- Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity
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Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (Ki? = 0.1-0.4 μM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC50 = 1-15 μM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC50 = 5-8 μM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.
- Chenna, Bala C.,Li, Linfeng,Mellott, Drake M.,Zhai, Xiang,Siqueira-Neto, Jair L.,Calvet Alvarez, Claudia,Bernatchez, Jean A.,Desormeaux, Emily,Alvarez Hernandez, Elizabeth,Gomez, Jana,McKerrow, James H.,Cruz-Reyes, Jorge,Meek, Thomas D.
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p. 3298 - 3316
(2020/04/08)
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- Preparation method of 2-(oxazolyl) ethylamine
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The invention discloses a preparation method of 2-(oxazolyl) ethylamine. According to the preparation method of 2-(oxazolyl) ethylamine, oxazole ring-opening side reaction is effectively avoided, therepeatability is good, the conversion rate and yield are high, and purification is easy; reaction conditions are mild, safety is high, potential safety hazards to operators are reduced, the operationsafety level of production is reduced, and the method is environmentally friendly; the obtained 2-(oxazolyl) ethylamine product is high in purity and good in quality, and industrialization is facilitated.
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Paragraph 0114; 0115; 0122; 0123
(2019/12/25)
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- HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN
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The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).
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Page/Page column 46
(2011/04/19)
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- Chemical Compounds
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This invention relates to non-steroidal compounds that are modulators of androgen, glucocorticoid, mineralocorticoid, and progesterone receptors, and also to the methods for the making and use of such compounds.
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Page/Page column 46
(2009/07/17)
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- 4- (IH-INDAZOL-S-YL-AMINO)-QUINAZOLINE COMPOUNDS AS ERBB RECEPTOR TYROSINE KINASE INHIBITORS FOR THE TREATMENT OF CANCER
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A quinazoline derivative of the Formula I: wherein the substituents are as defined in the text for use in the production of an anti proliferative effect which effect is produced alone or in part by inhibiting erbB2 receptor tyrosine kinase in a warm blood
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Page/Page column 93
(2008/06/13)
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- NOVEL ANDROGENS
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The compounds of the subject invention have a structure according to formula I: wherein X is S or SO2; R1 is (1C-6C)alkyl, (3C-6C)alkenyl, or (3C-6C)alkynyl, each optionally subst ituted with (3C-6C)cycloalkyl, OH, OC(O)(1C-4C)alkyl, (1C- 4C)alkoxy, halogen, cyano, formyl, C(O)(1C-4C)alkyl, CO2H, CO2(1C- 4C)alkyl, C(O)NR5R6, S(O)(1C-4C)alkyl or S(O)2(1C-4C)alkyl; R2 is hydrogen, (1C-4C)alkyl or C(O)(1C-4C)alkyl; R3 is a phenyl group optionally substituted with (1C-4C)alkyl, (1C-4C)fluoroalkyl, (1C-4C)alkoxy, (1C-4C)fluoroalkoxy, halogen, cyano or nitro; or R3 is a 5- or 6-membered aromatic heterocyclic ring structure optionally substituted with (1C-4C)alkyl, (1C-4C)fluoroalkyl, (1C-4C)alkoxy, halogen or cyano; R4 is a phenyl group or an aromatic 6-membered heterocycle, substituted at the ortho position with 1-hydroxy(1C-4C)alkyl, (1C-4C)alkoxy, C(O)(1C- 4C)alkyl, CO2(1C-4C)alkyl, C(O)NH2, cyano, nitro, or CH=NOR7, and optionally further substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen; R5 is 2-pyridyl optionally substituted with (1C-2C)alkyl, (1C- 2C)fluoroalkyl or halogen; or R5 and R6 are independently hydrogen or (1C-4C)alkyl; R7 is hydrogen or C(O)(1C-4C)alkyl; R8 , R9 , R10 are independently hydrogen, (1C-2C)alkyl, fluoro or chloro; or a salt or hydrate form thereof.
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Page/Page column 31-32
(2010/02/14)
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- Substituted 1,4-dihydropyridine compounds as bradykinin antagonists
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This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof wherein A is independently halo; Y is —(CH2)m—, —C(O)— or —S(O)—; R1 and R2 are independently C1-4 alkyl; R3 is C7-9 bicycloalkyl, C5-7 azacycloalkyl or C7-9 azabicycloalkyl, the C7-9 bicycloalkyl, C5-7 azacycloalkyl or C7-9 azabicycloalkyl being optionally substituted with one, two or three substituents are independently selected from oxo, hydroxyl, C1-4 alkyl, C1-4 alkyloxy, C1-4 alkyl-carbonyl, formyl, C1-4 alkylenedioxy, and phenyl-C1-4 alkyl; R4 is thiazolyl, imidazolyl or oxazolyl, the thiazolyl, imidazolyl or oxazolyl being optionally substituted with one or two substituents independently selected from C1-4 alkyl and halo; R5 is hydrogen or C1-4 alkyl;m is 0, 1 or 2; and n is 0, 1, 2, 3, 4 or 5. These compounds are usefuil for the treatment of medical conditions mediated by bradykinin such as inflammation, allergic rhinitis, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.
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