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COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Reaction Between Ethyl omega-Chloroalkylimidates and Hydrazides

It is already known that ethyl omega-chloroalkylimidate hydrochlorides and aroyl hydrazides gave, when reacted together in boiling ethanol, 2-aryl-5-omega-haloalkyl-1,3,4-oxadiazoles.It has now been found that the reaction follows a different course in the presence of triethylamine.In particular, 2-aryl-5,6,7,8-tetrahydro-1,2,4-triazolo<5,1-a>pyridines were obtained from ethyl delta-chlorovalerimidate, whereas N-aroylaminoiminopyrrolidines are the products obtained from ethyl gamma-chlorobutyrimidate.A similar case, in which the closure of the triazole ring to obtain a dihydropyrrolotriazole was found to be more difficult than the corresponding closure to a tetrahydrotriazolopyridine, is described.Also the reaction between the imidates and carbethoxyhydrazine, which gives piperidine and pyrrolidine derivatives, is reported.

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1-Pyrroline | C4H7N – PubChem

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The Effect of Ring Size on Tetrahedral Displacement Reactions of Cyclic Imidates. Synthesis of O-(Fluoroalkyl)lactims and Higher O-Alkyllactims from Lower O-Alkyllactims

A recently developed synthesis of 2-(perfluoroalkyl)ethanols (RFCH2CH2OH) is based on heating 2-(perfluoroalkyl)-1-iodoethanes RFCH2CH2I with an amide, e.g., N-methylformamide or a lactam, 2-pyrrolidinone.The presumed O-<2-(perfluoroalkyl)ethyl>lactim intermediates have now been prepared in good to excellent yields (60-90percent) by heating a lower molecular mass O-alkyllactim with a higher-boiling alcohol, e.g., with RFCH2CH2OH, to displace the lower boiling alcohol.Competitive rate experiments showed that a 7-membered O-methyllactim reacted four to five times faster than did the 5-membered O-methyllactim.This difference is attributed to increased eclipsing strain, commonly called “I-strain”.In a “planar” 5-membered lactim ring, the engendered eclipsing strain appears to be greater than in the more flexible 7-membered ring.Reactant ratio and reaction conditions also affected the yield of lactim ether.Preparatively, reaction of C6F13CH2CH2OH (3) with O-ethylbutyrolactim (6) gave O-<2-(perfluorohexyl)ethyl>butyrolactim (7) in an 89.2percent yield (on unrecovered 3) at 67.9percent conversion.Yield was limited by dealkylation and condensation reactions that occurred during long heating times.By contrast, alcohol 3 with O-methylcaprolactim (10) gave 7-membered O-<2-(F-hexyl)ethyl>caprolactim (11) in 98percent yield at 90percent conversion.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Synthesis of acetyl-substituted heterocyclic enamines and their reaction with diethyl azodicarboxylate

Acetyl-substituted heterocyclic enamines 4 were synthesized from lactim ethers 2 and acetylacetone through condensation and deacetylation reactions, and they, along with the ester-substituted heterocyclic enamines 6, reacted with diethyl azodicarboxylate to afford C-adducts 7 and 8 in excellent yields.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Cyclic amidine analogs as inhibitors of nitric oxide synthase

Disclosed herein are compounds of Formula I STR1 and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These disease and disorders include hypotension, septic shock, toxic shock syndrom, hemodialysis, IL-2 therapy such as in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn or psoriasis and respiratory conditions such as bronchitis, asthma, and acure respiratory distress (ARDS), myocarditis, heart failure, atherosclerosis, arthritis, rheumatoid arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn’s disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis. Compounds of Formula I are also usful in the treatment of hypoxia, hyperbaric oxygen convulsions and toxicity, dementia, Sydenham’s chorea, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, mulitple sclerosis, Korsakoff’s disease, imbecility related to cerebral vessel disorder, ischemic brain edema, sleeping disorders, schizophrenia, depression, PMS, anxiety, drug addiction, pain, migraine, immune complex disease, as immunosupressive agents and for preventing or reversing tolerance to opiates and diazepines.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Pyrrolidinohydroquinazolines – A novel class of CCR3 modulators

A novel class of CCR3 modulators is described. Starting with lead compound 4a (Ki: 110 nM), which turned out to be an antagonist of eotaxin at the CCR3 receptor, further optimization led to compound 8b (Ki: 28 nM), which surprisingly proved to be an agonist.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Synthesis of 4-(omega-aminoalkyl)- or 4-(omega-lactamiminoalkyl)thiazoles by ring chain transformation of isothioureas with lactam derivatives

CH-Acidic isothioureas 1 react with lactam acetals 2 at the unsubstituted N-atom as well as at the acidic S-methylene group giving 4-(omega-aminoalkyl)thiazoles 6. The latter are further transformed to 4-(omega-lactamiminoalkyl)thiazoles 8, if lactim ethers 3 are used in reactions with isothioureas 1.

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Pyrroline – Wikipedia,
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2,6-dimethoxyphenyl-substituted n-heterocyclic carbenes (NHCs): A family of highly electron-rich organocatalysts

Based on our recent finding that 2,6-dimethoxyphenyl-substituted NHCs show superior reactivity in the hydroacylation reactions of electron-neutral olefins compared with known NHCs, we now report the syntheses and crystal structures of four highly electron-rich 2,6-dimethoxyphenyl-substituted NHCs and show the increase in efficiency caused by the electron-rich aryl substituent in hydroacylation reactions. The synthesis and crystal structures of four highly electron-rich 2,6-dimethoxyphenyl-substituted NHCs are reported. These NHCs should have interesting applications as ligands or in NHC organocatalysis.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Tertiary amines

Tertiary amines of the formula STR1 wherein A1, A2, A3, A4, L, M, p, T, and Q are as defined herein, have antimycotic and cholesterol-lowering activity.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem

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Substituted ureas and processes for their preparation

Organic chemical compounds based upon the urea molecule are disclosed which have potent gastric secretion inhibitory properties. The urea is substituted with a heterocyclic ring which may be substituted with one or more loweralkyl groups. The urea is also substituted with loweralkyl and a lower-alkylamino loweralkyl group. The compounds have profound effects on the inhibition of gastric secretions in the gastro-intestinal tract, and compositions for such uses are also disclosed.

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Pyrroline – Wikipedia,
1-Pyrroline | C4H7N – PubChem