56657-76-2

Usage

Uses

Used in Pharmaceutical Industry:
CYANOACETIC ACID-OSU is used as a pharmaceutical intermediate for the synthesis of substituted pyrrolopyrimidinamines. These compounds serve as selective Janus kinase inhibitors, which are crucial in the treatment of autoimmune diseases and organ transplant rejection. The inhibition of Janus kinases helps regulate the immune response, reducing inflammation and preventing the body from attacking its own tissues or the transplanted organ.

InChI:InChI=1/C7H6N2O4/c8-4-3-7(12)13-9-5(10)1-2-6(9)11/h1-3H2

Upstream product

• 6066-82-6 1-hydroxy-pyrrolidine-2,5-dione 
• 372-09-8 cyanoacetic acid 

Downstream Products

• 1198764-48-5 2-Cyano-N-{5-[3-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl}-acetamide 
• 540737-29-9 Tofacitinib citrate 
• 540737-29-9 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile monocitrate 
• 1259404-17-5 tasocitinib 
• 1313279-94-5 (R)-benzyl 4-(6-(1-(2-cyanoacetyl)piperidin-3-ylamino)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-yl)piperazine-1-carboxylate 
• 870640-38-3 N-{2-(2-cyanoacetylamino)-1-[1-(2-cyanoacetylamino)methyl]ethyl}benzamide 
• 870640-28-1 N-[2-benzyloxy-3-(2-cyanoacetylamino)propyl]-2-cyanoacetamide 

Relevant academic research and scientific papers

PYRAZOLE DERIVATIVES AS JAK INHIBITORS

New pyrazole derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

THERAPEUTIC AGENTS

The invention provides a compound of formula (I): wherein R1, and W have any of the values defined in the application; or a salt thereof. The compounds and salts thereof have beneficial therapeutic properties (e.g. immunosuppressant properties).

Small molecule inhibitors of dynamin I GTPase activity: Development of dimeric tyrphostins

Dynamin I is a GTPase enzyme required for endocytosis and is an excellent target for the design of potential endocytosis inhibitors. Screening of a library of tyrphostins, in our laboratory, against the GTPase activity of dynamin I gave rise to a ìèpotent lead, 2-cyano-3-(3,4- dihydroxyphenyl)thioacrylamide (1, IC50 70 μM). Our initial investigations suggested that only the dimeric form of 1 displayed dynamin I GTPase inhibitory activity. Subsequent synthetic iterations were based on dimeric analogues and afforded a number of small molecules, low μM potent, inhibitors of dynamin I GTPase, in particular, symmetrical analogues with a minimum of two free phenolic -OHs: catechol-acrylamide (9) (IC50 = 5.1 ± 0.6 μM), its 3,4,5-trihydroxy congener (10) (IC50 = 1.7 ± 0.2 μM), and the corresponding 3-methyl ether (11) (IC 50 = 9 ± 3 μM). Increasing the length of the central alkyl spacer from ethyl to propyl (22-24) afforded essentially identical activity with IC50's of 1.7 ± 0.2, 1.7 ± 0.2, and 5 ± 1 μM, respectively. No decrease in activity was noted until the introduction of a hexyl spacer. Our studies highlight the requirement for two free amido NHs with neither the mono-N-methyl (86) nor the bis-N-methyl (87) analogues inhibiting dynamin I GTPase. A similar effect was noted for the removal of the nitrile moieties. However, modest potency was observed with the corresponding ester analogues of 9-11: ethyl ester (90), propyl ester (91), and butyl ester (92), with IC50's of 42 ± 3, 38 ± 2, and 61 ± 2 μM, respectively. Our studies reveal the most potent and promising dynamin I GTPase inhibitor in this series as (22), which is also known as BisT.

REACTIVITY OF N-HYDROXYSUCCINIMIDE ESTERS

The reactions of N-hydroxysuccinimide esters (OSu-esters) of benzyloxycarbonylamino acids and of simple carboxylic acid with p-anisidine in DMSO were studied kinetically at various temperatures.Activation parameters ΔH++ and ΔS++ for these data were determined.The rate constants for aminolysis of carboxylic acid esters fit the two-parameter Taft equation with reaction constants equal: ρ* = 1.08 and ρs = 1.1.The activation entropies are in the range -121.8 - -180.0 J/deg M.Transition state in these reactions is tetrahedral and zwitter ionic, in agreementwith the mechanism given by Cline and Hanna for aminolysis of succinimidyl benzoates.

Rifamycins as inhibitors of retroviral reverse transcriptase from M-MuLV, RAV-2, and HIV-1

29 Rifamycins were tested for inhibition of Reverse Transcriptase (RT) as potential anti HIV drugs. Two purified commercial enzymes from M-MuLV and RAV-2 were used. Anti-RT activity was also measured on a crude lysate of HIV-1. The results show that some derivatives have interesting levels of activity on isolated M-MuLV and RAV-2 RTs, while they are less active on the RT in the crude HIV-1 lysate. The active derivatives include oximes and hydrazones, alkylaminoderivatives, open ansa-chain derivatives and derivatives carrying a modified nucleoside.