874294-11-8Relevant articles and documents
FUSED TRICYCLIC COMPOUNDS FOR USE AS INHIBITORS OF JANUS KINASES
-
, (2013/03/26)
The invention provides novel compounds of formula (I) having the general formula (I) wherein R1, V, W, X, Y and Z are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.
PYRROLOPYRAZINE DERIVATIVES AS SYK AND JAK INHIBITORS
-
Page/Page column 64-65, (2011/12/04)
The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula (I), wherein the variables Q and R1 and R2 are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.
Syntheses and biological activities of octahydro-1H-cyclopenta[d]pyrimidine derivatives
Tian, Zhongzhen,Jiang, Zhaoxing,Li, Zhong,Song, Gonghua,Huang, Qingchun
, p. 143 - 147 (2008/02/03)
Various nitromethylene derivatives were synthesized regioselectively. Compounds 8a-f were obtained by the reaction of 1-((5-chloropyridin-2-yl)methyl) -2-(nitromethylene)-octahydro-1H-cyclopenta[d]-pyrimidine (3) with primary amines and formaldehyde. The synthesized compounds were identified by 1H NMR, HRMS (EI), and IR, and preliminary bioassays indicated that most of them showed moderate insecticidal activities against Aphis craccivora. The relationship between hydrophobicity and biological activity was also discussed.
An effective approach to the enantiomers of alicyclic β-aminonitriles by using lipase catalysis
Fitz, Monika,Lundell, Katri,Lindroos, Maria,Fueloep, Ferenc,Kanerva, Liisa T.
, p. 3690 - 3697 (2007/10/03)
Lipase-catalyzed N-acylations of racemic cis- and trans-2- aminocyclopentane- (and cyclohexane-) carbonitriles with 2,2,2-trifluoethyl butanoate in tert-butyl methyl ether (TBME) and in room-temperature ionic liquids (RTILs) were studied. The racemates were effectively resolved (E >200) on a preparative scale by lipase PS-C II (lipase from Burkholderia cepacia) in TBME, resulting in two enantiomers in their enantiopure forms at 50% conversion. The reactions in RTILs with Novozym 435 (Candida antarctica lipase B) were slow and proceeded with low enantioselectivity.
Synthesis and microbial transformation of β-amino nitriles
Winkler, Margit,Martínková, Ludmila,Knall, Astrid C.,Krahulec, Stefan,Klempier, Norbert
, p. 4249 - 4260 (2007/10/03)
Rhodococcus equi A4, Rhodococcus erythropolis NCIMB 11540 and Rhodococcus sp. R312 were investigated towards their ability to produce β-amino amides and acids from β-amino nitriles. The microorganisms show comparable trends: five-membered alicyclic 2-amino nitriles were transformed significantly faster than the six-membered compounds and the products of trans-2-amino nitriles (amides and acids) were formed considerably faster than the cis-counterparts (amides). The trans-five membered nitriles gave the amides (1b, 5b) in excellent enantiomeric excess (94-99%), the biotransformation of trans-six membered substrates resulted in the formation of the acid (3c, 7c) in excellent ee (87-99%). The ee's of the cis-compounds were throughout lower. Fifteen new substances were synthesized and characterized in the course of this work.
Assisted hydrolysis of cis-2-(3-phenylthioureido)cyclopentane-carbonitrile in alkaline solution. Solvent dependent switch from hydrolysis to rearrangement of the iminothiooxopyrimidine intermediate
Atay, Ergun,Blagoeva, Iva B.,Chubb, Francis L.,Edward, John T.,Pojarlieff, Ivan G.,Toteva, Maria M.
, p. 84 - 94 (2007/10/03)
The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile, 1, and the respective carboxamides, 3, and acids, 4, have been prepared. Acid cyclization of both nitriles, faster with the cis isomer, gave the more stable cis-2-thiooxo-cyclopenta[d]pyrimidin-4-one, 7. In base cis-1 formed the cis 4-imino-2-thiooxopyrimidine 2 which in aqueous alkali broke down via 3 to the acid 4; while in the presence of 66% acetonitrile 2 rearranged to the 4-phenyliminopyrimidine 5 to give as final product the thioureido acid 6 carrying no phenyl group. The 1H NMR data for imino and phenylimino derivatives 2 and 5 showed strong bias for conformation A with 1-N pseudoaxial in the cyclopentane ring. Spectra of the E and Z isomers of the iminopyrimidine 2 under slow exchange could be recorded in DMSO-d6. The phenylimino tautomer of 5 is observed in CD3OD and in CDCl3 with the E and Z isomers in a 1:1 ratio. In DMSO-d6 the phenylamino tautomer 5a is also detected. The first process in aqueous KOH, the conversion of nitrile cis-1 into the imino intermediate 2, reaches an equilibrium which shifts towards the nitrile at higher alkalinities because of ionization of the phenylthioureido group (Ke = [2]/[1] = 2.43 and pKAH = 12.74). The cyclization of 1 to 2 is first order in [OH-] while the slower breakdown of 2 is pH independent. The latter is 104 times faster than the hydrolysis of acetonitrile evidencing substantial anchimeric assistance. The change in the reaction route towards the rearranged phenyliminopyrimidine 5 upon addition of acetonitrile can be caused by the lower dielectric constant favouring the elimination step leading to the intermediate isothiocyanate, and by increased activity of OH- accelerating the (presumably) second order elimination step as opposed to the ph-independent hydrolysis of the imino derivative 2.
