formula IV, compound of formula XI, and acalabrutinib, a new generation of bruton tyrosine kinase (BTK) inhibitor.
- -
-
Page/Page column 11; 12
(2019/05/22)
-
- Synthesis of 2-Fluoroalkyl 4-Substituted Azepanes
-
Synthesis of di- and tri-substituted fluoroalkylated azepanes was achieved by ring expansion of pyrrolidines via a regioselective attack of nucleophiles on a bicyclic azetidinium intermediate. A broad scope of azepanes, substituted at C4 and bearing a α-t
- Masson, Guillaume,Rioton, Sarah,Gomez Pardo, Domingo,Cossy, Janine
-
supporting information
p. 5497 - 5507
(2019/09/06)
-
- SUBSTITUTED PYRROLIDINES AND THEIR USE
-
The invention discloses compounds of Formula (I) wherein R1, R2, R3, R3A, R4, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.
- -
-
Paragraph 0299; 0303
(2019/10/30)
-
- A Manufacturing Process to an Intermediate in the Synthesis of Acalabrutinib
-
Optimization and application of the reported synthesis of (3-chloropyrazin-2-yl)methanamine 3 have provided a high yielding, fully telescoped procedure to key intermediate 5 in the synthesis of acalabrutinib.
- Chen, Bo,Golden, Michael,Li, Zhonglian,Xu, Liwen,Xu, Zhaofu,Yao, Xiaolong
-
p. 1458 - 1460
(2018/10/15)
-
- NOVEL FUSED PYRIDINE DERIVATIVES USEFUL AS FAK/AURORA KINASE INHIBITORS
-
This invention relates to certain novel pyrimidine derivatives of the Formula (I). The invention also relates to process for the preparation of the compound of the formula (I), pharmaceutical agents or compositions containing the compound or a method of using the compound for the treatment of proliferative diseases, such as cancer.
- -
-
Page/Page column 36
(2018/02/28)
-
- N-methyl-D-aspartate receptor modulators and methods of making and using same
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Page/Page column 84; 108
(2018/06/25)
-
- Access to Enantio-enriched Substituted α-Trifluoromethyl Azepanes from l -Proline
-
4-Substituted α-trifluoromethyl azepanes C were synthesized via the ring expansion of trifluoromethyl pyrrolidines A, which were synthesized from l-proline via a regioselective ring-opening of a bicyclic azetidinium intermediate B by various nucleophiles.
- Masson, Guillaume,Rioton, Sarah,Gomez Pardo, Domingo,Cossy, Janine
-
supporting information
p. 5019 - 5022
(2018/08/24)
-
- Compound as apoptosis protein inhibitor, and application thereof
-
The present invention belongs to the field of medical chemistry, relates to a class of compounds of apoptosis protein inhibitors, and applications thereof, and particularly provides a compound represented by a formula I, or an isomer thereof, a pharmaceut
- -
-
Paragraph 0450; 0458; 0459; 0460
(2018/09/12)
-
- Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
-
Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.
- Chen, Tao,Reich, Nicholas William,Bell, Noah,Finn, Patricia D.,Rodriguez, David,Kohler, Jill,Kozuka, Kenji,He, Limin,Spencer, Andrew G.,Charmot, Dominique,Navre, Marc,Carreras, Christopher W.,Koo-Mccoy, Samantha,Tabora, Jocelyn,Caldwell, Jeremy S.,Jacobs, Jeffrey W.,Lewis, Jason Gustaf
-
supporting information
p. 7589 - 7613
(2018/09/12)
-
- Pharmaceutical combination of an atypical antipsychotic and an NMDA modulator for the treatment of schizophrenia,bipolar disorder, cognitive impairment and major depressive disorder
-
This disclosure features combinations of NMDA modulators and atypical antipsychotics. The disclosure provides for example, methods of treating schizophrenia, bipolar disorder, and/or cognitive impairment disorder in a patient in need thereof, comprising administering e.g., rapastinel and an atypical antipsychotic.
- -
-
Paragraph 0179; 0201
(2018/10/11)
-
- A N-benzyloxycarbonyl-L-prolinamide method for the preparation of
-
The invention relates to a preparation method of N-carbobenzoxy-L-prolinamide. The preparation method is characterized by comprising following steps of (1) putting L-proline and alkali into a solvent and dropwise adding benzyl chloroformate; at the end of reaction, heating up till backflow, separating out water, cooling down to obtain liquid N-carbobenzoxy-L-proline; (2) dropwise adding sulfoxide chloride into the liquid N-carbobenzoxy-L-proline, heating up till backflow, distilling at reduced pressure to obtain N-carbobenzoxy-L-prolyl chloride solution; and (3) introducing ammonia gas into the N-carbobenzoxy-L-prolyl chloride solution, and at the end of reaction, concentrating at reduced pressure till drying the solvent, adding dichloromethane, cooling down, regulating pH value of the system to be 12-13, standing to separate liquid to obtain a water layer, decoloring, filtering to obtain distilled residue, crystallizing, filtering, washing by petroleum ether, drying to obtain the N-carbobenzoxy-L-prolinamide. The preparation method is simple, has high yield, can prepare the product with high purity and optical purity and no inorganic salt, and can be used for industrial production of N-carbobenzoxy-L-prolinamide in large scale.
- -
-
Paragraph 0025; 0029
(2018/02/04)
-
- Bridged Ring compounds As Hepatitis C Virus (HCV) Inhibitors And Pharmaceutical Applications Thereof
-
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
- -
-
Paragraph 2454; 2455; 2456; 2457; 2458
(2015/03/28)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 00107; page 39
(2014/08/19)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 0112
(2014/08/19)
-
- Mechanism of forming trimer, self-assembling nano-particle and inhibiting tumor growth of small molecule CIPPCT
-
The mechanisms of small molecules forming nanospecies and the effect of the nanospecies of small molecules on their pharmacological actions remain to be elucidated. As one of our efforts here, a uPA inhibitor, (5aS,12S,14aS)-5,14-dioxo-12-(2-tryptophanylthreo-nylbenzylester-N-yl-ethyl-1-yl)-1,2,3,5,5a,6,11,12,14,14a-decahydro-5H,14H-pyrolo[1,2:4,5]-pyrazino[1,2:1,6]pyrido[3,4-b]indole (CIPPCT) was presented. Energy-minimization, FT-MS and 2-D ROESY spectra defined CIPPCT taking -like conformation, and the intermolecular association drove CIPPCT to form a finger ring-like trimer. Images from transmission electron, scanning electron and atomic force microscopies consistently visualized that in aqueous solution at pH 6.7 and 10-10 M concentration, CIPPCT generally assembled nanoparticles of 9-67 nm in diameter. Mesoscale simulation demonstrated that a nanoparticle 9.4 nm in diameter contained 350 trimers. In vivo CIPPCT dose-dependently inhibited tumor growth in S180 mice. An ELISA assay confirmed that CIPPCT concentration-dependently downregulated serum uPA. The nanoparticles of CIPPCT are capable of occurring in mouse plasma and adhering on HeLa cells, and nanosized CIPPCT directly correlates the downregulation of uPA with inhibition of tumor growth.
- Du, Fengxiang,Zhang, Xiaoyi,Li, Shan,Wang, Yaonan,Zheng, Meiqing,Wang, Yuji,Zhao, Shurui,Wu, Jianhui,Gui, Lin,Zhao, Ming,Peng, Shiqi
-
supporting information
p. 1634 - 1643
(2014/12/11)
-
- Pyrazolo[1,4]diazepines as non-peptidic probes of the oxytocin and vasopressin receptors
-
An improved synthesis of differently substituted pyrazolo[1,4]diazepine compounds is reported. In addition, we have used this methodology to obtain non-peptidic compounds to probe the oxytocin and vasopressin receptors.
- Reekie, Tristan A.,McGregor, Iain S.,Kassiou, Michael
-
p. 4568 - 4571
(2015/01/09)
-
- 2-aminoimidazolyl and 2-aminopyridyl (S)-prolinamides as versatile multifunctional organic catalysts for aldol, Michael, and Diels-Alder reactions
-
The synthesis of multifunctional organocatalysts, easily obtained by the condensation of (S)-proline with 2-aminopyridine, 2,6-diaminopyridine, or 2-aminoimidazole, is reported. These chiral prolinamides promoted the aldol condensation between cyclohexano
- Orlandi, Manuel,Benaglia, Maurizio,Raimondi, Laura,Celentano, Giuseppe
-
supporting information
p. 2346 - 2354
(2013/05/21)
-
- NON-SYSTEMIC TGR5 AGONISTS
-
Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
- -
-
Page/Page column 105
(2013/07/05)
-
- HETERO-BICYCLIC DERIVATIVES AS HCV INHIBITORS
-
Inhibitors of HCV replication of formula I, including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R and R' have the meaning as defined herein. The present invention also relates to processes for preparing said compounds
- -
-
Page/Page column 26
(2013/07/19)
-
- QUINAZOLINONE DERIVATIVES AS HCV INHIBITORS
-
Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, salts, and solvates thereof, wherein R and R' have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.
- -
-
Page/Page column 27
(2013/07/19)
-
- Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety
-
We report the synthesis of several enantiopure pyrrolidine derivatives containing a β-amino acid moiety. These novel chiral compounds were prepared through stereospecific chlorosulfonyl isocyanate (CSI) addition to the readily available, natural terpene (+)-α-pinene. Coupling of N-Boc-protected β-amino acid derivatives with various bulky amines and amino acids using the mixed anhydride activation method, followed by N-deprotection, afforded the corresponding chiral amino amides in good yields. Despite the severe steric hindrance anticipated in α-pinene-based heterocycles, efficient coupling of the amino amides and an amino ester with the acyl chloride of N-Cbz-protected (S)-proline provided the corresponding pyrrolidinic pinene derivatives in good yields. Moreover, a convenient synthesis of N-Cbz- and N-Boc-monoprotected (S)-prolinamine is reported. Georg Thieme Verlag Stuttgart New York.
- Vega-Penaloza, Alberto,Sanchez-Antonio, Omar,Escudero-Casao, Margarita,Tasnadi, Gabor,Fueloep, Ferenc,Juaristi, Eusebio
-
p. 2458 - 2468
(2013/09/23)
-
- HETERO-BICYCLIC DERIVATIVES AS HCV INHIBITORS
-
Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R and R' have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors,in HCV therapy.
- -
-
Page/Page column 44
(2012/02/13)
-
- HYDROXAMATE-BASED INHIBITORS OF DEACETYLASES
-
The present teachings relate to compounds of Formula (I): and pharmaceutically acceptable salts, hydrates, esters, and prodrugs thereof, wherein R1, R2, R3, R4, R5, ring A, and Z are as defined herein
- -
-
Page/Page column 38
(2012/03/26)
-
- Simple and effective synthetic approach to chiral 2-amino-4-piperidinyl pyridine derivatives
-
(Chemical Equation Presented) A facile way has been developed to provide a series of novel chiral N-(4- (piperidin-1-yl)pyridin-2-yl)amide derivatives as potential stereoselective catalysts. The key intermediate, 2-amino-4-piperidinyl pyridine, was obtained by nucleophilic substitution of 2-amino-4-chloropyridine with piperidine in good yields (up to 96%). The total control of enantioselectivity was obtained for the synthesis of L-proline and (R)-1,10-bi(2-naphthol) derivatives. Copyright Taylor & Francis Group, LLC.
- Tian, Hua,Liu, Qing-Wen,Xu, Hao,Huang, Wen-Bo,Lin, Jian,Zhang, Suo-Qin
-
experimental part
p. 2707 - 2714
(2012/07/14)
-
- Highly efficient bifunctional organocatalysts for the asymmetric Michael addition of ketones to nitroolefins
-
A type of secondary-secondary-tertiary triamine bifunctional organocatalysts have been properly designed and synthesized. In our study, the designed catalyst (S)-N-(pyrrolidin-2-ylmethyl)pyridin-2-amine 5 has been shown to be highly efficient to promote the asymmetric Michael addition of ketones to nitroolefins at room temperature, which afforded the corresponding adducts in excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to >99% ee).
- Yu, Chuanming,Qiu, Jun,Zheng, Fei,Zhong, Weihui
-
supporting information; experimental part
p. 3298 - 3302
(2011/06/28)
-
- NOVEL INHIBITORS OF HEPATITIS C VIRUS REPLICATION
-
The embodiments provide compounds of the general Formulae I, II, III, IV, or V as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
- -
-
Page/Page column 273-275
(2011/07/06)
-
- Hydroxamate-Based Inhibitors of Deacetylases
-
The present teachings relate to compounds of Formula I: and pharmaceutically acceptable salts, hydrates, esters, and prodrugs thereof, wherein R1, R2, R3, R4, R5, ring A, and Z are as defined herein.
- -
-
Page/Page column 20-21
(2011/04/18)
-
- Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate
-
The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.
- Fournier, Anne M.,Brown, Robert A.,Farnaby, William,Miyatake-Ondozabal, Hideki,Clayden, Jonathan
-
supporting information; experimental part
p. 2222 - 2225
(2010/08/04)
-
- Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide
-
A new inhibitor, containing a linked proline-piperidine structure, for the enzyme prolyl oligopeptidase (POP) has been synthesised and demonstrated to bind covalently with the enzyme at the active site. This provides evidence that covalent inhibitors of P
- Racys, Daugirdas Tomas,Rea, Dean,Fueloep, Vilmos,Wills, Martin
-
experimental part
p. 4775 - 4782
(2010/08/22)
-
- Chiral catalysts dually functionalized with amino acid and Zn2+ complex components for enantioselective direct aldol reactions inspired by natural aldolases: Design, synthesis, complexation properties, catalytic activities, and mechanistic study
-
Aldolases are enzymes that catalyze stereospecific aldol reactions in a reversible manner. Naturally occurring aldolases include class I aldolases, which catalyze aldol reactions via enamine intermediates, and class II aldolases, in which Zn2+ enolates of substrates react with acceptor aldehydes. In this work, Zn2+ complexes of Lprolyl-pendant[15] aneN5 (ZnL3), Lprolyl-pendant[12]aneN4 (ZnL4), and L-valyl-pendant[12]aneN4 (ZnL5) were designed and synthesized for use as chiral catalysts for enantioselective aldol reactions. The complexation constants for L3 to L5 with Zn2+ [logKs(ZnL)] were determined to be 14.1 (for ZnL3), 7.6 (for ZnL4), and 9.6 (for ZnL5), indicating that ZnL3 is more stable than ZnL4 and ZnL 5. The depro-tonation constants of Zn2+-bound water [pKa values] for ZnL3, ZnL4, and ZnL 5 were calculated to be 9.2 (for ZnL3), 8.2 (for ZnL 4), and 8.6 (for ZnL5), suggesting that the Zn 2+ ions in ZnL3 is a less acidic Lewis acid than in ZnL4 and ZnL5. These values also indicated that the amino groups on the side chains weakly coordinate to Zn2+. We carried out aldol reactions between acetone and 2-chlorobenzaldehyde and other aldehydes in the presence of catalytic amounts of the chiral Zn2+ complexes in acetone/H2O at 25 and 37°C. Whereas ZnL3 yielded the aldol product in 43% yield and 1 % ee (R), ZnL4 and ZnL5 afforded good chemical yields and high enantioselectivities of up to 89% ee (R). UV titrations of proline and ZnL4 with acetylacetone (acac) in DMSO/H2O (1:2) indicate that ZnL4 facilitates the formation of the ZnL4.(acac)- complex (Kapp = 2.1X102M-1), whereas L-proline forms a Schiff base with acac with a very small equilibrium constant. These results suggest that the amino acid components and the Zn2+ ions in ZnL4 and ZnL5 function in a cooperative manner to generate the Zn 2+-enolate of acetone, thus permitting efficient enantioselective C-C bond formation with aldehydes.
- Itoh, Susumu,Kitamura, Masanori,Yamada, Yasuyuki,Aoki, Shin
-
supporting information; experimental part
p. 10570 - 10584
(2010/05/02)
-
- INHIBITORS OF IAP
-
The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds having the general formula U1 - M - U2 wherein M is a linking group covalently joining R2, R3, R4 or R5 of U1 to an R2, R3, R4 or R5 group of U2; U1 and U2 have the general formula (I) and G, X1, X2, R2, R3, R3', R4, R4' and R5, are as described herein.
- -
-
Page/Page column 80
(2008/12/08)
-
- Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: Receptor modeling studies
-
A population of 100 graphics models of the human 5-HT6 serotonin receptor was constructed based on the structure of bovine rhodopsin. The endogenous tryptamine-based agonist serotonin (5-HT; 1) and the benzenesulfonyl-containing tryptamine-deri
- Dukat, Ma?gorzata,Mosier, Philip D.,Kolanos, Renata,Roth, Bryan L.,Glennon, Richard A.
-
p. 603 - 611
(2008/09/18)
-
- INHIBITORS OF IAP
-
The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula (I): wherein Q, X1, X2, Y, Z1, Z2, Z3, Z4, R1, R2, R3, R3', R4, R4', R5, R6, R6' and n are as described herein.
- -
-
Page/Page column 57
(2008/06/13)
-
- AMIDE DERIVATIVES AS KINASE INHIBITORS
-
The present invention relates to new AGC kinase inhibitors, in particular to compounds of Formula (I) or (II) or a stereoisomer, tautomer, racemic, metabolite, pro- or predrug, salt, hydrate, or solvate thereof, wherein Ar1, Ar2, R1, R3, p and n have the meaning defined in the claims. In particular, the present invention relates to more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease.
- -
-
Page/Page column 42-43
(2010/11/25)
-
- PDF INHIBITORS
-
The invention relates to novel compounds that are inhibitors of peptidyl deformylase (PDF). The compounds are useful as antimicrobials and antibiotics. The compounds of the invention display selective inhibition of peptidyl deformylase versus other metalloproteinases such as MMPs. Methods of preparation and uses of the compounds are also disclosed.
- -
-
Page/Page column 32
(2010/11/28)
-
- Parallel synthesis of a library of benzoxazoles and benzothiazoles using ligand-accelerated copper-catalyzed cyclizations of ortho-halobenzanilides
-
A general method for the formation of benzoxazoles via a copper-catalyzed cyclization of ortho-haloanilides is reported. This approach complements the more commonly used strategies for benzoxazole formation which require 2-aminophenols as substrates. The reaction involves an intramolecular C-O cross-coupling of the ortho-haloanilides and is believed to proceed via an oxidative insertion/reductive elimination pathway through a Cu(I)/Cu(III) manifold. The reaction is also applicable to the formation of benzothiazoles. A variety of ligands including 1,10-phenanthroline and N,N′- dimethylethylenediamine were shown to provide ligand acceleration/stabilization in the reaction. Optimal conditions for cyclization used a catalyst combination of CuI and 1,10-phenanthroline (10 mol %). The method was amenable to a parallel-synthesis approach, as demonstrated by the synthesis of a library of benzoxazoles and benzothiazoles substituted at various positions in the ring. Most examples utilized the cyclization of ortho-bromoanilides, but orthoiodoanilides and ortho-chloroanilides also undergo a reaction under these conditions. The rate of reaction of the ortho-haloanilides follows the order I > Br > Cl, consistent with oxidative addition being the rate-determining step.
- Evindar, Ghotas,Batey, Robert A.
-
p. 1802 - 1808
(2007/10/03)
-
- Structurally simple pyridine N-oxides as efficient organocatalysts for the enantioselective allylation of aromatic aldehydes
-
A series of structurally simple pyridine N-oxides have readily been assembled from inexpensive amino acids and tested as organocatalysts in the allylation of aldehydes with allyl(trichloro)silane to afford homoallylic alcohols. (S)-Proline-based catalysts
- Pignataro, Luca,Benaglia, Maurizio,Annunziata, Rita,Cinquini, Mauro,Cozzi, Franco
-
p. 1458 - 1463
(2007/10/03)
-
- Highly enantioselective addition of ketones to nitroolefins catalyzed by new thiourea-amine bifunctional organocatalysts
-
A new and effective organocatalytic system: primary amine derived chiral thiourea catalyst 4a and AcOH-H2O additive, which converts different ketones to γ-nitroketones in high yields (82-99%) and enantioselectivities (90-99%) has been described
- Tsogoeva, Svetlana B.,Wei, Shengwei
-
p. 1451 - 1453
(2008/02/05)
-
- Novel and potent cyclic cyanamide-based cathepsin K inhibitors
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Starting from a PDE IV inhibitor hit derived from high throughput screening of the compound collection, a key pyrrolidine cyanamide pharmacophore was identified. Modifications of the pyrrolidine ring produced enhancements in cathepsin K inhibition. An X-r
- Deaton, David N.,Hassell, Anne M.,McFadyen, Robert B.,Miller, Aaron B.,Miller, Larry R.,Shewchuk, Lisa M.,Tavares, Francis X.,Willard Jr., Derril H.,Wright, Lois L.
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p. 1815 - 1819
(2007/10/03)
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- Preparation of pyrrolidine-oxazoline containing ligands and their application in asymmetric transfer hydrogenation
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Nine members of a new ligand class incorporating both an oxazoline ring and a pyrrolidine unit were prepared in an efficient four-step synthesis starting from readily available chiral amino alcohols and proline. A study of these ligands in the asymmetric transfer hydrogenation of acetophenone showed that the catalysts formed from [Ir(cod)Cl]2 were the most active while those derived from [Ru(p-cymene)Cl2]2 gave the highest enantioselectivities (up to 61% ee).
- McManus, Helen A.,Barry, Sarah M.,Andersson, Pher G.,Guiry, Patrick J.
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p. 3405 - 3416
(2007/10/03)
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- A Mechanistically Guided Design Leads to the Synthesis of an Efficient and Practical New Reagent for the Highly Enantioselective, Catalytic Dihydroxylation of Olefins
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(Equation presented) The catalytic asymmetric dihydroxylation of olefins has been accomplished with high enantioselectivities using a proline-based catalyst. The pre-transition-state assembly for styrene is shown.
- Huang, Jinkun,Corey
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p. 3455 - 3458
(2007/10/03)
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- CONDENSED HETEROCYCLIC COMPOUNDS AS CALCITONIN AGONISTS
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The present invention relates to novel fused heterocyclic ring system compounds and methods for their use in the treatment and prevention of diseases or conditions which are related to irregular calcification.
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Page/Page column 26; 124-125
(2010/02/07)
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- Spiro β-lactams as β-turn mimetics. Design, synthesis, and NMR conformational analysis
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Molecular modeling calculations using high-level ab initio methods (MP2/6-31+G*) of a new type of spiro β-lactams predict that these systems could adopt a β-turn secondary structure in solution. Strong intramolecular hydrogen bonds stabilize the β-turn conformation with a geometry that is very close to the ideal type II β-turns. The synthesis of the spiro β-lactams is achieved by Staudinger reaction of a cyclic ketene derived from N-bencyloxycarbonyl-L-proline acid chloride with an imine. This reaction allows the formation of the spiranic backbone in a single-step with high diastereo-selectivity and good yields. The new spiro β-lactams obtained are the core for the preparation of different types of peptidomimetics using well-established peptide chemistry. The NMR conformational analysis shows that these compounds adopt β-turn conformation as predicted by the theoretical studies.
- Alonso,Lopez-Ortiz,Del Pozo,Peralta,Macias,Gonzales
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p. 6333 - 6338
(2007/10/03)
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- The synthesis of bicyclic piperazine-2-carboxylic acids from L-proline
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The stereocontrolled synthesis of two diastereomeric bicyclic piperazine-2-carboxylic acids from L-proline is described.
- Hanessian, Stephen,Sharma, Raman
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p. 1231 - 1239
(2007/10/03)
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- 5-arylindole derivatives
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Compounds of formula (I), wherein R 1 is (a), (b), (c) or (d); n is 0, 1 or 2; A, B, C and D are each independently nitrogen or carbon; R 2, R 3, R 4 and R 5 are each independently hydrogen, C 1 to C 6 alkyl, aryl, C 1 to C 3 alkyl-aryl, halogen (e.g. fluorine, chlorine, bromine or iodine), cyano, nitro, --(CH 2) m NR 14 R 15, --(CH 2) m OR 9, --SR 9, --SO 2 NR 14 R 15, --(CH 2) m NR 14 SO 2 R 15 --(CH 2) m NR 14 CO 2 R 9, --(CH 2) m NR 14 COR 9, --(CH 2) m NR 14 CONHR 9, --CONR 14 R 15, or --CO 2 R 9 ; R 2 and R 3, R 3 and R 4, or R 4 and R 5 may be taken together to form a five- to seven-membered alkyl ring, a six-membered aryl ring, a five- to seven-membered heteroalkyl ring having 1 heteroatom of N, O, or S, or a five- to six-membered heteroaryl ring having H 1 or 2 heteroatoms of N, O, or S and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and benzodiazepine agonists and antagonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vosodilators. STR1
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