Except As Provided In Subsection (4)(b)

Another premixed solution of n-Bu.sub.3Ph (49.9 mg, 0.247 mmol) and DIAMIDE (42.5 mg, 0.247 mmol) in 0.5 mL of THF was added at rt, and reaction mixture was refluxed for 1.5 h. The filtrate was concentrated, and the residue was purified via silica gel chromatography (Biotage 12 g, Hexanes-100% EtOAc) to give tert-butyl (4-(2-hydroxyethyl)cyclohexyl)carbamate (260 mg, 90% yield) as a mixture of two isomers. 1N Hydrochloric acid (6.73 ml, 6.73 mmol) was added, the aqueous layer was extracted with ethyl acetate (.times.3), and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and filtered, and the filtrate was evaporated in vacuo to give the crude product. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and filtered, and the filtrate was evaporated in vacuo to give the crude product. The mixture was stirred at rt for 4 h and then concentrated in vacuo. Sodium sulfate decahydrate (1 g) was added, and the reaction mixture was stirred at rt for 2 h.

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N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenes- ulfonamide (1.840 g, 4.13 mmol) was added, and the reaction mixture was stirred at rt for 12 h. Acetone was removed, water was added and the aqueous layer was extracted with ethyl acetate (.times.3). After 10 min RT, water was added and the aqueous layer was extracted with ethyl acetate (.times.3). C. for 1 h, and then warmed up to rt over a period of 15 min. The invention encompasses compounds of formula I, which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists, compositions containing them, and methods of using them, for example, in the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases. To generate fully human antibodies to human CD40, mice or transgenic or transchromosomal mice containing human immunoglobulin genes (e.g., HCo12, HCo7 or KM mice) can be immunized with a purified or enriched preparation of the CD40 antigen and/or cells expressing CD40, as described for other antigens, for example, by Lonberg et al.

Other combination therapies that may result in synergy with CD40 agonism through cell death are radiation, surgery, and hormone deprivation. Formyl peptide receptor 2 (FPR2) belongs to a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. 7. The method of claim 6 wherein the heart disease is selected from the group consisting of angina pectoris, unstable angina, myocardial infarction, heart failure, acute coronary disease, acute heart failure, chronic heart failure, and cardiac iatrogenic damage. 8. The method of claim 7 wherein the treatment is directed to post myocardial infarction. 5. A composition comprising a compound of claim 2, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. Ar.sup.1 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazinyl, oxadiazolyl, thiadiazolyl, or benzodioxyl, and is substituted with 1-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, and SO.sub.2R.sup.6; Ar.sup.2 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; Ar.sup.3 is aryl or heteroaryl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, (NR.sup.1R.sup.2)alkyl, (CO.sub.2R.sup.3)alkyl, (CONR.sup.4R.sup.5)alkyl, (SO.sub.2R.sup.6)alkyl, hydroxy, alkoxy, haloalkoxy, cycloalkoxy, NR.sup.1R.sup.2, CO.sub.2R.sup.3, CONR.sup.4R.sup.5, SO.sub.2R.sup.6, Oxo, aryl, and heteroaryl; R.sup.1 is hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, or haloalkylsulfonyl; R.sup.2 is hydrogen or alkyl; or NR.sup.1R.sup.2 taken together is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; and R.sup.3 is alkyl or haloalkyl; R.sup.4 is hydrogen, alkyl, or (R.sup.7R.sup.8N)alkyl; R.sup.5 is hydrogen or alkyl; or NR.sup.4R.sup.5 taken together is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; R.sup.6 is alkyl or sex and the city amazon prime R.sup.7R.sup.8N; R.sup.7 is hydrogen or alkyl; R.sup.8 is hydrogen or alkyl; or NR.sup.7R.sup.8 taken together is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; and X is hydrogen, halo, hydroxy, or alkoxy; or a pharmaceutically acceptable salt thereof.

Another aspect of the invention is a compound of formula I where Ar.sup.1 is phenyl, pyridinyl, pyridazinyl, thiazolyl, or benzodioxoyl and is substituted with 1-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and alkylthio; Ar.sup.2 is phenyl or pyridinyl and is substituted with 0-3 substituents selected from cyano and halo; Ar.sup.3 is phenyl, pyridinyl, pyrimidinyl, pyridinonyl, thienyl, pyrazolyl, isoxazolyl, benzodioxoyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, hydroxyalkyl, (NR.sup.1R.sup.2)alkyl, alkoxy, haloalkoxy, NR.sup.1R.sup.2, CO.sub.2R.sup.3, CONR.sup.4R.sup.5, and SO.sub.2R.sup.6. Another aspect of the invention is a compound of formula I where Ar.sup.2 is -1,4-substituted with respect to the nitrogen and the Ar.sup.3 to which it is attached. The term “isotopically enriched” refers to an atom having an isotopic composition other than the natural isotopic composition of that atom. ’s the purpose of having WickedWhims as a requirement, but I will be developing on related themes. We found a mini version by Goodnight Macaroon and our favorite lookalike by free live cam sites People for a fraction of the cost this LV one will be.

It will be evident to one skilled in the art that the present disclosure is not limited to the foregoing illustrative examples, and that it can be embodied in other specific forms without departing from the essential attributes thereof. Importantly, eicosanoid lipoxin A4, which belongs to a class of small pro-resolution mediators (SPMs), has been identified as a specific agonist for FPR2 (Ye RD., et al., Pharmacol. 6. A method for treating heart disease comprising administering a therapeutically effective amount of an FPR2 agonist to a patient in need thereof. Non-productive wound healing associated with cardiomyocyte death and pathological remodeling resulting from ischemia-reperfusion injury leads to scar formation, fibrosis, and progressive loss of heart function. The latter is primarily responsible for enhancing anti-fibrotic wound healing and returning of the injured tissue to homeostasis (Romano M., et al., Eur. Res., 2015, 105, 65-74; and Fredman G., et al., Sci. In the cardiovascular system both the FPR2 receptor and its pro-resolution agonists were found to be responsible for atherogenic-plaque stabilization and healing (Petri MH., et al., Cardiovasc. Sci., 2010, 31, 266-76) and I/R induced spinal cord injury (Liu ZQ., et al., Int. In addition to beneficial effects of targeting the FPR2 receptor with novel pro-resolution agonists for treatment of I/R induced injury therapeutic, utility of these ligands can also be applied to other diseases.

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