cas 139290-70-3, 1-Boc-4-[methoxy(methyl)carbamoyl]piperidine

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Heteroaromatic and aniline derivatives of piperidines as potent ligands for vesicular acetylcholine transporter
To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (Ki = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over σ1 and σ2 receptors (Ki = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[11C]24b (Ki = 0.78 nM for VAChT, 1200-fold over σ receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[11C]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.
Li, Junfeng,Zhang, Xiang,Zhang, Zhanbin,Padakanti, Prashanth K.,Jin, Hongjun,Cui, Jinquan,Li, Aixiao,Zeng, Dexing,Rath, Nigam P.,Flores, Hubert,Perlmutter, Joel S.,Parsons, Stanley M.,Tu, Zhude
p. 6216 - 6233
(2013)
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Iodonium ylides for one-step, no-carrier-added radiofluorination of electron rich arenes, exemplified with 4-(([18F]fluorophenoxy)- phenylmethyl)piperidine NET and SERT ligands
Iodonium ylide precursors of electron rich arenes, i.e. the NET and SERT ligands 4-((3- and 4-fluorophenoxy)phenylmethyl)piperidine, served as model compounds for the direct substitution with n.c.a. [18F]fluoride. Good radiochemical yields of a
Cardinale, Jens,Ermert, Johannes,Humpert, Sven,Coenen, Heinz H.
p. 17293 - 17299
(2014)
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Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors
A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC50's were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
Shen, Hong C.,Ding, Fa-Xiang,Zhou, Changyou,Xiong, Yusheng,Verras, Andreas,Chabin, Renee M.,Xu, Suoyu,Tong, Xinchun,Xie, Dan,Lassman, Michael E.,Bhatt, Urmi R.,Garcia-Calvo, Margarita M.,Geissler, Wayne,Shen, Zhu,Chen, Dunlu,Sinharoy, Ranabir,Hale, Jeffery J.,Tata, James R.,Pinto, Shirly,Shen, Dong-Ming,Colletti, Steven L.
p. 1299 - 1305
(2011)
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Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH)
Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information. So far, most PET tracers show irreversible binding patterns with FAAH, which would result in complicated quantitative processes. Herein, we have identified a new FAAH inhibitor (1-((1-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)(oxazol-2-yl)methanone (8) which inhibits the hydrolysis of AEA in the brain with high potency (IC50 value 11 nM at a substrate concentration of 0.5 μM), and without showing time-dependency. The PET tracer [11C]8 (also called [11C]FAAH-1906) was successfully radiolabeled with [11C]MeI in 17 ± 6% decay-corrected radiochemical yield (n = 7) with >74.0 GBq/μmol (2 Ci/μmol) molar activity and >99% radiochemical purity. Ex vivo biodistribution and blocking studies of [11C]8 in normal mice were also conducted, indicating good brain penetration, high brain target selectivity, and modest to excellent target selectivity in peripheral tissues. Thus, [11C]8 is a potentially useful PET ligand with enzyme inhibitory and target binding properties consistent with a reversible mode of action.
Cai, Qijun,Chen, Jiahui,Chen, Zhen,Fowler, Christopher J.,Gan, Jiefeng,Hou, Lu,Li, Guocong,Liang, Steven H.,Tan, Zhiqiang,Wang, Lu,Xu, Hao,Ye, Weijian,Zheng, Chao
(2020)
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1,2,3,4-Tetrahydroquinoline-containing αVβ 3 integrin antagonists with enhanced oral bioavailability
Selective reduction of the quinoline yielded potent α vβ53 antagonists with improved oral bioavailability relative to the corresponding quinoline derivatives. Reduction of the quinoline ring in an αvβ3 antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant αVβ3 antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative.
Ghosh, Shyamali,Santulli, Rosemary J.,Kinney, William A.,DeCorte, Bart L.,Liu, Li,Lewis, Joan M.,Proost, Jef C.,Leo, Gregory C.,Masucci, John,Hageman, William E.,Thompson, Andrew S.,Chen, Ian,Kawahama, Reiko,Tuman, Robert W.,Galemmo Jr., Robert A.,Johnson, Dana L.,Damiano, Bruce P.,Maryanoff, Bruce E.
p. 5937 - 5941
(2004)
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ALIPHATIC ACID AMIDE DERIVATIVE
The present invention relates to a compound represented by formula (1): the compound having antagonist activity against serotonin 5-HT2A receptors and serotonin 5-HT7 receptors; or a pharmaceutically acceptable salt of the compound. (In the formula, Z is a nitrogen atom and the like; Y is carbonyl and the like; m and n are 1 and the like; R1a through R1d, R2a through R2d, and R4a through R4d are a hydrogen atom and the like; R3 is alkyl and the like; and Q is a specific bicyclic group.)
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(2022/03/19)

METHODS AND COMPOSITIONS FOR TARGETING TREGS USING CCR8 INHIBITORS
Provided herein are compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.
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Paragraph 0317-0318

(2022/01/12)

TRPML MODULATORS
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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Paragraph 0374

(2021/06/26)

AZETIDINE AND SPIROAZETIDINE COMPOUNDS AND USES THEREOF
The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
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Page/Page column 45-46

(2021/12/30)

Oxazolone compound, application thereof and FAAH positron drug
The invention relates to an oxazolone compound, application thereof and an FAAH positron drug. The structure of the oxazolone compound is shown in the description. The FAAH positron drug prepared by using the oxazolone compound as a precursor has a high b
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Paragraph 0050; 0053-0057; 0068; 0071-0075

(2020/02/27)

Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis-and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.
Knez, Damijan,Colettis, Natalia,Iacovino, Luca G.,Sova, Matej,Pi?lar, Anja,Konc, Janez,Le?nik, Samo,Higgs, Josefina,Kamecki, Fabiola,Mangialavori, Irene,Dol?ak, Ana,?akelj, Simon,Trontelj, Jurij,Kos, Janko,Binda, Claudia,Marder, Mariel,Gobec, Stanislav
p. 1361 - 1387
(2020/03/10)

Design, Synthesis, and Pharmacological Characterization of Heterobivalent Ligands for the Putative 5-HT2A/mGlu2Receptor Complex
We report the synthesis of the first series of heterobivalent ligands targeting the putative heteromeric 5-HT2A/mGlu2 receptor complex, based on the 5-HT2A antagonist MDL-100,907 and the mGlu2 ago-PAM JNJ-42491293. The functional properties of monovalent and heterobivalent ligands were characterized in 5-HT2A-, mGlu2/Gqo5-, 5-HT2A/mGlu2-, and 5-HT2A/mGlu2/Gqo5-expressing HEK293 cells using a Ca2+ imaging assay and a [3H]ketanserin binding assay. Pronounced functional crosstalk was observed between the two receptors in 5-HT2A/mGlu2 and 5-HT2A/mGlu2/Gqo5 cells. While the synthesized monovalent ligands retained the 5-HT2A antagonist and mGlu2 ago-PAM functionalities, the seven bivalent ligands inhibited 5-HT-induced responses in 5-HT2A/mGlu2 cells and both 5-HT- and Glu-induced responses in 5-HT2A/mGlu2/Gqo5 cells. However, no definitive correlation between the functional potency and spacer length of the ligands was observed, an observation substantiated by the binding affinities exhibited by the compounds in 5-HT2A, 5-HT2A/mGlu2, and 5-HT2A/mGlu2/Gqo5 cells. In conclusion, while functional crosstalk between 5-HT2A and mGlu2 was demonstrated, it remains unclear how these heterobivalent ligands interact with the putative receptor complex.
Poulie, Christian B. M.,Liu, Na,Jensen, Anders A.,Bunch, Lennart
p. 9928 - 9949
(2020/09/12)

NOVEL COMPOUNDS FOR INHIBITION OF JANUS KINASE 1
An object of the invention is to provide compounds as selective JAK1 inhibitor, a process for preparation of the inhibitors, a composition containing the compounds and utility of the compounds.
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Page/Page column 112; 196

(2020/12/11)

NOVEL ARYLOXYPIPERIDINE PYRAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS
Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
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Page/Page column 92; 93

(2020/03/15)

CONDENSED LACTAM DERIVATIVE
The present invention relates to a medicament for treating neuropsychiatric diseases, comprising a compound of Formula (1): or a pharmaceutically acceptable salt thereof, as an active ingredient.
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Paragraph 0369; 0370; 0371

(2020/06/27)

Aromatic cycloamines derivative and application in multi-target antidepressant medicine
The invention discloses an aromatic cycloamines derivative and an application in multi-target antidepressant medicine. The aromatic cycloamines derivative has inhibitory activity on 5-HT reuptake, NEreuptake and DA reuptake, is a novel compound of a 5-HT/
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Paragraph 0079; 0080; 0088; 0089; 0120-0122

(2019/11/29)

NEW HETEROCYCLIC COMPOUNDS
The invention provides new heterocyclic compounds having the general formula (IA) wherein A, L, X, Y, m, n, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
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Page/Page column 67; 107

(2019/06/17)

TREATMENT OF INDOLENT OR AGGRESSIVE B-CELL LYMPHOMAS USING A COMBINATION COMPRISING BTK INHIBITORS
Disclosed herein is a method for the prevention, delay of progression or treatment of indolent or aggressive B-cell lymphomas in an individual in need thereof, comprising administering a Btk inhibitor (in particularly (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo-[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof) in combination with an anti-PD-1 antibody. The potent and selective BTK inhibitor in combination with the anti-PD-1 antibody have a manageable toxicity profile in patients with indolent and aggressive lymphomas.
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Paragraph 0109

(2019/06/17)

Synthesis and activity of functionalizable derivatives of the serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907
The approach of tethering together two known receptor ligands, to be used as molecular probes for the study of G protein-coupled receptor (GPCR) systems, has proven to be a valuable approach. Selective ligands that possess functionality that can be used to link to other ligands, are useful in the development of novel antagonists and agonists. Such molecules can also be attached to reporter molecules, such as fluorophores, for the study of GPCR dimerization and its role in signaling. The highly selective serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist M100907 (volinanserin) is of clinical interest in the treatment of neurological and mental health disorders. Here, we synthesized the most active (+)-M100907 enantiomer as well as a series of derivatives that possessed either an alkyne or an azide. The triazole resulting from the dipolar cycloaddition of these groups did not interfere with the ability of the bivalent ligand to act as an antagonist. Thus, we have synthesized a number of compounds which will prove useful in elucidating the role of the 5-HT2AR in the central nervous system.
Gilbertson, Scott R.,Chen, Ying-Chu,Soto, Claudia A.,Yang, Yaxing,Rice, Kenner C.,Cunningham, Kathryn A.,Anastasio, Noelle C.
p. 1381 - 1385
(2018/03/23)

USE OF A COMBINATION COMPRISING A BTK INHIBITOR FOR TREATING CANCERS
A method for the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject in need thereof a Btk inhibitor, particularly, (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor or a targeted therapy agent. A pharmaceutical combination comprising a Btk inhibitor, particularly, (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor or a targeted therapy agent.
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Paragraph 0102-0103

(2018/03/09)

CRYSTALLINE FORM OF (S)-7-(1-ACRYLOYLPIPERIDIN-4-YL)-2-(4-PHENOXYPHENYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE, PREPARATION, AND USES THEREOF
The present invention relates to a crystalline form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide for inhibiting Btk, methods of preparation thereof and pharmaceutical compositions, and use of the crystalline form above in the treatment of a disease, or in the manufacturing of a medicament for the treatment of a disease.
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Paragraph 0055; 0091; 0095

(2018/08/19)

CRYSTALLINE FORMS OF (S) -7- (1- (BUT-2-YNOYL) PIPERIDIN-4-YL) -2- (4-PHENOXYPHENYL) -4, 5, 6, 7-TETRAHY DROPYRAZOLO [1, 5-A] PYRIMIDINE-3-CARBOXAMIDE, PREPARATION, AND USES THEREOF
The present invention relates to a crystalline form of (S) -7- (1- (but-2-ynoyl) piperidin-4-yl) -2- (4-phenoxyphenyl) -4, 5, 6, 7-tetrahydropyrazolo [1, 5-a] pyri midine-3-carboxamide for inhibiting Btk, methods of preparation thereof and pharmaceutical compositions, and use of the crystalline form above in the treatment of a disease, or in the manufacturing of a medicament for the treatment of a disease.
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Paragraph 00137; 00138

(2018/09/08)

PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF BACTERIAL DISEASES
The present invention relates to novel compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein the integers are as defined in the description. The claimed compounds are useful for the treatment of a bacterial infection. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of a bacterial infection and a process for preparing the claimed compounds.
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(2017/12/27)

Copper(I)-Catalyzed Enantioselective Nucleophilic Borylation of Aliphatic Ketones: Synthesis of Enantioenriched Chiral Tertiary α-Hydroxyboronates
A new method was developed for the first catalytic enantioselective borylation of aliphatic ketones. A variety of substrates reacted efficiently with bis(pinacolato)diboron in the presence of a copper(I)/chiral N-heterocyclic carbene complex catalyst to furnish optically active tertiary α-hydroxyboronates with moderate to high enantioselectivities (up to 94 % ee). Notably, the product could be converted into the chiral tertiary alcohol derivative using a stereospecific boron functionalization process. The theoretical study of the mechanism for the enantioselectivity is also described.
Kubota, Koji,Osaki, Shun,Jin, Mingoo,Ito, Hajime
supporting information
p. 6646 - 6650
(2017/05/29)

Structure-Based Optimization of Pyridoxal 5′-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis
The pyridoxal 5′-phosphate (PLP)-dependent transaminase BioA catalyzes the second step in the biosynthesis of biotin in Mycobacterium tuberculosis (Mtb) and is an essential enzyme for bacterial survival and persistence in vivo. A promising BioA inhibitor 6 containing an N-aryl, N′-benzoylpiperazine scaffold was previously identified by target-based whole-cell screening. Here, we explore the structure-activity relationships (SAR) through the design, synthesis, and biological evaluation of a systematic series of analogues of the original hit using a structure-based drug design strategy, which was enabled by cocrystallization of several analogues with BioA. To confirm target engagement and discern analogues with off-target activity, each compound was evaluated against wild-type (WT) Mtb in biotin-free and -containing medium as well as BioA under- and overexpressing Mtb strains. Conformationally constrained derivative 36 emerged as the most potent analogue with a KD of 76 nM against BioA and a minimum inhibitory concentration of 1.7 μM (0.6 μg/mL) against Mtb in biotin-free medium.
Liu, Feng,Dawadi, Surendra,Maize, Kimberly M.,Dai, Ran,Park, Sae Woong,Schnappinger, Dirk,Finzel, Barry C.,Aldrich, Courtney C.
p. 5507 - 5520
(2017/07/22)

HETEROCYCLIC COMPOUND AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
The invention relates to a novel heterocyclic compound inhibiting a cyclin-dependent kinase (CDK) and a pharmaceutical composition comprising the same as an effective ingredient. The heterocyclic compound according to the present invention or pharmaceutically acceptable salt thereof can be effectively used in treating or preventing cancers, degenerative brain diseases, etc.
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(2018/01/11)

SMYD INHIBITORS
The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.
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Paragraph 0614; 0617-0619

(2017/07/18)

ISOXAZOLE CARBOXAMIDE COMPOUNDS
The present disclosure provides substituted isoxazole carboxamide compounds having Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, A, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.
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Paragraph 0268

(2016/06/01)

PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF BACTERIAL DISEASES
The present invention relates to novel compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein the integers are as defined in the description. The claimed compounds are useful for the treatment of a bacterial infection. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of a bacterial infection and a process for preparing the claimed compounds.
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(2015/03/31)

PIPERIDINE UREA DERIVATIVES
Compounds of the formula I in which R1-R3 have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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(2015/02/25)

CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS
Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.
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(2015/07/22)

Trisubstituted thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of alphaviruses
Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus and is transmitted to humans by Aedes mosquitoes. Despite the re-emergence of CHIKV as an epidemic threat, there is no approved effective antiviral treatment currently available for CHIKV. Herein, we report the synthesis and structure-activity relationship studies of a class of thieno[3,2-b]pyrroles and the discovery of a trisubstituted thieno[3,2-b]pyrrole 5-carboxamide 15c that exhibits potent inhibitory activity against in vitro CHIKV infection. Compound 15c displayed low micromolar activity (EC50 value of ca. 2 μM) and limited cytotoxic liability (CC50 > 100 μM) therefore furnishing a selectivity index of greater than 32. Notably, 15c not only controlled viral RNA production, but efficiently inhibited the expression of CHIKV nsP1, nsP3, capsid, and E2 proteins at a concentration as low as 2.5 μM. More importantly, 15c also demonstrated broad spectrum antiviral activity against other clinically important alphaviruses such as O'nyong-nyong virus and Sindbis virus.
Ching, Kuan-Chieh,Kam, Yiu-Wing,Merits, Andres,Ng, Lisa F. P.,Chai, Christina L. L.
p. 9196 - 9213
(2015/12/23)

Progress towards small molecule menin-mixed lineage leukemia (MLL) interaction inhibitors with in vivo utility
A series of substituted hydroxymethyl piperidine small molecule inhibitors of the protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) are described. Initial members of the series showed good inhibitory disruption of the menin-MLL
Senter, Timothy,Gogliotti, Rocco D.,Han, Changho,Locuson, Charles W.,Morrison, Ryan,Daniels, J. Scott,Cierpicki, Tomasz,Grembecka, Jolanta,Lindsley, Craig W.,Stauffer, Shaun R.
p. 2720 - 2725
(2015/06/08)

OXOQUINAZOLINYL-BUTANAMIDE DERIVATIVES
Compounds of the formula I in which R1-R3 and Z have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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Page/Page column 47; 48

(2015/02/25)

MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Paragraph 00135; 00136

(2014/10/04)

CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS
Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.
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(2014/01/17)

NON-PEPTIDIC NEUROPEPTIDE Y RECEPTOR MODULATORS
The invention provides compounds that are modulators of neuropeptide Y (NPY) receptors, which can be selective inhibitors of NPY receptor Y2R. NPY receptor modulatory compounds are of the general formula Ar2-Y-Ar1-W-Ar3, wherein the variables are as defined herein. Compounds of the invention can be used for treatment of malconditions in patients wherein modulation of an NPY receptor is medically indicated, for example including drug or alcohol abuse, anxiety disorders, depression, stress-related disorders, neurological disorders, nerve degeneration, osteoporosis or bone loss, sleep/wake disorders, cardiovascular diseases, obesity, anorexia, inovulation, fertility disorders, angiogenesis, cell proliferation, learning and memory disorders, migraine and pain.
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(2014/08/07)

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres
This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores.
Sheffler, Douglas J.,Nedelovych, Michael T.,Williams, Richard,Turner, Stephen C.,Duerk, Brittany B.,Robbins, Megan R.,Jadhav, Sataya B.,Niswender, Colleen M.,Jones, Carrie K.,Conn, P. Jeffrey,Daniels, R. Nathan,Lindsley, Craig W.
p. 1062 - 1066
(2014/03/21)

Highly enantioselective hydrogenation and transfer hydrogenation of cycloalkyl and heterocyclic ketones catalysed by an iridium complex of a tridentate phosphine-diamine ligand
Ir complexes of chiral phosphine-diamine ligands catalyse the hydrogenation and transfer hydrogenation of aryl-piperidin-4-yl methanones, and ketones bearing both an aryl group and secondary alkyl substituent with up to 98% e.e., and with substrate to catalyst ratios of up to 4000.
Fuentes, Jose A.,Carpenter, Ian,Kann, Nina,Clarke, Matthew L.
supporting information
p. 10245 - 10247
(2013/10/22)

NEW COMPOUNDS AND NEW USE
The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein the integers are as defined in the description. The claimed compounds are useful for the treatment of a bacterial infection. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of a bacterial infection and a process for preparing the claimed compounds.
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(2013/11/19)

Synthesis of quaternary α-amino acid-based arginase inhibitors via the Ugi reaction
The Ugi reaction has been successfully applied to the synthesis of novel arginase inhibitors. In an effort to decrease conformational flexibility of the previously reported series of 2-amino-6-boronohexanoic acid (ABH) analogs 1, we designed and synthesized a series of compounds, 2, in which a piperidine ring is linked directly to a quaternary amino acid center. Further improvement of in vitro activity was achieved by adding two carbon bridge in the piperidine ring, that is, tropane analogs 11. These improvements in activity are rationalized by X-ray crystallography analysis, which show that the tropane ring nitrogen atom moves into direct contact with Asp202 (arginase II numbering). The synthetic routes described here enabled the design of novel arginase inhibitors with improved potency and markedly different physico-chemical properties compared to ABH. Compound 11c represents the most in vitro active arginase inhibitor reported to date.
Golebiowski, Adam,Whitehouse, Darren,Beckett, R. Paul,Van Zandt, Michael,Ji, Min Koo,Ryder, Todd R.,Jagdmann, Erik,Andreoli, Monica,Lee, Yung,Sheeler, Ryan,Conway, Bruce,Olczak, Jacek,Mazur, Marzena,Czestkowski, Wojciech,Piotrowska, Wieslawa,Cousido-Siah, Alexandra,Ruiz, Francesc X.,Mitschler, Andre,Podjarny, Alberto,Schroeter, Hagen
p. 4837 - 4841
(2013/09/02)

HEPATITIS B ANTIVIRAL AGENTS
The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.
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Page/Page column 191

(2013/07/05)

Compounds comprising 4-benzoylpiperidine as a Sigma-1-selective ligand
Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for σ1 receptors. Some compounds are also highly selective for σ1 receptor compared to σ2 receptor. Compounds can compris
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(2012/01/12)

TASK CHANNEL ANTAGONISTS
This invention relates to TASK-1 and/or TASK-3 antagonists and/or their pharmaceutically acceptable salts, compositions and methods for treating and preventing disorders which are caused by activation or by an activated TASK-1 and/or TASK-3, and disorders
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(2011/09/21)

TASK CHANNEL ANTAGONISTS
This invention relates to TASK-1 and/or TASK-3 antagonists and/or their pharmaceutically acceptable salts, compositions and methods for treating and preventing disorders which are caused by activation or by an activated TASK-1 and/or TASK-3, and disorders
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(2011/09/30)

Design and synthesis of new peptidomimetics as potential inhibitors of MurE
With the continuing emergence and spread of multidrug-resistant bacteria, there is an urgent need for the development of new antimicrobial agents. One possible source of new antibacterial targets is the biosynthesis of the bacterial cellwall peptidoglycan
Zivec, Matej,Turk, Samo,Blanot, Didier,Gobec, Stanislav
experimental part
p. 95 - 109
(2012/05/04)

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS
Compounds of structural formula I 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, incl
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Page/Page column 47

(2011/12/02)

Synthesis of a C-14 labeled delta-opioid receptor agonist by carbonylation
Opioid drugs have long been known to bind to specific receptors in both the brain and periphery. First identified in the 1970s, these receptors are classified as mu, kappa and delta.1 While each of these receptors appear to be involved in regulation of pain pathways and of mood, the delta opioid receptor produces a unique pharmacology. AstraZeneca has designed a number of agonists for the receptor, and in order to better understand this receptor's pharmacology, a C14-labeled compound was prepared. The structure of this compound was ideal for a late stage carbonylation using C-14 carbon monoxide to give the C-14 labeled compound an 18% overall radiochemical yield. Copyright
Elmore, Charles S.,Frietze, William E.,Andisik, Donald W.,Ernst, Glen E.,Heys, J. Richard,Dantzman, Cathy L.
p. 394 - 397
(2011/04/24)

PYRAZINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS
Pyrazine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
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Page/Page column 64-65

(2010/06/15)

N,N'-2,4-DIANILINOPYRIMIDINE DERIVATIVES, PREPARATION THEREOF AS DRUGS, PHARMACEUTICAL COMPOSITIONS ESSENTIALLY AS IKK INHIBITORS
The disclosure relates to a compound of formula (I): wherein R, R1, R2, R3, R4, R5, R6 and Z are as defined in the specification, to compositions containing them, to processes for preparing them, and to their use in the treatment or prevention of conditio
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Page/Page column 46; 47

(2010/04/30)

Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
Radiolabelled piperidine derivatives such as [11C]MDL 100907 and [18F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with 18F-fluorine, were synthesized to improve molecular imaging properties of [11C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show Ki-values in the nanomolar range towards the 5-HT2A receptor and insignificant binding to other 5-HT receptor subtypes or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity profile similar to MDL 100907. These compounds could possibly be preferable antagonistic 18F-tracers for visualization of the 5-HT2A receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have Ki values between 30 and 120 nM. All promising compounds show log P values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of 18F-labelled analogues for 5-HT2A imaging with PET.
Herth, Matthias M.,Kramer, Vasko,Piel, Markus,Palner, Mikael,Riss, Patrick J.,Knudsen, Gitte M.,Roesch, Frank
scheme or table
p. 2989 - 3002
(2009/09/05)