14731-39-6

Upstream product

• 110-91-8 morpholine 
• 72486-09-0 methanesulfonic acid but-3-ynyl ester 
• 23418-85-1 3-butyn-1-yl p-toluenesulfonate 

Downstream Products

• 267243-52-7 4-[N-(3-chloro-4-fluorophenyl)amino]-6-fluoro-7-[(1E)-4-(4-morpholinyl)-1-butenyl]pyrido[3,2-d]pyrimidine 
• 1188547-06-9 4-[4-(3-(piperidin-1-ylmethyl)phenyl)but-3-ynyl]morpholine 
• 544707-24-6 4-[4-(4-(piperidin-1-ylmethyl)phenyl)but-3-ynyl]morpholine 
• 912353-71-0 C₂₆H₂₆ClFN₄O₂ 
• 1188490-23-4 (2S,3S,4R)-(5E,7E)-3-(4-methoxybenzyloxy)-2,4,6-trimethyl-10-morpholinodeca-5,7-dien-1-ol 
• 37183-13-4 1,2-bis(phenylselanyl)ethane 
• 267243-55-0 6-amino-4-[N-(3-chloro-4-fluorophenyl)amino]-7-[4-(4-morpholinyl)butyl]pyrido[3,2-d]pyrimidine 
• 267243-53-8 6-amino-4-[N-(3-chloro-4-fluorophenyl)amino]-7-[(1E)-4-(4-morpholinyl)-1-butenyl]pyrido[3,2-d]pyrimidine 
• 267243-54-9 4-[N-(3-chloro-4-fluorophenyl)amino]-6-fluoro-7-[4-(4-morpholinyl)butyl]pyrido[3,2-d]pyrimidine 

Relevant academic research and scientific papers

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.

Dioxane quinazoline and dioxane quinazoline type compound, and preparation method and application thereof

The invention relates to a dioxane quinazoline and dioxane quinazoline type compound having a formula (I) as described in the specification or a pharmaceutically acceptable salt thereof. The inventionalso provides preparation of the compound having the formula (I) and the pharmaceutically acceptable salt and application of the compound and the pharmaceutically acceptable salt as a medicine. The medicine is used as a tyrosine kinase (such as VEGFR-2, c-MET and RET) inhibitor for treating diseases relevant to tyrosine kinases.

Nickel-catalyzed sonogashira reactions of non-activated secondary alkyl bromides and iodides

A nicked reaction: The title reaction of terminal alkynes with non-activated secondary alkyl iodides and bromides was accomplished for the first time. This reaction provides a new and practical approach for the synthesis of substituted alkynes (see scheme; cod=cyclo-1,5-octadiene). Copyright

Diamine-based human histamine H3 receptor antagonists: (4-Aminobutyn-1-yl)benzylamines

A series of (4-aminobutyn-1-yl)benzylamines were prepared and the SAR around three key areas: (1) the amine attached to the butynyl linker (R3R4N-); (2) the benzylamine moiety (R1R2N-); and (3) the point of attachment of the benzylamine group (R1R2N- in the ortho, meta, or para positions) was examined. One compound, 4-[3-(4-piperidin-1-yl-but-1-ynyl)-benzyl]-morpholine (9s) was chosen for further profiling and found to be a selective histamine H3 antagonist with desirable drug-like properties. Ex vivo receptor occupancy studies established that 9s does occupy H3 binding sites in the brain of rats after oral administration. Subcutaneous doses of 9s (10 mg/kg) given during the natural sleep phase demonstrated robust wake-promoting effects.

Manganese- or iron-catalyzed homocoupling of grignard reagents using atmospheric oxygen as an oxidant

Atmospheric oxygen was used for the first time as an oxidant in metal-catalyzed homocoupling of Grignard reagents. These manganese- or iron-catalyzed reactions are efficient, cheap, and eco-friendly. They are applicable to the large-scale synthesis of symmetrical conjugated compounds. Copyright

ALKYNYL PYRROLOPYRIMIDINES AND RELATED ANALOGS AS HSP90-INHIBITORS

Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed.

Phenylalkynes

Substituted phenylalkynes of formula (I), compositions containing them, and methods of making and using them to treat histamine-mediated conditions.

Phenylalkynes

Substituted phenylalkynes of formula (I), compositions containing them, and methods of making and using them to treat histamine-mediated conditions.

Pyrroloquinolones as antiviral agents

The present invention provides a compound of formula I which is useful as antiviral agents, in particular, as agents against viruses of the herpes family.

Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4- (phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions

4-Anilinoquinazoline- and 4-anilinopyrido[3,2-d]pyrimidine-6-acrylamides substituted with solubilizing 7-alkylamine or 7-alkoxyamine side chains were prepared by reaction of the corresponding 6-amines with acrylic acid or acrylic acid anhydrides. In the pyrido[3,2-d]pyrimidine series, the intermediate 6-amino-7-alkylamines were prepared from 7-bromo-6- fluoropyrido[3,2-d]pyrimidine via Stille coupling with the appropriate stannane under palladium-(0) catalysis. This proved a versatile method for the introduction of cationic solubilizing side chains. The compounds were evaluated for their inhibition of phosphorylation of the isolated EGFR enzyme and for inhibition of EGF-stimulated autophosphorylation of EGFR in A431 cells and of heregulin-stimulated autophosphorylation of erbB2 in MDA-MB 453 cells. Quinazoline analogues with 7-alkoxyamine solubilizing groups were potent irreversible inhibitors of the isolated EGFR enzyme, with IC50([app]) values from 2 to 4 nM, and potently inhibited both EGFR and erbB2 autophosphorylation in cells. 7-Alkylamino- and 7- alkoxyaminopyrido[3,2-d]pyrimidines were also irreversible inhibitors with equal or superior potency against the isolated enzyme but were less effective in the cellular autophosphorylation assays. Both quinazoline- and pyrido[3,2- d]pyrimidine-6-acrylamides bound at the ATP site alkylating cysteine 773, as shown by electrospray ionization mass spectrometry, and had similar rates of absorptive and secretory transport in Caco-2 cells. A comparison of two 7- propoxymorpholide analogues showed that the pyrido[3,2-d]pyrimidine-6- acrylamide had greater amide instability and higher acrylamide reactivity, being converted to glutathione adducts in cells more rapidly than the corresponding quinazoline. This difference may contribute to the observed lower cellular potency of the pyrido[3,2-d]pyrimidine-6-acrylamides. Selected compounds showed high in vivo activity against A431 xenografts on oral dosing, with the quinazolines being superior to the pyrido[3,2-d]pyrimidines. Overall, the quinazolines proved superior to previous analogues in terms of aqueous solubility, potency, and in vivo antitumor activity, and one example (CI 1033) has been selected for clinical evaluation.