EXH - CAS 2211116-16-2

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Molecular Formula
C24H31FN4O4S
Molecular Weight
490.59

EXH

    • Specification
      • IUPAC Name
        (2R,3R,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
    • Properties
      • Boiling Point
        784.7±60.0 °C at 760 mmHg
        Density
        1.30±0.1 g/cm3
        InChI Key
        MNNVXLLCYGGFOQ-VNYTWHDVSA-N
        InChI
        InChI=1S/C24H31FN4O4S/c1-13-20(34-12-27-13)16-8-6-15(7-9-16)10-26-22(32)19-18(25)17(31)11-29(19)23(33)21(24(3,4)5)28-14(2)30/h6-9,12,17-19,21,31H,10-11H2,1-5H3,(H,26,32)(H,28,30)/t17-,18-,19-,21+/m0/s1
        Canonical SMILES
        CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3C(C(CN3C(=O)C(C(C)(C)C)NC(=O)C)O)F
    • Reference Reading
      • 1. Voluntary muscle and motor cortical activation during progressive exercise and passively induced hyperthermia
        Julien D Périard, Ryan J Christian, Wade L Knez, Sébastien Racinais Exp Physiol. 2014 Jan;99(1):136-48.doi: 10.1113/expphysiol.2013.074583.Epub 2013 Sep 13.
        This study examined whether central fatigue was exacerbated by an increase in muscle contractile speed caused by passive hyperthermia (PaH) and whether exercise-induced hyperthermia (ExH) combined with related peripheral fatigue influenced this response. The ExH was induced by cycling at 60% of maximal oxygen uptake in 38°C conditions and the PaH by sitting in a 48°C climate chamber. Ten men performed brief (≈ 5 s) and sustained (30 s) maximal voluntary isometric contractions (MVCs) of the knee extensors at baseline (CON, ~37.1°C) and during moderate (MOD, ≈ 38.5°C) and severe (SEV, ~39.5°C) hyperthermia. Motor nerve and transcranial magnetic stimulation were used to assess voluntary muscle and cortical activation level, along with contractile properties. Brief MVC force decreased to a similar extent during SEV-ExH (-8%) and SEV-PaH (-6%; P < 0.05 versus CON). Sustained MVC force also decreased during MOD-ExH (-10%), SEV-ExH (-13%) and SEV-PaH (-7%; P < 0.01 versus CON). Motor nerve and cortical activation were reduced on reaching MOD (≈ 3%) and SEV (≈ 5%) ExH and PaH during the brief and sustained MVCs (P < 0.01 versus CON). Peak twitch force decreased on reaching SEV-ExH and SEV-PaH (P < 0.05 versus CON). Following transcranial magnetic stimulation, during the brief and sustained MVCs the peak muscle relaxation rate increased in ExH and PaH (P < 0.01 versus CON). The increase was greatest during the sustained contraction in SEV-PaH (P < 0.01), but this did not exacerbate central fatigue relative to ExH. These results indicate that during fatiguing cycling exercise in the heat, quadriceps peak relaxation rate increases. However, the centrally mediated rate of activation appears sufficient to overcome even the largest increase in muscle relaxation rate, seen during SEV-PaH.
        2. Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans
        Lee M Romer, Hans C Haverkamp, Markus Amann, Andrew T Lovering, David F Pegelow, Jerome A Dempsey Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R598-606.doi: 10.1152/ajpregu.00269.2006.Epub 2006 Sep 7.
        We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean +/- SE maximum O(2) uptake (Vo(2 max)) = 56.5 +/- 2.7 ml x kg(-1) x min(-1)] cycled at > or =90% Vo(2 max) to exhaustion in normoxia [NORM-EXH; inspired O(2) fraction (Fi(O(2))) = 0.21, arterial O(2) saturation (Sp(O(2))) = 93 +/- 1%] and hypoxia (HYPOX-EXH; Fi(O(2)) = 0.13, Sp(O(2)) = 76 +/- 1%). The subjects also exercised in normoxia for a time equal to that achieved in hypoxia (NORM-CTRL; Sp(O(2)) = 96 +/- 1%). Quadriceps twitch force, in response to supramaximal single (nonpotentiated and potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10-100 Hz), was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated exercise-induced peripheral fatigue, as evidenced by a greater decrease in potentiated twitch force in HYPOX-EXH vs. NORM-CTRL (-39 +/- 4 vs. -24 +/- 3%, P < 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs. NORM-EXH (4.2 +/- 0.5 vs. 13.4 +/- 0.8 min, P < 0.01); however, peripheral fatigue was not different in HYPOX-EXH vs. NORM-EXH (-34 +/- 4 vs. -39 +/- 4%, P > 0.05). Blood lactate concentration and perceptions of limb discomfort were higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise.
        3. Effects of morning versus evening combined strength and endurance training on physical performance, muscle hypertrophy, and serum hormone concentrations
        Maria Küüsmaa, Moritz Schumann, Milan Sedliak, William J Kraemer, Robert U Newton, Jari-Pekka Malinen, Kai Nyman, Arja Häkkinen, Keijo Häkkinen Appl Physiol Nutr Metab. 2016 Dec;41(12):1285-1294.doi: 10.1139/apnm-2016-0271.
        This study investigated the effects of 24 weeks of morning versus evening same-session combined strength (S) and endurance (E) training on physical performance, muscle hypertrophy, and resting serum testosterone and cortisol diurnal concentrations. Forty-two young men were matched and assigned to a morning (m) or evening (e) E + S or S + E group (mE + S, n = 9; mS + E, n = 9; eE + S, n = 12; and eS + E, n = 12). Participants were tested for dynamic leg press 1-repetition maximum (1RM) and time to exhaustion (Texh) during an incremental cycle ergometer test both in the morning and evening, cross-sectional area (CSA) of vastus lateralis and diurnal serum testosterone and cortisol concentrations (0730 h; 0930 h; 1630 h; 1830 h). All groups similarly increased 1RM in the morning (14%-19%; p < 0.001) and evening (18%-24%; p < 0.001). CSA increased in all groups by week 24 (12%-20%, p < 0.01); however, during the training weeks 13-24 the evening groups gained more muscle mass (time-of-day main effect; p < 0.05). Texh increased in all groups in the morning (16%-28%; p < 0.01) and evening (18%-27%; p < 0.001), however, a main effect for the exercise order, in favor of E + S, was observed on both testing times (p < 0.051). Diurnal rhythms in testosterone and cortisol remained statistically unaltered by the training order or time. The present results indicate that combined strength and endurance training in the evening may lead to larger gains in muscle mass, while the E + S training order might be more beneficial for endurance performance development. However, training order and time seem to influence the magnitude of adaptations only when the training period exceeded 12 weeks.
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