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Sustainable Route Toward N-Boc Amines: AuCl3/CuI-Catalyzed N-tert-butyloxycarbonylation of Amines at Room Temperature
N-tert-butoxycarbonyl (N-Boc) amines are useful intermediates in synthetic/medicinal chemistry. Traditionally, they are prepared via an indirect phosgene route with poor atom economy. Herein, a step- and atom-economic synthesis of N-Boc amines from amines, t-butanol, and CO was reported at room temperature. Notably, this N-tert-butyloxycarbonylation procedure utilized ready-made substrates, commercially available AuCl3/CuI as catalysts, and O2 from air as the sole oxidant. This catalytic system provided unique selectivity for N-Boc amines in good yields. More significantly, gram-scale preparation of medicinally important N-Boc amine intermediates was successfully implement, which demonstrated a potential application prospect in industrial syntheses. Furthermore, this approach also showed good compatibility with tertiary and other useful alcohols. Investigations of the mechanisms revealed that gold catalyzed the reaction and copper acted as electron transfer mediator in the catalytic cycle.
Cao, Yanwei,Huang, Yang,He, Lin
(2021/12/22)

Nickel-Catalyzed Deaminative Cyanation: Nitriles and One-Carbon Homologation from Alkyl Amines
A nickel-catalyzed deaminative cyanation of Katritzky pyridinium salts has been developed. When it is coupled with formation of the pyridinium salt from primary amines, this method enables alkyl amines to be converted to alkyl nitriles. A less toxic cyanide reagent, Zn(CN)2, is utilized, and diverse functional groups and heterocycles are tolerated. The method also enables a one-carbon homologation of alkyl amines via reduction of the nitrile products, in addition to many other potential transformations of the versatile nitrile group.
Xu, Jianyu,Twitty, J. Cameron,Watson, Mary P.
supporting information
p. 6242 - 6245
(2021/08/23)

Nickel-Catalyzed Cyanation of Unactivated Alkyl Sulfonates with Zn(CN)2
Cyanation of unactivated primary and secondary alkyl mesylates with Zn(CN)2 catalyzed by nickel has been developed. The reaction provides an efficient route for the synthesis of alkyl nitriles with wide substrate scope, good functional group tolerance, and compatibility with heterocyclic compounds. Mechanistic studies indicate that alkyl iodide generated in situ serves as the reactive intermediate and the gradual release of alkyl iodide is crucial for the success of the reaction.
Xia, Aiyou,Lv, Peizhuo,Xie, Xin,Liu, Yuanhong
supporting information
p. 7842 - 7847
(2020/11/02)

Synthesis of 1,4- and 1,4,4-substituted piperidines for the inhibition of neuronal T-type Ca2+ channels and mitigation of neuropathic pain in mice
A dysregulation in function of neuronal low-voltage-activated T-channel causes neuropathic pain. A group of ten 1,4-disubstituted and 1,4,4-trisubstituted piperidines were synthesized through short sequences of reactions from 4-cyanopiperidine, which may potentially produce a library of analogs. Inhibitions of T-channel in rat dorsal root ganglion neurons and/or Cav3.2 channel in human embryonic kidney-293 cells were screened, and subsequent analgesic effects and inhibition of seizure in pentylenetetrazole-induced seizure mouse model were examined. The two most promising piperidine molecules showed analgesic effects in rat model using a spared nerve injury protocol. One displayed a long withdrawal latency in response to thermal stimulation, and an 80% increase in mechanical threshold assessment studies.
Gunaratna, Medha J.,Hua, Duy H.,Zou, Bende,Pascual, Conrado,Cao, William,Zhang, Man,Weerasekara, Sahani,Nguyen, Thi D.T.,Xiao, Kui,Xie, Xinmin Simon
p. 22 - 39
(2019/03/08)

Decarboxylative Cyanation of Aliphatic Carboxylic Acids via Visible-Light Flavin Photocatalysis
An operationally simple method is disclosed for the decarboxylative cyanation of aliphatic carboxylic acids at room temperature. Riboflavin tetraacetate, which is an inexpensive organic photocatalyst, promotes the oxidation of carboxylic acids upon visible-light activation. After decarboxylation, the generated radicals are trapped by TsCN, yielding the desired nitriles without any further additive, in a redox-neutral process. Importantly, this protocol can be adapted to flow conditions.
Ramirez, Nieves P.,K?nig, Burkhard,Gonzalez-Gomez, Jose C.
supporting information

(2019/03/08)

ION CHANNEL INHIBITORY COMPOUNDS, PHARMACEUTICAL FORMULATIONS AND USES
The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and / or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.
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Paragraph 00352

(2017/06/07)

A practical iodine-catalyzed oxidative conversion of aldehydes to nitriles
A simple and efficient method for the direct synthesis of nitriles from aldehydes using ammonium acetate as the nitrogen source has been developed. The reactions were performed with iodine as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant under mild conditions. A variety of aromatic, heteroaromatic, aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.
Fang, Chaojie,Li, Meichao,Hu, Xinquan,Mo, Weimin,Hu, Baoxiang,Sun, Nan,Jin, Liqun,Shen, Zhenlu
p. 1484 - 1489
(2017/01/21)

Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19
The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 (CCT251921), a potent, selective, and orally bioavailable inhibitor of CDK8 with equipotent affinity for CDK19. We describe a structure-based design approach leading to the discovery of a 3,4,5-trisubstituted-2-aminopyridine series and present the application of physicochemical property analyses to successfully reduce in vivo metabolic clearance, minimize transporter-mediated biliary elimination while maintaining acceptable aqueous solubility. Compound 109 affords the optimal compromise of in vitro biochemical, pharmacokinetic, and physicochemical properties and is suitable for progression to animal models of cancer.
Mallinger, Aurélie,Schiemann, Kai,Rink, Christian,Stieber, Frank,Calderini, Michel,Crumpler, Simon,Stubbs, Mark,Adeniji-Popoola, Olajumoke,Poeschke, Oliver,Busch, Michael,Czodrowski, Paul,Musil, Djordje,Schwarz, Daniel,Ortiz-Ruiz, Maria-Jesus,Schneider, Richard,Thai, Ching,Valenti, Melanie,De Haven Brandon, Alexis,Burke, Rosemary,Workman, Paul,Dale, Trevor,Wienke, Dirk,Clarke, Paul A.,Esdar, Christina,Raynaud, Florence I.,Eccles, Suzanne A.,Rohdich, Felix,Blagg, Julian
supporting information
p. 1078 - 1101
(2016/02/23)

INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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Page/Page column 49-50

(2016/05/19)

Deboronative cyanation of potassium alkyltrifluoroborates: Via photoredox catalysis
A photoredox catalytic method was developed for the direct cyanation of alkyltrifluoroborates. This reaction provides a new and useful transformation of the easily available alkyltrifluoroborates. The photocatalytic reaction can tolerate a variety of functional groups with mild reaction conditions. Mechanistic investigations are consistent with the present reaction following a radical pathway.
Dai, Jian-Jun,Zhang, Wen-Man,Shu, Yong-Jin,Sun, Yu-Yang,Xu, Jun,Feng, Yi-Si,Xu, Hua-Jian
p. 6793 - 6796
(2016/06/01)

Visible-Light-Mediated Alkenylation, Allylation, and Cyanation of Potassium Alkyltrifluoroborates with Organic Photoredox Catalysts
Iridium- and ruthenium-free approaches to protected allylic amines and alkyl nitriles under photoredox conditions are reported. An inexpensive organic dye, eosin Y, catalyzes coupling of Boc-protected potassium α-aminomethyltrifluoroborates with a variety of substituted alkenyl sulfones through an α-aminomethyl radical addition-elimination pathway. Allylic and homoallylic amines were formed in moderate yields with high E/Z selectivity. The mechanistic approach was extended using tosyl cyanide as a radical trap, enabling the conversion of alkyltrifluoroborates to nitriles via a Fukuzumi acridinium-catalyzed process.
Heitz, Drew R.,Rizwan, Komal,Molander, Gary A.
p. 7308 - 7313
(2016/08/30)

A Mild TEMPO-Catalyzed Aerobic Oxidative Conversion of Aldehydes into Nitriles
An efficient method to prepare nitriles from aldehydes using hexamethyldisilazane (HMDS) as the nitrogen source has been developed. The reactions were performed with 2,2,6,6-tetramethylpiperidine l-oxyl (TEMPO) as the catalyst, NaNO2 or TBN as the co-catalyst, and molecular oxygen as the terminal oxidant under mild conditions. A variety of aromatic, heteroaromatic, aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.
Fang, Chaojie,Li, Meichao,Hu, Xinquan,Mo, Weimin,Hu, Baoxiang,Sun, Nan,Jin, Liqun,Shen, Zhenlu
p. 1157 - 1163
(2016/04/19)

Aliphatic nitrile catalytic oxidation synthesis method
The invention discloses an aliphatic nitrile catalytic oxidation synthesis method. With aliphatic aldehyde serving as reaction substrate, 2, 2, 6, 6-tetramethylpiperidine-1-oxygen radical (TEMPO), alkali metal salt and tert-butyl nitrite (TBN) as catalysts, hexamethyl-disilazane (HMDS) as the nitrogen source and oxygen as an oxidizing agent, the reaction substrate is reacted in organic solvent at normal pressure at the temperature of 25-50 DEG C, and aftertreatment is performed after reaction to obtain the aliphatic nitrile. The method is easy and safe to operate, and environment cost is lowered.
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Paragraph 0041; 0042

(2016/10/17)

PYRIDYL PIPERIDINES
The invention provides novel substituted pyridyl piperidine compounds according to Formula (I) which are Wnt pathway inhibitors, their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.
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Page/Page column 67

(2015/12/31)

SERINE/THREONINE KINASE INHIBITORS
Compounds having the formula I wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
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Paragraph 0367; 0581

(2015/02/19)

Palladium-Catalyzed α,β-Dehydrogenation of Esters and Nitriles
A highly practical and general palladium-catalyzed methodology for the α,β-dehydrogenation of esters and nitriles is reported. Generation of a zinc enolate or (cyanoalkyl)zinc species followed by the addition of an allyl oxidant and a palladium catalyst results in synthetically useful yields of α,β-unsaturated esters, lactones, and nitriles. Preliminary mechanistic investigations are consistent with reversible β-hydride elimination and turnover-limiting, propene-forming reductive elimination.
Chen, Yifeng,Romaire, Justin P.,Newhouse, Timothy R.
p. 5875 - 5878
(2015/05/27)

Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E
The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.
Keita, Massaba,Vandamme, Mathilde,Paquin, Jean-Fran?ois
p. 3758 - 3766
(2015/11/28)

Photoinduced, Copper-Catalyzed Carbon-Carbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature
We have recently reported that, in the presence of light and a copper catalyst, nitrogen nucleophiles such as carbazoles and primary amides undergo C-N coupling with alkyl halides under mild conditions. In the present study, we establish that photoinduced, copper-catalyzed alkylation can also be applied to C-C bond formation, specifically, that the cyanation of unactivated secondary alkyl chlorides can be achieved at room temperature to afford nitriles, an important class of target molecules. Thus, in the presence of an inexpensive copper catalyst (CuI; no ligand coadditive) and a readily available light source (UVC compact fluorescent light bulb), a wide array of alkyl halides undergo cyanation in good yield. Our initial mechanistic studies are consistent with the hypothesis that an excited state of [Cu(CN)2]- may play a role, via single electron transfer, in this process. This investigation provides a rare example of a transition metal-catalyzed cyanation of an alkyl halide, as well as the first illustrations of photoinduced, copper-catalyzed alkylation with either a carbon nucleophile or a secondary alkyl chloride.
Ratani, Tanvi S.,Bachman, Shoshana,Fu, Gregory C.,Peters, Jonas C.
p. 13902 - 13907
(2016/01/15)

C2-AZASPIRO IMINOTHIAZINE DIOXIDES AS BACE INHIBITORS
In its many embodiments, the present invention provides certain C2-azaspirosubstituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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Page/Page column 56

(2014/10/04)

Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4- piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Cav3.2) inhibitor
The T-type calcium channel inhibitor Mibefradil was reported to protect the heart from atrial remodeling, a key process involved in the development of atrial fibrillation and arrhythmias. Mibefradil is not a selective T-type calcium channel inhibitor and also affects the function of different ion channels. Our aim was to develop a selective T-type calcium channel inhibitor to validate the importance of T-type-related pharmacology in atrial fibrillation. Structural optimisation of a previously disclosed hit series focussed on minimising exposure to the central nervous system and improving pharmacokinetic properties, while maintain adequate potency and selectivity. This resulted in the design of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4- piperidyl]methyl]-3,5-dichloro-benzamide, a novel, selective, peripherally restricted chemical probe to verify the role of T-type calcium channel inhibition on atrial fibrillation protection.
Giordanetto, Fabrizio,W?llberg, Andreas,Knerr, Laurent,Selmi, Nidhal,Ullah, Victoria,Thorstensson, Fredrik,Lindelo, Asa,Karlsson, Staffan,Nikitidis, Grigorios,Llinas, Antonio,Wang, Qing-Dong,Lindqvist, Anders,H?gberg, ?got,Lindhardt, Emma,Astrand, Annika,Duker, G?ran
supporting information
p. 119 - 124
(2013/02/25)

Conversion of aldoximes into nitriles and amides under mild conditions
A series of Pd(en)X2 salts were used as catalysts for the conversion of aldoximes into nitriles and amides. Highlights of this protocol include the use of inexpensive polar solvents, including water, and moderate reaction temperatures. A high degree of selectivity in the reaction outcome was observed when using aliphatic vs. aromatic/conjugated aldoximes. The Royal Society of Chemistry 2013.
Tambara, Koujiro,Pantos, G. Dan
supporting information
p. 2466 - 2472
(2013/06/05)

A chemoselective, one-pot transformation of aldehydes to nitriles
This paper describes a procedure for direct conversion of aldehydes to nitriles using O-(diphenylphosphinyl)hydroxylamine (DPPH). Aldehydes are smoothly transformed to their corresponding nitriles by heating with DPPH in toluene. The reaction can be accomplished in the presence of alcohol, ketone, ester, or amine functionality.
Laulhe, Sebastien,Gori, Sadakatali S.,Nantz, Michael H.
p. 9334 - 9337,4
(2012/12/12)

A chemoselective, one-pot transformation of aldehydes to nitriles
This paper describes a procedure for direct conversion of aldehydes to nitriles using O-(diphenylphosphinyl)hydroxylamine (DPPH). Aldehydes are smoothly transformed to their corresponding nitriles by heating with DPPH in toluene. The reaction can be accomplished in the presence of alcohol, ketone, ester, or amine functionality.
Laulhé, Sébastien,Gori, Sadakatali S.,Nantz, Michael H.
p. 9334 - 9337
(2013/01/15)

Synthesis and biological evaluation of 4-piperidinecarboxylate and 4-piperidinecyanide derivatives for T-type calcium channel blockers
To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives were prepared and evaluated for in vitro and in vivo activity against α1G calcium channel. Among them, several compounds showed good T-type calcium channel inhibitory activity and minimal off-target activity over hERG channel (% inhibition at 10 μM = 61.85-71.99, hERG channel IC50 = 1.57 ± 0.14-4.98 ± 0.36 μM). Selected compound 31a was evaluated on SNL model of neuropathic pain and showed inhibitory effect on mechanical allodynia.
Woo, Hyun Min,Lee, Yun Suk,Roh, Eun Joo,Seo, Seon Hee,Song, Chi Man,Chung, Hye Jin,Pae, Ae Nim,Shin, Kye Jung
scheme or table
p. 5910 - 5915
(2011/10/09)

HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE
Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.
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Page/Page column 85

(2011/06/26)

COMPOUNDS HAVING A POTENTIATING EFFECT ON THE ACTIVITY OF ETHIONAMIDE AND USES THEREOF
The present invention relates to the use of compounds with a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, for the preparation of a medicament for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy, to pharmaceutical compositions comprising them in combination with an antibiotic that is activatable via the EthA pathway, to compounds having a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, to pharmaceutical compositions comprising them and to their use as medicaments, especially medicaments for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy.
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Page/Page column 35

(2011/06/24)

A practical and cost-efficient, one-pot conversion of aldehydes into nitriles mediated by 'activated DMSO'
Participation of activated DMSO in the one-pot transformation of aldehydes to nitriles has been described by reacting aldehydes with NHHHCl in DMSO in the absence of any added base or catalyst. The method is applicable to access a wide range of aromatic, heterocyclic, and aliphatic nitriles, in which only water is a byproduct. A straightforward and practical procedure is demonstrated on a multigram scale. Georg Thieme Verlag Stuttgart - New York.
Augustine, John Kallikat,Bombrun, Agnes,Atta, Rajendra Nath
scheme or table
p. 2223 - 2227
(2011/10/31)

NOVEL HETEROCYCLIC METHYLENE PIPERIDINE DERIVATIVES AND THEIR USE
The present invention is directed to compounds of formula (I) compositions comprising them and their use.
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Page/Page column 94

(2009/03/07)

Synthesis of 7-(4-piperidyl)- [1,6]naphthyridin-5-one and 3-(4-piperidyl)isoqunolin-1-one
7-(4-Piperidyl)[1,6]napththiridin-5-one was synthesized on the basis of 2-methylnicotinic acid. 3-(4-Piperidyl)isoquinolin-1-one was synthesized from the diethylamide of o-toluic acid and Weinreb′s amide of N-Boc-isonipecotic acid.
Kovalskiy,Perevalov
experimental part
p. 1503 - 1507
(2010/07/04)

Propylphosphonic anhydride (T3P): A remarkably efficient reagent for the one-pot transformation of aromatic, heteroaromatic, and aliphatic aldehydes to nitriles
Propylphosphonic anhydride has been demonstrated to be an efficient reagent for the transformation of aromatic, heteroaromatic, and aliphatic aldehydes to respective nitriles in excellent yields. This procedure offers simple and one-pot access to nitriles and highlights the synthetic utility of T3P as a versatile reagent in organic chemistry. Georg Thieme Verlag Stuttgart - New York.
Augustine, John Kallikat,Atta, Rajendra Nath,Ramappa, Balakrishna Kolathur,Boodappa, Chandrakantha
experimental part
p. 3378 - 3382
(2010/03/03)

SUBSTITUTED PIPERIDINES CONTAINING A HETEROARYLAMIDE OR HETEROARYLPHENYL MOIETY
The invention provides compounds of the formula (I) having PKA and PKB kinase inhibiting compounds of the formula (I): GP 1 J T 2 J N 4 R N H (I) or salts, solvates, tautomers or N-oxides thereof, wherein (1) GP is a group GP1: HET 2a a Q G (HNCO)f 7 (R )x N * (GP1) (2) GP is a group GP2: 10 (R )r O 2a a QG (CH2)w N V H N * (GP2) wherein HET is a monocyclic or bicyclic heterocyclic group containing up to 4 heteroatom ring members; the ring V is a monocyclic or bicyclic heteroaryl group of 5 to 10 ring members; and J1, J2, R4, R7, R10, Q2a, Ga, x, w and f are as defined in the claims
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Page/Page column 126

(2008/12/06)

BENZOXAZINYL-AMIDOCYCLOPENTYL-HETEROCYCLIC MODULATORS OF CHEMOKINE RECEPTORS
Cyclopentyl compounds linked to a benzoxazinyl group through an amido moiety utilizing the ring nitrogen of the benzoxazine, and further substituted with a heterocyclic moiety, such compounds represented by formula I: which are used to modulate the CCR-2 chemokine receptor to prevent or treat inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis; and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions.
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Page/Page column 44-45

(2010/11/28)

Nitrilase-catalyzed enantioselective synthesis of pyrrolidine- And piperidinecarboxylic acids
The enantioselective synthesis of the nonproteinogenic amino acids β-proline and nipecotic acids from their readily available nitriles is achieved in high enantiomeric excess by commercially available nitrilases. The presented procedure comprises not more than 4 steps, thus considerably reducing the multiple steps generally required. Amide formation is also observed for specific heterocyclic nitriles.
Winkler, Margit,Meischler, Dorith,Klempier, Norbert
p. 1475 - 1480
(2008/09/16)

Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors
Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine- 4-carboxamide 38, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclinical species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clinically useful antiviral agent.
Pace, Paola,Di Francesco, M. Emilia,Gardelli, Cristina,Harper, Steven,Muraglia, Ester,Nizi, Emanuela,Orvieto, Federica,Petrocchi, Alessia,Poma, Marco,Rowley, Michael,Scarpelli, Rita,Laufer, Ralph,Paz, Odalys Gonzalez,Monteagudo, Edith,Bonelli, Fabio,Hazuda, Daria,Stillmock, Kara A.,Summa, Vincenzo
p. 2225 - 2239
(2007/10/03)

INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
The present invention can provide a cancer treatment drug containing, as an active ingredient, a substance selected from the group consisting of an indazole compound of the following formula (I), a pharmaceutically acceptable salt, a hydrate, a water adduct and a solvate:
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Page/Page column 19

(2010/11/24)

CHEMICAL COMPOUNDS
Compounds of formula (I): compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating CCR5 receptor activity in a warm blooded animal).
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Page 37

(2010/02/09)

BENZOXAZINYL-AMIDOCYCLOPENTYL-HETEROCYCLIC MODULATORS OF CHEMOKINE RECEPTORS
Cyclopentyl compounds linked to a benzoxazinyl group through an amido moiety utilizing the ring nitrogen of the benzoxazine, and further substituted with a heterocyclic moiety, such compounds represented by formula (I): which are used to modulate the CCR-
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Page 88

(2010/02/09)

SUBSTITUTED 3- AND 4- AMINOMETHYLPIPERIDINES FOR USE AS BETA-SECRETASE IN THE TREATMENT OF ALZHEIMER’S DISEASE
The invention relates to novel compounds, which are substituted chiral or achiral derivatives of 3- or 4- aminomethylpiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula (I) and especially their use as inhibitors of beta-secretases for the treatment of Alzheimer’s disease.
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Page/Page column 21-22; 39-40

(2008/06/13)

Syntheses and Binding Studies of New [(Aryl)(aryloxy)methyl]piperidine Derivatives and Related Compounds as Potential Antidepressant Drugs with High Affinity for Serotonin (5-HT) and Norepinephrine (NE) Transporters
In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT1A and 5-HT2A receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT 1A and 5-HT2A receptors. Some of these racemic mixtures were resolved to their enantiomers and tested for binding to norepinephrine (NE) transporter (NET), dopamine (DA) transporter (DAT), and α2 receptor. Several of these enantiomers [(-)-15b, (-)-15j, (-)-15t, (+)-15u] displayed a dual binding profile with affinities for SERT and NET with K i i = 1.9 and 13.5 nM, respectively), and further pharmacological characterization is in progress for its evaluation as a antidepressant.
Orjales, Aurelio,Mosquera, Ramón,Toledo, Antonio,Pumar, M. Carmen,García, Neftalí,Cortizo, Lourdes,Labeaga, Luis,Innerárity, Ana
p. 5512 - 5532
(2007/10/03)

4-substituted piperidines
New 4-substituted piperidines of the following general formula (I) are disclosed in which R1and R2are substituted in unsubstituted aryl radicals, which compounds are obtained as racemic mixtures and as pure enantiomers. The compounds
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(2008/06/13)

Amidine compounds
A compound of the formula [I] wherein R1, R2and R3are the same or different and each is hydrogen atom, wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the presen
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(2008/06/13)

New 4 - substituted piperidines
New 4-substituted piperidines of the following general formula (I) are disclosed in which R1 and R2 are substituted in unsubstituted aryl radicals, which compounds are obtained as racemic mixtures and as pure enantiomers. The compoun
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(2008/06/13)

Pyrrolidine modulators of chemokine receptor activity
The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6, R14and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
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(2008/06/13)

Studies on new platelet aggregation inhibitors 1. Synthesis of 7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives
A series of 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-ones were prepared and tested for platelet aggregation inhibitory effect, cardiotonic activity and chronotropic activity. These compounds appeared to show selective inhibitory activity against platelet aggregation. Among them, 6-(4-ethoxycarbonylpiperidino)-7-nitro-3,4-dihydroquinoline-2(1H)-one (22f) showed the most potent inhibitory activity and high selectivity. A divergent synthetic route to 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives has also been investigated.
Iyobe,Uchida,Kamata,Hotel,Kusama,Harada
p. 822 - 829
(2007/10/03)

INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras
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(2008/06/13)

Synthesis of 2,2-Dialkyl-3-halopropanenitriles from 2,2-Dialkylethanenitriles and Dihalomethanes
A simple high-yielding synthesis of 2,2-dialkyl-3-halopropanenitriles is described which involves the alkylation of 2,2-dialkylethanenitriles with bromochloromethane.
Cliffe, Ian A.,Todd, Richard S.,White, Alan C.
p. 1757 - 1767
(2007/10/02)

Nitriles
Novel 3-halo-2,2-disubstituted propanenitriles of formula STR1 wherein Z represents bromo or chloro and A, together with the carbon atom to which it is attached, represents a 5,6 or 7 membered saturated carbocyclic or heterocyclic ring, are useful as inte
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(2008/06/13)

Tetrazole analogues of GABA-mimetic agents
Six tetrazole analogues of GABA-mimetic compounds were synthesized. In vitro only two compounds, analogues of GABA and isoguvacine, showed a weak affinity for GABA-A and GABA-B receptors. In vivo compounds were inactive in a psychopharmacological screening in mice. The results were interpreted in terms of intercharge distance, electronic delocalisation and ability of membrane crossing.
Schlewer,Wermuth,Chambon
p. 181 - 186
(2007/10/02)