Use of β 2-adrenergic receptor agonists in treating muscle wasting

Abstract

There is provided herein a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

Description

[0001]USE OF β2-ADRENERGIC RECEPTOR AGONISTS IN TREATING MUSCLE WASTING Field of the Invention The present invention relates to methods for the treatment of muscle wasting. In particular, the invention relates to methods for the treatment of muscle wasting caused by a treatment with a therapeutic agent, involving follow-on treatment with a β2- adrenergic receptor agonist, and to compositions, combination treatments and kits-of- parts for use in such methods. Background of the Invention The listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge. Muscular atrophy and weakness are pathological manifestations of various neurological, neuromuscular and myogenic disorders (Wei et al., Int J Mol Sci, 21, 9589 (2020)). These can also present themselves as secondary symptoms in conditions such as cancer, cardiopulmonary disorders and are also hallmarks of progressive aging. While gene modification has gained traction as curative therapy for some of these diseases, there is renewed interest in developing novel treatments as adjuncts and for conditions that are not genetic in origin. At present, pharmacological approaches to the treatment of such diseases and disorders are limited to mitigating secondary and downstream pathological mechanisms. Current research is focused on strategies based on somatic gene editing therapies, which may become effective treatments for muscle wasting disorders resulting from genetic abnormalities. However, considerable progress must be made to improve the delivery and safety of these technologies, and thus far there is no effective treatment on the market. A related therapeutic area that would benefit from the development of effective treatments for muscle wasting is prevention of muscular atrophy in patients who have undergone weight loss treatment or any other treatment with a therapeutic agent that has the direct or indirect effect of decreasing muscle mass (lean mass). Obesity is a global health epidemic affecting, with the World Health Organisation reporting that global instances have tripled since 1975. At present, almost 2 billion adults worldwide are affected, leading to serious health concerns. Numerous treatments have been proposed to address obesity and to generate weight loss in those classified as overweight. These include non-medical interventions, such as adjustments to diet and the adoption of exercise regimes, and medical interventions, such as pharmaceutical and surgical treatments. Despite ongoing research and a clear public health need, there are still relatively few effective and well-tolerated treatments for obesity, with those treatments approved thus far typically suffering from limitations derived from their mode of action (such as undesirable side effects). A key feature of weight loss treatments is the initiation of body fat reduction through the restriction of caloric intake and / or stimulation of an increase in metabolism, resulting in the depletion of fat stores. However, an unintended consequence of weight loss treatments is the loss of muscle mass, resulting from catabolism of muscle tissue as an energy source. Therapeutic agents for use in treating obesity and / or decreasing body mass, such as GLP-1 agonists, have also been observed to have the unwanted side-effect of loss of muscle mass. Recently, β-agonists have been explored as a potential treatment option for diseases characterised by muscle wasting. Such compounds have been observed to preserve muscle mass and restore muscle function in genetic conditions as Duchenne Muscular Dystrophy (DMD), and Spinal Muscular Atrophy (SMA) and Spinal Bulbar Muscular Atrophy (SBMA) among others. Additionally, these compounds observed to counteract muscle wasting due to disuse as a consequence of injury and aging (Ryall and Lynch, Pharmacol Ther, 120, 219 (2008)). However, there are pitfalls in the use of β-agonists in these diseases primarily due to side effects such as tremors, increased fatiguability and tachycardia, and an eventual loss of efficacy due to β-arrestin recruitment and subsequent receptor desensitization. The β2-adreneric receptor is the major isoform of β-adrenergic receptors in skeletal muscle cells. Adrenergic receptors (ARs) are G protein coupled receptors (GPCRs) which signal through classical secondary messengers, such as the canonical cyclic adenosine monophosphate (cAMP)-pathway. Generally, following β2-AR stimulation, the receptor couples to the Gαs-subunit and activates adenylate cyclase, generating cAMP. Elevated cAMP levels drive multiple parallel signalling pathways that play critical roles in regulating skeletal muscle and CNS, among others. cAMP activates cAMP-dependent protein kinase A (PKA) which enters the cell nucleus and phosphorylates the ubiquitous transcription factor CREB. Multiple studies have established a key role for CREB in the regulation of muscle mass. CREB regulates the expression of numerous genes involved in skeletal myocyte differentiation, the enhancement of protein synthesis, and inhibition of protein degradation (Bartus R.T. et al., Neurobiology of disease, 2016, 11-24). Therefore, the hypertrophic and anti-atrophy effects of β2-AR agonists on skeletal muscle are thought to be mediated by activation of the cAMP / PKA / CREB pathway (Joassard Q.R. et al., Int J Biochem Cell Bio, 2013, 2309; Bartus R.T. et al., Neurobiology of disease, 2016, 11-24). As cAMP release is linked to side effects such as tremors, increased fatiguability and tachycardia, there are clear disadvantages in relation to the use of β2-AR agonists for treating muscle wasting (such as preserving muscle mass in a patient undergoing weight loss). A further concern in relation to the use of β2-AR agonists is an eventual loss of efficacy due to β-arrestin recruitment and subsequent receptor desensitization. There remains, therefore, a need for new treatments capable of at least partially reversing the muscle wasting caused by the treatment with a therapeutic agent that causes such loss of muscle mass as an unwanted side-effect, including treatments capable of at least partially reversing the loss of muscle mass in patients who have undergone weight loss treatment. In particular, there exists a need for follow-on treatments to be used in respect of treatments that have caused (i.e. induced, directly or indirectly, as an effect thereof) muscle wasting, such that said muscle wasting may be, at least to some extent, reversed. Description of the Invention We have now surprisingly found that activation of the β2-adrenergic receptor (β2-AR) represents a promising strategy for the treatment of muscle wasting, in a subject that has experienced muscle wasting as a result of treatment with a therapeutic agent that is known to directly or indirectly induce muscle wasting (e.g. therapeutic agent for the treatment or prophylaxis of obesity, the lowering of body fat composition and / or the reduction of body weight). Moreover, we have found that such effects can be provided through activation of the β2-adrenergic receptor without significant production of cAMP. This effect is particularly surprising given that it is believed in the existing literature that β2-AR agonists provide beneficial hypertrophic and / or anti-atrophy effects by mediating via cAMP (Joassard Q.R. et al., Int J Biochem Cell Bio, 2013, 2309; Bartus R.T. et al., Neurobiology of disease, 2016, 11-24). Furthermore, such effects have been demonstrated to be achieved without significant recruitment of β-arrestin. Medical treatments In a first aspect of the invention there is provided a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. Unless indicated otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. For the avoidance of doubt, β2-adrenergic receptor agonists, such as those described herein, may be referred to as “compounds of the invention” or “the β2-adrenergic receptor agonists of the invention”, or the like. For the avoidance of doubt, the therapeutic agent that directly or indirectly induces muscle wasting, such as those described herein, may be referred to as “the therapeutic agent of the invention”, or the like. Preferences and options for a given aspect, embodiment, feature or parameter of the invention should, unless the context indicates otherwise, be regarded as having been disclosed in combination with any and all preferences and options for all other aspects, features and parameters of the invention. Wherever the word “about” is employed herein (for example, in the context of doses of active ingredients) it will be appreciated that such variables are approximate and as such may vary by ± 10%, for example ± 5% and preferably ± 2% (e.g. ± 1%) from the numbers specified herein. Wherever the word “optionally” is employed in relation to features described herein it will take its normal meaning, namely that the relevant feature may or may not be present. For the avoidance of doubt, compounds for use, uses, methods, compositions, combinations and kits-of-parts of other aspects of the invention as described herein (including all embodiments thereof) may have any of the particular features described for the first aspect of the invention, including all combinations thereof. For the avoidance of doubt, treatments (and associated prophylaxis) as described herein may be referred to herein as the “treatments of the invention”, or the like. The skilled person will understand that references to the “treatment of” a particular condition (and similarly “treating”) take their normal meanings in the field of medicine. In particular, the terms may refer to achieving a reduction in the severity of one or more clinical symptom associated with the condition. In particular, the terms may refer to achieving a reduction in the severity of one or more clinical symptom associated with the condition (e.g. muscle wasting). As used herein, references to patients will refer to a living subject being treated, including mammalian (e.g. human) patients. In particular embodiments of the relevant aspects of the invention (e.g. the first aspect of the invention), the treatment is in a mammal (e.g. a human). The terms “patient” and “subject” may be used interchangeably. As used herein, the term “therapeutically effective amount” will refer to an amount of a compound that confers a therapeutic effect on the treated patient. The effect may be objective (i.e. measurable by some test or marker) or subjective (i.e. the subject gives an indication of and / or feels an effect). As used herein, the term prophylaxis includes references to the prevention of (and, similarly, preventing) the disease or disorder (and vice-versa). As such, references to prevention may also be references to prophylaxis, and vice versa. In particular, the term may refer to achieving a reduction in the likelihood of the patient (or healthy subject) developing the condition (for example, at least a 10% reduction, such as at least a 20%, 30% or 40% reduction, e.g. at least a 50% reduction). In particular embodiments, references to use in and methods for the treatment or prophylaxis of diseases and disorders as specified herein will refer in particular to uses in and methods for treatment of (i.e. treating) such diseases and disorders. The skilled person will understand that a particular disease or disorder may be muscle wasting. The term “treatment cycle” refers to a period of time during which a patient is administered therapy, which period may be followed by a period of rest before further administration of therapy or may be followed by administration of a different therapy (such as administaration of a different therapeutic agent). The further administraton of therapy may be part of a subsequent treatment cycle. The skilled person will understand that a treatment cycle refers to a period of time in which one or more doses of the relevant therapy (e.g. a therapeutic agent) are administered. A treatment cycle may be of any suitable length of time, for example about 1 month, about 3 months or about 6 months, wherein the therapeutic agent may be administered periodically, for example once daily or once weekly. The “discontinuation” of a treatment cycle refers to the end of the treatment cycle. In cases where the treatment cycle comprises the administration of a therapeutic agent, the discontinuation of the treatment cycle may refer to the time that the final dose of the therapeutic agent is administred to the patient, as part of the relevant treatment cycle. The skilled person will undertand that references to first and second treatment cycles (e.g. in the first aspect of the invention) will refer to cycles that form part of (i.e. are within) the same therapeutic intervention (which may also be referred to as the same treatment programme or treatment protocol, as prescribed by a physician). “Therapeutic intervention” or “treatment programme” or “treatment protocol” refers to a course of treatment which may comprise one or more treatment cycles, wherein the course of treatment targets one or more, related or unrelated, health conditions. Therapeutic interventions are often tailored to the patient’s specific needs and can be adjusted over time based on the patient’s progress and response to the treatment. A therapeutic intervention would be considered the “same therapeutic intervention” even if the therapeutic intervention is adjusted over time, such as by changing the administration pattern of a therapeutic agent, changing the timings of administration, changing the nature of an administered therapeutic agent, or the like. The skilled person will understand that follow-on treatments, follow-up treatments and adjuvant therapies are considered part of the “same therapeutic intervention”. In particular, follow-on or follow-up treatments that are managing side-effects caused by an initial therapy are considered part of the “same therapeutic intervention” (i.e. the therapeutic intervention comprises the initial therapy and the follow-on or follow-up treatments, including if the initial therapy and the follow-on or follow-up treatments are under the supervision of different physicians). Therapeutic interventions may be of any suitable length of time, for example at least 6 weeks, at least 10 weeks, at least 3 months, at least 6 months or at least one year (e.g. at least 3 months, at least 6 months or at least one year), comprising one or more treatment cycles of suitable length(s) of time. As described herein, certain therapeutic agents may directly or indirectly induce muscle wasting. The term “induce(s)” may also be referred to as “cause(s)” or, when such an effect has occurred, it may indicate that it “has caused”, “results in”, “has resulted in”, and the like. As used herein, the term “induce(s)” includes “has induced”, “induced”, and the like. A therapeutic agent which directly or indirectly induces muscle wasting will include those having muscle wasting as a primary purpose (i.e. those labelled and / or marketed for the purposes of achieving such an effect) and those having muscle wasting as a secondary effect (i.e. those labelled as muscle wasting as an effect that is not the primary purpose, e.g. as a potential adverse event / side effect associated with the therapeutic agent). In particular, “indirectly” includes the muscle wasting being an adverse (i.e. unwanted) side-effect associated with the therapeutic agent. The therapeutic agent that directly or indirectly induces muscle wasting includes a therapeutic agent that is known to cause muscle wasting (for example, the product summary and / or the marketing authorisation of the therapeutic agent includes muscle wasting as a side effect). For the avoidance of doubt, the term “disease or disorder characterised by muscle wasting” will take its normal meaning in the art, e.g. referring to primary and secondary manifestations of diseases leading to a progressive loss of muscle mass and function. For the avoidance of doubt, “disease or disorder characterised by muscle wasting” and “muscle wasting” may be used interchangeably. The skilled person will understand that muscle wasting, as referred to herein, may also be referred to as muscular atrophy, and vice versa. As such, the disease or disorder characterised by muscle wasting may also be referred to as the disease or disorder characterised by muscular atrophy. The skilled person will understand that references to muscle wasting and muscular atrophy will take their usual meaning in the art, such as by referring to the loss of muscle mass (i.e. a decrease in size and / or weight of muscle) and wasting of muscle tissue (e.g. a reduction of muscle strength, i.e. muscle weakening). As such, muscular atrophy and muscle wasting may also be referred to herein as loss of lean muscle mass. In particular embodiments, references to muscle wasting will refer to muscular atrophy, and vice-versa. In particular embodiments, references to muscle wasting and muscular atrophy will refer to loss of muscle mass. In more particular embodiments, references to muscle wasting and muscular atrophy will refer to loss of lean muscle mass (which may be referred to as lean mass). The term “lean muscle mass” will take its usual meaning in the art, such as by referring to the proportion of total body weight of the patient (or subject) that is not fat mass (i.e. Lean Body Mass (LBM) of Patient = Total Weight of Patient – Fat Mass of Patient). The skilled person will be able to identify levels of muscle mass and lean mass, and therefore monitor changes in the same, using techniques well-known to those skilled in the art. In some embodiments, the method of treatment of the first aspect of the invention is for treating muscle wasting. In some embodiments, the treatment comprising the β2-adrenergic receptor agonist, or the pharmaceutically acceptable salt thereof (e.g. the second treatment cycle or the follow-on treatment as defined below) is for treating muscle wasting. In some embodiments, the subject has been identified as likely to benefit from thetreatment comprising the β2-adrenergic receptor agonist, or the pharmaceuticallyacceptable salt thereof (e.g. the second treatment cycle or the follow-on treatment as defined below), based on the severity of the muscle wasting caused by the therapeutic agent that directly or indirectly induces muscle wasting. In some embodiments, the treatment comprising administering the β2-adrenergic receptor agonist, or the pharmaceutically acceptable salt thereof (e.g. the second treatment cycle or the follow-on treatment as defined below) is for at least partially reversing the muscle wasting caused by the therapeutic agent (i.e. the therapeutic agent that directly or indirectly causes muscle wasting). Without limiting the scope of the invention, the skilled person will understand that symptoms of muscular atrophy may also include muscle numbness and / or tingling in the limbs. In some embodiments, the treatment or prophylaxis of muscular atrophy is in a patient who does not have (for example, has not been diagnosed with, is not experiencing symptoms associated with and / or is not undergoing treatment for) hyperglycaemia or a disorder characterized by hyperglycaemia, such as in a patient who does not have diabetes (e.g. type 2 diabetes), which may be referred to as a non- diabetic (e.g. non-type 2 diabetic) patient. The skilled person will understand that treatment and prophylaxis of the invention, as described herein, may further comprise (i.e. be combined with) further (i.e. additional / other) treatment(s) for the same condition. In some embodiments, the second treatment cycle is administered (e.g. first dose of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, of the second treatment cycle is administered) to the subject at least 1 hour (such as at least 24 hours) after the discontinuation of the first treatment cycle and / or at most 6 months (such as at most 3 months) after the discontinuation of the first treatment cycle. In some embodiments, the second treatment cycle is administered (e.g. first dose of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, of the second treatment cycle is administered) to the subject at least 2 days (such as at least 4 days, 7 days, or 2 weeks) after the discontinuation of the first treatment cycle. In some embodiments, the second treatment cycle is administered (e.g. first dose of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, of the second treatment cycle is administered) to the subject at most 6 months (such as at most 5 months, 4 months, 3 months or 1 month) after the discontinuation of the first treatment cycle. The period of time separating a treatment cycle from the prior treatment cycle (e.g. the period of time between the discontinuation of a first treatment cycle and the start of the second treatment cycle) may be referred to as an “interval”, “rest phase”, or the like. In some embodiments, the interval between the first treatment cycle and the second treatment cycle is at most 6 months, such as at most 3 months. In particular embodiments, the interval between the first treatment cycle and the second treatment cycle is between 1 day and 6 months, such as between 7 days and 6 months, or between 2 weeks and 6 months. In some embodiments, the second treatment cycle does not comprise administration of the therapeutic agent of the first treatment cycle (i.e. the therapeutic agent that directly or indirectly induces muscle wasting). In some embodiments, the second treatment cycle represents (i.e. is administered as) a monotherapy, i.e. the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, is administered as a monotherapy (i.e. in the absence of other therapeutic agents for the treatment of the same disease or disorder, such as muscle wasting). In some embodiments, the first treatment cycle represents (i.e. is administered as) a monotherapy. The skilled person will understand that the treatment of muscle wasting (which may be referred to as the second treatment cycle), such as that described herein, may be therapeutic (i.e. in a patient in medical need of such treatment) or non-therapeutic (e.g. cosmetic). In particular, the treatment may be therapeutic. Compounds of the invention (β2-adrenergic receptor agonist) As described herein, the present invention requires the use of a β2-adrenergic receptor agonist, examples of which will be known to those skilled in the art. The skilled person will understand that compounds referred to herein, such as compounds referred to as agonists, may be provided in the form of a pharmaceutically acceptable salt. Pharmaceutically acceptable salts include acid addition salts and base addition salts, each of which may be in the form of salts in varying ratios of compound to counter ion (e.g. including hemi salts). Such salts may be formed by conventional means, for example by reaction of a free acid or a free base form of a compound comprised in the formulations of the invention with one or more equivalents of an appropriate acid or base, optionally in a solvent, or in a medium in which the salt is insoluble, followed by removal of said solvent, or said medium, using standard techniques (e.g. by rotary evaporation under reduced pressure, by freeze-drying or by filtration). Salts may also be prepared by exchanging a counter-ion of a compound comprised in the formulations of the invention in the form of a salt with another counter-ion, for example using a suitable ion exchange resin. Particular acid addition salts that may be mentioned include carboxylate salts (e.g. formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, α-hydroxybutyrate, lactate, tartrate, hemi-tartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, 1-naphtoate, 2-naphtoate, 1-hydroxy- 2-naphtoate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate or terephthalate salts), halide salts (e.g. chloride, bromide or iodide salts), sulphonate salts (e.g. benzenesulphonate, methyl-, bromo- or chloro-benzenesulphonate, xylenesulphonate, methanesulphonate, ethanesulphonate, propanesulphonate, hydroxyethanesulphonate, 1,2-ethanedisulphonate, 1- or 2- naphthalene-sulphonate or 1,5-naphthalenedisulphonate salts) or sulphate, pyrosulphate, bisulphate, sulphite, bisulphite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate or nitrate salts, and the like. Particular base addition salts that may be mentioned include salts formed with alkali metals (such as Na and K salts), alkaline earth metals (such as Mg and Ca salts), organic bases (such as ethanolamine, diethanolamine, triethanolamine, tromethamine and lysine) and inorganic bases (such as ammonia and aluminium hydroxide). More particularly, base addition salts that may be mentioned include Mg, Ca and, most particularly, K and Na salts. For the avoidance of doubt, compounds as described herein may exist as solids, and thus the scope of the invention includes all amorphous, crystalline and part crystalline forms thereof, and may also exist as oils. Where such compounds exist in crystalline and part crystalline forms, such forms may include solvates, which are included in the scope of the invention. The compounds may also exist in solution. The skilled person will understand that references to an agonist will refer to compounds suitable for acting as such when administrated to a subject to be treated (i.e. a patient, e.g. a human, in need thereof). Suitable compounds may include compounds which provide the required effect and compounds which are converted to compounds providing the required effect after administration (i.e. in vivo), which compounds may be referred to as pro-drugs. Particular compounds that may be mentioned are compounds which elicit the required effect. For the avoidance of doubt, the term “agonist” may be understood to indicate an agent (i.e. a compound) that induces activation of the relevant receptor to produce a biological response (e.g. in a subject, such as a human), such as by binding to the relevant receptor. As such, the term may also refer to partial agonists (which will be understood to refer to compounds that activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist). The term “agonist” may include positive allosteric modulators. Agonists (and partial agonists) may display, for example, half maximal effective concentration (EC50) values of less than about 1 mM, such as less than about 100 µM, or less than about 10 µM, such as less than about 1 µM (e.g. less than about 200, about 150, about 120, about 100, about 10 or about 1 nM). Unless otherwise stated or clear from the context, references herein to agonists will also include pharmaceutically-acceptable (e.g. “protected”) derivatives of compounds which may not possess the relevant activity per se, but may be administered (e.g. parenterally or orally) to a patient and thereafter be metabolised in the body to form compounds possessing the required activity, which compounds may be referred to as prodrugs. Suitable prodrugs of compounds as described herein will be known to those skilled in the art, such as suitable esters (e.g. methyl or ethyl esters, and the like). For the avoidance of doubt, unless otherwise stated or clear from the context, references to compounds that are agonists, and pharmaceutically acceptable salts thereof, will include compounds that are prodrugs of such agonists, and pharmaceutically acceptable salts thereof. Suitable β2-adrenergic receptor agonists (which may also be referred to as β2- agonists) may include those known to those skilled in the art. In certain embodiments, suitable β2-adrenergic receptor agonists will include those that are selective, which term will be known to those skilled in the art (i.e. compounds that are agonists of the relevant receptor(s) but which do not cause significant activation of other β-adrenergic receptors). Suitable β2-adrenergic receptor agonists can be identified using techniques known to those skilled in the art, including those as described in the examples provided herein. Suitable β2-adrenergic receptor agonists that may be employed in the various aspects of the invention include, but are not limited to, those described in: WO 2004 / 071388, EP 0 272 976, FR 2647310, DE 2 157 040, DE 2212600, DE 2015573, ZA 6705591, DE 2128258, WO 91 / 09596, GB 1 199 630, DE 4209989, BE 611502, NL 7804582, EP 0 043 807, WO 2008 / 022038, DE 2413102, US 2,308,232, BE 823841, BE 660244, WO 2000 / 075114, WO 2005 / 102350, WO 2005 / 110990, JP 56055355, AT 285583, US 4,223,137, US 3,056,836, FR 1324914, DE 638650, DD 45721, US 3,801,631, DE 2259282, DE 2300614, EP 0 290 122, US 2004 / 0266867, US 2010 / 0022658, US 2010 / 0022659, DE 2157040, GB 2133986, WO 2006 / 122788, Woo et al., Molecular Pharmacology, (2009), 75(1) 158-165, Baur et al., J. Med. Chem., (2010), 53(9), 3675-3684, Kaiser et al., J. Med. Chem. (1974), 17(1) 49-57, Baker et al., J. Pharmacology and Experimental Therapeutics, (2006), 319(1), 439-446, Engelhardt et al., Arzneimittel-Forschung, (1972), 22(5), 869-76, WO 2019 / 241744, WO 2019 / 241736, WO 2020 / 198466, WO 2021 / 003161, WO 2021 / 081292, WO 2021 / 127210 and WO 2021 / 247934, the relevant disclosures of each of which (e.g. the examples compounds described therein, and pharmaceutically acceptable salts thereof, and associated methods of preparation) are hereby incorporated by reference in their entirety. For the avoidance of doubt, references to patent publications will typically refer to the initial publication of the full patent specification with the relevant publication number (which may be indicated by the suffix “A1”). Further suitable β2-adrenergic receptor agonists that may be employed in the various aspects of the invention (which compounds may be identified as also being suitable β2- adrenergic receptor agonists) include those described in the following publications, the contents of which are hereby incorporated herein in their entirety (in particular, the biological examples, the generic compound definitions, including all embodiments thereof and associated definitions, and the example compounds provided therein, including pharmaceutically acceptable salts thereof, and associated methods of preparation): WO 2017 / 153737 WO 2019 / 053429 WO 2019 / 053426 WO 2019 / 053425 WO 2019 / 053427 WO 2020 / 188299 WO 2020 / 188301 WO 2022 / 063895 WO 2022 / 063889 WO 2023 / 046885 WO 2023 / 046882 WO 2023 / 105035 WO 2023 / 203223 A particular β2-adrenergic receptor agonist that may be mentioned is the following compound: and pharmaceutically acceptable salts thereof. Thus, a particular β2-adrenergic receptor agonist that may be mentioned is (R)-2-(tert- butylamino)-1-(3-fluorophenyl)ethan-1-ol, and pharmaceutically acceptable salts thereof. Particular pharmaceutically acceptable salts of (R)-2-(tert-butylamino)-1-(3- fluorophenyl)ethan-1-ol that may be mentioned include the HCl (hydrochloride) salt. A further particular β2-adrenergic receptor agonist that may be mentioned is the following compound: and pharmaceutically acceptable salts thereof. Thus, a particular β2-adrenergic receptor agonist that may be mentioned is (R)-2-(tert- butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol, and pharmaceutically acceptable salts thereof. Particular pharmaceutically acceptable salts of the above-mentioned compound (i.e. (R)-2-(tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol) that may be mentioned include the hemi-tartrate, maleate and dihydrochloride salts (such as the hemi-tartrate salt). A further particular β2-adrenergic receptor agonist that may be mentioned is the following compound: and pharmaceutically acceptable salts thereof. Thus, a particular β2-adrenergic receptor agonist that may be mentioned is (R)-1-(3- amino-2,4-difluorophenyl)-2-(tert-butylamino)-1-ethanol, and pharmaceutically acceptable salts thereof. Particular pharmaceutically acceptable salts of the above-mentioned compound (i.e. (R)-1-(3-amino-2,4-difluorophenyl)-2-(tert-butylamino)-1-ethanol) that may be mentioned include the hydrochloride, dihydrochloride and maleate salts. Various β2-adrenergic receptor agonists are known in the art, such as those selected from the group consisting of formoterol, arformoterol, salmeterol, (R)-salmeterol, vilanterol, zilpaterol, clenbuterol, (R)-clenbuterol, bitolterol, salbutamol, levosalbutamol, terbutaline, metaproterenol, pirbuterol, bambuterol, fenoterol, methoxyfenoterol, isoprenaline, procaterol, ritodrine, indacaterol, olodaterol, colterol, hexaprenaline, carmoterol, isoxsuprine, isoetarine, zinterol, bamethane, (R)- bamethane, clencyclohexerol, tulobuterol, BRL-47672, trantinterol, clenproperol, clenpenterol, brombuterol, ractopamine and abediterol, and pharmaceutically acceptable salts thereof. Further certain examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of formoterol, arformoterol, salmeterol, (R)-salmeterol, vilanterol, zilpaterol, clenbuterol, (R)-clenbuterol, bitolterol, salbutamol, levosalbutamol, terbutaline, metaproterenol, pirbuterol, bambuterol, fenoterol, methoxyfenoterol, isoprenaline, procaterol, ritodrine, indacaterol, olodaterol, colterol, hexaprenaline, carmoterol, isoxsuprine, isoetarine, zinterol, bamethane, (R)-bamethane, clencyclohexerol, tulobuterol, BRL-47672 and trantinterol, and pharmaceutically acceptable salts thereof. Particular examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of formoterol, arformoterol, salmeterol, (R)-salmeterol, vilanterol, zilpaterol, clenbuterol, (R)-clenbuterol, indacaterol, olodaterol, carmoterol, bamethane, (R)-bamethane, clencyclohexerol, tulobuterol, trantinerol and abediterol, and pharmaceutically acceptable salts thereof. Further particular examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of formoterol, arformoterol, salmeterol, (R)-salmeterol, vilanterol, zilpaterol, clenbuterol, (R)-clenbuterol, indacaterol, olodaterol, carmoterol, bamethane, (R)-bamethane, clencyclohexerol, tulobuterol and trantinerol, and pharmaceutically acceptable salts thereof. More particular examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of formoterol, arformoterol, clenbuterol, (R)-clenbuterol, bamethane, (R)-bamethane, tulobuterol, and abediterol, and pharmaceutically acceptable salts thereof. Yet more particular examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of formoterol, arformoterol, clenbuterol, (R)-clenbuterol, bamethane, tulobuterol, and (R)-bamethane, and pharmaceutically acceptable salts thereof. For the avoidance of doubt, the structures of bamethane (CAS: 3703-79-5) and (R)- bamethane (CAS: 912804-58-1) are shown below. For the avoidance of doubt, in the case of a discrepancy between the name of the compound and the structure drawn in this specification, the structure should prevail. Further examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of formeterol, arformeterol, clenbuterol, tulobuterol, bambuterol, vilanterol, indacaterol, olodaterol, carmoterol and abediterol, and pharmaceutically acceptable salts thereof. Yet further examples of β2-adrenergic receptor agonists known in the art include those selected from the group consisting of salbutamol, ritodrine, colterol, hexaprenaline, tulobuterol and isoxsuprine, and pharmaceutically acceptable salts thereof. Particular examples of β2-adrenergic receptor agonists known in the art are clenbuterol and (R)-clenbuterol, or a pharmaceutically acceptable salt thereof. For the avoidance of doubt, the compound clenbuterol may be understood to have the following structure: Particular examples of β2-adrenergic receptor agonists known in the art are tulobuterol and (R)-tulobuterol, or a pharmaceutically acceptable salt thereof. For the avoidance of doubt, the compound tulobuterol may be understood to have the following structure: For the avoidance of doubt, the international nonpropriety name (INN) or developmental drug code (e.g. BRL-47672) for a compound generally indicates the stereochemical configuration of the compound, or a particular mixture of stereoisomers (e.g. a racemate). Within the scope of the present invention, where relevant and unless context indicates otherwise (for example where both the racemate and a single stereoisomer are explicitly named), such names may also be considered to encompass separate stereoisomers that display the relevant biological activity, and which have not presently been assigned an alternative INN or developmental drug code. In particular embodiments, the INN or developmental drug code should be understood to represent the compound to which the relevant name or code has been assigned only. Where no INN or developmental drug code is available for a compound, the compound may be identified by its Chemical Abstracts Service Registry Number (CAS number). As referred to herein, the indication “CAS: XXXXXX-XX-X” (wherein the number of figures in the first group may vary) is used to identify such compounds. Where relevant and unless context indicates otherwise, the CAS number for a compound may also be considered to encompass other stereoisomers, or mixtures thereof, that display the relevant biological activity, and which have not presently been assigned alternative CAS numbers (as described above for INNs and developmental drug codes). In particular embodiments, the CAS number should be understood to represent the compound to which the relevant name or code has been assigned only. In particular embodiments, the β2-adrenergic receptor agonist is selected from the group consisting of (R)-bamethane, bamethane, clencyclohexerol, radopamine, tulobuterol, and (R)-tulobuterol. In particular embodiments, references to a specific stereoisomer of a compound may refer to the specific stereoisomer being present (e.g. in a composition or formulation comprising the same) in the substantial absence of the corresponding opposite stereoisomer. As used herein, references to the substantial absence of the corresponding opposite stereoisomer may refer to the desired stereoisomer being present at a purity of at least 80% (e.g. at least 90%, such as at least 95%) relative to the opposite stereoisomer. Alternatively, in such instances, compounds may be indicated to be present in the substantial absence of the compound in the other configuration, which may indicate that the compound in the relevant configuration is present in an enantiomeric excess (e.e.) of at least 80% (such as at least 90%, at least 95%, at least 98% or, particularly, at least 99%, for example at least 99.9%). The present invention also embraces pharmaceutical formulations comprising isotopically-labelled compounds, which are identical to the compounds recited herein but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature (or the most abundant one found in nature). All isotopes of any particular atom or element as specified herein are contemplated within the scope of the compounds of the invention. Hence, the invention also encompasses pharmaceutical formulations comprising deuterated compounds, i.e. in which one or more hydrogen atoms are replaced by the hydrogen isotope deuterium. As described herein, it will also be understood that certain compounds acting as β2- adrenergic receptor agonists are able to activate the β2-adrenergic receptor without inducing significant cAMP production, e.g. at therapeutic relevant doses. Thus, particular β2-adrenergic receptor agonists that may be mentioned include those able to activate the β2-adrenergic receptor without (or with only a minimal effect in) inducing cAMP production. Further, in particular embodiments, the methods and uses as described herein may be performed without inducing (or without inducing significant levels of) cAMP production. In particular, the β2-adrenergic receptor agonist as described herein may be further described as being a β2-adrenergic receptor agonist that does not induce significant cAMP (i.e. levels and / or production thereof). The skilled person will be able to determine the level of cAMP production provided by compounds, such as those referred to herein, using techniques known to those skilled in the art, such as those described in the examples as provided herein. For example, the level of cAMP production induced by a given compound can be determined by reference to the amount induced by a defined concentration of that compound relative to that induced by the same concentration of a reference compound, such as isoprenaline, using techniques known to those skilled in the art (e.g. following the protocol as described in the biological examples provided herein, i.e. in cells, such as differentiated L6-myotubes, having been stimulated with isoprenaline or the compound with a final concentration of 1x10-5M, for 15 min in stimulation buffer, such as HBSS supplemented with 1 % BSA, 5 mM HEPES and 1 mM IBMX, at pH 7.4). In such embodiments, compounds that do not induce significant cAMP may be defined as being compounds that induce less than 50% (or, in some embodiments, less than 25%) of the cAMP induced by isoprenaline (e.g. in accordance with the protocol described above). Particular compounds acting as β2-adrenergic receptor agonists which are able to activate the β2-adrenergic receptor without (or with only a minimal effect in) inducing cAMP production include those described in the following publications, the contents of which are incorporated herein in their entirety (in particular, the biological examples, the generic compound definitions, including all embodiments thereof and associated definitions, and the example compounds provided therein, including pharmaceutically acceptable salts thereof, and associated methods of preparation): WO 2017 / 153737 WO 2019 / 053429 WO 2019 / 053426 WO 2019 / 053425 WO 2019 / 053427 WO 2022 / 063895 WO 2022 / 063889 WO 2023 / 046885 WO 2023 / 046882 WO 2023 / 105035 WO 2023 / 203223 More particular compounds acting as β2-adrenergic receptor agonists which are able to activate the β2-adrenergic receptor without (or with only a minimal effect in) inducing cAMP production include those described in the following publications, the contents of which are incorporated herein in their entirety (in particular, the biological examples, the generic compound definitions, including all embodiments thereof and associated definitions, and the example compounds provided therein, including pharmaceutically acceptable salts thereof, and associated methods of preparation): WO 2020 / 198466 US 10 / 947,196 US 11 / 040,944 WO 2021 / 247934 Compounds described in publications referenced and incorporated herein were screened in accordance with the procedures outlined in Biological example 2 and Biological example 3. Test results are given in Table 1. If a compound at 10 µM shows activity of more than 75 % of that of isoproterenol at 10 µM, the activity is denoted with +++; if it is between 75 and 50 % it is denoted with ++; if it is between 50 and 25 % it is denoted with +; if it less than 25 % it is denoted with -. Compounds are drawn as salt-free molecules in Table 1, but the tested compounds might have been containing additional salt or solvent components that do not contribute to the biological activity. In the event that there is a discrepancy between nomenclature and the structure of compounds as depicted graphically, it is the latter that presides (unless contradicted by any experimental details that may be given and / or unless it is clear from the context). Synthetic procedures and further biological data will be found in the relevant publications. Therefore, particular β2-adrenergic receptor agonists that may be mentioned are provided in Table 1 below. Table 1. Particular compounds of the invention Biological Biological Structure Name example 2 example 3 (GU) (cAMP) 2-(butylamino)-1-(p- 1 hydroxyphenyl)-1- +++ - ethanol 2-(butylamino)-1-(m- 2 + - chlorophenyl)-1-ethanol p-{2- [(cyclopropylmethyl)ami 3 ++ - no]-1- hydroxyethyl}phenol 2-(tert-butylamino)-1- 4 (p-hydroxyphenyl)-1- +++ + ethanol 2-(sec-butylamino)-1- 5 (p-hydroxyphenyl)-1- ++ - ethanol 2- [(cyclohexylmethyl)ami 6 no]-1-(p- +++ - hydroxyphenyl)-1- ethanol 2- 7 [(cyclohexylmethyl)ami + - no]-1-phenyl-1-ethanol 1-(p-hydroxyphenyl)-2- 8 (1-methylbutylamino)- ++ + 1-ethanol (R)-2-(butylamino)-1- 9 (p-hydroxyphenyl)-1- +++ - ethanol p-[2- (cyclopentylamino)-1- ++ - hydroxyethyl]phenol p-[2-(1- adamantanylamino)-1- + - hydroxyethyl]phenol 2-(butylamino)-1-(p- hydroxyphenyl)-1- ++ - propanol 1-(p-hydroxyphenyl)-2- (1-methylbutylamino)- ++ - 1-propanol 1-(m-hydroxyphenyl)-2- (1-methylbutylamino)- +++ - 1-ethanol 2-(butylamino)-1-(m- hydroxyphenyl)-1- ++ - ethanol 2-(2- cyclohexylethylamino)- + - 1-(p-hydroxyphenyl)-1- ethanol 2-(hexylamino)-1-(p- hydroxyphenyl)-1- + - ethanol 1-(p-hydroxyphenyl)-2- + - (octylamino)-1-ethanol 1-(3-chloro-4- hydroxyphenyl)-2-(1- + - methylbutylamino)-1- ethanol 2-(butylamino)-1-(3- chloro-4- + - hydroxyphenyl)-1- ethanol 2-(3- +++ - cyclohexylpropylamino)- 1-(p-hydroxyphenyl)-1- ethanol 1-(4-amino-3,5- dichlorophenyl)-2-(1- +++ ++ methylbutylamino)-1- ethanol 2-(butylamino)-1-(3,5- dichloro-4- - - hydroxyphenyl)-1- ethanol p-[2-(2- cyclopropylethylamino)- ++ - 1-hydroxyethyl]phenol 1-(3,5-dichloro-4- hydroxyphenyl)-2-(1- - - methylbutylamino)-1- ethanol 5-[2-(butylamino)-1- ++ - hydroxyethyl]resorcinol (R)-2-[(R)-1- methylbutylamino]-1- +++ + (p-hydroxyphenyl)-1- ethanol (R)-2-[(R)-1- methylbutylamino]-1- +++ ++ (m-hydroxyphenyl)-1- ethanol 1-(4-amino-3,5- dichlorophenyl)-2- +++ + (butylamino)-1-ethanol 2-(3- cyclopropylpropylamino) +++ - -1-(p-hydroxyphenyl)- 1-ethanol 1-(p-hydroxyphenyl)-2- ++ n / a (4,4,4- trifluorobutylamino)-1- ethanol 1-[4-amino-3-chloro-5- (trifluoromethyl)phenyl] +++ + -2-(butylamino)-1- ethanol 1-[4-amino-3-chloro-5- (trifluoromethyl)phenyl] -2-(1- ++ +++ methylbutylamino)-1- ethanol 2-(butylamino)-1-(4- chloro-3- +++ - hydroxyphenyl)-1- ethanol 1-(4-chloro-3- hydroxyphenyl)-2-(1- +++ - methylbutylamino)-1- ethanol 1-(3-amino-4- chlorophenyl)-2- + - (butylamino)-1-ethanol 1-(4-amino-3,5- difluorophenyl)-2- +++ +++ (butylamino)-1-ethanol Racemic mixture of (R)- [(2S,5S)-5-methyl-2- pyrrolidinyl]phenylmeth anol and (S)-[(2R,5R)- + - 5-methyl-2- pyrrolidinyl]phenylmeth anol Racemic mixture of (R)- [(2R,5R)-5-methyl-2- pyrrolidinyl]phenylmeth ++ - anol and (S)-[(2S,5S)- 5-methyl-2- pyrrolidinyl]phenylmeth anol Racemic mixture of m- {(R)-[(2S,5S)-5- methyl-2- pyrrolidinyl]hydroxymet ++ - hyl}phenol and m-{(S)- [(2R,5R)-5-methyl-2- pyrrolidinyl]hydroxymet hyl}phenol Racemic mixture of m- {(R)-[(2R,5R)-5- methyl-2- pyrrolidinyl]hydroxymet +++ - hyl}phenol and m-{(S)- [(2S,5S)-5-methyl-2- pyrrolidinyl]hydroxymet hyl}phenol N-{3-[2-(butylamino)- 1-hydroxyethyl]-2,6- + - difluorophenyl}acetamid e 1-(3-amino-2,4- difluorophenyl)-2- +++ - (butylamino)-1-ethanol 1-(3-amino-4- fluorophenyl)-2- ++ - (butylamino)-1-ethanol (R)-[(2R,6R)-6-propyl- 2-piperidyl](m- +++ - hydroxyphenyl)methano l (R)-2-(butylamino)-1- (p-fluorophenyl)-1- ++ - ethanol (R)-2-(butylamino)-1- (m-fluorophenyl)-1- ++ - ethanol 2-(butylamino)-1-(4- + - pyridyl)-1-ethanol 2-(butylamino)-1-(3- ++ - pyridyl)-1-ethanol (R)-2-[(R)-1- methylbutylamino]-1- +++ - (m-fluorophenyl)-1- ethanol (R)-2-[(S)-1- methylbutylamino]-1- +++ - (m-fluorophenyl)-1- ethanol (R)-2-[(R)-1- methylbutylamino]-1- ++ - (p-fluorophenyl)-1- ethanol (R)-2-[(S)-1- methylbutylamino]-1- ++ - (p-fluorophenyl)-1- ethanol (R)-2-(tert-butylamino)- 1-(m-fluorophenyl)-1- +++ - ethanol 2-(butylamino)-1-(3,5- difluorophenyl)-1- ++ - ethanol 2-(butylamino)-1-(3,4- difluorophenyl)-1- ++ - ethanol m-{(R)-[(2R,5R)-5- propyl-2- +++ ++ pyrrolidinyl]hydroxymet hyl}phenol (R)-[(2R,5R)-5-propyl- 2-pyrrolidinyl](m- +++ + fluorophenyl)methanol (R)-[(2R,6R)-6-propyl- 2-piperidyl](m- + - fluorophenyl)methanol (S)-[(2R,6R)-6-propyl- 2-piperidyl](m- + - fluorophenyl)methanol (R)-2-(1,1- dimethylbutylamino)-1- +++ - (m-fluorophenyl)-1- ethanol 4-[2-(butylamino)-1- hydroxyethyl]-2(1H)- + - pyridinone 5-[2-(butylamino)-1- hydroxyethyl]-2(1H)- + - pyridinone (R)-[(2R,6S)-6-propyl- 2-piperidyl](m- +++ - hydroxyphenyl)methano l (S)-[(2R,6S)-6-propyl- 2-piperidyl](3,4- + - difluorophenyl)methanol (S)-[(2R,6S)-6-propyl- 2-piperidyl](3,5- + - difluorophenyl)methanol (R)-[(2R,6S)-6-propyl- 2-piperidyl](3,4- + - difluorophenyl)methanol (R)-[(2R,6S)-6-propyl- 2-piperidyl](3,5- ++ - difluorophenyl)methanol (R)-[(2R,6S)-6-propyl- 2-piperidyl](m- ++ - fluorophenyl)methanol (S)-[(2R,6S)-6-propyl- 2-piperidyl](m- ++ - fluorophenyl)methanol (S)-1-(2-amino-1,3- thiazol-4-yl)-2- + - (butylamino)-1-ethanol (S)-2-(butylamino)-1- [2-(trifluoromethyl)- + - 1,3-thiazol-4-yl]-1- ethanol (S)-1-(2-amino-4- pyrimidinyl)-2- + - (butylamino)-1-ethanol N-{5-[(S)-2- (butylamino)-1- hydroxyethyl]-1,3- + - thiazol-2-yl}2- methylpropionamide (S)-1-(2-amino-1,3- thiazol-5-yl)-2- + - (butylamino)-1-ethanol (R)-2-(tert-butylamino)- 1-(2,3-difluorophenyl)- +++ + 1-ethanol (R)-2-(butylamino)-1- (2,3-difluorophenyl)-1- +++ - ethanol (R)-2-(tert-butylamino)- 1-(o-fluorophenyl)-1- +++ + ethanol (R)-2-(butylamino)-1- (o-fluorophenyl)-1- +++ - ethanol (R)-2-(tert-butylamino)- 1-(4-fluoro-2- ++ - hydroxyphenyl)-1- ethanol (R)-2-(butylamino)-1- (4-fluoro-2- ++ - hydroxyphenyl)-1- ethanol (R)-1-(m-fluorophenyl)- 2-(1- +++ - methylcyclopropylamino )-1-ethanol (R)-1-(m-fluorophenyl)- 2-(1- +++ + methylcyclobutylamino) -1-ethanol (R)-2-(tert-butylamino)- 1-(4-fluoro-3- +++ ++ hydroxyphenyl)-1- ethanol (R)-2-(butylamino)-1- (4-fluoro-3- +++ - hydroxyphenyl)-1- ethanol (R)-2-(tert-butylamino)- 1-(2-fluoro-3- ++ ++ hydroxyphenyl)-1- ethanol (R)-2-(butylamino)-1- (2-fluoro-3- +++ + hydroxyphenyl)-1- ethanol N-{5-[(R)-2- (butylamino)-1- hydroxyethyl]-2- ++ - pyrimidinyl}2- methylpropionamide (R)-1-(2-amino-5- pyrimidinyl)-2- ++ - (butylamino)-1-ethanol (R)-1-(3-amino-2- fluorophenyl)-2- ++ - (butylamino)-1-ethanol (R)-1-(3-amino-2- fluorophenyl)-2-(tert- +++ + butylamino)-1-ethanol (R)-[(2R,6S)-6-propyl- 2-piperidyl](p- + - fluorophenyl)methanol (R)-[(2R,6S)-6-propyl- 2-piperidyl](o- + - fluorophenyl)methanol (R)-[(2R,6R)-6-propyl- 2-piperidyl](p- ++ - fluorophenyl)methanol 6-[(S)-2-(tert- butylamino)-1- ++ - hydroxyethyl]-3- pyridinol (S)-2-(tert-butylamino)- 1-(5-fluoro-2-pyridyl)- ++ - 1-ethanol (R)-[(2R,6R)-6-propyl- 2-piperidyl](o- ++ - fluorophenyl)methanol 4-[(R)-2-(tert- butylamino)-1- hydroxyethyl]-1- +++ - methyl-2(1H)- pyridinone (R)-2-(tert-butylamino)- 1-(5-fluoro-3-pyridyl)- +++ + 1-ethanol 5-[(R)-2-(tert- butylamino)-1- +++ - hydroxyethyl]-3- pyridinol (S)-[(R)-6,6-dimethyl- 2-piperidyl](m- + - fluorophenyl)methanol (R)-[(R)-6,6-dimethyl- 2-piperidyl](m- ++ - fluorophenyl)methanol (S)-[(R)-6,6-dimethyl- 2-piperidyl](m- + - hydroxyphenyl)methano l (R)-[(R)-6,6-dimethyl- 2-piperidyl](m- + - hydroxyphenyl)methano l (S)-[(2R,6S)-6-propyl- 2-piperidyl](p- + - fluorophenyl)methanol (S)-[(2R,6S)-6-propyl- 2-piperidyl](o- + - fluorophenyl)methanol (S)-[(2R,6R)-6-propyl- 2-piperidyl](o- + - fluorophenyl)methanol (R)-2-(tert-butylamino)- 1-(3-fluoro-4-pyridyl)- + - 1-ethanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](m- + - fluorophenyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](m- +++ - fluorophenyl)methanol m-{(S)-[(R)-5,5- dimethyl-2- ++ - pyrrolidinyl]hydroxymet hyl}phenol m-{(R)-[(R)-5,5- dimethyl-2- +++ - pyrrolidinyl]hydroxymet hyl}phenol (S)-[(2S,6R)-6-propyl- 2-piperidyl](m- ++ - hydroxyphenyl)methano l (S)-[(2S,6R)-6-propyl- 2-piperidyl](m- + - chlorophenyl)methanol (R)-[(2S,6R)-6-propyl- 2-piperidyl](m- +++ - chlorophenyl)methanol (R)-[(2S,6R)-6-propyl- 2-piperidyl](m- + - fluorophenyl)methanol (R)-1-(m-fluorophenyl)- 2-(neopentylamino)-1- + - ethanol (R)-1-(m-fluorophenyl)- 2-[1- ++ - (trifluoromethyl)cyclopr opylamino]-1-ethanol (S)-[(2S,6S)-6-propyl- 2-piperidyl](m- + - fluorophenyl)methanol (R)-[(2S,6S)-6-propyl- 2-piperidyl](m- ++ - fluorophenyl)methanol (S)-[(2S,6S)-6-propyl- 2-piperidyl](m- +++ - hydroxyphenyl)methano l (R)-[(2S,6S)-6-propyl- 2-piperidyl](m- ++ - hydroxyphenyl)methano l (R)-[(2S,6S)-6-propyl- 2-piperidyl](m- + - chlorophenyl)methanol (R)-[(2R,5S)-5-propyl- 2-pyrrolidinyl](m- ++ - fluorophenyl)methanol m-{(R)-[(2R,5S)-5- ++ - propyl-2- pyrrolidinyl]hydroxymet hyl}phenol (S)-[(2R,5R)-5-propyl- 2-pyrrolidinyl](m- + - fluorophenyl)methanol m-{(S)-[(2R,5R)-5- propyl-2- + - pyrrolidinyl]hydroxymet hyl}phenol (R)-[(2R,6S)-6-propyl- 2-piperidyl](m- + - chlorophenyl)methanol (S)-[(2R,6S)-6-propyl- 2-piperidyl](m- + - chlorophenyl)methanol (R)-[(2S,5S)-5-propyl- 2-pyrrolidinyl](m- + - fluorophenyl)methanol (S)-[(2S,5S)-5-propyl- 2-pyrrolidinyl](m- ++ - fluorophenyl)methanol (R)-[(2S,5R)-5-propyl- 2-pyrrolidinyl](m- + - fluorophenyl)methanol (S)-[(2S,5R)-5-propyl- 2-pyrrolidinyl](m- ++ - fluorophenyl)methanol 4-[2-(tert-butylamino)- 1-hydroxyethyl]-3- +++ - pyridinol (R)-[(2R,6S)-6-propyl- 2-piperidyl](o- + - chlorophenyl)methanol (R)-[(2S,6R)-6-propyl- 2-piperidyl](m- +++ - hydroxyphenyl)methano l (S)-[(2R,6R)-6-propyl- 2-piperidyl](m- + - hydroxyphenyl)methano l (R)-2-(tert-butylamino)- 1-(5-chloro-3-pyridyl)- +++ +++ 1-ethanol (S)-[(2R,6S)-6-propyl- 2-piperidyl](5-fluoro-3- - - pyridyl)methanol (R)-[(2R,6S)-6-propyl- 2-piperidyl](5-fluoro-3- - - pyridyl)methanol (R)-[(2R,5R)-5-propyl- 2-pyrrolidinyl](m- ++ - chlorophenyl)methanol m-{(R)-[(S)-5,5- dimethyl-2- + - pyrrolidinyl]hydroxymet hyl}phenol m-{(S)-[(S)-5,5- dimethyl-2- - - pyrrolidinyl]hydroxymet hyl}phenol (R)-[(S)-5,5-dimethyl- 2-pyrrolidinyl](m- - - fluorophenyl)methanol (S)-[(S)-5,5-dimethyl- 2-pyrrolidinyl](m- + - fluorophenyl)methanol (S)-2-(tert-butylamino)- 1-(3-chloro-2-pyridyl)- + - 1-ethanol (S)-2-(tert-butylamino)- 1-(5-chloro-2-pyridyl)- + - 1-ethanol (R)-[(2R,5R)-5-propyl- 2-pyrrolidinyl](o- +++ - chlorophenyl)methanol (R)-1-(3-amino-2,4- difluorophenyl)-2-(tert- +++ + butylamino)-1-ethanol (R)-2-(tert-butylamino)- 1-(3-fluoro-2-tolyl)-1- +++ + ethanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](o- - - chlorophenyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](o- +++ - chlorophenyl)methanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](m- + - chlorophenyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](m- +++ - chlorophenyl)methanol (S)-[(2R,6S)-6-propyl- 2-piperidyl](m- - - hydroxyphenyl)methano l (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](5-fluoro- - - 3-pyridyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](5-fluoro- +++ - 3-pyridyl)methanol (S)-[(R)-5,5-dipropyl-2- pyrrolidinyl](m- - - fluorophenyl)methanol (R)-[(R)-5,5-dipropyl-2- pyrrolidinyl](m- ++ - fluorophenyl)methanol (R)-[(2R,5R)-5-propyl- 2-pyrrolidinyl](5-fluoro- +++ - 3-pyridyl)methanol (S)-[(2R,5R)-5-propyl- 2-pyrrolidinyl](5-fluoro- + - 3-pyridyl)methanol (R)-[(R)-6,6-dimethyl- 2-piperidyl](o- + - chlorophenyl)methanol (S)-[(R)-6,6-dimethyl- 2-piperidyl](o- +++ - chlorophenyl)methanol (S)-[(R)-6,6-dimethyl- 2-piperidyl](m- ++ - chlorophenyl)methanol (R)-[(R)-6,6-dimethyl- 2-piperidyl](m- + - chlorophenyl)methanol 5-{(S)-[(R)-5,5- dimethyl-2- + - pyrrolidinyl]hydroxymet hyl}-3-pyridinol 5-{(R)-[(R)-5,5- dimethyl-2- ++ - pyrrolidinyl]hydroxymet hyl}-3-pyridinol (R)-{(R)-1-aza-2- spiro[4.4]nonyl}(m- ++ + fluorophenyl)methanol (S)-{(R)-1-aza-2- spiro[4.4]nonyl}(m- - - fluorophenyl)methanol (R)-{(R)-4-aza-5- spiro[2.4]heptyl}(m- ++ - fluorophenyl)methanol (S)-{(R)-4-aza-5- spiro[2.4]heptyl}(m- + - fluorophenyl)methanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](p- - - fluorophenyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](p- ++ - fluorophenyl)methanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](o- - - fluorophenyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](o- +++ + fluorophenyl)methanol (S)-[(R)-6,6-dimethyl- 2-piperidyl](o- +++ + fluorophenyl)methanol (R)-[(R)-6,6-dimethyl- 2-piperidyl](o- ++ - fluorophenyl)methanol (S)-(m-fluorophenyl)(4- methyl-7- + - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- methyl-7- ++ - azabicyclo[2.2.1]hept- 1-yl)methanol (S)-(o-fluorophenyl)(4- methyl-7- +++ - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(o-fluorophenyl)(4- methyl-7- +++ - azabicyclo[2.2.1]hept- 1-yl)methanol (S)-(m-fluorophenyl)(4- propyl-7- - - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- propyl-7- ++ + azabicyclo[2.2.1]hept- 1-yl)methanol (S)-(5-fluoro-3- pyridyl)(4-methyl-7- ++ - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(5-fluoro-3- pyridyl)(4-methyl-7- +++ - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ ++ yl}(m- fluorophenyl)methanol (S)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- + - yl}(m- fluorophenyl)methanol (R)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- - - yl}(m- fluorophenyl)methanol (S)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- ++ - yl}(m- fluorophenyl)methanol (R)-[(S)-6,6-dimethyl- 2-piperidyl](m- +++ - fluorophenyl)methanol (S)-[(S)-6,6-dimethyl- 2-piperidyl](m- + - fluorophenyl)methanol (S)-[(S)-6,6-dimethyl- 2-piperidyl](o- + - fluorophenyl)methanol (R)-[(S)-6,6-dimethyl- 2-piperidyl](o- +++ + fluorophenyl)methanol (S)-(o-chlorophenyl)(4- methyl-7- +++ - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(o-chlorophenyl)(4- methyl-7- +++ - azabicyclo[2.2.1]hept- 1-yl)methanol (S)-(m-chlorophenyl)(4- methyl-7- + - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-chlorophenyl)(4- methyl-7- +++ - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-[(R)-4,4-dimethyl- 2-azetidinyl](m- +++ + fluorophenyl)methanol (S)-[(S)-4,4-dimethyl- 2-azetidinyl](m- + - fluorophenyl)methanol (R)-[(S)-4,4-dimethyl- 2-azetidinyl](m- - - fluorophenyl)methanol (S)-[(R)-4,4-dimethyl- 2-azetidinyl](m- - - fluorophenyl)methanol (R)-[(S)-4,4-dimethyl- 2-azetidinyl](o- - - fluorophenyl)methanol (S)-[(R)-4,4-dimethyl- 2-azetidinyl](o- + - fluorophenyl)methanol (R)-[(R)-4,4-dimethyl- 2-azetidinyl](o- +++ + fluorophenyl)methanol (S)-[(S)-4,4-dimethyl- 2-azetidinyl](o- + - fluorophenyl)methanol (R)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ - yl}(m- chlorophenyl)methanol (S)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- + - yl}(m- chlorophenyl)methanol (S)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- ++ - yl}(m- chlorophenyl)methanol (R)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- + - yl}(m- chlorophenyl)methanol (R)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ +++ yl}(o- fluorophenyl)methanol (S)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ - yl}(o- fluorophenyl)methanol (S)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ - yl}(o- fluorophenyl)methanol (R)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ - yl}(o- fluorophenyl)methanol (R)-[(R)-4,4-dimethyl- 2-azetidinyl](5-fluoro-3- +++ - pyridyl)methanol (S)-[(S)-4,4-dimethyl- 2-azetidinyl](5-fluoro-3- + - pyridyl)methanol (R)-[(S)-4,4-dimethyl- 2-azetidinyl](5-fluoro-3- + - pyridyl)methanol (S)-[(R)-4,4-dimethyl- 2-azetidinyl](5-fluoro-3- + - pyridyl)methanol (S)-[(2R,7R)-7-propyl- 2-azepanyl](5-fluoro-3- - - pyridyl)methanol (R)-[(2R,7R)-7-propyl- 2-azepanyl](5-fluoro-3- - - pyridyl)methanol (R)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ - yl}(5-fluoro-3- pyridyl)methanol (S)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- ++ - yl}(5-fluoro-3- pyridyl)methanol (S)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- - - yl}(5-fluoro-3- pyridyl)methanol (R)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- + - yl}(5-fluoro-3- pyridyl)methanol (R)-1-(m-fluorophenyl)- 2-{2-[(1r,4R)-4- + - methoxycyclohexyl]ethy lamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{2-[(1r,4R)- 4- ++ - methoxycyclohexyl]ethy lamino}-1-ethanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](3-amino- + - 2- fluorophenyl)methanol (R)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](3-amino- +++ - 2- fluorophenyl)methanol (R)-1-(m-fluorophenyl)- 2-({[(1r,4R)-4- ++ - methoxycyclohexyl]met hyl}amino)-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1r,4R)-4- ++ - methoxycyclohexyl]met hyl}amino)-1-ethanol (R)-[(R)-4,4-dimethyl- 2-azetidinyl](m- +++ - chlorophenyl)methanol (S)-[(S)-4,4-dimethyl- 2-azetidinyl](m- + - chlorophenyl)methanol (R)-[(S)-4,4-dimethyl- 2-azetidinyl](m- + - chlorophenyl)methanol (S)-[(R)-4,4-dimethyl- 2-azetidinyl](m- - - chlorophenyl)methanol (R)-[(2S,7S)-7-propyl- 2-azepanyl](5-fluoro-3- +++ - pyridyl)methanol (S)-[(2S,7S)-7-propyl- 2-azepanyl](5-fluoro-3- - - pyridyl)methanol (S)-[(R)-5,5-dimethyl- 2-pyrrolidinyl](4-amino- +++ + 3,5- difluorophenyl)methanol (R)-1-(m-fluorophenyl)- 2-{2-[(1s,4S)-4- ++ - methoxycyclohexyl]ethy lamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{2-[(1s,4S)- 4- +++ - methoxycyclohexyl]ethy lamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1r,4R)-4- +++ - methoxycyclohexyl]ethy lamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1r,4R)-4- +++ - methoxycyclohexyl]ethy lamino}-1-ethanol (R)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- +++ - yl}(3-amino-2- fluorophenyl)methanol (S)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- ++ - yl}(3-amino-2- fluorophenyl)methanol (S)-{(R)-1-methyl-2- azabicyclo[2.1.1]hex-3- ++ - yl}(3-amino-2- fluorophenyl)methanol (R)-{(S)-1-methyl-2- azabicyclo[2.1.1]hex-3- ++ - yl}(3-amino-2- fluorophenyl)methanol (R)-1-(m-fluorophenyl)- 2-({[(1s,4S)-4- ++ - methoxycyclohexyl]met hyl}amino)-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1s,4S)-4- ++ - methoxycyclohexyl]met hyl}amino)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- methoxycyclohexyl]ethy +++ - lamino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- methoxycyclohexyl]ethy +++ - lamino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- methoxycyclohexyl]ethy +++ - lamino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- methoxycyclohexyl]ethy ++ - lamino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1s,4S)-4- - - methoxycyclohexyl]ethy lamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1s,4S)-4- - - methoxycyclohexyl]ethy lamino}-1-ethanol (S)-(3-fluoro-4- pyridyl)(4-methyl-7- - - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(3-fluoro-4- pyridyl)(4-methyl-7- - - azabicyclo[2.2.1]hept- 1-yl)methanol (R)-2-{1-[(1S,3R)-3- methoxycyclohexyl]-1- methylethylamino}-1- +++ - (m-fluorophenyl)-1- ethanol (R)-2-{1-[(1R,3S)-3- methoxycyclohexyl]-1- methylethylamino}-1- +++ + (m-fluorophenyl)-1- ethanol (R)-2-{1-[(1S,3R)-3- methoxycyclohexyl]-1- methylethylamino}-1- ++ - (5-fluoro-3-pyridyl)-1- ethanol (R)-1-(m-fluorophenyl)- 2-{3-[(1s,4R)-4- +++ ++ methoxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{3-[(1r,4S)-4- + - methoxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(5-fluoro-3- +++ - pyridyl)-2-{3-[(1s,4R)- 4- methoxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{3-[(1r,4S)- 4- - - methoxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-({[(1s,4S)-4- (benzyloxy)cyclohexyl] + - methyl}amino)-1- ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1s,4S)-4- (benzyloxy)cyclohexyl] +++ - methyl}amino)-1- ethanol (R)-2-{1,1-dimethyl-3- [(1s,4R)-4- methoxycyclohexyl]prop +++ + ylamino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-3- [(1r,4S)-4- methoxycyclohexyl]prop ++ - ylamino}-1-(m- fluorophenyl)-1-ethanol (1s,4R)-4- methoxycyclohexyl]prop +++ - ylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-3- [(1r,4S)-4- methoxycyclohexyl]prop + - ylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-1-(m-fluorophenyl)- 2-({[(1s,4S)-4- + - hydroxycyclohexyl]meth yl}amino)-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1s,4S)-4- + - hydroxycyclohexyl]meth yl}amino)-1-ethanol (R)-2-{1-[(1R,3S)-3- methoxycyclohexyl]-1- methylethylamino}-1- +++ ++ (5-fluoro-3-pyridyl)-1- ethanol (R)-1-(m-fluorophenyl)- 2-({[(1r,4R)-4- (benzyloxy)cyclohexyl] + - methyl}amino)-1- ethanol (R)-1-(m-fluorophenyl)- 2-({[(1r,4R)-4- + - hydroxycyclohexyl]meth yl}amino)-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1r,4R)-4- (benzyloxy)cyclohexyl] + - methyl}amino)-1- ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1r,4R)-4- - - hydroxycyclohexyl]meth yl}amino)-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{3-[(1s,4R)- 4- ++ - (benzyloxy)cyclohexyl]p ropylamino}-1-ethanol (R)-1-(5-fluoro-3- + - pyridyl)-2-{3-[(1r,4S)- 4- (benzyloxy)cyclohexyl]p ropylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{3-[(1s,4R)-4- + - (benzyloxy)cyclohexyl]p ropylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{3-[(1r,4S)-4- + - (benzyloxy)cyclohexyl]p ropylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1r,4R)-4- ++ - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1s,4S)-4- +++ - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1r,4R)-4- ++ - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1s,4S)-4- ++ - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1r,4R)-4- ++ - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-1-(m-fluorophenyl)- ++ - 2-{1-methyl-1- [(1s,4S)-4- hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1r,4R)-4- ++ - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1s,4S)-4- + - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{2-[(1s,4S)-4- ++ - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{2-[(1r,4R)-4- + - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-2-{1,1-dimethyl-3- [(1r,4S)-4- hydroxycyclohexyl]prop + - ylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-3- [(1r,4S)-4- hydroxycyclohexyl]prop + - ylamino}-1-(m- fluorophenyl)-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{2-[(1s,4S)- 4- ++ - (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(5-fluoro-3- - - pyridyl)-2-{2-[(1r,4R)- 4- (benzyloxy)cyclohexyl]e thylamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{2-[(1s,4S)- 4- + - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{2-[(1r,4R)- 4- + - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-2-{1,1-dimethyl-3- [(1s,4R)-4- hydroxycyclohexyl]prop +++ - ylamino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-3- [(1s,4R)-4- hydroxycyclohexyl]prop +++ - ylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-1-(m-fluorophenyl)- 2-{2-[(1s,4S)-4- ++ - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{2-[(1r,4R)-4- + - hydroxycyclohexyl]ethyl amino}-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- hydroxycyclohexyl]ethyl ++ - amino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-2- +++ - [(1r,4R)-4- hydroxycyclohexyl]ethyl amino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- hydroxycyclohexyl]ethyl +++ - amino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- hydroxycyclohexyl]ethyl ++ - amino}-1-(m- fluorophenyl)-1-ethanol (R)-1-(m-fluorophenyl)- 2-{3-[(1r,4S)-4- ++ - hydroxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{3-[(1s,4R)- 4- ++ - hydroxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{3-[(1r,4S)- 4- + - hydroxycyclohexyl]prop ylamino}-1-ethanol (R)-1-(m-fluorophenyl)- 2-{3-[(1s,4R)-4- + - hydroxycyclohexyl]prop ylamino}-1-ethanol N-[(1S,4s)-4-{[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]met ++ - hyl}cyclohexyl]acetamid e N-[(1R,4r)-4-{[(R)-2- ++ - (m-fluorophenyl)-2- hydroxyethylamino]met hyl}cyclohexyl]acetamid e N-[(1R,4r)-4-{[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]met ++ - hyl}cyclohexyl]acetamid e N-[(1S,4s)-4-{[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]met + - hyl}cyclohexyl]acetamid e (R)-1-(m-fluorophenyl)- 2-({[(1r,4R)-4- (mesylamino)cyclohexyl ++ - ]methyl}amino)-1- ethanol (R)-1-(m-fluorophenyl)- 2-({[(1s,4S)-4- (mesylamino)cyclohexyl ++ - ]methyl}amino)-1- ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1r,4R)-4- (mesylamino)cyclohexyl + - ]methyl}amino)-1- ethanol (R)-1-(5-fluoro-3- pyridyl)-2-({[(1s,4S)-4- (mesylamino)cyclohexyl ++ - ]methyl}amino)-1- ethanol N-[(1R,4r)-4-{[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]met +++ - hyl}cyclohexyl]benzami de N-[(1S,4s)-4-{[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]met ++ - hyl}cyclohexyl]benzami de N-[(1R,4r)-4-{[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]met ++ - hyl}cyclohexyl]benzami de N-[(1S,4s)-4-{[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]met ++ - hyl}cyclohexyl]benzami de (R)-2-{1,1-dimethyl-3- [(1r,4S)-4- hydroxycyclohexyl]prop +++ - ylamino}-1-(o- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-3- [(1s,4R)-4- hydroxycyclohexyl]prop +++ + ylamino}-1-(o- fluorophenyl)-1-ethanol (1S,4s)-8-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-7- ++ - methoxy-p-menthan-7- one methyl (1S,4s)-4-{2- [(R)-2-(5-fluoro-3- pyridyl)-2- +++ - hydroxyethylamino]-2- methylpropyl}cyclohexa necarboxylate (1S,4s)-8-[(R)-2-(5- + ++ fluoro-3-pyridyl)-2- hydroxyethylamino]-7- hydroxy-p-menthan-7- one (1S,4s)-4-{2-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-2- + - methylpropyl}cyclohexa necarboxylic acid (S)-[(2R,5S)-5- {[(1r,4S)-4- methoxycyclohexyl]met +++ - hyl}-2-pyrrolidinyl](m- fluorophenyl)methanol (R)-[(2R,5S)-5- {[(1r,4S)-4- methoxycyclohexyl]met +++ - hyl}-2-pyrrolidinyl](m- fluorophenyl)methanol methyl (1S,4s)-4-{2- [(R)-2-(m- fluorophenyl)-2- +++ - hydroxyethylamino]-2- methylpropyl}cyclohexa necarboxylate (1S,4s)-8-[(R)-2-(m- fluorophenyl)-2- hydroxyethylamino]-7- +++ - methoxy-p-menthan-7- one (S)-(m-fluorophenyl){4- (methoxymethyl)-7- + - azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- (methoxymethyl)-7- +++ - azabicyclo[2.2.1]hept- 1-yl}methanol (1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- + - methylpropyl}cyclohexa necarboxylic acid (S)-[(2R,5S)-5- {[(1r,4S)-4- methoxycyclohexyl]met + - hyl}-2-pyrrolidinyl](5- fluoro-3- pyridyl)methanol (R)-[(2R,5S)-5- {[(1r,4S)-4- methoxycyclohexyl]met + - hyl}-2-pyrrolidinyl](5- fluoro-3- pyridyl)methanol (S)-[(2R,5R)-5- {[(1r,4R)-4- methoxycyclohexyl]met + - hyl}-2-pyrrolidinyl](m- fluorophenyl)methanol (R)-[(2R,5R)-5- {[(1r,4R)-4- methoxycyclohexyl]met +++ - hyl}-2-pyrrolidinyl](m- fluorophenyl)methanol (S)-[(2R,5S)-5- {[(1r,4S)-4- methoxycyclohexyl]met + - hyl}-2-pyrrolidinyl](o- fluorophenyl)methanol (R)-[(2R,5S)-5- {[(1r,4S)-4- methoxycyclohexyl]met +++ - hyl}-2-pyrrolidinyl](o- fluorophenyl)methanol (S)-[(2R,5R)-5- {[(1r,4R)-4- methoxycyclohexyl]met ++ - hyl}-2-pyrrolidinyl](o- fluorophenyl)methanol (R)-[(2R,5R)-5- {[(1r,4R)-4- methoxycyclohexyl]met +++ + hyl}-2-pyrrolidinyl](o- fluorophenyl)methanol (S)-[(2R,5R)-5- {[(1r,4R)-4- methoxycyclohexyl]met + - hyl}-2-pyrrolidinyl](5- fluoro-3- pyridyl)methanol (R)-[(2R,5R)-5- {[(1r,4R)-4- methoxycyclohexyl]met +++ - hyl}-2-pyrrolidinyl](5- fluoro-3- pyridyl)methanol methyl (1R,4r)-4-{3- [(R)-2-(5-fluoro-3- pyridyl)-2- +++ - hydroxyethylamino]-3- methylbutyl}cyclohexan ecarboxylate (1R,4r)-4-{3-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-3- + - methylbutyl}cyclohexan ecarboxylic acid (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1r,4R)-4- - - aminocyclohexyl]ethyla mino}-1-ethanol (R)-1-(5-fluoro-3- pyridyl)-2-{1-methyl-1- [(1r,4R)-4- + - (mesylamino)cyclohexyl ]ethylamino}-1-ethanol N-[(1R,4r)-4-{1-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-1- +++ - methylethyl}cyclohexyl] acetamide (1S,4s)-4-{3-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-3- +++ - methylbutyl}cyclohexan ecarboxylic acid (1R,4r)-4-{3-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-3- - - methylbutyl}cyclohexan ecarboxylic acid methyl (1S,4s)-4-{3- [(R)-2-(5-fluoro-3- pyridyl)-2- +++ + hydroxyethylamino]-3- methylbutyl}cyclohexan ecarboxylate methyl (1R,4r)-4-{3- [(R)-2-(m- fluorophenyl)-2- +++ - hydroxyethylamino]-3- methylbutyl}cyclohexan ecarboxylate methyl (1S,4s)-4-{3- [(R)-2-(m- fluorophenyl)-2- +++ + hydroxyethylamino]-3- methylbutyl}cyclohexan ecarboxylate (1S,4s)-4-{3-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-3- + - methylbutyl}cyclohexan ecarboxylic acid methyl (1R,4r)-4-{2- [(R)-2-(m- fluorophenyl)-2- +++ - hydroxyethylamino]-2- methylpropyl}cyclohexa necarboxylate methyl (1R,4r)-4-{2- [(R)-2-(5-fluoro-3- pyridyl)-2- ++ - hydroxyethylamino]-2- methylpropyl}cyclohexa necarboxylate (1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexa necarboxylic acid (1R,4r)-4-{2-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-2- - - methylpropyl}cyclohexa necarboxylic acid N-[(1R,4r)-4-{2-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexy l]acetamide (R)-2-{1,1-dimethyl-3- [(1r,4R)-4- aminocyclohexyl]propyl + - amino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- aminocyclohexyl]ethyla +++ - mino}-1-(5-fluoro-3- pyridyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (mesylamino)cyclohexyl +++ - ]ethylamino}-1-(5- fluoro-3-pyridyl)-1- ethanol N-[(1R,4r)-4-{3-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-3- +++ - methylbutyl}cyclohexyl] acetamide (R)-2-{1,1-dimethyl-3- [(1r,4R)-4- (mesylamino)cyclohexyl ++ - ]propylamino}-1-(5- fluoro-3-pyridyl)-1- ethanol (S)-[(2R,5S)-5-methyl- 5-{[(1r,4S)-4- methoxycyclohexyl]met +++ - hyl}-2-pyrrolidinyl](m- fluorophenyl)methanol (R)-[(2R,5S)-5-methyl- 5-{[(1r,4S)-4- methoxycyclohexyl]met +++ ++ hyl}-2-pyrrolidinyl](m- fluorophenyl)methanol (S)-{(2R,5R)-5-[(p- methoxyphenyl)methyl] -5-methyl-2- +++ - pyrrolidinyl}(m- fluorophenyl)methanol (R)-{(2R,5R)-5-[(p- methoxyphenyl)methyl] -5-methyl-2- +++ + pyrrolidinyl}(m- fluorophenyl)methanol (1R,4r)-8-[(R)-2-(m- fluorophenyl)-2- hydroxyethylamino]-7- +++ + methoxy-p-menthan-7- one (1R,4r)-8-[(R)-2-(m- fluorophenyl)-2- hydroxyethylamino]-7- + - hydroxy-p-menthan-7- one (1S,4s)-8-[(R)-2-(m- fluorophenyl)-2- hydroxyethylamino]-7- ++ - hydroxy-p-menthan-7- one (1R,4r)-8-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-7- +++ - methoxy-p-menthan-7- one (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- aminocyclohexyl]ethyla +++ - mino}-1-(m- fluorophenyl)-1-ethanol (S)-{(2R,5S)-5-[(p- methoxyphenyl)methyl] +++ - -2-pyrrolidinyl}(m- fluorophenyl)methanol (R)-{(2R,5S)-5-[(p- methoxyphenyl)methyl] +++ + -2-pyrrolidinyl}(m- fluorophenyl)methanol (R)-{(2R,5R)-5-[(p- methoxyphenyl)methyl] +++ - -2-pyrrolidinyl}(m- fluorophenyl)methanol (S)-{(2R,5R)-5-[(p- methoxyphenyl)methyl] +++ - -2-pyrrolidinyl}(m- fluorophenyl)methanol (R)-2-(tert-butylamino)- 1-(2-methyl-3-pyridyl)- 1-ethanol +++ + (S)-{(2R,5S)-5-[(p- methoxyphenyl)methyl] -2-pyrrolidinyl}(5- +++ - fluoro-3- pyridyl)methanol (R)-{(2R,5S)-5-[(p- methoxyphenyl)methyl] -2-pyrrolidinyl}(5- +++ - fluoro-3- pyridyl)methanol (R)-{(2R,5R)-5-[(p- methoxyphenyl)methyl] -2-pyrrolidinyl}(5- +++ - fluoro-3- pyridyl)methanol (S)-{(2R,5R)-5-[(p- methoxyphenyl)methyl] -2-pyrrolidinyl}(5- +++ - fluoro-3- pyridyl)methanol (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1r,4R)-4- ++ - aminocyclohexyl]ethyla mino}-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (mesylamino)cyclohexyl +++ + ]ethylamino}-1-(m- fluorophenyl)-1-ethanol N-[(1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ + methylpropyl}cyclohexy l]acetamide N-[(1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ +++ methylpropyl}cyclohexy l]benzamide (R)-1-(m-fluorophenyl)- 2-{1-methyl-1- [(1r,4R)-4- ++ - (mesylamino)cyclohexyl ]ethylamino}-1-ethanol N-[(1R,4r)-4-{1-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-1- +++ - methylethyl}cyclohexyl] acetamide 6-[(S)-2-(tert- butylamino)-1- +++ + hydroxyethyl]-2- pyridinecarbonitrile (R)-(4-benzyl-7- azabicyclo[2.2.1]hept- +++ + 1-yl)(m- fluorophenyl)methanol (S)-(4-benzyl-7- azabicyclo[2.2.1]hept- ++ - 1-yl)(m- fluorophenyl)methanol (1R,4r)-8-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-7- ++ - hydroxy-p-menthan-7- one (S)-{(2R,5S)-5-[(p- chlorophenyl)methyl]-2- ++ - pyrrolidinyl}(m- fluorophenyl)methanol (R)-{(2R,5S)-5-[(p- chlorophenyl)methyl]-2- +++ - pyrrolidinyl}(m- fluorophenyl)methanol (R)-{(2R,5R)-5-[(p- chlorophenyl)methyl]-2- +++ - pyrrolidinyl}(m- fluorophenyl)methanol (S)-{(2R,5R)-5-[(p- chlorophenyl)methyl]-2- ++ - pyrrolidinyl}(m- fluorophenyl)methanol (S)-(4-{[(p- chlorophenyl)methoxy] methyl}-7- ++ - azabicyclo[2.2.1]hept- 1-yl)(m- fluorophenyl)methanol (R)-(4-{[(p- chlorophenyl)methoxy] methyl}-7- +++ - azabicyclo[2.2.1]hept- 1-yl)(m- fluorophenyl)methanol (S)-2-(tert-butylamino)- 1-[6-(trifluoromethyl)- +++ - 2-pyridyl]-1-ethanol ethyl [(1R,4r)-4-{1- +++ - [(R)-2-(m- fluorophenyl)-2- hydroxyethylamino]-1- methylethyl}cyclohexyl oxy]acetate (1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ + methylpropyl}cyclohexa necarbonitrile (S)-(m-fluorophenyl){4- [(p- methoxyphenyl)methyl] ++ - -7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- [(p- methoxyphenyl)methyl] +++ - -7- azabicyclo[2.2.1]hept- 1-yl}methanol [(1R,4r)-4-{1-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-1- ++ - methylethyl}cyclohexyl oxy]acetic acid (S)-{(2R,5S)-5-[(p- chlorophenyl)methyl]-2- ++ - pyrrolidinyl}(5-fluoro-3- pyridyl)methanol (R)-{(2R,5S)-5-[(p- chlorophenyl)methyl]-2- +++ - pyrrolidinyl}(5-fluoro-3- pyridyl)methanol (S)-{(2R,5R)-5-[(p- chlorophenyl)methyl]-2- +++ - pyrrolidinyl}(5-fluoro-3- pyridyl)methanol (R)-{(2R,5R)-5-[(p- chlorophenyl)methyl]-2- +++ - pyrrolidinyl}(5-fluoro-3- pyridyl)methanol ethyl [(1S,4s)-4-{1- [(R)-2-(m- fluorophenyl)-2- ++ - hydroxyethylamino]-1- methylethyl}cyclohexyl oxy]acetate [(1S,4s)-4-{1-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-1- ++ - methylethyl}cyclohexyl oxy]acetic acid ethyl [(1R,4r)-4-{1- [(R)-2-(5-fluoro-3- pyridyl)-2- +++ - hydroxyethylamino]-1- methylethyl}cyclohexyl oxy]acetate (S)-(m-fluorophenyl)(4- {2-[(1r,4R)-4- methoxycyclohexyl]ethy ++ - l}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- {2-[(1r,4S)-4- methoxycyclohexyl]ethy +++ ++ l}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (S)-(m-fluorophenyl){4- [(p- fluorophenyl)methyl]-7- ++ - azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- [(p- fluorophenyl)methyl]-7- +++ - azabicyclo[2.2.1]hept- 1-yl}methanol (1R,4s)-4-{2-[(S)-2-(6- cyano-2-pyridyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexy l 2-methyl-2- propanecarbamate 6-[(R)-2-{1,1-dimethyl- 2-[(1r,4R)-4- aminocyclohexyl]ethyla ++ - mino}-1-hydroxyethyl]- 2-pyridinecarbonitrile 6-[(R)-2-{1,1-dimethyl- 2-[(1s,4S)-4- aminocyclohexyl]ethyla ++ - mino}-1-hydroxyethyl]- 2-pyridinecarbonitrile 6-[(S)-2-{1,1-dimethyl- 2-[(1r,4S)-4- aminocyclohexyl]ethyla +++ + mino}-1-hydroxyethyl]- 2-pyridinecarbonitrile 6-[(S)-2-{1,1-dimethyl- 2-[(1s,4R)-4- aminocyclohexyl]ethyla ++ - mino}-1-hydroxyethyl]- 2-pyridinecarbonitrile [(1R,4r)-4-{1-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-1- ++ - methylethyl}cyclohexyl oxy]acetic acid (1R,4r)-4-{2-[(R)-2- ++ + (m-fluorophenyl)-2- hydroxyethylamino]-2- methylpropyl}cyclohexy l 2-methyl-2- propanecarbamate N-[(1R,4s)-4-{2-[(S)-2- (6-cyano-2-pyridyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexy l]acetamide 6-[(S)-2-{1,1-dimethyl- 2-[(1s,4R)-4- (mesylamino)cyclohexyl ++ - ]ethylamino}-1- hydroxyethyl]-2- pyridinecarbonitrile N-[(1S,4s)-4-{2-[(R)-2- (6-cyano-2-pyridyl)-2- hydroxyethylamino]-2- - - methylpropyl}cyclohexy l]acetamide 6-[(R)-2-{1,1-dimethyl- 2-[(1s,4S)-4- (mesylamino)cyclohexyl + - ]ethylamino}-1- hydroxyethyl]-2- pyridinecarbonitrile N-[(1S,4r)-4-{2-[(S)-2- (6-cyano-2-pyridyl)-2- hydroxyethylamino]-2- +++ + methylpropyl}cyclohexy l]acetamide 6-[(S)-2-{1,1-dimethyl- 2-[(1r,4S)-4- (mesylamino)cyclohexyl +++ - ]ethylamino}-1- hydroxyethyl]-2- pyridinecarbonitrile N-[(1R,4r)-4-{2-[(R)-2- (6-cyano-2-pyridyl)-2- hydroxyethylamino]-2- - - methylpropyl}cyclohexy l]acetamide 6-[(R)-2-{1,1-dimethyl- 2-[(1r,4R)-4- (mesylamino)cyclohexyl - - ]ethylamino}-1- hydroxyethyl]-2- pyridinecarbonitrile N-[(1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ + methylpropyl}cyclohexy l]2,2- dimethylpropionamide (R)-2-{1,1-dimethyl-2- [(1r,4R)-4-(3,3- dimethylureido)cyclohex +++ ++ yl]ethylamino}-1-(m- fluorophenyl)-1-ethanol N-[(1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ ++ methylpropyl}cyclohexy l]cyclobutanecarboxami de N-[(1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ +++ methylpropyl}cyclohexy l]cyclopropanecarboxam ide N-[(1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- +++ + hydroxyethylamino]-2- methylpropyl}cyclohexy l]trifluoroacetamide N-[(1R,4r)-4-{2-[(R)-2- hydroxy-2-(2-methyl-3- pyridyl)ethylamino]-2- +++ - methylpropyl}cyclohexy l]acetamide (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (mesylamino)cyclohexyl + - ]ethylamino}-1-(2- methyl-3-pyridyl)-1- ethanol N-[(1S,4s)-4-{2-[(R)-2- hydroxy-2-(2-methyl-3- pyridyl)ethylamino]-2- ++ - methylpropyl}cyclohexy l]acetamide (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (mesylamino)cyclohexyl + - ]ethylamino}-1-(2- methyl-3-pyridyl)-1- ethanol (S)-(m-fluorophenyl)(4- {[(p- fluorophenyl)methoxy] - - methyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- {[(p- fluorophenyl)methoxy] +++ + methyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (S)-{4-[(p- chlorophenoxy)methyl]- 7- +++ - azabicyclo[2.2.1]hept- 1-yl}(m- fluorophenyl)methanol (R)-{4-[(p- chlorophenoxy)methyl]- 7- +++ - azabicyclo[2.2.1]hept- 1-yl}(m- fluorophenyl)methanol (S)-(4-{[(p- fluorophenyl)methoxy] methyl}-7- + - azabicyclo[2.2.1]hept- 1-yl)(5-fluoro-3- pyridyl)methanol (R)-(4-{[(p- fluorophenyl)methoxy] methyl}-7- +++ + azabicyclo[2.2.1]hept- 1-yl)(5-fluoro-3- pyridyl)methanol (R)-(o-fluorophenyl){4- [2-(3-pyridyl)ethyl]-7- +++ ++ azabicyclo[2.2.1]hept- 1-yl}methanol (S)-(m-fluorophenyl){4- [2-(3-pyridyl)ethyl]-7- +++ - azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- [2-(3-pyridyl)ethyl]-7- +++ ++ azabicyclo[2.2.1]hept- 1-yl}methanol N-[(1S,4s)-4-{2-[(R)-2- +++ - (m-fluorophenyl)-2- hydroxyethylamino]-2- methylpropyl}cyclohexy l]cyclopropanecarboxam ide N-[(1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexy l]cyclobutanecarboxami de (1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexy l 2-methyl-2- propanecarbamate (1R,4s)-4-(2-{(S)-2- hydroxy-2-[6- (trifluoromethyl)-2- pyridyl]ethylamino}-2- - - methylpropyl)cyclohexyl 2-methyl-2- propanecarbamate (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (propylsulfonylamino)cy ++ + clohexyl]ethylamino}-1- (m-fluorophenyl)-1- ethanol N-[(1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexy l]acetamide (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- +++ - (mesylamino)cyclohexyl ]ethylamino}-1-(m- fluorophenyl)-1-ethanol N-[(1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexy l]trifluoroacetamide N-[(1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexy l]2,2- dimethylpropionamide (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- aminocyclohexyl]ethyla +++ - mino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4-(3,3- dimethylureido)cyclohex +++ + yl]ethylamino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (trifluoromesylamino)cy +++ - clohexyl]ethylamino}-1- (m-fluorophenyl)-1- ethanol (1S,4r)-4-(2-{(S)-2- hydroxy-2-[6- (trifluoromethyl)-2- pyridyl]ethylamino}-2- +++ - methylpropyl)cyclohexyl 2-methyl-2- propanecarbamate N-[(1S,4r)-4-(2-{(S)-2- ++ - hydroxy-2-[6- (trifluoromethyl)-2- pyridyl]ethylamino}-2- methylpropyl)cyclohexyl ]acetamide (S)-2-{1,1-dimethyl-2- [(1r,4S)-4- (mesylamino)cyclohexyl + - ]ethylamino}-1-[6- (trifluoromethyl)-2- pyridyl]-1-ethanol N-[(1R,4s)-4-(2-{(S)-2- hydroxy-2-[6- (trifluoromethyl)-2- + - pyridyl]ethylamino}-2- methylpropyl)cyclohexyl ]acetamide (S)-2-{1,1-dimethyl-2- [(1s,4R)-4- (mesylamino)cyclohexyl ++ - ]ethylamino}-1-[6- (trifluoromethyl)-2- pyridyl]-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (dimethylaminosulfonyl) + + cyclohexyl]ethylamino}- 1-(m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (dimethylaminosulfonyl) ++ + cyclohexyl]ethylamino}- 1-(5-fluoro-3-pyridyl)- 1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- ++ - aminocyclohexyl]ethyla mino}-1-(5-fluoro-3- pyridyl)-1-ethanol N-[(1S,4s)-4-{2-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexy l]acetamide (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (mesylamino)cyclohexyl +++ - ]ethylamino}-1-(5- fluoro-3-pyridyl)-1- ethanol (1S,4s)-4-{2-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexy l 2-methyl-2- propanecarbamate (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (dimethylaminosulfonyl) +++ + cyclohexyl]ethylamino}- 1-(m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (dimethylaminosulfonyl) +++ ++ cyclohexyl]ethylamino}- 1-(5-fluoro-3-pyridyl)- 1-ethanol (S)-[4-({p-[(benzyl)-N- mesylamino]phenyl}me thyl)-7- + - azabicyclo[2.2.1]hept- 1-yl](m- fluorophenyl)methanol (R)-[4-({p-[(benzyl)-N- mesylamino]phenyl}me thyl)-7- + - azabicyclo[2.2.1]hept- 1-yl](m- fluorophenyl)methanol (S)-(m-fluorophenyl)(4- {[p- (mesylamino)phenyl]me ++ - thyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- {[p- (mesylamino)phenyl]me ++ - thyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (methylaminosulfonyl)c +++ + yclohexyl]ethylamino}- 1-(m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (methylaminosulfonyl)c ++ - yclohexyl]ethylamino}- 1-(m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (methylaminosulfonyl)c + - yclohexyl]ethylamino}- 1-(5-fluoro-3-pyridyl)- 1-ethanol N-[(1R,4s)-4- - - ({(2S,5R)-5-[(S)-(m- fluorophenyl)hydroxyme thyl]-2- pyrrolidinyl}methyl)cycl ohexyl]-N- benzylacetamide N-[(1R,4s)-4- ({(2S,5R)-5-[(R)-(m- fluorophenyl)hydroxyme thyl]-2- - - pyrrolidinyl}methyl)cycl ohexyl]-N- benzylacetamide N-[(1S,4r)-4-({(2S,5R)- 5-[(S)-(m- fluorophenyl)hydroxyme thyl]-2- - - pyrrolidinyl}methyl)cycl ohexyl]-N- benzylacetamide N-[(1S,4r)-4-({(2S,5R)- 5-[(R)-(m- fluorophenyl)hydroxyme thyl]-2- - - pyrrolidinyl}methyl)cycl ohexyl]-N- benzylacetamide N-[(1R,4s)-4- ({(2S,5R)-5-[(S)-(m- fluorophenyl)hydroxyme - - thyl]-2- pyrrolidinyl}methyl)cycl ohexyl]acetamide N-[(1R,4s)-4- ({(2S,5R)-5-[(R)-(m- fluorophenyl)hydroxyme ++ - thyl]-2- pyrrolidinyl}methyl)cycl ohexyl]acetamide N-[(1S,4r)-4-({(2S,5R)- 5-[(R)-(m- fluorophenyl)hydroxyme ++ - thyl]-2- pyrrolidinyl}methyl)cycl ohexyl]acetamide N-[(1S,4r)-4-({(2S,5R)- 5-[(S)-(m- fluorophenyl)hydroxyme ++ - thyl]-2- pyrrolidinyl}methyl)cycl ohexyl]acetamide (S)-(m-fluorophenyl)(4- {[(p- trifluoromethoxyphenyl) - - methoxy]methyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- {[(p- trifluoromethoxyphenyl) - - methoxy]methyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (S)-(5-fluoro-3- pyridyl)(4-{[(p- trifluoromethoxyphenyl) - - methoxy]methyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(5-fluoro-3- pyridyl)(4-{[(p- trifluoromethoxyphenyl) ++ - methoxy]methyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol N-[(1R,4r)-4-{2-[(R)-2- +++ - (m-fluorophenyl)-2- hydroxyethylamino]-2- methylpropyl}cyclohexy l]-N-methylacetamide N-[(1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- + - methylpropyl}cyclohexy l]-N-methylacetamide (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (trifluoromesylamino)cy + - clohexyl]ethylamino}-1- (m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (cyclopropylsulfonylami + - no)cyclohexyl]ethylamin o}-1-(m-fluorophenyl)- 1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (methylaminosulfonyl)c ++ - yclohexyl]ethylamino}- 1-(5-fluoro-3-pyridyl)- 1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (cyclopropylsulfonylami ++ - no)cyclohexyl]ethylamin o}-1-(m-fluorophenyl)- 1-ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (propylsulfonylamino)cy ++ - clohexyl]ethylamino}-1- (m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4-(N-mesyl-N- methylamino)cyclohexyl + - ]ethylamino}-1-(m- fluorophenyl)-1-ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4-(N-mesyl-N- methylamino)cyclohexyl + - ]ethylamino}-1-(m- fluorophenyl)-1-ethanol (S)-(m-fluorophenyl){4- [(p- trifluoromethoxyphenyl) - - methyl]-7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- [(p- trifluoromethoxyphenyl) - - methyl]-7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-[(2R,5S)-5- ({(1r,4S)-4-[(benzyl)- N- mesylamino]cyclohexyl} - - methyl)-2- pyrrolidinyl](m- fluorophenyl)methanol (S)-[(2R,5S)-5- ({(1r,4S)-4-[(benzyl)- N- mesylamino]cyclohexyl} - - methyl)-2- pyrrolidinyl](m- fluorophenyl)methanol (R)-[(2R,5S)-5- ++ - {[(1r,4S)-4- (mesylamino)cyclohexyl ]methyl}-2- pyrrolidinyl](m- fluorophenyl)methanol (S)-[(2R,5S)-5- {[(1r,4S)-4- (mesylamino)cyclohexyl - - ]methyl}-2- pyrrolidinyl](m- fluorophenyl)methanol N-[(1R,4r)-4-{2-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-2- +++ + methylpropyl}cyclohexy l]-N-methylacetamide N-[(1S,4s)-4-{2-[(R)-2- (5-fluoro-3-pyridyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexy l]-N-methylacetamide (R)-[(2R,5S)-5- ({(1s,4R)-4-[(benzyl)- N- mesylamino]cyclohexyl} - - methyl)-2- pyrrolidinyl](m- fluorophenyl)methanol (S)-[(2R,5S)-5- ({(1s,4R)-4-[(benzyl)- N- mesylamino]cyclohexyl} - - methyl)-2- pyrrolidinyl](m- fluorophenyl)methanol (R)-[(2R,5S)-5- {[(1s,4R)-4- +++ - (mesylamino)cyclohexyl ]methyl}-2- pyrrolidinyl](m- fluorophenyl)methanol (S)-[(2R,5S)-5- {[(1s,4R)-4- (mesylamino)cyclohexyl + - ]methyl}-2- pyrrolidinyl](m- fluorophenyl)methanol (S)-[4-({m-[(benzyl)-N- mesylamino]phenyl}me thyl)-7- - - azabicyclo[2.2.1]hept- 1-yl](m- fluorophenyl)methanol (R)-[4-({m-[(benzyl)-N- mesylamino]phenyl}me thyl)-7- + - azabicyclo[2.2.1]hept- 1-yl](m- fluorophenyl)methanol (S)-(m-fluorophenyl)(4- {[m- (mesylamino)phenyl]me ++ - thyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (R)-(m-fluorophenyl)(4- {[m- (mesylamino)phenyl]me ++ + thyl}-7- azabicyclo[2.2.1]hept- 1-yl)methanol (1R,4r)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexa nesulfonamide (1S,4s)-4-{2-[(R)-2- (m-fluorophenyl)-2- hydroxyethylamino]-2- + - methylpropyl}cyclohexa nesulfonamide (1R,4r)-4-{2-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-2- ++ - methylpropyl}cyclohexa nesulfonamide (1S,4s)-4-{2-[(R)-2-(5- fluoro-3-pyridyl)-2- hydroxyethylamino]-2- +++ - methylpropyl}cyclohexa nesulfonamide (R)-2-{1,1-dimethyl-2- [(1s,4S)-4-(N-mesyl-N- methylamino)cyclohexyl ++ - ]ethylamino}-1-(5- fluoro-3-pyridyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4-(N-mesyl-N- methylamino)cyclohexyl ++ - ]ethylamino}-1-(5- fluoro-3-pyridyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (trifluoromesylamino)cy +++ - clohexyl]ethylamino}-1- (5-fluoro-3-pyridyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- ++ - (propylsulfonylamino)cy clohexyl]ethylamino}-1- (5-fluoro-3-pyridyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1s,4S)-4- (ethylsulfonylamino)cycl ++ - ohexyl]ethylamino}-1- (m-fluorophenyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (ethylsulfonylamino)cycl ++ - ohexyl]ethylamino}-1- (5-fluoro-3-pyridyl)-1- ethanol (R)-2-{1,1-dimethyl-2- [(1r,4R)-4- (isobutylsulfonylamino)c ++ - yclohexyl]ethylamino}- 1-(5-fluoro-3-pyridyl)- 1-ethanol (S)-{4-[2-(p- chlorophenyl)ethyl]-7- azabicyclo[2.2.1]hept- - - 1-yl}(m- fluorophenyl)methanol (R)-{4-[2-(p- chlorophenyl)ethyl]-7- azabicyclo[2.2.1]hept- - - 1-yl}(m- fluorophenyl)methanol (S)-{4-[(E)-3-phenyl-2- propenyl]-7- azabicyclo[2.2.1]hept- + - 1-yl}(5-fluoro-3- pyridyl)methanol (R)-{4-[(E)-3-phenyl-2- propenyl]-7- +++ + azabicyclo[2.2.1]hept- 1-yl}(5-fluoro-3- pyridyl)methanol (S)-(5-fluoro-3- pyridyl){4-(3- phenylpropyl)-7- ++ - azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(5-fluoro-3- pyridyl){4-(3- phenylpropyl)-7- ++ + azabicyclo[2.2.1]hept- 1-yl}methanol (S)-{4-[(E)-3-phenyl-2- propenyl]-7- azabicyclo[2.2.1]hept- - - 1-yl}(m- fluorophenyl)methanol (R)-{4-[(E)-3-phenyl-2- propenyl]-7- azabicyclo[2.2.1]hept- +++ - 1-yl}(m- fluorophenyl)methanol (S)-(m-fluorophenyl){4- (3-phenylpropyl)-7- + - azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- (3-phenylpropyl)-7- +++ + azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(4-{[(benzyl)-N- mesylamino]methyl}-7- azabicyclo[2.2.1]hept- ++ + 1-yl)(m- fluorophenyl)methanol (S)-(4-{[(benzyl)-N- mesylamino]methyl}-7- azabicyclo[2.2.1]hept- ++ - 1-yl)(m- fluorophenyl)methanol (S)-(m-fluorophenyl){4- [2-(p- methoxyphenyl)ethyl]- - - 7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- [2-(p- methoxyphenyl)ethyl]- ++ + 7- azabicyclo[2.2.1]hept- 1-yl}methanol (S)-(5-fluoro-3- pyridyl){4-[2-(p- methoxyphenyl)ethyl]- - - 7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(5-fluoro-3- pyridyl){4-[2-(p- methoxyphenyl)ethyl]- ++ + 7- azabicyclo[2.2.1]hept- 1-yl}methanol (S)-(5-fluoro-3- pyridyl){4-[2-(p- trifluoromethoxyphenyl) - - ethyl]-7- azabicyclo[2.2.1]hept- 1-yl}methanol (S)-(m-fluorophenyl){4- [2-(p- - - trifluoromethoxyphenyl) ethyl]-7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(5-fluoro-3- pyridyl){4-[2-(p- trifluoromethoxyphenyl) 545 - - ethyl]-7- azabicyclo[2.2.1]hept- 1-yl}methanol (R)-(m-fluorophenyl){4- [2-(p- trifluoromethoxyphenyl) 546 - - ethyl]-7- azabicyclo[2.2.1]hept- 1-yl}methanol (S)-(o-fluorophenyl){4- [2-(3-pyridyl)ethyl]-7- 547 +++ - azabicyclo[2.2.1]hept- 1-yl}methanol In particular embodiments, the β2-adrenergic receptor agonist is selected from the group consisting of: 2-(butylamino)-1-(p-hydroxyphenyl)-1-ethanol; 2-(tert-butylamino)-1-(p-hydroxyphenyl)-1-ethanol; 2-[(cyclohexylmethyl)amino]-1-(p-hydroxyphenyl)-1-ethanol; (R)-2-(butylamino)-1-(p-hydroxyphenyl)-1-ethanol; 1-(m-hydroxyphenyl)-2-(1-methylbutylamino)-1-ethanol; 2-(3-cyclohexylpropylamino)-1-(p-hydroxyphenyl)-1-ethanol; (R)-2-[(R)-1-methylbutylamino]-1-(p-hydroxyphenyl)-1-ethanol; 1-(4-amino-3,5-dichlorophenyl)-2-(butylamino)-1-ethanol; 2-(3-cyclopropylpropylamino)-1-(p-hydroxyphenyl)-1-ethanol; 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(butylamino)-1-ethanol; 2-(butylamino)-1-(4-chloro-3-hydroxyphenyl)-1-ethanol; 1-(4-chloro-3-hydroxyphenyl)-2-(1-methylbutylamino)-1-ethanol; m-{(R)-[(2R,5R)-5-methyl-2-pyrrolidinyl]hydroxymethyl}phenol and m-{(S)- [(2S,5S)-5-methyl-2-pyrrolidinyl]hydroxymethyl}phenol; 1-(3-amino-2,4-difluorophenyl)-2-(butylamino)-1-ethanol; (R)-[(2R,6R)-6-propyl-2-piperidyl](m-hydroxyphenyl)methanol; (R)-2-[(R)-1-methylbutylamino]-1-(m-fluorophenyl)-1-ethanol; (R)-2-[(S)-1-methylbutylamino]-1-(m-fluorophenyl)-1-ethanol; (R)-2-(tert-butylamino)-1-(m-fluorophenyl)-1-ethanol; (R)-[(2R,5R)-5-propyl-2-pyrrolidinyl](m-fluorophenyl)methanol; (R)-2-(1,1-dimethylbutylamino)-1-(m-fluorophenyl)-1-ethanol; (R)-[(2R,6S)-6-propyl-2-piperidyl](m-hydroxyphenyl)methanol; (R)-2-(tert-butylamino)-1-(2,3-difluorophenyl)-1-ethanol; (R)-2-(butylamino)-1-(2,3-difluorophenyl)-1-ethanol; (R)-2-(tert-butylamino)-1-(o-fluorophenyl)-1-ethanol; (R)-2-(butylamino)-1-(o-fluorophenyl)-1-ethanol; (R)-1-(m-fluorophenyl)-2-(1-methylcyclopropylamino)-1-ethanol; (R)-1-(m-fluorophenyl)-2-(1-methylcyclobutylamino)-1-ethanol; (R)-2-(butylamino)-1-(4-fluoro-3-hydroxyphenyl)-1-ethanol; (R)-2-(butylamino)-1-(2-fluoro-3-hydroxyphenyl)-1-ethanol; (R)-1-(3-amino-2-fluorophenyl)-2-(tert-butylamino)-1-ethanol; 4-[(R)-2-(tert-butylamino)-1-hydroxyethyl]-1-methyl-2(1H)-pyridinone; (R)-2-(tert-butylamino)-1-(5-fluoro-3-pyridyl)-1-ethanol; 5-[(R)-2-(tert-butylamino)-1-hydroxyethyl]-3-pyridinol; (R)-[(R)-5,5-dimethyl-2-pyrrolidinyl](m-fluorophenyl)methanol; m-{(R)-[(R)-5,5-dimethyl-2-pyrrolidinyl]hydroxymethyl}phenol; (R)-[(2S,6R)-6-propyl-2-piperidyl](m-chlorophenyl)methanol; (S)-[(2S,6S)-6-propyl-2-piperidyl](m-hydroxyphenyl)methanol; 4-[2-(tert-butylamino)-1-hydroxyethyl]-3-pyridinol; (R)-[(2S,6R)-6-propyl-2-piperidyl](m-hydroxyphenyl)methanol; (R)-[(2R,5R)-5-propyl-2-pyrrolidinyl](o-chlorophenyl)methanol; (R)-1-(3-amino-2,4-difluorophenyl)-2-(tert-butylamino)-1-ethanol; (R)-2-(tert-butylamino)-1-(3-fluoro-2-tolyl)-1-ethanol; (R)-[(R)-5,5-dimethyl-2-pyrrolidinyl](o-chlorophenyl)methanol; (R)-[(R)-5,5-dimethyl-2-pyrrolidinyl](m-chlorophenyl)methanol; (R)-[(R)-5,5-dimethyl-2-pyrrolidinyl](5-fluoro-3-pyridyl)methanol; (R)-[(2R,5R)-5-propyl-2-pyrrolidinyl](5-fluoro-3-pyridyl)methanol; (S)-[(R)-6,6-dimethyl-2-piperidyl](o-chlorophenyl)methanol; (R)-[(R)-5,5-dimethyl-2-pyrrolidinyl](o-fluorophenyl)methanol; (S)-[(R)-6,6-dimethyl-2-piperidyl](o-fluorophenyl)methanol; (S)-(o-fluorophenyl)(4-methyl-7-azabicyclo[2.2.1]hept-1-yl)methanol; (R)-(o-fluorophenyl)(4-methyl-7-azabicyclo[2.2.1]hept-1-yl)methanol; (R)-(5-fluoro-3-pyridyl)(4-methyl-7-azabicyclo[2.2.1]hept-1-yl)methanol; (R)-[(S)-6,6-dimethyl-2-piperidyl](m-fluorophenyl)methanol; (R)-[(S)-6,6-dimethyl-2-piperidyl](o-fluorophenyl)methanol; (R)-(o-chlorophenyl)(4-methyl-7-azabicyclo[2.2.1]hept-1-yl)methanol; (R)-(m-chlorophenyl)(4-methyl-7-azabicyclo[2.2.1]hept-1-yl)methanol; (R)-[(R)-4,4-dimethyl-2-azetidinyl](m-fluorophenyl)methanol; (R)-[(R)-4,4-dimethyl-2-azetidinyl](o-fluorophenyl)methanol; (R)-{(R)-1-methyl-2-azabicyclo[2.1.1]hex-3-yl}(m-chlorophenyl)methanol; (S)-{(S)-1-methyl-2-azabicyclo[2.1.1]hex-3-yl}(o-fluorophenyl)methanol; (S)-{(R)-1-methyl-2-azabicyclo[2.1.1]hex-3-yl}(o-fluorophenyl)methanol; (R)-{(S)-1-methyl-2-azabicyclo[2.1.1]hex-3-yl}(o-fluorophenyl)methanol; (R)-[(R)-4,4-dimethyl-2-azetidinyl](5-fluoro-3-pyridyl)methanol; (R)-{(R)-1-methyl-2-azabicyclo[2.1.1]hex-3-yl}(5-fluoro-3-pyridyl)methanol; (R)-[(R)-5,5-dimethyl-2-pyrrolidinyl](3-amino-2-fluorophenyl)methanol; (R)-[(R)-4,4-dimethyl-2-azetidinyl](m-chlorophenyl)methanol; (R)-[(2S,7S)-7-propyl-2-azepanyl](5-fluoro-3-pyridyl)methanol; (S)-[(R)-5,5-dimethyl-2-pyrrolidinyl](4-amino-3,5-difluorophenyl)methanol; (R)-1-(5-fluoro-3-pyridyl)-2-{2-[(1s,4S)-4-methoxycyclohexyl]ethylamino}-1- ethanol; (R)-1-(m-fluorophenyl)-2-{1-methyl-1-[(1r,4R)-4-methoxycyclohexyl]ethylamino}- 1-ethanol; (R)-1-(5-fluoro-3-pyridyl)-2-{1-methyl-1-[(1r,4R)-4- methoxycyclohexyl]ethylamino}-1-ethanol; (R)-{(R)-1-methyl-2-azabicyclo[2.1.1]hex-3-yl}(3-amino-2-fluorophenyl)methanol; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-methoxycyclohexyl]ethylamino}-1-(m- fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-methoxycyclohexyl]ethylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-methoxycyclohexyl]ethylamino}-1-(m- fluorophenyl)-1-ethanol; (R)-2-{1-[(1S,3R)-3-methoxycyclohexyl]-1-methylethylamino}-1-(m-fluorophenyl)- 1-ethanol; (R)-2-{1-[(1R,3S)-3-methoxycyclohexyl]-1-methylethylamino}-1-(m-fluorophenyl)- 1-ethanol; (R)-1-(5-fluoro-3-pyridyl)-2-{3-[(1s,4R)-4-methoxycyclohexyl]propylamino}-1- ethanol; (R)-1-(5-fluoro-3-pyridyl)-2-({[(1s,4S)-4-(benzyloxy)cyclohexyl]methyl}amino)-1- ethanol; (R)-2-{1,1-dimethyl-3-[(1s,4R)-4-methoxycyclohexyl]propylamino}-1-(m- fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-3-[(1s,4R)-4-methoxycyclohexyl]propylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol; (R)-1-(m-fluorophenyl)-2-{1-methyl-1-[(1s,4S)-4- (benzyloxy)cyclohexyl]ethylamino}-1-ethanol; (R)-2-{1,1-dimethyl-3-[(1s,4R)-4-hydroxycyclohexyl]propylamino}-1-(m- fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-3-[(1s,4R)-4-hydroxycyclohexyl]propylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-hydroxycyclohexyl]ethylamino}-1-(m- fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-hydroxycyclohexyl]ethylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol; N-[(1R,4r)-4-{[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]methyl}- cyclohexyl]benzamide; (R)-2-{1,1-dimethyl-3-[(1r,4S)-4-hydroxycyclohexyl]propylamino}-1-(o- fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-3-[(1s,4R)-4-hydroxycyclohexyl]propylamino}-1-(o-fluoro- phenyl)-1-ethanol; methyl (1S,4s)-4-{2-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-2-methyl- propyl}cyclohexanecarboxylate; (S)-[(2R,5S)-5-{[(1r,4S)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl](m-fluoro- phenyl)methanol; (R)-[(2R,5S)-5-{[(1r,4S)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl](m-fluoro- phenyl)methanol; methyl (1S,4s)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methyl- propyl}cyclohexanecarboxylate; (1S,4s)-8-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-7-methoxy-p-menthan-7- one; (R)-(m-fluorophenyl){4-(methoxymethyl)-7-azabicyclo[2.2.1]hept-1-yl}methanol; (R)-[(2R,5R)-5-{[(1r,4R)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl](m-fluoro- phenyl)methanol; (R)-[(2R,5S)-5-{[(1r,4S)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl](o-fluoro- phenyl)methanol; (R)-[(2R,5R)-5-{[(1r,4R)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl](o-fluoro- phenyl)methanol; (R)-[(2R,5R)-5-{[(1r,4R)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl](5-fluoro-3- pyridyl)methanol; methyl (1R,4r)-4-{3-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-3-methyl- butyl}cyclohexanecarboxylate; N-[(1R,4r)-4-{1-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-1- methylethyl}cyclohexyl]acetamide; (1S,4s)-4-{3-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-3-methylbutyl}- cyclohexanecarboxylic acid; methyl (1S,4s)-4-{3-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-3-methyl- butyl}cyclohexanecarboxylate; methyl (1R,4r)-4-{3-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-3-methylbutyl}- cyclohexanecarboxylate; methyl (1S,4s)-4-{3-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-3-methylbutyl}- cyclohexanecarboxylate; methyl (1R,4r)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methyl- propyl}cyclohexanecarboxylate; N-[(1R,4r)-4-{2-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]acetamide; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-aminocyclohexyl]ethylamino}-1-(5-fluoro-3- pyridyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-(mesylamino)cyclohexyl]ethylamino}-1-(5-fluoro- 3-pyridyl)-1-ethanol; N-[(1R,4r)-4-{3-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-3-methylbutyl}- cyclohexyl]acetamide; (S)-[(2R,5S)-5-methyl-5-{[(1r,4S)-4-methoxycyclohexyl]methyl}-2-pyrrolidinyl]- (m-fluorophenyl)methanol; (S)-{(2R,5R)-5-[(p-methoxyphenyl)methyl]-5-methyl-2-pyrrolidinyl}(m-fluoro- phenyl)methanol; (R)-{(2R,5R)-5-[(p-methoxyphenyl)methyl]-5-methyl-2-pyrrolidinyl}((m-fluoro- phenyl)methanol; (1R,4r)-8-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-7-methoxy-p-menthan-7- one; (1R,4r)-8-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-7-methoxy-p-menthan- 7-one; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-aminocyclohexyl]ethylamino}-1-(m-fluorophenyl)- 1-ethanol; (S)-{(2R,5S)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(m-fluorophenyl)- methanol; (R)-{(2R,5S)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(m-fluorophenyl)- methanol; (R)-{(2R,5R)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(m-fluorophenyl)- methanol; (S)-{(2R,5R)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(m-fluorophenyl)- methanol; (R)-2-(tert-butylamino)-1-(2-methyl-3-pyridyl)-1-ethanol; (S)-{(2R,5S)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; (R)-{(2R,5S)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; (R)-{(2R,5R)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; (S)-{(2R,5R)-5-[(p-methoxyphenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-(mesylamino)cyclohexyl]ethylamino}-1-(m-fluoro- phenyl)-1-ethanol; N-[(1R,4r)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]acetamide; N-[(1R,4r)-4-{1-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-1-methylethyl}- cyclohexyl]acetamide; 6-[(S)-2-(tert-butylamino)-1-hydroxyethyl]-2-pyridinecarbonitrile; (R)-(4-benzyl-7-azabicyclo[2.2.1]hept-1-yl)(m-fluorophenyl)methanol; (R)-{(2R,5S)-5-[(p-chlorophenyl)methyl]-2-pyrrolidinyl}(m-fluorophenyl)methanol; (R)-{(2R,5R)-5-[(p-chlorophenyl)methyl]-2-pyrrolidinyl}(m-fluorophenyl)methanol; (R)-(4-{[(p-chlorophenyl)methoxy]methyl}-7-azabicyclo[2.2.1]hept-1-yl)(m- fluorophenyl)methanol; (S)-2-(tert-butylamino)-1-[6-(trifluoromethyl)-2-pyridyl]-1-ethanol; ethyl [(1R,4r)-4-{1-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-1-methylethyl}- cyclohexyloxy]acetate; (1S,4s)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexanecarbonitrile; (R)-(m-fluorophenyl){4-[(p-methoxyphenyl)methyl]-7-azabicyclo[2.2.1]hept-1-yl}- methanol; (R)-{(2R,5S)-5-[(p-chlorophenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; (S)-{(2R,5R)-5-[(p-chlorophenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; (R)-{(2R,5R)-5-[(p-chlorophenyl)methyl]-2-pyrrolidinyl}(5-fluoro-3-pyridyl)- methanol; ethyl [(1R,4r)-4-{1-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-1-methyl- ethyl}cyclohexyloxy]acetate; (R)-(m-fluorophenyl){4-[(p-fluorophenyl)methyl]-7-azabicyclo[2.2.1]hept-1-yl}- methanol; 6-[(S)-2-{1,1-dimethyl-2-[(1r,4S)-4-aminocyclohexyl]ethylamino}-1-hydroxyethyl]- 2-pyridinecarbonitrile; N-[(1R,4s)-4-{2-[(S)-2-(6-cyano-2-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]acetamide; N-[(1S,4r)-4-{2-[(S)-2-(6-cyano-2-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]acetamide; 6-[(S)-2-{1,1-dimethyl-2-[(1r,4S)-4-(mesylamino)cyclohexyl]ethylamino}-1- hydroxyethyl]-2-pyridinecarbonitrile; N-[(1R,4r)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]2,2-dimethylpropionamide; N-[(1R,4r)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl- }cyclohexyl]trifluoroacetamide; N-[(1R,4r)-4-{2-[(R)-2-hydroxy-2-(2-methyl-3-pyridyl)ethylamino]-2-methyl- propyl}cyclohexyl]acetamide; (R)-(m-fluorophenyl)(4-{[(p-fluorophenyl)methoxy]methyl}-7-azabicyclo[2.2.1]hept- 1-yl)methanol; (S)-{4-[(p-chlorophenoxy)methyl]-7-azabicyclo[2.2.1]hept-1-yl}(m-fluorophenyl- )methanol; (R)-{4-[(p-chlorophenoxy)methyl]-7-azabicyclo[2.2.1]hept-1-yl}(m-fluorophenyl)- methanol; (R)-(4-{[(p-fluorophenyl)methoxy]methyl}-7-azabicyclo[2.2.1]hept-1-yl)(5-fluoro-3- pyridyl)methanol; (S)-(m-fluorophenyl){4-[2-(3-pyridyl)ethyl]-7-azabicyclo[2.2.1]hept-1-yl}methanol; N-[(1S,4s)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]cyclopropanecarboxamide; N-[(1S,4s)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]acetamide; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-(mesylamino)cyclohexyl]ethylamino}-1-(m-fluoro- phenyl)-1-ethanol; N-[(1S,4s)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]trifluoroacetamide; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-aminocyclohexyl]ethylamino}-1-(m-fluorophenyl)- 1-ethanol; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-(3,3-dimethylureido)cyclohexyl]ethylamino}-1- (m-fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-(trifluoromesylamino)cyclohexyl]ethylamino}-1- (m-fluorophenyl)-1-ethanol; (1S,4r)-4-(2-{(S)-2-hydroxy-2-[6-(trifluoromethyl)-2-pyridyl]ethylamino}-2-methyl- propyl)cyclohexyl 2-methyl-2-propanecarbamate; N-[(1S,4s)-4-{2-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]acetamide; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-(mesylamino)cyclohexyl]ethylamino}-1-(5-fluoro- 3-pyridyl)-1-ethanol; (1S,4s)-4-{2-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl 2-methyl-2-propanecarbamate; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-(dimethylaminosulfonyl)cyclohexyl]ethylamino}-1- (m-fluorophenyl)-1-ethanol; (R)-2-{1,1-dimethyl-2-[(1r,4R)-4-(methylaminosulfonyl)cyclohexyl]ethylamino}-1- (m-fluorophenyl)-1-ethanol; N-[(1R,4r)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]-N-methylacetamide; N-[(1R,4r)-4-{2-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexyl]-N-methylacetamide; (R)-[(2R,5S)-5-{[(1s,4R)-4-(mesylamino)cyclohexyl]methyl}-2-pyrrolidinyl]- (m-fluorophenyl)methanol; (1R,4r)-4-{2-[(R)-2-(m-fluorophenyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexanesulfonamide; (1S,4s)-4-{2-[(R)-2-(5-fluoro-3-pyridyl)-2-hydroxyethylamino]-2-methylpropyl}- cyclohexanesulfonamide; (R)-2-{1,1-dimethyl-2-[(1s,4S)-4-(trifluoromesylamino)cyclohexyl]ethylamino}-1- (5-fluoro-3-pyridyl)-1-ethanol; (R)-{4-[(E)-3-phenyl-2-propenyl]-7-azabicyclo[2.2.1]hept-1-yl}(5-fluoro-3-pyridyl)- methanol; (R)-{4-[(E)-3-phenyl-2-propenyl]-7-azabicyclo[2.2.1]hept-1-yl}(m-fluorophenyl)- methanol; (R)-(m-fluorophenyl){4-(3-phenylpropyl)-7-azabicyclo[2.2.1]hept-1-yl}methanol; and (S)-(o-fluorophenyl){4-[2-(3-pyridyl)ethyl]-7-azabicyclo[2.2.1]hept-1-yl}methanol, and pharmaceutically acceptable salts thereof. As described herein, it will also be understood that certain compounds acting as β2- adrenergic receptor agonists are able to activate the β2-adrenergic receptor without significant recruitment of β-arrestin. Thus, particular β2-adrenergic receptor agonists that may be mentioned include those able to activate the β2-adrenergic receptor without significant recruitment of β-arrestin. Further, in particular embodiments, the methods and uses as described herein may be performed without significant recruitment of β-arrestin. The skilled person will be able to determine the level of recruitment of β-arrestin provided by compounds, such as those referred to herein, using techniques known to those skilled in the art, such as those described in the examples as provided herein. Muscle wasting The skilled person will understand that compounds and pharmaceutical formulations for use, and methods of the invention, as defined herein are useful in the treatment or prophylaxis of a disease or disorder characterised by muscle wasting. The skilled person will understand that a disease or disorder characterised by muscle wasting will refer to a disease or disorder of which muscle wasting (which will include muscular atrophy, increased muscle weakness / reduced muscle strength and / or reduced muscle mass) is a significant clinical manifestation. Therapeutic agents of the invention (therapeutic agents that directly or indirectly induce muscle wasting) The skilled person will be aware of various therapeutic agents treatment with which may induce (i.e. directly or indirectly cause) muscle wasting. Such agents may include, but are not limited to, therapeutic weight loss agents, corticosteroids (e.g. glucocorticoids), statins, sulfonylureas and glinides. In particular embodiments, treatment with the therapeutic agent that induces muscle wasting (e.g. the treatment cycle referring to the use of a therapeutic agent that induces muscle wasting, e.g. the first treatment cycle or the prior treatment, as described herein) will be (or is) a long-term treatment, which may refer to a treatment period of greater than one month (e.g. greater than six weeks, greater than ten weeks, greater than three months (e.g. 12 weeks), greater than six months or greater than one year, such as greater than 3 months, greater than six months or greater than one year). In particular embodiments, the first treatment cycle or the prior treatment, as described herein is administered to the subject for a period greater than six weeks or greater than twelve weeks, such as greater than six weeks. In particular embodiments, the treatment with the β2-adrenergic receptor agonist (e.g. the second treatment cycle or the follow-on treatment, as described herein) will be (or is) a long-term treatment, which may refer to a treatment period of greater than one month (e.g. greater than six weeks, greater than ten weeks, greater than three months (e.g. 12 weeks), greater than six months or greater than one year). In particular embodiments, the second treatment cycle or the follow-on treatment, as described herein is administered to the subject for a period greater than six weeks or greater than twelve weeks, such as greater than six weeks. In more particular embodiments, both the treatment with the therapeutic agent that induces muscle wasting (e.g. the first treatment cycle or the prior treatment, as described herein) and the treatment with the β2-adrenergic receptor agonist (e.g. the second treatment cycle or the follow-on treatment, as described herein) are long-term treatments, which may independently refer to treatment periods of greater than one month (e.g. greater than six weeks, greater than ten weeks, greater than three months (e.g. 12 weeks), greater than six months or greater than one year). Thus, in even more particular embodiments, both the first treatment cycle (or prior treatment) as described herein and the second treatment cycle (or the follow-on treatment) as described herein are administered to the subject for a period greater than six weeks or greater than twelve weeks, such as greater than six weeks. In particular embodiments, the therapeutic agent of the invention (i.e. the therapeutic agent that directly or indirectly induces muscle wasting) is an incretin-mimetic. In particular embodiments, the therapeutic agent of the invention (i.e. the therapeutic agent that directly or indirectly induces muscle wasting) is a corticosteroid, such as a glucocorticoid. In particular embodiments, the therapeutic agent of the invention (i.e. the therapeutic agent that directly or indirectly induces muscle wasting) is a weight loss agent, such as a therapeutic weight loss agent. The skilled person will understand that a “therapeutic weight loss agent” is a therapeutic agent administered in weight loss treatment. Particular therapeutic weight loss agents include those described herein below. The skilled person will understand that weight loss treatments, such as those described herein, may be therapeutic (i.e. in a patient in medical need of such treatment, such as in an obese patient) or non-therapeutic (e.g. cosmetic). In some embodiments, the first treatment cycle comprises (e.g. is) weight loss treatment. In more particular embodiments, the treatment with the therapeutic agent of the invention will have weight loss as a primary purpose, which may be referred to as weight loss treatment, such as therapeutic weight loss treatment. For example, weight loss treatments may refer to those in which the weight loss is induced through reduction of caloric intake and / or increased energy expenditure (i.e. increased metabolism), which may be voluntary (i.e. resulting from the actions of the patient) or induced (i.e. the result of an intervention, such as a therapeutic intervention conducted by a clinician or other health practitioner). In certain embodiments, weight loss treatments described herein will be therapeutic. In alternative embodiments, weight loss treatments described herein will be non- therapeutic (e.g. cosmetic). Particular weight loss treatments that may be mentioned are medical weight loss treatments, which will include treatments with therapeutic agents (i.e. pharmaceutical treatments). Particular weight loss treatments that may be mentioned are medical weight loss treatments with therapeutic agents (i.e. pharmaceutical treatments). Particular weight loss treatments that may be mentioned include those in which the weight loss is induced through reduction of caloric intake and / or increase in metabolism (such that the patient will experience overall caloric deficiency). In a particular embodiment, the weight loss treatment is treatment with a therapeutic (i.e. pharmaceutical) agent, which may be referred to herein as a therapeutic weight loss agent. In particular embodiments, weight loss treatment (e.g. treatment with a therapeutic weight loss agent) will refer to: (i) the treatment or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight. Thus, in particular embodiments, the therapeutic agent of the present invention (i.e. the therapeutic agent that directly or indirectly induces muscle wasting) is an agent for: (i) the treatment and / or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight. In more particular embodiments, such weight loss treatment will refer to the treatment or prophylaxis of obesity. Therefore, the therapeutic agent of the invention may be an agent for the treatment or prophylaxis of obesity. In yet more particular embodiments, such weight loss treatment will refer to the treatment or prophylaxis of chronic obesity. Therefore, the therapeutic agent of the invention may be an agent for the treatment or prophylaxis of chronic obesity. In alternative embodiments, such weight loss treatment will refer to lowering body fat composition and / or reducing body weight. Therefore, the therapeutic agent of the invention may be an agent for lowering body fat composition and / or reducing body weight. For the avoidance of doubt, the term “obesity” as used herein will be understood by those skilled in the art to refer to a condition characterised by abnormal or excessive fat accumulation that may impair health, which conditions will be readily identified by those skilled in the art. For example, in particular embodiments obesity may be understood to be a condition characterised by abnormal or excessive fat accumulation that may impair health in which the subject (e.g. an adult subject) has a body mass index (BMI) of 30.0 or higher (e.g. 30.0 to 39.9). The skilled person will understand that the term “chronic” will take its normal meaning in the art, such as persisting for an extended time (e.g. such as a period of greater than one month, such as greater than three months, greater than six months or greater than one year). For the aviodance of doubt, references to obesity will include references to conditions referred to as “morbid” and / or “clinical” obesity. For the avoidance of doubt, references to the “lowering of body fat composition” will refer to the lowering of the amount of body fat in the patient, which may be indicated by a reduction in body fat percentage. In particular, references to the lowering of body fat composition will refer to reducing levels of body fat in the form of adipose tissue. Similarly, references to the treatment or prophylaxis of obesity may refer to the treatment or prophylaxis of obesity by reducing levels of body fat in the form of adipose tissue. In particular, references to the treatment or prophylaxis of obesity may include references to the treatment or prophylaxis of obesity by lowering body fat composition (e.g. by reducing levels of body fat in the form of adipose tissue) and / or reducing body weight. For example, references to the treatment or prophylaxis of obesity may include references to the treatment or prophylaxis of obesity by lowering body fat composition (e.g. by reducing levels of body fat in the form of adipose tissue). In particular embodiments, the patient is obese. In more particular embodiments, the patient is obese during (at least part of) the first treatment cycle, such as at the beginning of the first treatment cycle, for example at the time that the first dose of the therapeutic agent part of the first treatment cycle is administered to the patient. In particular embodiments, references to lowering body fat composition and / or reducing body weight may refer to therapeutic methods and uses in the lowering body fat composition and / or reducing body weight, such as uses and methods performed in an obese patient. In particular embodiments, references to lowering body fat composition and / or reducing body weight may refer to lowering body fat composition and / or reducing body weight in a patient (or subject) in need thereof, e.g. a patient who has an above- normal body weight or BMI (e.g. a BMI of 30 or greater, i.e. an obese patient), which may be referred to as therapeutically lowering body fat composition and / or reducing body weight. Alternatively, references to lowering body fat composition and / or reducing body weight may refer to in lowering body fat composition and / or reducing body weight in a patient (or subject) who has a normal body weight or who is overweight (in each case, with a corresponding BMI). In particular instances, such subjects (e.g. adult subjects) will be non-obese (e.g. having a BMI of less than 30.0), e.g. subjects being overweight (BMI 25.0 to 29.9) or of a healthy weight (BMI 18.5 to 24.9), which may be referred to as non-therapeutically lowering body fat composition and / or reducing body weight. As such, the skilled person will understand that such uses may be performed in patients who are not defined as being obese (e.g. in patients who are defined as being of a healthy weight or overweight but not obese). In particular embodiments, the patient (or subject) is overweight. In more particular embodiments, the patient is overweight during (at least part of) the first treatment cycle, such as at the beginning of the first treatment cycle, for example at the time that the first dose of the therapeutic agent part of the first treatment cycle is administered to the patient. For the avoidance of doubt, references to non-therapeutic uses and methods will refer to uses and methods in patients that are not directed to the treatment of a medical condition but which provide the relevant effects for other purposes, such as for cosmetic purposes. As described herein, other uses in medical treatment as described herein may be understood to be further characterised by lowering body fat composition and / or reducing body weight. For example, the treatment or prophylaxis of obesity as described herein may be achieved by lowering body fat composition and / or reducing body weight (e.g. lowering body fat composition). For the avoidance of doubt, references herein to body fat may refer in particular to body fat in the form of adipose tissue. As described herein, the weight loss treatment may comprise (or will consist of) weight loss treatment with a therapeutic agent (i.e. a pharmaceutical), which may be referred to as a therapeutic weight loss agent. As described herein, the therapeutic weight loss agent is a therapeutic agent of the invention, i.e. a therapeutic agent that directly or indirectly induces muscle wasting. For the avoidance of doubt, therapeutic weight loss agents (including therapeutic agents for the treatment or prophylaxis of obesity, and / or lowering body fat composition and / or reducing body weight) will be known to those skilled in the art and will include those having weight loss as a primary purpose (i.e. those labelled and / or marketed for the purposes of achieving such an effect). Thus, in particular embodiments, the term “therapeutic weight loss agents” will refer to therapeutic agents having weight loss as a primary purpose. In particular embodiments, the weight loss treatment will comprise (or will consist of) treatment (i.e. weight loss treatment) with one or more (e.g. one) therapeutic weight loss agent for: (i) the treatment or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight. In more particular embodiments, the weight loss treatment will comprise (or will consist of) treatment with one or more therapeutic weight loss agent for the treatment or prophylaxis of obesity. In more particular embodiments, the weight loss treatment will comprise (or will consist of) treatment with one or more therapeutic weight loss agent for the treatment or prophylaxis of chronic obesity. In alternative embodiments, the weight loss treatment will comprise treatment with one or more therapeutic weight loss agent for lowering body fat composition and / or reducing body weight. For the avoidance of doubt, the therapeutic agent may be referred to as a therapeutic weight loss agent. In particular, therapeutic weight loss agents for the treatment or prophylaxis of obesity and / or lowering body fat composition and / or reducing body weight will include those acting by inducing a reduction in caloric intake and / or an increase in metabolism. Particular therapeutic weight loss agents (e.g. therapeutic agents for the treatment or prophylaxis of obesity) that may be mentioned include GLP-1 receptor agonists. Thus, in particular embodiments, the therapeutic weight loss agent (i.e. the weight loss treatment) is a GLP-1 receptor agonist. In particular embodiments, the therapeutic weight loss agent (i.e. the weight loss treatment) is a GLP-1 receptor agonist. Therefore, in particular embodiments, the patient undergoing weight loss is undergoing weight loss as a consequence of (i.e. a result of / an effect of) treatment with a GLP-1 receptor agonist. Thus, for the avoidance of doubt, within the scope of the present invention is a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in the treatment or prophylaxis of muscular atrophy in a patient having been treated (or having undergone treatment) with a therapeutic weight loss agent (such as a GLP-1 receptor agonist). In such embodiments, the first treatment cycle comprises (e.g. is) weight loss treatment and the therapeutic agent of the first treatment cycle is a therapeutic weight loss agent (such as a GLP-1 receptor agonist). Also within the scope of the present invention is a method for the treatment or prophylaxis of muscular atrophy in a patient having been treated (or having undergone treatment) with a therapeutic weight loss agent (such as a GLP-1 receptor agonist) comprising administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to a patient in need thereof. In such embodiments, the first treatment cycle comprises (e.g. is) weight loss treatment and the therapeutic agent of the first treatment cycle is a therapeutic weight loss agent (such as a GLP-1 receptor agonist). Various GLP-1 receptor agonists will be known to those skilled in the art and will include those currently authorised for marketing in the US (i.e. by the Food and Drug Administration) and Europe (e.g. by the European Medicines Agency). Particular GLP-1 receptor agonists that may be mentioned include exenatide, exenatide extended-release, tirzepatide, liraglutide, lixisenatide, semaglutide, albiglutide and dulaglutide. In particular embodiments, the GLP-1 receptor agonist is liraglutide or semaglutide. In more particular embodiments, the GLP-1 receptor agonist is liraglutide. The skilled person will understand that GLP-1 receptor agonists, i.e. agonists of the Glucagon-like peptide 1 receptor, as well as derivatives thereof, mimic the action of Glucagon-like peptide 1. The GLP-1 receptor agonist may have affinity to the GIP receptor, i.e. the Gastric Inhibitory Polypeptide receptor, in addition to the GLP-1 receptor. Alternatively, the GLP-1 receptor agonist may be free or substantially free from affinity to the GIP receptor. The skilled person will understand that the GLP-1 receptor agonist may be a small molecule, such as danuglipron. The skilled person will understand that GLP-1 receptor agonist may be a peptide. Further, it may be provided as a liquid or suspension, in injectable form such as in a prefilled pen for injection and / or as an extended release formulation. In an example, the GLP-1 receptor agonist may be administrated subcutaneously. The GLP-1 receptor agonist may be administered once or several times daily or weekly. The following are examples of GLP-1 receptor agonists. Exenatide, which has the CAS number 141758-74-9, is a peptide sold under the trade names Byetta and Bydureon. It may be administered subcutaneously and / or in a dosage from 5 micrograms to 2 mg. Tirzepatide, which has the CAS number 2023788-19-2, is a linear polypeptide of 39 amino acids that has been chemically modified by lipidation. It is sold under the trade name Mounjaro. It may be administered subcutaneously as an injectable solution. The dosage may be from 2.5 mg / 0.5 mL to 15 mg / 0.5 mL. Liraglutide, which has the CAS number 204656-20-2, is a peptide sold under the brand names Saxenda, Victoza and Xultophy. It may be administered subcutaneously as an injectable solution. The dosage may be from 0.6 mg to 1.8 mg such as once daily for a week or more. For example, the dosage may be 0.6 mg, 1.2 mg or 1.8 such as once daily for a week or more. Lixisenatide, which has the CAS number 320367-13-3, sold under the brand names Lyxumia and Adlyxin. It may be administrated in injectable form such as subcutaneously. For example, it may be administrated once daily. The dosage may be from 10 micrograms to 20 micrograms such as once weekly. Semaglutide, which has the CAS number 910463-68-2, is a peptide sold under the brand names Ozempic, Rybelsus and Wegovy. It may be administrated in injectable form, such as subcutaneously (Ozempic and Wegovy), or orally (Rybelsus). The dosage may be from 0.25 mg to 2 mg, administered weekly. Albiglutide, which has the CAS number 782500-75-8, is a peptide sold under the trade names Eperzan and Tanzeum. It may also be referred to as GSK-716155. It may be administrated in injectable form such as subcutaneously. The dosage may be from 30 mg to 50 mg such as once weekly. Dulaglutide, which has the CAS number 923950-08-7, is a peptide sold under the brand name Trulicity among others. It may be administered in a pen for injection. For instance, it may be administered subcutaneously. The dosage of Dulaglutide may be 0.75 mg / 0.5 mL, 1.5 mg / 0.5 mL, 3 mg / 0.5 mL or 4.5 mg / 0.5 mL. In a second aspect of the invention, there is provided a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. In an alternative second aspect of the invention, there is provided a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in a follow-on treatment in a subject who has been treated with a therapeutic agent that directly or indirectly induces muscle wasting. The skilled person will understand that the terms “follow-on” and “follow-on treatment” will take their normal meanings in the art. In particular, such terms will refer to a therapy or treatment that is administered after, and to follow on from, an earlier treatment, as defined in the context. The skilled person will understand that such follow-on treatments may also be referred to as adjuvant treatments and follow-up treatments. Thus, it will be understood that a reference to a “follow-on” treatment includes a “follow-up” treatment and adjuvant therapy. As described herein, the skilled person will understand that references to a second treatment being used as a follow-on treatment in respect of a first treatment will include the first and second treatments forming part of the same therapeutic intervention, which may also be referred to as the same treatment programme or treatment protocol. Thus, the skilled person will understand that “follow-on” treatment refers to therapy that is provided after an initial treatment. In particular, “follow-on" treatment includes treatment for managing any side effects resulting from the initial treatment. Therefore, the “second treatment cycle” of the first aspect of the invention may be considered a “follow-on” treatment to the first treatment cycle. The treatment wherein the subject has been treated with the therapeutic agent that directly or indirectly induces muscle wasting may be referred to as a “prior treatment” and may have any of the features of the “prior treatment” of the further second aspect of the invention described below and any of the features described above for the “first treatment cycle” of the first aspect of the invention. In a further alternative second aspect of the invention, there is provided a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in a method of treatment in a subject, wherein the subject has received and has discontinued a prior treatment comprising administration of a therapeutic agent that directly or indirectly induces muscle wasting. The treatment comprising administration of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, may be considered a “follow-on” treatment to the prior treatment. Therefore, the “first treatment cycle” of the first aspect may be considered the “prior treatment”. For the avoidance of doubt, the compound (β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof) for use of the second aspect of the invention as described herein (including all embodiments thereof) may have any of the particular features described for the first aspect of the invention, including all combinations thereof. In particular, the use of the compound (β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof) may have any of the features described for the “second treatment cycle” of the first aspect of the invention. The prior treatment may have any of the features described for the “first treatment cycle” of the first aspect of the invention. In a third aspect of the invention, there is provided a therapeutic agent for use in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. In an alternative third aspect of the invention, there is provided a therapeutic agent that causes muscle wasting for use in the treatment of a disease or disorder susceptible to treatment with such a therapeutic agent, wherein the treatment further comprises a follow-on treatment comprising administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof. For the avoidance of doubt, the compound (therapeutic agent or a pharmaceutically acceptable salt thereof) for use of the third aspect of the invention as described herein (including all embodiments thereof) may have any of the particular features described for the first aspect of the invention, including all combinations thereof. For example, the therapeutic agent that causes muscle wasting may have any of the features of the “therapeutic agent that directly or indirectly induces muscle wasting” described for the first and second aspects of the invention. In particular embodiments, the therapeutic agent that directly or indirectly induces muscle wasting and the therapeutic agent that causes muscle wasting, may be a therapeutic weight loss agent (such as described in the first aspect of the invention). In some embodiments, the therapeutic weight loss agent is an agent for: (i) the treatment and / or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight. In some embodiments, the therapeutic weight loss agent is a GLP-1 agonist. In some embodiments, the GLP-1 agonist is liraglutide or semaglutide, such as liraglutide. Pharmaceutical formulations The skilled person will understand that the β2-adrenergic receptor agonist, or pharmaceutically acceptable salt thereof, may be administered in the form of a pharmaceutical formulation, which may optionally further comprise one or more pharmaceutically acceptable excipient. Suitable pharmaceutical formulations may be commercially available or otherwise are described in the literature, such as, Remington, The Science and Practice of Pharmacy, 19th ed., Mack Printing Company, Easton, Pennsylvania (1995), and Martindale – The Complete Drug Reference (35thEdition), and the documents referred to therein, the relevant disclosures in all of which documents are hereby incorporated by reference in their entirety. Otherwise, the preparation of suitable formulations, and in particular combined preparations including both a β2-adrenergic receptor agonist, or pharmaceutically acceptable salts thereof, and optionally the therapeutic weight loss agent may be achieved by the skilled person using routine techniques. References to pharmaceutically acceptable excipient(s) may be understood to include pharmaceutically acceptable, diluents, carriers and / or adjuvants, as known to those skilled in the art. In a fourth aspect of the invention, there is provided a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipient, for use in a method of treatment of a subject, wherein the treatment comprises: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. In an alternative fourth aspect of the invention, there is provided a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipient, for use in a follow-on treatment in a subject who has been treated with a therapeutic agent that directly or indirectly induces muscle wasting. In a further alternative fourth aspect of the invention, there is provided a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipient, for use in a method of treatment in a subject, wherein the subject has received and has discontinued a prior treatment comprising administration of a therapeutic agent that directly or indirectly induces muscle wasting. For the avoidance of doubt, the formulations for use of the fourth aspect of the invention as described herein (including all embodiments thereof) may have any of the particular features described for the first, second, and third aspects of the invention, including all combinations thereof. Suitable pharmaceutical formulations may be commercially available or otherwise are described in the literature, such as, Remington, The Science and Practice of Pharmacy, 19th ed., Mack Printing Company, Easton, Pennsylvania (1995), and Martindale – The Complete Drug Reference (35thEdition), and the documents referred to therein, the relevant disclosures in all of which documents are hereby incorporated by reference in their entirety. Otherwise, the preparation of suitable formulations, and in particular combined preparations including both a β2-adrenergic receptor agonist, or pharmaceutically acceptable salts thereof, and optionally the therapeutic weight loss agent may be achieved by the skilled person using routine techniques. References to pharmaceutically acceptable excipient(s) may be understood to include pharmaceutically acceptable, diluents, carriers and / or adjuvants, as known to those skilled in the art. The skilled person will understand that the therapeutic agent of the invention, or pharmaceutically acceptable salt thereof, may be administered in the form of a pharmaceutical formulation, which may optionally further comprise one or more pharmaceutically acceptable excipient. In a fifth aspect of the invention, there is provided a pharmaceutical composition comprising a therapeutic agent, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipient, for use in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. In an alternative fifth aspect of the invention, there is provided a pharmaceutical formulation comprising a therapeutic agent directly or indirectly induces muscle wasting for use in the treatment of a disease or disorder susceptible to treatment with such a therapeutic agent, wherein the treatment further comprises a follow-on treatment comprising administration of a therapeutically effective amount of a β2- adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof. For the avoidance of doubt, the formulations for use of the fifth aspect of the invention as described herein (including all embodiments thereof) may have any of the particular features described for the first, second, and third aspects of the invention, including all combinations thereof. In a more particular embodiment, the pharmaceutical formulation of the fourth and fifth aspects of the invention is for use in the treatment or prophylaxis of muscular atrophy in a patient undergoing weight loss treatment, as defined herein. In an alternative fourth and fifth aspect of the invention, there is provided a method of treatment (such as the method of treatment of the first aspect), comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical formulation of the fourth and / or fifth aspects of the invention. The skilled person will understand that such a method of treatment comprises: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a pharmaceutical formulation according to the fifth aspect of the invention, to a subject in need thereof; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a pharmaceutical formulation of the fourth aspect of the invention, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. For the avoidance of doubt, the formulations of the fourth and fifth aspects of the invention may have any of the particular features described above for the first, second, and third aspects of the invention, including all combinations thereof. Thus, in particular embodiments of the fourth and fifth aspects of the invention the therapeutic agent is a weight loss agent, such as described in the first aspect of the invention (including all embodiments and features thereof). Combinations and kits-of-parts The skilled person will understand that the present invention includes a combination (i.e. a combination product) of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and a therapeutic agent (e.g. a therapeutic weight loss agent), which may also be provided in the form of a kit-of-parts comprising the same. In a sixth aspect of the invention, there is provided a combination or kit-of-parts comprising components: (A) a pharmaceutical formulation comprising a therapeutic agent, or a pharmaceutically acceptable salt thereof, that directly or indirectly induces muscle wasting, optionally in admixture with one or more pharmaceutically acceptable excipient; and / or (B) a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, optionally in admixture with one or more pharmaceutically acceptable excipient; and instructions to use the pharmaceutical composition (A) and / or (B) (e.g. and) in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. In a particular embodiment, the combination or kit-of-parts comprises components: (B) a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, optionally in admixture with one or more pharmaceutically acceptable excipient; and instructions to use the pharmaceutical formulation (B) in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of the pharmaceutical formulation (B) to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. In particular such embodiments, the method of treatment is for treating muscle wasting. In an alternative sixth aspect of the invention, there is provided a combination or kit-of-parts comprising components: (A) a pharmaceutical formulation comprising a therapeutic agent, or a pharmaceutically acceptable salt thereof, that directly or indirectly induces muscle wasting, optionally in admixture with one or more pharmaceutically acceptable excipient; and / or (B) a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, optionally in admixture with one or more pharmaceutically acceptable excipient; and instructions to use the pharmaceutical composition (A) and / or (B) (e.g. and) in a use or treatment as described in the second or third aspects of the invention. In a particular embodiment, the combination or kit-of-parts comprises components: (B) a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, optionally in admixture with one or more pharmaceutically acceptable excipient; and instructions to use the pharmaceutical formulation (B) in a use or treatment as described in the second or third aspects of the invention. In particular such embodiments, the use or treatment is for treating muscle wasting. In a particular embodiment, the combination or kit-of-parts of the sixth aspect is for use in the treatment or prophylaxis of muscular atrophy in a patient undergoing weight loss. In a particular embodiment, the combination or kit-of-parts of the sixth aspect is for use in the treatment or prophylaxis of muscular atrophy in a patient who has undergone weight loss (e.g. weight loss treatment). In a particular embodiment, there is provided a method for the treatment or prophylaxis of muscular atrophy in a patient who has undergone weight loss comprising administering to a patient in need thereof a therapeutically effective amount of the combination or kit-of-parts. In a particular embodiment, the kit-of-parts of the sixth aspect of the invention further comprises instructions to use each component in conjunction with the other in the treatment or prophylaxis of muscular atrophy in a patient who has undergone weight loss treatment. For the avoidance of doubt, combination and kit-of-parts of the sixth aspect of the invention may have any of the particular features described above for the first, second, third, fourth, and fifth aspects of the invention, including all combinations thereof. In certain embodiments, the combination and kits-of-parts described herein may comprise more than one formulation including an appropriate quantity / dose of a β2- adrenergic receptor agonist, or pharmaceutically acceptable salt and / or pro drug thereof, and / or more than one formulation including an appropriate quantity / dose of a therapeutic weight loss agent, in order to provide for repeat dosing. If more than one formulation (comprising either active compound) is present, such formulations may be the same, or may be different in terms of the dose of either compound, chemical composition(s) and / or physical form(s). The skilled person will understand that, in relation to the treatments, formulations, combinations and kits-of-parts as described herein, references to treatment with or administration of each component will refer to said component being administered in conjunction with the other. Use in manufacture In a further aspect (i.e. seventh aspect) of the invention, there is provided the use of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. For the avoidance of doubt, the use of the seventh aspect of the invention may have any of the particular features described above for the first, second, third, fourth, fifth, and sixth aspects of the invention (including combinations thereof). In a further aspect (i.e. eight aspect) there is provided the use of a therapeutic agent, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention. For the avoidance of doubt, the use of eighth aspect of the invention may have any of the particular features described above for the first, second, third, fourth, fifth, and sixth previous aspects of the invention (including combinations thereof). Other medical uses The skilled person will understand that formulations, combinations and kits-of-parts comprising therapeutic weight loss agents, as described herein, may also be used in the treatment of disorders such as obesity and the reduction of body weight, which will be particularly suitable for use in patients having or at risk of developing muscular atrophy, as defined herein. Thus, in alternative embodiments of the first, second, third, fourth, fifth, and sixth aspects of the invention, the therapeutic agent of the invention, pharmaceutical formulation, combination or kit-of-parts is for: (i) the treatment and / or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight. In further alternative embodiments of the first, second, third, fourth, fifth, and sixth aspects of the invention, there is provided a method for: (i) the treatment and / or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight, comprising administering to a patient in need thereof a therapeutically effective amount of the therapeutic agent of the invention, pharmaceutical formulation, combination or kit-of-parts. As described herein, certain therapeutic weight loss agents will induce weight loss (and muscle loss) as a secondary effect and will have a primary effect in the treatment of another disease or disorder, such as diabetes. Thus, in further alternative embodiments of the first, second, third, fourth, fifth, and sixth aspects of the invention, where the therapeutic weight loss agent is a therapeutic agent for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes), the therapeutic agent for use, pharmaceutical formulation, combination or kit-of-parts is for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes). In particular such embodiments, the first treatment cycle or the prior treatment, as appropriate, is for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes). In further alternative embodiments of the first, second, third, fourth, fifth, and sixth aspects of the invention, where the therapeutic weight loss agent is a therapeutic agent for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes), there is provided a method for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes), comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical formulation, combination or kit-of-parts. In particular such embodiments, the first treatment cycle or the prior treatment, as appropriate, represents a method for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes). For the avoidance of doubt, all embodiments and features of the first, second, third, fourth, fifth, and sixth aspects of the invention will apply to the corresponding alternatives. Thus, in a particular embodiment, the therapeutic weight loss agent is a GLP-1 receptor agonist (which may be understood to also be a therapeutic agent for the treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes)). In a more particular embodiment, the therapeutic weight loss agent is liraglutide. Moreover, a particular β2-adrenergic receptor agonist that may be mentioned is the following compound: and pharmaceutically acceptable salts thereof. A further β2-adrenergic receptor agonist that may be mentioned is the following compound: and pharmaceutically acceptable salts thereof. A further β2-adrenergic receptor agonist that may be mentioned is the following compound: and pharmaceutically acceptable salts thereof. In particular embodiments, the - treatment and / or prophylaxis of obesity, and / or lowering body fat composition and / or reducing body weight, or - treatment of type 1 or type 2 diabetes (e.g. type 2 diabetes) is in a patient having (i.e. experiencing, such as having been diagnosed with) or at risk of developing muscular atrophy. In particular embodiments, the treatment and / or prophylaxis of obesity, and / or lowering body fat composition and / or reducing body weight, is the treatment of obesity. Other uses (non-therapeutic) In a further aspect of the invention there is provided the non-therapeutic (i.e. cosmetic) use of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, in a subject who has been treated with a therapeutic agent that directly or indirectly induces muscle wasting. The treatment with the therapeutic agent that directly or indirectly induces muscle wasting may have any of the particular features of the first to sixth aspects of the invention, including all combinations thereof. For example, the treatment may have any of the features of the “first treatment cycle” of the first aspect of the invention. In some embodiments, the use is for increasing the muscle mass in a subject. In a further aspect of the invention there is provided the non-therapeutic (i.e. cosmetic) use of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, in a subject, wherein the subject has received and has discontinued a prior treatment comprising administration of a therapeutic agent that directly or indirectly induces muscle wasting. The prior treatment may have any of the particular features of the first to sixth aspects of the invention, including all combinations thereof. For example, the prior treatment may have any of the features of the “first treatment cycle” of the first aspect of the invention. In some embodiments, the use is for increasing the muscle mass in the subject. Methods of administration The skilled person will understand that compounds and pharmaceutical formulations as defined herein will normally be administered orally, intravenously, subcutaneously, buccally, rectally, dermally, transdermally, nasally, tracheally, bronchially, sublingually, intranasally, topically, by any other parenteral route or via inhalation, in a pharmaceutically acceptable dosage form. Pharmaceutical formulations as described herein will include compositions in the form of tablets, capsules or elixirs for oral administration, suppositories for rectal administration, sterile solutions or suspensions for parenteral or intramuscular administration, and the like. In particular embodiments, compounds and pharmaceutical formulations as described herein are administered orally. As such, in certain embodiments pharmaceutical formulations as described herein may be described as oral pharmaceutical formulations. Thus, in particular embodiments, the pharmaceutical formulation(s) is / are provided in a pharmaceutically acceptable dosage form, including tablets or capsules, liquid forms to be taken orally or by injection, suppositories, creams, gels, foams, transdermal patches, plasters, inhalants (e.g. to be applied intranasally). For the avoidance of doubt, in such embodiments, compounds of the invention may be present as a solid (e.g. a solid dispersion), liquid (e.g. in solution) or in other forms, such as in the form of micelles. In more particular embodiments, the pharmaceutical formulation(s) is / are provided in a pharmaceutically acceptable oral dosage form, including tablets or capsules, which forms may be prepared using techniques known to those skilled in the art. For example, in the preparation of pharmaceutical formulations for oral administration, the compound may be mixed with solid, powdered ingredients such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin, or another suitable ingredient, as well as with disintegrating agents and lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylene glycol waxes. The mixture may then be processed into granules or compressed into tablets. Soft gelatin capsules may be prepared with capsules containing one or more active compounds (e.g. compounds of the first and, therefore, second to fifth aspects of the invention, and optionally additional therapeutic agents), together with, for example, vegetable oil, fat, or other suitable vehicle for soft gelatin capsules. Similarly, hard gelatine capsules may contain such compound(s) in combination with solid powdered ingredients such as lactose, saccharose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives or gelatin. Dosage units for rectal administration may be prepared (i) in the form of suppositories which contain the compound(s) mixed with a neutral fat base; (ii) in the form of a gelatin rectal capsule which contains the active substance in a mixture with a vegetable oil, paraffin oil, or other suitable vehicle for gelatin rectal capsules; (iii) in the form of a ready-made micro enema; or (iv) in the form of a dry micro enema formulation to be reconstituted in a suitable solvent just prior to administration. Liquid preparations for oral administration may be prepared in the form of syrups or suspensions, e.g. solutions or suspensions, containing the compound(s) and the remainder of the formulation consisting of sugar or sugar alcohols, and a mixture of ethanol, water, glycerol, propylene glycol and polyethylene glycol. If desired, such liquid preparations may contain colouring agents, flavouring agents, saccharine and carboxymethyl cellulose or other thickening agent. Liquid preparations for oral administration may also be prepared in the form of a dry powder to be reconstituted with a suitable solvent prior to use. Solutions for parenteral administration may be prepared as a solution of the compound(s) in a pharmaceutically acceptable solvent. These solutions may also contain stabilizing ingredients and / or buffering ingredients and are dispensed into unit doses in the form of ampoules or vials. Solutions for parenteral administration may also be prepared as a dry preparation to be reconstituted with a suitable solvent extemporaneously before use. The skilled person will understand that the compounds described herein, and formulations and kits-of parts comprising the same, may be administered (for example, as formulations as described hereinabove) at varying doses, with suitable doses being readily determined by one of skill in the art. In any event, the skilled person (e.g. the physician) will be able to determine the actual dosage which will be most suitable for an individual patient, which is likely to vary with the route of administration, the type and severity of the condition that is to be treated, as well as the species, age, weight, sex, renal function, hepatic function and response of the particular patient to be treated. The above-mentioned dosages are exemplary of the average case; however, there can, of course, be individual instances where higher or lower dosage ranges are merited, and such are included within the scope of this invention. For example, suitable doses of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, may include those discussed in the above-mentioned publications, as incorporated herein by reference. Similarly, suitable doses of therapeutic agents (e.g. therapeutic weight loss agents) may include those described herein and those known to those skilled in the art (including those indicated in relevant drug formularies, such as the British National Formulary 85thEdition, the contents of which are incorporated herein by reference). As described herein above, the skilled person will understand that the treatments (and methods of prophylaxis) as described here may further comprise (i.e. be combined with) additional (i.e. other) treatment(s) for the same condition. In particular, treatments (and methods of prophylaxis) described herein may be combined with other means for the treatment of excess body weight or a disoder characterized by excess body weight (as defined herein, such as obesity), such as treatment with one or more other therapeutic agent that is useful in the treatment of excess body weight or a disorder characterized by excess body weight (as defined herein, such as obesity). Similarly, treatments (and methods of prophylaxis) described herein may be combined with other means for the treatment or prophylaxis of muscular atrophy. Such agents will be readily identified by those skilled in the art and include, in particular, such therapeutic agents that are commercially available (e.g. agents that the subject of a marketing authorization in one or more territory, such as a European or US marketing authorization). The skilled person will understand that in certain embodiments the present invention (i.e. the pharmaceutical formulations, combinations, kits-of-parts, compounds for use, uses and methods of treatment as described herein, including all embodiments and particular features thereof) relates to two components, namely a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and a therapeutic agent which causes (e.g. directly or indirectly induces) muscle wasting being administered in conjunction with each other. References to each component being administered in conjunction with the other will include the components being administered, sequentially, or separately, as part of a medical intervention directed towards treatment of the relevant condition(s) (e.g. weight loss and treatment of muscle wasting). The skilled person will understand that references to the components (i.e. the β2- adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and the therapeutic weight loss agent) being administered sequentially (and, therefore, separately) will include that individual doses of each component are administered (i.e. taken by the patient, such as being taken orally) as part of separate treatment cycles, such as at least within 48 hours (e.g. within 24 hours, 12 hours, 6 hours, 3 hours, 2 hours, 1 hour, 45 minutes, 30 minutes, 20 minutes or 10 minutes) of each other. In a particular embodiment, the components are administered (i.e. taken by the patient, such as being taken orally) sequentially (and, therefore, as separate doses). For example, in a particular embodiment, the components are administered sequentially at least 2 hours apart (i.e. the interval between the administration of each component to the patient, e.g. orally, is at least 4 hours), such as between 2 hours and 48 hours apart, or between 2 hours and 24 hours apart, or between 2 hours and 12 hours apart. The skilled person will understand that the interval between the administration of each component to the patient may refer to the interval between two separate treatment cycles, such as the first and second treatment cycles. For the avoidance of doubt, references to the components as the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and the therapeutic agent of the invention (i.e. the therapeutic agent that directly or indirectly causes muscle wasting) will include references to the respective components (A) and (B) of the sixth aspect of the invention (i.e. the respective components (A) and (B) of the combination or kit-of-parts of the sixth aspect of the invention). Methods of preparation of formulations and kits-of-parts Pharmaceutical formulations as described herein may be prepared in accordance with standard and / or accepted pharmaceutical practice. Thus, in a further aspect of the invention there is provided a process for the preparation of a pharmaceutical composition / formulation, as hereinbefore defined, which process comprises bringing into association a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, with one or more pharmaceutically- acceptable excipients (e.g. an adjuvant, diluent and / or carrier). In some embodiments, the process comprises bringing into association a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and a therapeutic weight loss agent, with one or more pharmaceutically-acceptable excipients (e.g. an adjuvant, diluent and / or carrier). There is further provided a method of preparing a kit-of-parts as defined hereinbefore, which method comprises bringing component (A) into association with component (B), thus rendering the two components suitable for administration in conjunction with each other. As such, references to bringing into association will mean that the two components are rendered suitable for administration in conjunction with each other. Thus, in relation to the process for the preparation of a kit-of-parts as hereinbefore defined, by bringing the two components “into association with” each other, it is contemplated that the two components of the kit of parts may be: (i) provided as separate formulations (i.e. independently of one another), which are subsequently brought together for use in conjunction with each other in combination therapy; or (ii) packaged and presented together as separate components of a “combination pack” for use in conjunction with each other in combination therapy (i.e. in the same therapeutic intervention). The skilled person will understand that the uses of compounds and pharmaceutical formulations as described herein, and methods relating to the same, may have the advantage that, in the treatment of the conditions mentioned hereinbefore, they may be more convenient for the physician and / or patient than, be more efficacious than, be less toxic than, have a broader range of activity than, be more potent than, produce fewer side effects than, or may have other useful pharmacological properties over, similar methods (treatments) known in the prior art whether for use in the above- stated indications or otherwise. In particular, such pharmaceutical formulations, kits of parts, methods and uses may have the advantage that they are more efficacious and / or exhibit advantageous properties in vivo. Without wishing to be bound by theory, it is believed that β2-adrenergic receptor agonists as described herein may provide potent in vivo effects allowing for effective treatment of muscular wasting, in a follow-on treatment to an initial treatment with a therapeutic agent that caused muscle wasting in the patient. In particular, such effects may be even more effectively delivered by compounds that activate the β2-adrenergic receptor without significantly increasing cAMP, such as compounds A, B and C, thus allowing for treatment without significant levels of adverse events resulting from increased cAMP. Further, such effects may be delivered by compounds that do not induce significant recruitment of beta-arrestin, thus preventing β2-AR internalization and resulting desensitization. Further, an increase in skeletal muscle mass without a detrimental increase in cardiac muscle mass may be advantageously delivered by certain compounds of the invention, such as those of Table 1, e.g. compounds A, B and C. Without wishing to be bound by theory, it is believed that the use a β2-adrenergic receptor agonist allows for the prevention and / or treatment of muscular atrophy, in particular the loss of lean muscle mass, that may arise in a patient undergoing or who has undergone weight loss treatment, such as weight loss treatment with a therapeuticweight loss agent. In particular, the use a β2-adrenergic receptor agonist allows to atleast partially reverse the muscle wasting caused by the therapeutic agent (e.g. therapeutic weight loss agent). Notably, it has been previously thought that the beneficial effect on muscle mass observed with β-agonists is mediated via a cAMP-dependent pathway. However, it has now been surprisingly found that certain β2-adrenergic receptor agonists that do not cause a significant release of cAMP are also able to deliver beneficial effects on muscle mass (such as treating muscular atrophy or preventing muscle loss). Importantly, such β2-adrenergic receptor agonists allow for treatment without significant levels of adverse events resulting from increased cAMP. Advantageously, the compounds of the invention may produce a “repartitioning effect” by inducing an increase in lean tissue and decrease in body fat. Moreover, the compounds of the invention may lead to improvements in the function and quality of the muscle tissue (such as improvements in organisation of the muscular fibres and / or reduction of fat tissue embedded in the muscle tissue). Brief Description of the Figures Figures 1a to 1c show that the glucose uptake promoted by Compounds A, B and C, respectively, is inhibited in a dose-dependent manner by the selective β2-adrenergic receptor antagonist ICI-118551. In this document, the antagonist ICI-118551 is understood to have CAS number 72795-01-8. Figures 2a to 2d show that Compounds A, B, and C give significantly less cAMP formation compared to isoprenaline, whereas all four compounds give full glucose uptake (GU). Figures 3a to 3c show that Compounds A, B, and C, respectively, recruit significantly less β-arrestin 2 compared to isoprenaline. Figure 4 shows that Compound A reverses dexamethasone induced reduction of body weight in mice. Figure 5 shows that Compound A reverses dexamethasone induced reduction of lean mass in mice. Figure 6 shows the organization of muscular fibres in a wild-type sibling control zebrafish embryo (with dystrophin protein, upper image) and dystrophin (- / -) K.O. zebrafish embryo (bottom image). Figures 7a and 7b shows the effect of increasing concentrations of salbutamol relative to control. Figures 8a and 8b shows the effect of increasing concentrations of Compound A relative to control. Figures 9a and 9b show cumulative food intake for Compounds B and C, respectively, over the period of the experiment described in Biological Examples 7 and 8. Figures 10a and 10b show the change in body weight for Compounds B and C, respectively, over the period of the experiment described in Biological Examples 7 and 8. Figures 11a and 11b show the change in fat mass for Compounds B and C, respectively, over the period of the experiment described in Biological Examples 7 and 8. Figures 12a and 12b show the change in lean mass for Compounds B and C, respectively, over the period of the experiment described in Biological Examples 7 and 8. Figure 13 shows the change in body weight for a control (saline), for liraglutide, after a switch to saline after liraglutide and after a switch to Compound B after liraglutide as described in Biological Example 9. Figure 14 shows the change in fat mass for a control (saline), for liraglutide, after a switch to saline after liraglutide and after a switch to Compound B after liraglutide as described in Biological Example 9. Figure 15 shows the change in lean mass for a control (saline), for liraglutide, after a switch to saline after liraglutide and after a switch to Compound B after liraglutide as described in Biological Example 9. Figure 16 shows the food intake for a control (saline), for liraglutide, after a switch to saline after liraglutide and after a switch to Compound B after liraglutide as described in Biological Example 9. Figure 17 shows the change in gastrocnemius muscle weight for vehicle and Compound B, as described in Biological Example 10. Figure 18 shows the change in heart weight for vehicle and Compound B, as described in Biological Example 10. Figures 19a and 19b show the effect on bodyweight for vehicle, compound C or Liraglutide following initial treatment with Liraglutide, as described in Biological Example 11. Figures 20a and 20b show the effect on fat mass for vehicle, compound C or Liraglutide following initial treatment with Liraglutide, as described in Biological Example 11. Figures 21a and 21b show the effect on lean mass for vehicle, compound C or Liraglutide following initial treatment with Liraglutide, as described in Biological Example 11. Figures 22 shows the effect on food intake for vehicle, compound C or Liraglutide following initial treatment with Liraglutide, as described in Biological Example 11. Figure 23 shows the effect on gastrocnemius and soleus muscle weight for vehicle and Compound C, as described in Biological Example 12. Figure 24 shows the effect on heart weight for vehicle and Compound C, as described in Biological Example 12. Figure 25 shows the muscle function (weight lifting) at day 12 of treatment for vehicle, liraglutide and liraglutide+Compound C, as described in Biological Example 13. Figure 26 shows body weight change during the treatment and two weeks after termination of treatment for vehicle, liraglutide and liraglutide+Compound C, as described in Biological Example 13. Figure 27 shows fat mass change during the treatment and two weeks after termination of treatment for vehicle, liraglutide and liraglutide+Compound C, as described in Biological Example 13. Figure 28 shows lean mass change during the treatment and two weeks after termination of treatment for vehicle, liraglutide and liraglutide+Compound C, as described in Biological Example 13. Examples The present invention is illustrated by way of the following examples, which are not intended to be limiting on the overall scope of the invention. For the avoidance of doubt, in the case of a discrepancy between the name of the compound and the structure drawn in this specification, the structure should prevail. The synthesis of (R)-2-(tert-butylamino)-1-(3-fluorophenyl)ethan-1-ol and biological testing thereof is described in WO 2019 / 053426 (see, e.g., Example 5 therein), the contents of which are incorporated herein by reference. The synthesis of (R)-2-(tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol dihydrochloride and biological testing thereof is described in WO 2019 / 053427 (see, e.g., Example 17 therein), the contents of which are incorporated herein by reference. The preparation of the corresponding hemi-tartrate (Compound B) is described in WO 2023 / 105035, the contents of which are incorporated herein by reference. The synthesis of (R)-2-(tert-butylamino)-1-(3-fluorophenyl)ethan-1-o and biological testing thereof is described in WO 2019 / 053426 (see, e.g., Example 31 therein), the contents of which are incorporated herein by reference. Example compounds Compound Example 1 Compound A: (R)-2-(tert-Butylamino)-1-(3-fluorophenyl)ethan-1-ol hydrochloride (a) (R)-2-Bromo-1-(3-fluorophenyl)ethan-1-ol Borane (1 M in THF, 0.68 mL, 0.68 mmol) was added dropwise to a mixture of (R)-2- methyl-CBS-oxazaborolidine (1 M in toluene, 0.85 mL, 0.85 mmol) and tetrahydrofuran (THF; 0.8 mL) at room temperature (rt). The mixture was stirred 15 min at rt and a solution of 3-fluorophenacyl bromide (185 mg, 0.85 mmol) in THF (1.9 mL) was added dropwise (0.09 mL / min). After 6 h at rt, MeOH (10 mL) was added. The mixture was stirred for 30 min and concentrated. Purification by chromatography gave the sub-title compound (150 mg, 0.68 mmol, 80 %).(b) (R)-2-(3-Fluorophenyl)oxirane K2CO3 (137 mg, 0.99 mol) was added to a mixture of (R)-2-bromo-1-(3-fluorophenyl)- ethan-1-ol ( 145 mg, 0.66 mmol) in MeOH (6.8 mL) at rt. The mixture was stirred for 30 min, filtered and concentrated. The residue was extracted with CH2Cl2. The combined extracts were concentrated to give the sub-title compound (70 mg, 0.51 mmol, 77 %), which was used in the next step without further purification.(c) (R)-2-(tert-Butylamino)-1-(3-fluorophenyl)ethan-1-ol A mixture of (R)-2-(3-fluorophenyl)oxirane (30 mg, 0.22 mmol), tert-butylamine (66 mg, 0.90 mmol) and MeOH (0.2 mL) was stirred at reflux for 16 h, cooled and concentrated and dissolved in a Et2O. Et2O / pentane (1:3) was added and the solution was kept at - 20 °C overnight. The solid formed was collected to give the title compound (25 mg, 0.12 mmol, 54 %).1H NMR (400 MHz, CDCl3): δ 7.33 – 7.26 (m, 1H), 7.14 – 7.09 (m, 2H), 6.98 – 6.93 (m, 1H), 4.57 (dd, J = 8.4, 3.6 Hz, 1H), 2.92 (dd, J = 12.0, 4.0 Hz, 1H), 2.55 (dd, J = 12.0, 8.4 Hz, 1H), 1.10 (s, 9H). The compound was used in the biological examples described herein in the form of the HCl salt thereof (obtained using standard techniques as known to those skilled in the art), referred to herein as Compound A. Compound Example 2 The following compound, which be referred to herein as Compound B, was used in the biological examples provided herein in the salt form as specified (and, in the context of which, references to Compound B will refer to that salt form). Compound B: The synthesis of Compound B is described in WO 2019 / 053427 (see Example 17 therein), the contents of which are incorporated herein by reference. Compound Example 2a Compound B: (R)-2-(tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol (a) 2-Chloro-1-(5-fluoropyridin-3-yl)ethan-1-one Isopropylmagnesium chloride (2 M in THF, 10.47 mL, 20.94 mmol) was added to a solution of LiCl (887.69 mg, 20.94 mmol) in THF (8 mL) at rt. After 15 min at rt, 3- bromo-5-fluoropyridine (3.35 g, 19.04 mmol) in THF (30 mL) was added dropwise at 0 °C. The mixture was stirred at rt for 2 h and cooled in an ice-bath. A solution of 2- chloro-N-methoxy-N-methylacetamide (2.62 g, 19.04 mmol)I in THF (30 mL) was added dropwise, and the mixture was stirred at rt for 2 h. NH4Cl (aq, 10 %) was added and the mixture was extracted with Et2O. The combined extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography to give the sub-title compound (1.52 g, 20.94 mmol, 46 %).(b) (R)-2-Chloro-1-(5-fluoropyridin-3-yl)ethan-1-one RhClCp*[(1S,2S)-p-TsNCH(C6H5)CH(C6H5)NH2] / HCl.Et3N (68.0 mg, 87.6 µmol), prepared from dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer, (1S,2S)- (+)-N-(4-toluenesulphonyl)-1,2-diphenylethylene diamine and Et3N as described in WO 2008 / 054155, was added to a mixture of 2-chloro-1-(5-fluoropyridin-3-yl)ethan- 1-one (1.52 g, 8.76 mmol) in DMF (75 mL). Formic acid / Et3N (5:2, 25 mL) was added and the mixture was stirred at rt for 15 min. H2O (60 mL) and EtOAc (60 ml) where added and the layers were separated. The aq layer was washed with EtOAc (2x60 mL) and the combined organic phases were washed with H2O, dried (Na2SO4), filtered and concentrated. The residue was purified by chromatography to give the sub-title compound (1.35 g, 7.69 mmol, 88 %, ee = 92.5 %).(c) (R)-2-(tert-Butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol tert-Butylamine (11.37 mL, 108.21 mmol) followed by NaOH (476.08 mg, 11.90 mmol) were added to a mixture of 2-chloro-1-(5-fluoropyridin-3-yl)ethan-1-one (1.90 g, 10.82 mmol) and iPrOH (1.66 mL, 21.64 mmol) at rt. The mixture was heated at 75 °C for 4 h, allowed to cool, diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The residue was dissolved in hot EtOAc and allowed to cool. Pentane was added and the mixture kept at -20 °C overnight. The solids were collected and purified by chromatography to give the title compound (1.43 g, 6.74 mmol, 62 %, ee = 98 %).1H NMR (400 MHz, CDCl3): δ 8.43 – 8.27 (m, 2H), 7.57 – 7.42 (m, 1H), 4.62 (dd, J = 8.8, 3.7 Hz, 1H), 2.94 (dd, J = 12.1, 3.8 Hz, 1H), 2.53 (dd, J = 12.1, 8.8 Hz, 1H), 1.10 (s, 9H). Compound Example 2b Compound B hemi-tartrate: (R)-2-(tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan-1- ol hemi-tartrate A solution of L-(+)-tartaric acid (6.21g, 0.5 eq) in EtOH (175 mL) was added to a solution of (R)-2-(tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol (17.57 g) in EtOH (525 mL, 30 vol) and H2O (7 mL) at rt. The mixture was refluxed until all precipitate was dissolved, then cooled. The resultant slurry was stirred at rt overnight and then at 0 to 5 °C for 2 h. The solids were collected to give the title salt of (R)-2- (tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol (19.9 g, 83%, 100.0% purity by HPLC, 99.8% e.e. by HPLC). Formation of the hemi-tartrate was confirmed by1H-NMR spectrum, which indicated an amine:acid ratio of 2:1. Compound Example 2c Compound B dihydrochloride: (R)-2-(tert-butylamino)-1-(5-fluoropyridin-3-yl)ethan- 1-ol dihydrochloride HCl (48 mmol, 2 M in Et2O, 24 mL) was added dropwise to a solution of (R)-2-(tert- butylamino)-1-(5-fluoropyridin-3-yl)ethan-1-ol (5.10 g, 24 mmol) in Et2O (90 mL) at rt. After 15 min the precipitate was collected, dried in vacuo and recrystallized from MeCN (250 mL). After having reached rt, the mixture was kept in the refrigerator for 5 h, and the solid was collected and dried in vacuo over P2O5over 5 d to give the title compound, (6.41 g, 94 %). Elemental analysis found: C, 46.45 %; H, 6.75 %; N, 9.80 %. C11H19Cl2FN2requires: C, 46.32 %; H, 6.71 %; N, 9.82 %. Compound Example 3 The following compound, which be referred to herein as Compound C, was used in the biological examples provided herein in the salt form as specified (and, in the context of which, references to Compound C will refer to that salt form). Compound Example 3a Compound C maleate: (R)-1-(3-Amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan- 1-ol maleate (a) N-(2,6-Difluoro-3-methylphenyl)acetamide The sub-title compound was prepared from 2,6-difluoro-3-methylaniline in accordance with the procedure in Example 6, Step (a) of WO 2019 / 053426.(b) 3-Acetamido-2,4-difluorobenzoic acid The sub-title compound was prepared from N-(2,6-difluoro-3-methylphenyl)acetamide in accordance with the procedure in Example 7, Step (b) of WO 2019 / 053426.(c) N-(3-(2-Chloroacetyl)-2,6-difluorophenyl)acetamide A mixture of 3-acetamido-2,4-difluorobenzoic acid (250 mg, 1.16 mmol) and SOCl2(2.6 mL) was heated at 60 °C for 4 h and allowed to cool. Toluene was added and the mixture concentrated. The procedure of adding toluene followed by concentration was repeated three times. The residue was dissolved in CH2Cl2 and trimethylsilyl diazomethane (1.16 mL, 2.32 mmol) was added dropwise at 0 °C. The mixture was allowed to come to rt over 18 h and cooled to 0 °C. HCl (4 M in dioxane, 1.45 mL, 5.81 mmol) was added dropwise. The mixture was allowed to come to rt over 1 h, diluted with EtOAc and washed with Na2CO3 (aq, sat), dried over MgSO4 and concentrated. The residue was purified by chromatography to give the sub-title compound (198 mg, 0.80 mmol, 69 %).(d) (R)-N-(3-(2-Chloro-1-hydroxyethyl)-2,6-difluorophenyl)acetamide RhClCp*[(1S,2S)-p-TsNCH(C6H5)CH(C6H5)NH2] / HCl.Et3N (5.02 mg, 0.0065 mmol), prepared from dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, (1S, 2S)- (+)-N-(4-toluenesulphonyl)-1,2-diphenylethylene diamine and Et3N as described in WO 2008 / 054155, was added to a mixture of N-(3-(2-chloroacetyl)-2,6- difluorophenyl)acetamide (160 mg, 0.65 mmol) in DMF (2.7mL). Formic acid / Et3N (5:2, 0.90 mL) was added and the mixture was stirred at rt for 20 min. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The residue was crystallized from CH2Cl2 / hexane to give the sub-title compound (101 mg, 0.41 mmol, 63 %, ee = 97 %).(e) (R)-N-(3-(2-(tert-Butylamino)-1-hydroxyethyl)-2,6-difluorophenyl)acetamide The sub-title compound was prepared from (R)-N-(3-(2-chloro-1-hydroxyethyl)-2,6- difluorophenyl)acetamide in accordance with the procedure in Example 25, Step (d) of WO 2019 / 053426.(f) (R)-1-(3-Amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-ol NaOH (aq, 10%, 0.52 mL) was added to a solution of (R)-N-(3-(2-(tert-butylamino)- 1-hydroxyethyl)-2,6-difluorophenyl)acetamide (52 mg, 0.18 mmol) in EtOH (0.52 mL) and the mixture was heated at 75 °C for 20 h. The EtOH was removed in vacuo and the residue extracted with CH2Cl2. The combined extracts were washed with water, dried over Na2SO4, filtered and concentrated to give sub-title product (44 mg, 0.18 mmol, 99% yield). 1H NMR (400 MHz, CDCl3) δ 6.91 – 6.74 (m, 2H), 4.82 (ddd, J = 8.5, 3.8, 1.0 Hz, 1H), 4.6-3.5 (br s, 1H), 3.70 (s, 2H), 2.93 (ddd, J = 11.9, 3.7, 1.0 Hz, 1H), 2.56 (ddd, J = 12.0, 8.4, 0.9 Hz, 1H), 2.1-0.6 (br s, 1H), 1.10 (s, 9H).(g) (R)-1-(3-Amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-olhydrochloride (R)-1-(3-Amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-ol (44 mg, 0.18 mmol) was dissolved in Et2O (1 mL) and HCl (2 M in Et2O, 0.13 mL, 0.27 mmol) was added. The solids were collected and dried to give the sub-title compound (32 mg, 0.11 mmol, 63% yield). 1H NMR (400 MHz, D2O): δ 7.11 – 7.01 (m, 2H), 5.29 – 5.15 (dd, J = 9.6, 3.2 Hz, 1H), 3.36 – 3.23 (m, 2H), 1.40 (s, 9H).(h) (R)-1-(3-Amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-ol maleate A solution of maleic acid (43 mg, 0.37 mmol) in iPrOH (0.4 mL) was added to a solution of (R)-1-(3-amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-ol (98 mg, 0.40 mmol, free base, prepared as in Step (f)) in iPrOH (1.5 mL) at rt. The mixture was stirred at rt for 1 h and centrifuged. The supernatant was removed and the residue was dried, crystallized from EtOAc and dried to give the title compound (71 mg, 0.20 mmol, 50 %). Formation of the maleate was confirmed by1H-NMR spectrum, which indicated an amine:acid ratio of 1:1 The compound was used in the biological examples described herein referred to herein as Compound C. Compound Example 3b Compound C hemi-succinate: (R)-1-(3-Amino-2,4-difluorophenyl)-2-(tert- butylamino)ethan-1-ol hemisuccinate A solution of succinic acid (229 mg, 1.94 mmol) in iPrOH (8 mL) was added to (R)-1- (3-amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-ol (947 mg, 3.88 mmol) dissolved in iPrOH (18 mL). The resulting solution was stirred at r.t.. A precipitate started to form and the suspension was stirred for 20 min, then heated until the solids dissolved. The flask was cooled to r.t. and placed in the freezer for 16h. The precipitate was filtered off, washed on the filter with Et2O (2x5 mL) and dried in air giving (R)-1- (3-amino-2,4-difluorophenyl)-2-(tert-butylamino)ethan-1-ol hemisuccinate as a white solid (1.01 g, 86%). m.p. 151.7 °C, [α]D20 -44.0 (c 1.0, MeOH). 1H NMR (400 MHz, MeOD) δ 7.00 – 6.79 (m, 2H), 6.25 (s, 2H), 5.26 – 5.06 (m, 1H), 3.19 (dd, J = 12.5, 2.8 Hz, 1H), 3.04 (dd, J = 12.4, 10.3 Hz, 1H), 1.39 (s, 9H) ppm. HPLC purity: 99%. Column: Apollo® C18 (4.6x150 mm, 5µm), 15 min gradient 5-95% MeCN in 0.1% H3PO4; 5 min isocratic 95% MeCN; 2 min gradient 95-5% MeCN, 3 min isocratic 5% MeCN; flow rate 1.0 mL / min; 40 °C. Sample preparation c=0.5 mg / mL 5%MeCN in 0.1%H3PO4, detection: 254 nm. Biological examples Biological example 1: Glucose uptake in the presence of a selective β2-adrenergic receptor inhibitor L6-myoblasts were grown in Dulbecco’s Modified Eagle’s Medium (DMEM) containing 1 g / L glucose supplemented with 10 % fetal bovine serum (FBS), 2 mM L-glutamine, 50 U / mL penicillin, 50 µg / mL streptomycin and 10 mM HEPES. Cells were plated at 1x 105cells per mL in 24-well plates. After reaching 90 % confluence the cells were grown in medium containing 2 % FBS for 7 days where upon cells differentiated into myotubes. The differentiated L6-myotubes were serum-starved overnight in medium containing 0.5 % fatty-acid free BSA and stimulated with the test compound at a final concentration of 1x10-5M in the presence of different concentrations of the selective β2-adrenergic receptor antagonist ICI-118551. After 1 h 40 min the cells were washed with warm, glucose free medium twice and another portion of agonist was added to the glucose free medium. After another 20 min of incubation the cells were exposed to 50 nM3H-2-deoxyglucose for 10 min before washed in ice cold glucose free medium three times and lysed in 400µL / well 0.2 M NaOH for 1 h at 60 °C. The cell lysate was mixed with 4 ml scintillation buffer (Emulsifier Safe, Perkin Elmer) and the radioactivity was detected in a β-counter (Tri-Carb 4810TR, Perkin Elmer). The results are presented in Figures 1a, 1b and 1c, which show that the glucose uptake promoted by Compounds A, B , and C , respectively, are inhibited in a dose-dependent manner by the selective β2-adrenergic receptor antagonist ICI-118551, which proves that the glucose uptake promoted by the compounds is mediated through the β2- adrenergic receptor. In this document, the antagonist ICI-118551 is understood to have CAS number 72795-01-8. Compound A was used in this example in the form of the hydrochloride salt. Compound B was used in this example in the form of the dihydrochloride (2 HCl) salt. Compound C was used as the maleate in this example. Biological example 2: Glucose uptake Differentiated L6-myotubes were serum-starved overnight in medium containing 0.5 % fatty-acid free BSA and stimulated with isoprenaline or the test compound, with a final concentration of 1x10-5M. After 1 h 40 min the cells were washed with warm glucose free medium or PBS twice and another portion of agonist was added to the glucose free medium. After 20 min the cells were exposed to 50 nM3H-2-deoxyglucose for 10 min before washed with ice cold glucose free medium or PBS three times and lysed with 0.2 M NaOH, 400µL / well, for 1 h at 60 °C. The cell lysate was mixed with 4 mL scintillation buffer (Emulsifier Safe, Perkin Elmer) and the radioactivity was detected in a β-counter (Tri-Carb 4810TR, Perkin Elmer). The results for various compounds tested are given in Table 1. Biological example 3: Measurement of intracellular cAMP levels Differentiated L6-myotubes were serum-starved overnight and stimulated with isoprenaline or the test compound with a final concentration of 1x10-5M, for 15 min in stimulation buffer (HBSS supplemented with 1 % BSA, 5 mM HEPES and 1 mM IBMX, pH 7.4). The medium was aspirated and 100 µL of 95 % EtOH was added to each well of the 24-well plate and cells were kept at -20 °C overnight. The EtOH was allowed to evaporate and 500 µL of lysis buffer (1 % BSA, 5 mM HEPES and 0.3 % Tween- 20, pH 7.4) was added to each well. The plate was kept at -80 °C for 30 min and then at -20 °C until the day of detection when the samples were thawed. Intracellular cAMP levels were detected using an alpha screen cAMP kit (6760635D from Perkin Elmer). The results are presented in Figure 2a, which shows the glucose uptake and the intracellular cAMP levels when cells are treated with isoprenaline; Figure 2b, which shows the glucose uptake and the intracellular cAMP levels when cells are treated with Compound A; Figure 2c, which shows the glucose uptake and the intracellular cAMP levels when cells are treated with Compound B; and Figure 2d, which shows the glucose uptake and the intracellular cAMP levels when cells are treated with Compound C; showing that isoprenaline and Compounds A, B and C, all give a full glucose uptake response, whereas Compounds A, B and C, in contrast to isoprenaline, only exhibits low intracellular cAMP levels. Additional results for other compounds tested are given in Table 1. Biological example 4: Measurement of β-arrestin recruitment HEK293 cells are transfected with both the β2-adrenergic receptor attached with a Large BiT SNAP-tag protein, and with β-arrestin 2 attached to a Small BiT SNAP-tag protein. When cells are stimulated and the receptor recruits β-arrestin 2, the Small- and Large-BiT proteins merge, forming a functional luciferase enzyme, that in presence of furimazine generates light. After 31 min, the light is measured with a luminescence plate reader. The results are presented in Figure 3a, which shows the difference between the β- arrestin 2 recruitment of isoprenaline and Compound A; Figure 3b, which shows the difference between the β-arrestin 2 recruitment of isoprenaline and Compound B; and Figure 3c, which shows the difference between the β-arrestin 2 recruitment of isoprenaline and Compound C, showing that, in contrast to isoprenaline, Compounds A, B and C only give minimal β-arrestin 2 recruitment. Compound B was used as the hemitartrate in this example. Compound C was used as the hydrochloride in this example. Biological example 5: Effects on body weight and lean mass when Compound A is administered to mice treated with dexamethasone 40 eight-week-old male C57Bl / 6 mice kept on standard chow diet were grouped-caged (2-3 mice per cage) at 21 °C. The mice had similar body weight and body composition and were divided into four groups (n=10) and were treated daily with subcutaneous injections for 3 weeks with either dexamethasone sodium phosphate (10 mg / kg) or Compound A (47.1 µmol / kg (corresponding to dose 10 mg / kg of the free base)), or a combination of dexamethasone and Compound A. Control mice received saline. Body weight and lean mass were measured after 6, 12 and 20 days of treatment. The results are presented in: Figure 4, which shows that mice lose weight compared to control when treated with dexamethasone and that the effect is reversed when they are treated simultaneously with Compound A; and Figure 5, which shows that mice lose lean mass compared to control when treated with dexamethasone and that the effect is reversed when they are treated simultaneously with Compound A. Biological example 6: Zebra fish model Sepje zebrafish lacks the dystrophin gene, and such as in humans, lack of dystrophin leads to a progressive disorganization of muscular fibres and subsequent loss of muscle mass. The sepje model is equivalent to the MDX mouse, which also lacks the dystrophin gene. Figure 6 shows the organization of muscular fibres in a wild-type sibling control zebrafish embryo (with dystrophin protein, upper image) and dystrophin (- / -) K.O. zebrafish embryo (bottom image), measured by birefringence microscopy. Lacking dystrophin results in poor fibre organization, and sepje often begin to die at 4- 5 days post fertilization (dpf). Wild-type or dystrophin (- / -) embryos were treated from 1 to 5 dpf with vehicle control or increasing concentrations of salbutamol or Compound A (10, 30, and 100 µM). Figure 7a shows the effect of increasing concentrations of salbutamol on birefringence relative to control. Figure 7b shows the effect of increasing concentrations of salbutamol on the organization of muscular fibres, measured by birefringence microscopy. Figure 8a shows the effect of increasing concentrations of Compound A on birefringence relative to control. Figure 8b shows the effect of increasing concentrations of Compound A on the organization of muscular fibres, measured by birefringence microscopy. Biological example 7: Combination of Compound B and liraglutide 2.5 Months old male C57Bl / 6N mice were grouped caged (4-5 mice per cage), kept at 30 °C and fed with high-fat, high-sucrose diet (45 % fat) for 5.5 months. The mice were divided into four groups (2-3 mice per cage) according to their fasting blood glucose levels, glucose tolerance, body weight, body fat and lean mass, and treated daily for 2 weeks, subcutaneously with either vehicle, liraglutide (0.1 mg / kg), Compound B (1.4 mg / kg), or a mixture of liraglutide (0.1 mg / kg) and Compound A (1.4 mg / kg). Food intake was measured twice a week; body weight, body fat and lean mass were measured weekly. The results obtained over the period of the experiment are presented as follows: Figure 9a shows cumulative food intake; Figure 10a shows the change in body weight; Figure 11a shows the change in fat mass; Figure 12a shows the change in lean mass. These data confirm that administration of liraglutide, and a combination of liraglutide and Compound B, respectively, reduced food intake as compared to the control. Further, both liraglutide, and a combination of liraglutide and Compound B, resulted in a significant reduction of body weight and fat mass. However, the change in lean mass for the combination of liraglutide and Compound B was significantly lower as compared to administration of liraglutide alone. Compound B was used as the hemitartrate salt in this example. Biological example 8: Combination of Compound C and liraglutide 2.5 Months old male C57Bl / 6N mice were grouped caged (4-5 mice per cage), kept at 30 °C and fed with high-fat, high-sucrose diet (45 % fat) for 5 months. The mice were divided into four groups (2-3 mice per cage) according to their fasting blood glucose levels, glucose tolerance, body weight, body fat and lean mass, and treated daily for 2 weeks, subcutaneously with either vehicle, liraglutide (0.1 mg / kg), Compound C (5 mg / kg), or a mixture of liraglutide (0.1 mg / kg) and Compound C (5 mg / kg). Food intake and body weight were measured every other day; body fat and lean mass were measured weekly. The results obtained over the period of the experiment are presented as follows: Figure 9b shows cumulative food intake; Figure 10b shows the change in body weight; Figure 11b shows the change in fat mass; Figure 12b shows the change in lean mass. These data confirm that administration of liraglutide, and a combination of liraglutide and Compound C, respectively, reduced food intake as compared to the control. Further, all three treatments resulted in a significant reduction of body weight and fat mass. However, the change in lean mass for the combination of liraglutide and Compound C, as well as Compound C alone, was significantly lower as compared to administration of liraglutide alone. Compound C was used as the maleate in this example. Biological example 9: Treatment with Compound B after discontinuation of treatment with liraglutide Male C57BL / 6J mice were housed at thermoneutrality (30 °C) and had free access to a high-fat, high-sucrose diet (45% kcal from fat) from the age of 3 months. After 4 months (i.e. at 7 months of age), the mice were divided into 5 groups (2-3 mice per cage) with similar average body composition (body weight, fat mass and lean mass). During the first 7 days of the experiment, mice were treated with either 0.4 mg / kg liraglutide (n = 20) or vehicle (saline, n = 10). During these 7 days, daily body weight and food intake were measured. On day 8, MRI was performed to assess body composition. On day 8, the mice that were treated with liraglutide were divided into two groups with similar average body composition. One group (n = 9) was switched to saline treatment and another group (n = 11) was switched to Compound B (hemi-tartrate) (4 mg / kg). The mice that were treated with saline during the first 7 days, proceeded to receive saline treatment. From day 8 until day 21, body weight and food intake were measured daily. MRI was performed on days 14 and 21. The results obtained over the period of the experiment are presented as follows: Figure 13 shows body weight; Figure 14 shows fat mass; Figure 15 shows lean mass; Figure 16 shows food intake. These data confirm that after liraglutide-induced loss of fat mass and lean mass likely through reduced food intake, treatment with Compound B results in similar body weight regain as saline treatment. However, compared to saline treatment, Compound B results in lower mean fat mass and higher mean lean mass. Compound B was used in this example in the form of the hemi-tartrate salt. Biological Example 10: Effects on heart and muscle weight by Compound B treatment 7 month old Goto-Kakazaki (GK) rats (a lean model of type 2 diabetes characterized by muscle atrophy) were kept on standard rodent diet and grouped-caged (2-3 rats per cage) at 21 °C. The rats had similar body weight and were divided into two groups (n=12) and compound B at a dose of 10 mg / kg / day or vehicle was administered via osmotic pumps for 8 weeks. The results obtained over the period of the experiment are presented as follows: Figure 17 shows gastrocnemius muscle weight and Figure 18 shows heart weight. Treatment with compound B led to a significant increase in skeletal muscle mass. Specifically, compound B increased gastrocnemius muscle weight by 30% compared to control rats. Importantly, this increase was selective to skeletal muscle, as heart weight remained unaffected by the treatment. Treatment with Compound B thus only affects skeletal muscle, but not cardiac muscle. Compound B was used in this example in the form of the hemi-tartrate salt. Biological example 11: Treatment with Compound C after discontinuation of treatment with liraglutide Male C57BL / 6J mice were housed at thermoneutrality (30 °C) and had free access to a high-fat, high-sucrose diet (45% kcal from fat) from the age of 3 months. At 9.5 months of age the mice were divided into 6 groups (2-3 mice per cage) with similar average body composition (body weight, fat mass and lean mass). During the first 8 days of the experiment, mice were treated with either 0.4 mg / kg liraglutide (n = 20), 30 mg / kg Compound C (n=8), liraglutide in combination with Compound C (n=8) or vehicle (saline, n = 8). Body weight and food intake were measured on day 1, 2, 5 and 8. On day 8, MRI was performed to assess body composition. On day 8, the mice that were treated with liraglutide were divided into three groups with similar average body composition. One group (n = 6) was switched to saline treatment. One group (n = 7) was switched to Compound C (30 mg / kg), and one group (n=7) continued with liraglutide treatment. Body weight and food intake were measured on days 12, 15, 19 and 22. MRI was performed on day 22. The results obtained over the period of the experiment are presented as follows: Figure 19a and 19b shows body weight (a) and body weight change (b); Figure 20a and 20b shows fat mass (a) and fat mass change (b); Figure 21 shows lean mass (a) and lean mass change (b); Figure 22 shows food intake. These data confirm that after liraglutide-induced loss of fat mass and lean mass likely through reduced food intake, treatment with Compound C results in similar body weight regain as saline treatment. However, compared to saline treatment, Compound C results in lower mean fat mass and higher mean lean mass. Compound C was used in this example in the form of the hemi-succinate. Biological Example 12: Effects on heart and muscle weight by Compound C treatment Male C57BL / 6J mice were housed at thermoneutrality (30 °C) and had free access to a high-fat, high-sucrose diet (45% kcal from fat) from the age of 3 months. After 5 months (i.e. at 8 months of age), the mice were divided into 4 groups (2-3 mice per cage) with similar average body composition (body weight, fat mass and lean mass). Mice were treated with Compound C at doses 3 mg / kg (n=11), 10 mg / kg (n=11), 30 mg / kg(n=10) and vehicle (saline, n=11), for 47 days. The results obtained over the period of the experiment are presented as follows: Figure 23 shows gastrocnemius + soleus muscle weight and Figure 24 shows heart weight. Treatment with compound C, (all doses) led to a significant increase in mass of gastrocnemius and soleus muscle. Importantly, this increase was selective to skeletal muscle, as heart weight remained unaffected by the treatment. Treatment with Compound C thus only affects skeletal muscle, but not cardiac muscle. Compound C was used in this example in the form of maleic acid salt. Biological Example 13: Treatment with Compound C in combination with liraglutide, effects on muscle function. Male C57BL / 6J mice were housed at thermoneutrality (30 °C) and had free access to a high-fat, high-sucrose diet (45% kcal from fat) from the age of 3 months. After 6 months (i.e. at 9 months of age), the mice were transferred to room temperature (21 °C). After assessments of body composition, mice were divided into 3 groups (single caged). Mice were treated with daily subcutaneous injections with either vehicle (saline, n=6), 0.4 mg / kg liraglutide (n=7) or 0.4 mg / kg liraglutide + 30 mg / kg Compound C (n=7) Muscle function was assessed on day 12 of treatment through a weightlifting experiment. Mice were held by the base of the tail and were allowed to grab different weights, starting from light and increasing in weight (18.5; 28.3; 38.6, 46.2 and 58 g). If a mouse grabbed a weight and held it for 3 seconds, the next weight was introduced, and so on. Mouse was allowed to have 3 attempts before concluding that mouse was not able to hold the weight and the measurement was finished. If mouse was able to hold the weight for less than 3 seconds, it was noted and used in the calculation. Mouse was allowed to rest for 5-10 seconds between attempts. In the end, muscle strength was calculated as sum of each weight multiplied by time it was held (1-3 seconds), for example: 18.5*3 + 28.3*3 + 38.6*1. Body composition was assessed by MRI on days 7, 14 and 21 of treatment, and two weeks after discontinuation of all treatments. The results obtained over the period of the experiment are presented as follows: Figure 25 shows muscle function at day 12; figure 26 shows body weight change during the treatment and two weeks after termination of treatment; figure 27 shows fat mass change during the treatment and two weeks after termination of treatment; figure 28 shows lean mass change during the treatment and two weeks after termination of treatment. The results obtained show that treatment with liraglutide and Compound C combined is increasing muscle function in mice. The result also shows that combination treatment with liraglutide and Compound C is maintaining lean mass compared to treatment with liraglutide alone, and that this maintenance is preserved even 14 days after treatment discontinuation. Compound C was used in this example in the form of the hemi-succinate.

Claims

Claims 1. A method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

2. A β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

3. A β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in a follow-on treatment in a subject who has been treated with a therapeutic agent that directly or indirectly induces muscle wasting.

4. A β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, for use in a method of treatment in a subject, wherein the subject has received andhas discontinued a prior treatment comprising administration of a therapeutic agent that directly or indirectly induces muscle wasting.

5. A pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipient, for use in a method of treatment of a subject, wherein the treatment comprises: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

6. The use of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

7. A therapeutic agent for use in a method of treatment comprising:(i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

8. A therapeutic agent that causes muscle wasting for use in the treatment of a disease or disorder susceptible to treatment with such a therapeutic agent, wherein the treatment further comprises a follow-on treatment comprising administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a therapeutic agent, or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipient, for use in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

10. The use of a therapeutic agent, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in a method of treatment comprising:(i) a first treatment cycle comprising administration of a therapeutically effective amount of a therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject, wherein the first and second treatment cycles are within the same therapeutic intervention.

11. A combination or kit-of-parts comprising components: (A) a pharmaceutical formulation comprising a therapeutic agent, or a pharmaceutically acceptable salt thereof, that directly or indirectly induces muscle wasting, optionally in admixture with one or more pharmaceutically acceptable excipient; and / or (B) a pharmaceutical formulation comprising a β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, optionally in admixture with one or more pharmaceutically acceptable excipient; and instructions to use the pharmaceutical composition (A) and / or (B) in a method of treatment comprising: (i) a first treatment cycle comprising administration of a therapeutically effective amount of the therapeutic agent, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the therapeutic agent directly or indirectly induces muscle wasting; and (ii) a second treatment cycle following the discontinuation of the first treatment cycle, wherein the second treatment cycle comprises administration of a therapeutically effective amount of the β2-adrenergic receptor agonist, or a pharmaceutically acceptable salt thereof, to the subject,wherein the first and second treatment cycles are within the same therapeutic intervention.

12. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the first dose of the β2-adrenergic receptor agonist of the second treatment cycle is administered to the subject at least 24 hours after the discontinuation of the first treatment cycle and / or at most 3 months after the discontinuation of the first treatment cycle.

13. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein (a) the first treatment cycle or the prior treatment is administered to the patient for a period greater than six weeks, such as greater than ten weeks, greater than three months, greater than six months or greater than one year; and / or (e.g. and) (b) the second treatment cycle or the follow-on treatment is administered to the patient for a period greater than six weeks, such as greater than ten weeks, greater than three months, greater than six months or greater than one year.

14. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the method of treatment is for the treatment of muscle wasting.

15. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the second treatment cycle or the follow-on treatment is for the treatment of muscle wasting.

16. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the treatment of muscle wasting is treatment of loss of lean mass.

17. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the subject has been identified as likely to benefit from the treatment comprising the β2-adrenergic receptor agonist, or the pharmaceutically acceptable salt thereof, based on the severity of the muscle wasting caused by the therapeutic agent that directly or indirectly induces muscle wasting.

18. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the second treatment cycle or the follow-on treatment is for at least partially reversing the muscle wasting caused by the therapeutic agent.

19. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use,pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the therapeutic agent that directly or indirectly induces muscle wasting or the therapeutic agent that causes muscle wasting is a therapeutic weight loss agent.

20. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts of Claim 19, wherein the therapeutic weight loss agent is an agent for: (i) the treatment and / or prophylaxis of obesity; and / or (ii) lowering body fat composition and / or reducing body weight.

21. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to Claim 19 or 20, wherein the therapeutic weight loss agent is a GLP-1 agonist.

22. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to Claim 21, wherein the GLP-1 agonist is liraglutide or semaglutide, such as liraglutide.

23. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of the preceding claims, wherein the β2-adrenergic receptor agonist is a compound of Table 1.

24. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of Claims 1 to 23, wherein the β2-adrenergic receptor agonist is:.

25. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of Claims 1 to 23, wherein the β2-adrenergic receptor agonist is:.

26. The method, β2-adrenergic receptor agonist for use, therapeutic agent for use, pharmaceutical formulation for use, use, combination or kit-of-parts according to any one of Claims 1 to 23, wherein the β2-adrenergic receptor agonist is:.

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