Glucose-dependent insulinotropic polypeptide receptor antagonists and uses thereof

Abstract

Described herein are GIPR antagonists; pharmaceutical compositions containing such compounds and salts; and the use of such compounds and salts to treat or prevent, for example, obesity, weight gain, and / or T2DM.

Description

[0001] PC073085A GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE RECEPTOR ANTAGONISTS AND USES THEREOF FIELD OF THE INVENTION The present invention relates to new pharmaceutical compounds, pharmaceutical compositions containing the compounds, processes for preparing the compounds; and use of the compounds as glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonists, for example, in treating diseases, conditions or disorders modulated by GIPR in a human. BACKGROUND OF THE INVENTION Glucose-dependent insulinotropic polypeptide (GIP, formerly called gastric inhibitory polypeptide) is a 42-amino acid peptide secreted from K-cells in the small intestine (duodenum and jejunum). Human GIP is derived from the processing of proGIP, a 153-amino acid precursor encoded by a gene localized on chromosome 17 (See e.g., Inagaki et al., Mol Endocrinol 1989; 3:1014-1021; and Fehmann et al. Endocr Rev.1995; 16:390-410). GIP secretion is induced by food ingestion. GIP is a known insulinotropic factor (or “incretin”) that enhances glucose- dependent insulin secretion. GIP has additional physiological effects in multiple tissues, including the promotion of fat storage in the adipose. Intact GIP is rapidly inactivated by dipeptidyl peptidase 4 (DPPIV). The GIP receptor (GIPR) belongs to the glucagon subfamily of class B1 G protein-coupled receptors (GPCRs) characterized by an extracellular N-terminal domain, seven transmembrane domains and an intracellular C-terminus (See e.g. Zhao et al. Nat Commun.2022, 13:1057). The N-terminal extracellular domain forms the primary peptide recognition and binding site of the receptor. Upon stimulation with GIP, GIPR undergoes structural changes from inactive to active conformations, thereby triggering a Gαs-mediated increase in cAMP production. GIPR is expressed in various tissues, including the pancreas, gut, adipose tissue, vasculature, heart, and brain (see e.g. Hammoud et al. Nat Rev Endocrinol 2023; 18: 201-216). Human GIPR comprises 466 amino acids and is encoded by a gene located on chromosome 19 (see e.g. Gremlich et al., Diabetes.1995; 44:1202-8; and Volz et al., FEBS Lett. 1995, 373:23-29). Studies suggest that alternative mRNA splicing results in the production of GIPR variants with differing length (see e.g., Harada et al. Am J Physiol Endocrinol Metab.2008.294: E61–E68; and Marti-Solano et al. Nature. 2020, 587: 650–656). GIPR knockout mice are resistant to high fat diet-induced weight gain and have improved insulin sensitivity and lipid profiles (see e.g. Yamada et al. Diabetes.2006, 55:S86; and Miyawaki et al. Nature Med.2002, 8:738-742). Recent data supports that heterozygous loss of function in GIPR results in lower BMI and obesity risk in humans (see e.g. Akbari et al. Science.2021, 373: 6550). Small molecules, peptides, and monoclonal antibodies with antagonist activity at GIPR have been shown to prevent weight gain and insulin resistance in preclinical obesity models (see e.g. Nakamura et al. Diabetes Metab Syndr Obes. 2021,14:1095-1105; Yang et al. Mol Metab.2022, 66: 101638; and Killion et al. Sci. Transl. Med., 2018, 10:eaat3392). The combination of GIPR modulators with GLP-1R agonists has been associated with superior weight loss (see e.g. Lu et al. Cell Rep Med.2021, 2(5):100263). Collectively, these links to obesity and metabolic diseases suggest that GIPR inhibition is a useful approach for therapeutic intervention, both as monotherapy and in combination with other agents including GLP-1R agonists. Moreover, human epicardial adipose tissue - which plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure - has been found to express GIPR genes and proteins. See e.g. Malavazos et al., European Journal of Preventive Cardiology (2023) 00, 1-14. There continues to be a need for new or alternative GIPR antagonists, for example, for developing new and / or improved pharmaceuticals (e.g., more effective, more selective, less toxic, improved patient compliance, and / or having improved biopharmaceutical properties such as physical stability; solubility; oral bioavailability; appropriate metabolic stability; clearance; half life) to treat or prevent GIPR-related conditions, diseases, or disorders, such as those described herein. The present invention is directed to these and other important ends. SUMMARY OF THE INVENTION In one embodiment, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. In another embodiment, the present invention provides a compound that is a crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. In another embodiment, the present invention provides a compound that is a hydrate form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. In another embodiment, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt, sesquihydrate. In another embodiment, the present invention provides a compound that is Form 1 of 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, which is a sesquihydrate. In another embodiment, the present invention provides a compound that is Form 2 of 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, which is anhydrous. In another embodiment, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt. In another embodiment, the present invention provides a compound that is a crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt. In another embodiment, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-arginine salt. In another embodiment, the present invention provides a compound that is a crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-arginine salt. In another embodiment, the present invention provides a compound that is an anhydrous crystalline form (Form 1) of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D- prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-arginine salt. In another embodiment, the present invention provides a pharmaceutical composition that includes 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid lysine salt and a pharmaceutically acceptable excipient or carrier. The present invention also provides a method for treating or preventing a GIPR-related condition, disease, or disorder in a patient (e.g., a mammal or a human), which method includes administering to the patient (e.g., the mammal or human) 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. The present invention also provides 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D- prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt for use in treating or preventing a GIPR- related condition, disease, or disorder. In another embodiment, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt. In another embodiment, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-arginine salt. In another embodiment, the present invention provides a compound that is Form 1 of 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L- arginine salt, which is anhydrous. In another embodiment, the present invention provides a pharmaceutical composition that includes 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid arginine salt and a pharmaceutically acceptable excipient or carrier. In another embodiment, the present invention provides a pharmaceutical composition that includes 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid L-arginine salt and a pharmaceutically acceptable excipient or carrier. The present invention also provides a method for treating or preventing a GIPR-related condition, disease, or disorder in a patient (e.g., a mammal or a human), which method includes administering to the patient (e.g., the mammal or human) 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt. The present invention also provides 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D- prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt for use in treating or preventing a GIPR-related condition, disease, or disorder. The GIPR-related condition, disease, or disorder includes one selected from diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease, macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug). The present invention also provides a method for antagonizing a glucose-dependent insulinotropic polypeptide receptor (GIPR), which method includes contacting the GIPR with 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. BRIEF DESCRIPTION OF FIGURES FIG.1 shows an observed powder X-ray diffraction pattern (PXRD) for a sesquihydrate crystalline form (Form 1) of L-lysine salt of Compound 1 carried out on a Bruker AXS D8 Endeavor diffractometer equipped with a Cu radiation source. FIG.2 shows an illustrative single crystal structure of Form 1 of L-lysine salt of Compound 1 (sesquihydrate) according to an initial analysis. FIG.3 shows partial asymmetric unit with representative labeling scheme of single crystal structure of Form 1 of L-lysine salt of Compound 1 (sesquihydrate) according to an initial analysis. FIG.4 shows an observed differential scanning calorimetry (DSC) thermogram of an anhydrous crystalline form (Form 2) of L-lysine salt of Compound 1. FIG.5 shows an observed powder X-ray diffraction pattern for an anhydrous crystalline form (Form 2) of L-lysine salt of Compound 1 carried out on a Bruker AXS D8 Endeavor diffractometer equipped with a Cu radiation source. FIG.6 shows an observed differential scanning calorimetry (DSC) thermogram of an anhydrous crystalline form (Form 1) of L-arginine salt of Compound 1 (anhydrous). FIG.7 shows an observed powder X-ray diffraction pattern for Form 1 of L-arginine salt of Compound 1 carried out on a Bruker AXS D8 Endeavor diffractometer equipped with a Cu radiation source. FIG.8 shows an observed Raman spectrum for Form 1 of L-lysine salt of Compound 1 (sesquihydrate). FIG.9 shows a representative observed13C ssNMR spectrum for Form 1 of L-lysine salt of Compound 1 (sesquihydrate). FIG.10 shows an observed Raman spectrum for Form 2 of L-lysine salt of Compound 1. FIG.11 shows a representative observed13C ssNMR spectrum for Form 2 of L-lysine salt of Compound 1. FIG.12 shows an observed Raman spectrum for Form 1 of L-arginine salt of Compound 1. FIG.13 shows a representative observed13C ssNMR spectrum for Form 1 of L-arginine salt of Compound 1. FIG.14 shows an illustrative single crystal structure of Form 1 of L-lysine salt of Compound 1 (sesquihydrate) according to an updated analysis. FIG.15 shows partial asymmetric unit with representative labeling of single crystal structure of Form 1 of L-lysine salt of Compound 1 (sesquihydrate) according to an updated analysis. DETAILED DESCRIPTION OF THE INVENTION The present invention may be understood more readily by reference to the following detailed description of exemplary embodiments of the invention and the examples included therein. Some additional exemplary embodiments of the invention are described herein below. In a first aspect, the present invention provides a compound that is 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. In some further embodiments, the present invention provides a compound that is 4'-[(1- {[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, the chemical structure of which can be represented, for example, by the following. or Some further embodiments provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt. In some further embodiments, the present invention provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt. Some further embodiments provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt, wherein crystalline form is anhydrous. Some further embodiments provides a crystalline form of 4'-[(1- {[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, wherein crystalline form is anhydrous. Some further embodiments provides Form 2 of an anhydrous crystalline form of 4'-[(1- {[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt (“Form 2 of L-lysine salt of Compound 1”), wherein Form 2 has a powder X-ray diffraction pattern (PXRD) comprising at least one peak, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, and 10.3+ 0.2º. In some further embodiments, Form 2 has a PXRD comprising one peak, in terms of 2θ, at 4.4 + 0.2º. In some other embodiments, Form 2 has a PXRD comprising one peak, in terms of 2θ, at 8.8 + 0.2º. In some further embodiments, Form 2 has a PXRD comprising one peak, in terms of 2θ, at 10.3 + 0.2º. In some further embodiments, Form 2 has a PXRD comprising one peak, in terms of 2θ, at 5.9 + 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a powder X-ray diffraction pattern (PXRD) comprising at least one peak, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, and 10.3+ 0.2º, and another peak, in terms of 2θ, at 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, and 10.3+ 0.2º. In some further embodiments, Form 2 has a PXRD comprising two peaks, at 4.4 + 0.2º and 8.8 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising two peaks, at 4.4 + 0.2º and 10.3 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising two peaks, at 4.4 + 0.2º and 5.9 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising two peaks, at 8.8 + 0.2º + 0.2º and 10.3 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising two peaks, at 8.8 + 0.2º and 5.9 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising two peaks, at 10.3 + 0.2º and 5.9 + 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, in terms of 2θ, at 4.4 + 0.2º and 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, in terms of 2θ, at 5.9 + 0.2º and 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, 10.3+ 0.2º, and 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising at least three peaks, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, and 10.3+ 0.2º. In some further embodiments, Form 2 has a PXRD comprising three peaks, at 4.4 + 0.2º, 8.8 + 0.2º, and 10.3 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising three peaks, at 4.4 + 0.2º, 8.8 + 0.2º, and 5.9 + 0.2º. In other further embodiments, Form 2 has a PXRD comprising three peaks, at 8.8 + 0.2º, 5.9 + 0.2º, and 10.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising at least three peaks, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, 10.3+ 0.2º, and 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising four peaks, in terms of 2θ, at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, and 10.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising at least four peaks, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, 10.3+ 0.2º, and 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD comprising five peaks, in terms of 2θ, at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, 10.3+ 0.2º, and 18.3+ 0.2º. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a PXRD substantially as shown in FIG.5. In some embodiments, Form 2 of L-lysine salt of Compound 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 219.9 + 10.0 ºC. In some embodiments, Form 2 of L-lysine salt of Compound 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 219.9 + 2.0 ºC. In some further embodiments, Form 2 has differential scanning calorimetry trace comprising an endotherm having an onset at about 219.9 + 1.5 ºC. In some further embodiments, Form 2 has differential scanning calorimetry trace comprising an endotherm having an onset at about 219.9 + 1.0 ºC. In some further embodiments, Form 2 has differential scanning calorimetry trace comprising an endotherm having an onset at about 219.9 + 0.5 ºC. In some further embodiments Form 2 of L-lysine salt of Compound 1 has differential scanning calorimetry trace as FIG.4. In some embodiments, Form 2 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), selected from those at the position of 1283 ± 2 cm-1, 1606 ± 2 cm-1, and 1666 ± 2 cm-1. In some further embodiments, Form 2 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1283 ± 2 cm-1, 1606 ± 2 cm-1, and 1666 ± 2 cm-1. In some yet further embodiments, Form 2 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1283 ± 2 cm-1, 1606 ± 2 cm-1, and 1666 ± 2 cm-1. In some embodiments, Form 2 of L-lysine salt of Compound 1 has an FT-Raman spectrum substantially as FIG.10. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, selected from those at 32.2 ± 0.2 ppm, 120.9 ± 0.2 ppm, 127.3 ± 0.2 ppm, and 177.4 ± 0.2 ppm. In some further embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least two peaks, in terms of chemical shifts, selected from those at 32.2 ± 0.2 ppm, 120.9 ± 0.2 ppm, 127.3 ± 0.2 ppm, and 177.4 ± 0.2 ppm. In some further embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least three peaks, in terms of chemical shifts, selected from those at 32.2 ± 0.2 ppm, 120.9 ± 0.2 ppm, 127.3 ± 0.2 ppm, and 177.4 ± 0.2 ppm. In some further embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising peaks, in terms of chemical shifts, selected from those at 32.2 ± 0.2 ppm, 120.9 ± 0.2 ppm, 127.3 ± 0.2 ppm, and 177.4 ± 0.2 ppm. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, at 127.3 ± 0.2 ppm. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, at 32.2 ± 0.2 ppm. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, at 120.9 ± 0.2 ppm. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 127.3 ± 0.2 ppm and 32.2 ± 0.2 ppm. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising three peaks, in terms of chemical shifts, at 127.3 ± 0.2 ppm, 32.2 ± 0.2 ppm, and 120.9 ± 0.2 ppm. In some embodiments, Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum substantially as FIG.11. Some further embodiments provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt, wherein crystalline form is a solvate. Some further embodiments provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, wherein crystalline form is a solvate. Some further embodiments provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt, wherein crystalline form is a hydrate. Some further embodiments provides a crystalline form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, wherein crystalline form is a hydrate. Some further embodiments provides an amorphous form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt (including the L- lysine salt). Some further embodiments provides an amorphous form of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt. In a second aspect, the present invention provides a compound that is a hydrate of 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt In some further embodiments, the hydrate of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}- D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt is a hydrate of 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt. In a third aspect, the present invention provides a compound that is 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt, sesquihydrate. In some further embodiments, the present invention provides a compound that is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt, sesquihydrate. Some further embodiments provides Form 1 of crystalline form of sesquihydrate of 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt (“Form 1 of L-lysine salt of Compound 1”), wherein Form 1 of L-lysine salt of Compound 1 has a powder X-ray diffraction pattern (PXRD) comprising at least one peak, in terms of 2θ, selected from those at 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising one peak, in terms of 2θ, at 18.6 + 0.2º. In some other embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising one peak, in terms of 2θ, at 19.7 + 0.2º. In some further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising one peak, in terms of 2θ, at 17.9 + 0.2º. In some further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising one peak, in terms of 2θ, at 16.7 + 0.2º. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, selected from those at 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, at 18.6 + 0.2º and 19.7 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, at 18.6 + 0.2º and 17.9 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, at 18.6 + 0.2º, and 16.7 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, at 19.7 + 0.2º, and / or 17.9 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, at 16.7 + 0.2º, and 19.7 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising two peaks, at 16.7 + 0.2º, and / or 17.9 + 0.2º. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, selected from those at 7.3 + 0.2º, 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 18.6 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 19.7 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 17.9 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 16.7 + 0.2º. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising at least three peaks, in terms of 2θ, selected from those at 7.3 + 0.2º, 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 18.6 + 0.2º, and 17.9 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 18.6 + 0.2º, and 16.7 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 19.7 + 0.2º, and 17.9 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 19.7 + 0.2º, and 16.7 + 0.2º. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising at least four peaks, in terms of 2θ, selected from those at 7.3 + 0.2º, 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising four peaks, at 7.3 + 0.2º, 18.6 + 0.2º, 19.7 + 0.2º, and 17.9 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising four peaks, at 7.3 + 0.2º, 18.6 + 0.2º, 19.7 + 0.2º, and 16.7 + 0.2º. In other further embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising four peaks, at 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD comprising five peaks, in terms of 2θ, at 7.3 + 0.2º, 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a PXRD substantially as shown in FIG.1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), selected from those at the position of 1284 ± 2 cm-1, 1604± 2 cm-1, and 1636 ± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), at the position of 1284 ± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), at the position of 1604± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), at the position of 1636± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least two peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1284 ± 2 cm-1, 1604± 2 cm-1, and 1636 ± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), at the position of 1284 ± 2 cm-1and 1604± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising peaks, in terms of wavenumbers (cm-1), at the position of 1284 ± 2 cm-1, 1604± 2 cm-1, and 1636 ± 2 cm-1. In some embodiments, Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum substantially as FIG.8. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, selected from those at 24.5 ± 0.2 ppm, 47.1± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising one peak, in terms of chemical shifts, at 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising one peak, in terms of chemical shifts, at 131.3 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least two peaks, in terms of chemical shifts, selected from those at 24.5 ± 0.2 ppm, 47.1± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 131.3 ± 0.2 ppm and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 24.5 ± 0.2 ppm and 131.3 ± 0.2 ppm. In some embodiments, Form 1 of L- lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 24.5 ± 0.2 ppm and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L- lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 47.1 ± 0.2 ppm and 131.3 ± 0.2 ppm. In some embodiments, Form 1 of L- lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 47.1 ± 0.2 ppm and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least three peaks, in terms of chemical shifts, selected from those at 24.5 ± 0.2 ppm, 47.1± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising three peaks, in terms of chemical shifts, at 24.5 ± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising three peaks, in terms of chemical shifts, at 47.1± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising peaks, in terms of chemical shifts, at 24.5 ± 0.2 ppm, 47.1± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm. In some embodiments, Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum substantially as FIG.9. In a fourth aspect, the present invention provides a compound that is 4'-[(1-{[4-(Propan- 2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt, the structure of which can be presented, for example, by the following.

[0002] In some further embodiments, the present invention provides a compound that is 4'-[(1- {[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-arginine salt. In some further embodiments, the present invention provides a compound that is a crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid L-arginine salt. In some further embodiments, the present invention provides Form I of an anhydrous crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid L-arginine salt (“Form 1 of L-arginine salt of Compound 1”), wherein Form 1 has a powder X-ray diffraction pattern (PXRD) comprising at least one peak, in terms of 2θ, at 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising one peak, in terms of 2θ, at 20.0 + 0.2º. In some other embodiments, Form 1 has a PXRD comprising one peak, in terms of 2θ, at 18.3 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising one peak, in terms of 2θ, at 17.6 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising one peak, in terms of 2θ, at 14.6 + 0.2º. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, at 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising two peaks, at 20.0 + 0.2º and 18.3 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 20.0 + 0.2º and 17.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 20.0 + 0.2º, and 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 18.3 + 0.2º, and 17.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 18.3 + 0.2º, and / or 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 17.6 + 0.2º, and 14.6 + 0.2º. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, at 7.3 + 0.2º, 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 20.0 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 18.3 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 17.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising two peaks, at 7.3 + 0.2º and 14.6 + 0.2º. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a PXRD comprising at least three peaks, in terms of 2θ, at 7.3 + 0.2º, 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 20.0 + 0.2º, and 18.3 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 20.0+ 0.2º, and 17.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 20.0+ 0.2º, and 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 18.3 + 0.2º, and 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising three peaks, at 7.3 + 0.2º, 17.6 + 0.2º, and 14.6 + 0.2º. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a PXRD comprising at least four peaks, in terms of 2θ, at 7.3 + 0.2º, 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º. In some further embodiments, Form 1 has a PXRD comprising four peaks, at 7.3 + 0.2º, 20.0 + 0.2º, 18.3 + 0.2º, and 17.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising four peaks, at 7.3 + 0.2º, 20.0 + 0.2º, 18.3 + 0.2º, and 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising four peaks, at 7.3 + 0.2º, 20.0 + 0.2º, 17.6 + 0.2º, and 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising four peaks, at 7.3 + 0.2º, 18.3 + 0.2º, 17.6 + 0.2º, and 14.6 + 0.2º. In other further embodiments, Form 1 has a PXRD comprising four peaks, at 20.0 + 0.2º, 18.3 + 0.2º, 17.6 + 0.2º, and 14.6 + 0.2º. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a PXRD comprising five peaks, in terms of 2θ, at 7.3 + 0.2º, 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a PXRD substantially as shown in FIG.7. In some embodiments, Form 1 of L-arginine salt of Compound 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 221.2 + 10.0 ºC. In some embodiments, Form 1 of L-arginine salt of Compound 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 221.2 + 2.0 ºC. In some further embodiments, Form 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 221.2 + 1.5 ºC. In some further embodiments, Form 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 221.2 + 1.0 ºC. In some further embodiments, Form 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 221.2 + 0.5 ºC. In some further embodiments Form 1 of L-arginine salt of Compound 1 has differential scanning calorimetry trace substantially as FIG.6. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), selected from those at the position of 1279 ± 2 cm-1, 1602 ± 2 cm-1, and 1611 ± 2 cm-1. In some further embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1279 ± 2 cm-1, 1602 ± 2 cm-1, and 1611 ± 2 cm-1. In some yet further embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1279 ± 2 cm-1, 1602 ± 2 cm-1, and 1611 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising one peak, in terms of wavenumbers (cm-1), at the position of 1279 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising one peak, in terms of wavenumbers (cm-1), at the position of 1602 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising one peak, in terms of wavenumbers (cm-1), at the position of 1611 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), at the position of 1279 ± 2 cm-1and 1602 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), at the position of 1602 ± 2 cm-1and 1611 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), at the position of 1279 ± 2 cm-1and 1611 ± 2 cm-1. In some embodiments, Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum substantially as FIG.12. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, selected from those at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm. In some further embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising at least two peaks, in terms of chemical shifts, selected from those at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm. In some further embodiments, Form 1 of L- arginine salt of Compound 1 has a13C ssNMR spectrum comprising at least three peaks, in terms of chemical shifts, selected from those at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm. In some further embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising peaks, in terms of chemical shifts, selected from those at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising one peak, in terms of chemical shifts, at 46.3 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising one peak, in terms of chemical shifts, at 138.2 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising one peak, in terms of chemical shifts, at 140.1 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising one peak, in terms of chemical shifts, at 176.3 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 46.3 ± 0.2 ppm and 138.2 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 46.3 ± 0.2 ppm and 140.1 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising three peaks, in terms of chemical shifts, at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, and 140.1 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising three peaks, in terms of chemical shifts, at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, and 176.3 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising three peaks, in terms of chemical shifts, at 46.3 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm. In some embodiments, Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum substantially as FIG.13. In a fifth aspect, the present invention provides a pharmaceutical composition comprising a compound of any one of the embodiments in the first, second, third, and fourth aspects of the present invention (including all further embodiments described herein) and a pharmaceutically acceptable excipient. In a sixth aspect, the present invention provides a method for treating or preventing a condition, disease, or disorder in a patient comprising administering to the patient a compound of any one of the embodiments in the first, second, third, and fourth aspects of the present invention (including all further embodiments described herein), wherein the condition, disease, or disorder is selected from the group consisting of diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), overweight, excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug); or a method for weight management (e.g. chronic weight management) of a human comprising administering to the human a compound of any one of Embodiments A1 to A86 including the further embodiments described herein. As used herein, treating diabetes (e.g. T2DM) in a diabetic patient (e.g. a patient with T2DM) includes, among other things, improving glycemic control. In some further embodiments, the condition, disease, or disorder is selected from the group consisting of obesity, weight gain, T2DM, Heart Failure (e.g. HFpEF and HFrEF); CKD; NAFLD, NASH, atherosclerosis, PAD, obstructive sleep apnea, diabetic retinopathy, and diabetic neuropathy. In some further embodiments, the method is for preventing weight gain. In some further embodiments, the method is for preventing obesity. In some further embodiments, the method is for treating obesity. In some further embodiments, the method is for weight management, for example chronic weight management, of a human. In some further embodiments, the human is obese or overweight when the weight management (e.g. chronic weight management) is initiated; and in such a situation, the weight management (e.g. chronic weight management) is also a method for treating obesity or overweight. In some further embodiments, the human is obese when the weight management (e.g. chronic weight management) treatment is initiated; and in such a situation, the weight management (e.g. chronic weight management) is also a method for treating obesity. In a seventh aspect, the present invention provides use of a compound of any one of the embodiments in the first, second, third, and fourth aspects of the present invention (including all further embodiments described herein) for treating or preventing a condition, disease, or disorder, or use of the compound in manufacturing a medicament for treating or preventing a condition, disease, or disorder, wherein the condition, disease, or disorder is selected from the group consisting of diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), overweight, excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post- prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug); or use of a compound of any one of Embodiments A1 to A86 including the further embodiments described herein for weight management (e.g. chronic weight management). In some further embodiments, the condition, disease, or disorder is selected from the group consisting of obesity, weight gain, T2DM, Heart Failure (e.g. HFpEF and HFrEF); CKD; NAFLD, NASH, atherosclerosis, PAD, obstructive sleep apnea, diabetic retinopathy, and diabetic neuropathy. In some further embodiments, the use for preventing weight gain. In some further embodiments, the use is in manufacturing a medicament for preventing weight gain. In some further embodiments, the use for treating obesity. In some further embodiments, the use is in manufacturing a medicament for obesity. In some further embodiments, the use is in manufacturing a medicament for weight management, for example chronic weight management of a human. In some further embodiments, the human is obese or overweight when the weight management (e.g. chronic weight management) is initiated; and in such a situation, the weight management is also a method for treating obesity or overweight. In some further embodiments, the human is obese when the weight management (e.g. chronic weight management) treatment is initiated; and in such a situation, the weight management is also a method for treating obesity. In an eighth aspect, the present invention provides a compound of any one of the embodiments in the first, second, third, and fourth aspects of the present invention (including all further embodiments described herein) for use in a method for treating or preventing a condition, disease, or disorder in a patient, wherein the condition, disease, or disorder is selected from the group consisting of diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), overweight, excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post- prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug); or use of a compound of any one of the embodiments in the first, second, third, and fourth aspects of the present invention (including all further embodiments described herein) for use in a method for weight management (e.g. chronic weight management). In some further embodiments, the condition, disease, or disorder is selected from the group consisting of obesity, weight gain, T2DM, Heart Failure (e.g. HFpEF and HFrEF); CKD; NAFLD, NASH, atherosclerosis, PAD, obstructive sleep apnea, diabetic retinopathy, and diabetic neuropathy. In some further embodiments, the compound is for use in a method for use in a method for preventing weight gain. In some further embodiments, the compound is for use in a method for treating obesity. In some further embodiments, the compound is for use in a method for weight management (e.g. chronic weight management). In some further embodiments, the human is obese or overweight when the weight management (e.g. chronic weight management) is initiated; and in such a situation, the weight management is also a method for treating obesity or overweight. In some further embodiments, the human is obese when the weight management (e.g. chronic weight management) treatment is initiated; and in such a situation, the weight management is also a method for treating obesity. In an nighth aspect, the present invention provides a method for modulating (e.g. antagonizing) a GIPR (either in vitro or in vivo), comprising contacting (including incubating) the GIPR with a compound of any one of the embodiments in the first, second, third, and fourth aspects of the present invention (including all further embodiments described herein). In some further embodiments, the modulating is antagonizing. It is to be understood that this invention is not limited to specific synthetic methods of preparation described in the schemes herein. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings: As used herein in the specification, "a" or "an" may mean one or more. As used herein in the claim(s), when used in conjunction with the word "comprising", the words "a" or "an" may mean one or more than one. As used herein "another" may mean at least a second or more. The term “about” refers to a relative term denoting an approximation of plus or minus 10% of the nominal value to which it refers, in one embodiment, to plus or minus 5%, in another embodiment, to plus or minus 2%. For the field of this disclosure, this level of approximation is appropriate unless the value is specifically stated to require a tighter range. “Compound” when used herein includes any pharmaceutically acceptable form, derivative or variation, including solvates, hydrates, anhydrates, amorphous forms, isomorphs, polymorphs, and tautomers. The term “patient” refers to a mamal, for example, a human. “Mammals” refers to warm-blooded vertebrate animals characterized by the secretion of milk by females for the nourishment of the young, such as guinea pigs, mice, rats, gerbils, cats, rabbits, dogs, cattle, goats, sheep, horses, monkeys, chimpanzees, and humans. The term “pharmaceutically acceptable” means the substance (e.g., the compounds of the invention) and any salt thereof, or composition containing the substance or salt of the invention that is suitable for administration to a patient. As used herein, the expressions "reaction-inert solvent" and "inert solvent" refer to a solvent or a mixture thereof which does not interact with starting materials, reagents, intermediates or products in a manner which adversely affects the yield of the desired product. As used herein, the term "selectivity" or "selective" refers to a greater effect of a compound in a first assay, compared to the effect of the same compound in a second assay. For example, in “gut-selective” compounds, the first assay is for the half-life of the compound in the intestine and the second assay is for the half-life of the compound in the liver. “Therapeutically effective amount” means an amount of a compound of the present invention that (i) treats or prevents the particular disease, condition, or disorder; (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder; or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein. The term "treating", "treat", or "treatment" as used herein embraces both preventative, i.e., prophylactic, and palliative treatment, including reversing, relieving, alleviating, or slowing the progression of the disease (or disorder or condition) or any tissue damage associated with one or more symptoms of the disease (or disorder or condition). As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” GIPR with a compound of the invention includes the administration of a compound of the present invention to a mammal, such as a human, having the GIPR, as well as, for example, introducing a compound of the invention into a sample containing a cellular or purified preparation containing the GIPR. Every embodiment, Example, or pharmaceutically acceptable salt thereof may be claimed individually or grouped together in any combination with any number of each and every embodiment described herein. The compound of the invention can be used in any of the pharmaceutical compositions, uses, and methods of the invention described herein. Pharmaceutical Compositions The present invention also provides a composition (e.g., a pharmaceutical composition) comprising the compound of the invention. Accordingly, in one embodiment, the invention provides a pharmaceutical composition comprising (a therapeutically effective amount of) the compound of the invention and optionally comprising a pharmaceutically acceptable carrier. In addition to the compounds of the invention, the pharmaceutical composition of the invention may also contain, or be co-administered (e.g. simultaneously, sequentially, together, or separately) with, one or more pharmacological agents of value in treating one or more disease conditions referred to herein. In one further embodiment, the invention provides a pharmaceutical composition comprising (a therapeutically effective amount of) a compound of Formula I or a pharmaceutically acceptable salt thereof, optionally comprising a pharmaceutically acceptable carrier and, optionally, at least one additional medicinal or pharmaceutical agent (such as an anti-diabetic agent or weight management agent). In one embodiment, the additional medicinal or pharmaceutical agent is anti-diabetic agent as described below. A "pharmaceutical composition" of the invention refers to a mixture of (1) one or more of the compounds of the invention as an active ingredient (e.g. a compound of Formula I or a pharmaceutically acceptable salt, including any solvate, hydrate, solid form, stereoisomer, tautomer, or prodrug) and (2) at least one pharmaceutically acceptable excipient. The term ’excipient’ is used herein to describe any ingredient other than the compound(s) of the invention. The choice of excipient will to a large extent depend on factors such as the mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form. As used herein, "excipient” includes any and all solvents, dispersion media, coatings, antibacterial agents, antifungal agents, isotonic agents, absorption delaying agents, carriers, diluents and the like that are physiologically compatible. Examples of excipients include one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof, and may include isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol, or sorbitol in the composition. Examples of excipients also include various organic solvents (such as hydrates and solvates). The pharmaceutical compositions may, if desired, contain additional excipients such as flavorings, binders / binding agents, lubricating agents, disintegrants, sweetening or flavoring agents, coloring matters or dyes, and the like. For example, for oral administration, tablets containing various excipients, such as citric acid may be employed together with various disintegrants such as starch, alginic acid and certain complex silicates and with binding agents such as sucrose, gelatin and acacia. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often useful for tableting purposes. Solid compositions of a similar type may also be employed in soft and hard filled gelatin capsules. Non-limiting examples of excipients, therefore, also include lactose or milk sugar and high molecular weight polyethylene glycols. When aqueous suspensions or elixirs are desired for oral administration the active compound therein may be combined with various sweetening or flavoring agents, coloring matters or dyes and, if desired, emulsifying agents or suspending agents, together with additional excipients such as water, ethanol, propylene glycol, glycerin, or combinations thereof. Examples of excipients also include pharmaceutically acceptable substances such as wetting agents or minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives, or buffers, which enhance the shelf life or effectiveness of the compound. The compositions of this invention may be in a variety of forms. These include, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, capsules, pills, powders, liposomes and suppositories. The form depends on the intended mode of administration and therapeutic application. Some compositions are in the form of injectable or infusible solutions, such as compositions similar to those used for passive immunization of humans with antibodies in general. One mode of administration is parenteral (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular). In another embodiment, the compound is administered by intravenous infusion or injection. In yet another embodiment, the compound is administered by intramuscular or subcutaneous injection. Oral administration of a solid dosage form may be, for example, presented in discrete units, such as hard or soft capsules, pills, cachets, lozenges, or tablets, each containing a predetermined amount of at least one compound of the invention. In another embodiment, the oral administration may be in a powder or granule form. In another embodiment, the oral dosage form is sub-lingual, such as, for example, a lozenge. In such solid dosage forms, the compounds of the invention are ordinarily combined with one or more adjuvants. Such capsules or tablets may comprise a controlled release formulation. In the case of capsules, tablets, and pills, the dosage forms also may comprise buffering agents or may be prepared with enteric coatings. In another embodiment, oral administration may be in a liquid dosage form. Liquid dosage forms for oral administration include, for example, pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art (e.g., water). Such compositions also may comprise adjuvants, such as one or more of wetting, emulsifying, suspending, flavoring (e.g., sweetening), or perfuming agents. In another embodiment, the invention comprises a parenteral dosage form. "Parenteral administration" includes, for example, subcutaneous injections, intravenous injections, intraperitoneal injections, intramuscular injections, intrasternal injections, and infusion. Injectable preparations (i.e., sterile injectable aqueous or oleaginous suspensions) may be formulated according to the known art using one or more of suitable dispersing, wetting agents, or suspending agents. In another embodiment, the invention comprises a topical dosage form. "Topical administration" includes, for example, dermal and transdermal administration, such as via transdermal patches or iontophoresis devices, intraocular administration, or intranasal or inhalation administration. Compositions for topical administration also include, for example, topical gels, sprays, ointments, and creams. A topical formulation may include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. When the compounds of this invention are administered by a transdermal device, administration will be accomplished using a patch either of the reservoir and porous membrane type or of a solid matrix variety. Typical formulations for this purpose include gels, hydrogels, lotions, solutions, creams, ointments, dusting powders, dressings, foams, films, skin patches, wafers, implants, sponges, fibers, bandages and microemulsions. Liposomes may also be used. Typical excipients include alcohol, water, mineral oil, liquid petrolatum, white petrolatum, glycerin, polyethylene glycol and propylene glycol. Penetration enhancers may be incorporated - see, for example, B. C. Finnin and T. M. Morgan, J. Pharm. Sci., vol.88, pp.955- 958, 1999. Formulations suitable for topical administration to the eye include, for example, eye drops wherein the compound of this invention is dissolved or suspended in a suitable excipient. A typical formulation suitable for ocular or aural administration may be in the form of drops of a micronized suspension or solution in isotonic, pH-adjusted, sterile saline. Other formulations suitable for ocular and aural administration include ointments, biodegradable (i.e., absorbable gel sponges, collagen) and non-biodegradable (i.e., silicone) implants, wafers, lenses and particulate or vesicular systems, such as niosomes or liposomes. A polymer such as crossed linked polyacrylic acid, polyvinyl alcohol, hyaluronic acid, a cellulosic polymer, for example, hydroxypropylmethylcellulose, hydroxyethylcellulose, or methylcellulose, or a heteropolysaccharide polymer, for example, gelan gum, may be incorporated together with a preservative, such as benzalkonium chloride. Such formulations may also be delivered by iontophoresis. For intranasal administration, the compounds of the invention are conveniently delivered in the form of a solution or suspension from a pump spray container that is squeezed or pumped by the patient or as an aerosol spray presentation from a pressurized container or a nebulizer, with the use of a suitable propellant. Formulations suitable for intranasal administration are typically administered in the form of a dry powder (either alone, as a mixture, for example, in a dry blend with lactose, or as a mixed component particle, for example, mixed with phospholipids, such as phosphatidylcholine) from a dry powder inhaler or as an aerosol spray from a pressurized container, pump, spray, atomizer (preferably an atomizer using electrohydrodynamics to produce a fine mist), or nebulizer, with or without the use of a suitable propellant, such as 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoropropane. For intranasal use, the powder may comprise a bioadhesive agent, for example, chitosan or cyclodextrin. In another embodiment, the invention comprises a rectal dosage form. Such rectal dosage form may be in the form of, for example, a suppository. Cocoa butter is a traditional suppository base, but various alternatives may be used as appropriate. Other excipients and modes of administration known in the pharmaceutical art may also be used. Pharmaceutical compositions of the invention may be prepared by any of the well- known techniques of pharmacy, such as effective formulation and administration procedures. The above considerations in regard to effective formulations and administration procedures are well known in the art and are described in standard textbooks. Formulation of drugs is discussed in, for example, Ansel, Howard C., et al., Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lippincott, Williams & Wilkins, 2004; Gennaro, Alfonso R., et al. Remington: The Science and Practice of Pharmacy. Philadelphia: Lippincott, Williams & Wilkins, 2000; Rowe, Raymond C. Handbook of Pharmaceutical Excipients. Chicago, Pharmaceutical Press, 2005; Stahl, P. Heinrich and Camilli G. Wermuth, Eds. Handbook of Pharmaceutical Salts: Properties, Selection, and Use. New York: Wiley-VCH, 2011; and Brittain, Harry G., Ed. Polymorphism in Pharmaceutical Solids. New York: Informa Healthcare USA, Inc., 2016. Acceptable excipients are nontoxic to subjects at the dosages and concentrations employed, and may comprise one or more of the following: 1) buffers such as phosphate, citrate, or other organic acids; 2) salts such as sodium chloride; 3) antioxidants such as ascorbic acid or methionine; 4) preservatives such as octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol; 5) alkyl parabens such as methyl or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol, or m-cresol; 6) low molecular weight (less than about 10 residues) polypeptides; 7) proteins such as serum albumin, gelatin, or immunoglobulins; 8) hydrophilic polymers such as polyvinylpyrrolidone; 9) amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; 10) monosaccharides, disaccharides, or other carbohydrates including glucose, mannose, or dextrins; 11) chelating agents such as EDTA; 12) sugars such as sucrose, mannitol, trehalose or sorbitol; 13) salt-forming counter-ions such as sodium, metal complexes (e.g., Zn-protein complexes), or 14) non-ionic surfactants such as polysorbates (e.g., polysorbate 20 or polysorbate 80), poloxamers or polyethylene glycol (PEG). For oral administration, the compositions may be provided in the form of tablets or capsules containing 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 75.0, 100, 125, 150, 175, 200, 250 or 500 milligrams of the active ingredient for the symptomatic adjustment of the dosage to the patient. A medicament typically contains from about 0.01 mg to about 500 mg, from about 0.01 mg to about 100 mg, from about 1.0 mg to about 20.0 mg, or from about 5.0 mg to about 10.0 mg of the active ingredient, or in another embodiment, from about 1 mg to about 100 mg of active ingredient. Intravenously, doses may range from about 0.01 to about 10 mg / kg / minute during a constant rate infusion. In some embodiments, an oral composition (e.g. a tablet or capsule) of the present invention contains about 0.01, about 0.05, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 1.0, about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, about 9.0, about 9.5, about 10.0, about 10.5, about 11.0, about 11.5, about 12.0, about 12.5, about 13.0, about 13.5, about 14.0, about 14.5, about 15.0, about 15.5 about 15.0, about 16.5, about 17.0, about 17.5, about 18.0, about 18.5, about 19.0, about 19.5, about 20.0, about 21.0, about 22.0, about 23.0, about 24.0, about 25.0, about 30.0, about 35.0, about 40.0, about 45.0, about 50.0, about 75.0, about 100, about 125, about 150, about 175, about 200, about 250, about 500, from about 0.01 to 0.05, about 0.05 to about 0.1, about 0.1 to about 0.5, about 0.5 to about 1.0, about 1.0 to about 2.0, from about 2.0 to about 20.0, from about 2.0 to about 10.0, from about 4.0 to about 8.0, from about 5.0 to about 10.0, from about 6.0 to about 10.0, from about 6.0 to about 8.0, from about 10.0 to about 15.0, or from about 15.0 to about 20.0 milligrams of the active ingredient (e.g. a compound of the present invention such as L-lysine salt of Compound 1, or Form 1 or Form 2 thereof; or L-arginine salt of Compound 1 or Form 1 thereof). In some further embodiments, the oral composition of the present invention is administered to a patient (e.g. a human) once or twice a day. In some yet further embodiments, the oral composition of the present invention is administered to a patient (e.g. a human) once a day. In some embodiments, an oral composition (e.g. a tablet or capsule) of the present invention contains a compound of the present invention (e.g. L-lysine salt of Compound 1, or Form 1 or Form 2 thereof; or L-arginine salt of Compound 1 or Form 1 thereof) in an amount equivalent to about 0.01, about 0.05, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 1.0, about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, about 9.0, about 9.5, about 10.0, about 10.5, about 11.0, about 11.5, about 12.0, about 12.5, about 13.0, about 13.5, about 14.0, about 14.5, about 15.0, about 15.5 about 15.0, about 16.5, about 17.0, about 17.5, about 18.0, about 18.5, about 19.0, about 19.5, about 20.0, about 21.0, about 22.0, about 23.0, about 24.0, about 25.0, about 30.0, about 35.0, about 40.0, about 45.0, about 50.0, about 75.0, about 100, about 125, about 150, about 175, about 200, about 250, about 500, from about 0.01 to 0.05, from about 0.05 to about 0.1, from about 0.1 to about 0.5, from about 0.5 to about 1.0, from about 1.0 to about 2.0, from about 2.0 to about 20.0, from about 2.0 to about 10.0, from about 4.0 to about 8.0, about from 5.0 to about 10.0, from about 6.0 to about 10.0, from about 6.0 to about 8.0, from about 10.0 to about 15.0, or from about 15.0 to about 20.0 milligrams of Compound 1. In some further embodiments, the oral composition of the present invention is administered to a patient (e.g. a human) once or twice a day. In some yet further embodiments, the oral composition of the present invention is administered to the patient (e.g. the human) once a day. Liposome-containing compounds of the invention may be prepared by methods known in the art (See, for example, Chang, H.I.; Yeh, M.K.; Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy; Int J Nanomedicine 2012; 7; 49- 60). Particularly useful liposomes may be generated by the reverse phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Compounds of the invention may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington, The Science and Practice of Pharmacy, 20th Ed., Mack Publishing (2000). Sustained-release preparations may be used. Suitable examples of sustained-release preparations include semi-permeable matrices of solid hydrophobic polymers containing a compound of the invention, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or 'poly(vinylalcohol)), polylactides, copolymers of L-glutamic acid and 7 ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as those used in leuprolide acetate for depot suspension (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), sucrose acetate isobutyrate, and poly-D-(-)-3-hydroxybutyric acid. The formulations to be used for intravenous administration must be sterile. This is readily accomplished by, for example, filtration through sterile filtration membranes. Compounds of the invention are generally placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle. Suitable emulsions may be prepared using commercially available fat emulsions, such as a lipid emulsions comprising soybean oil, a fat emulsion for intravenous administration (e.g., comprising safflower oil, soybean oil, egg phosphatides and glycerin in water), emulsions containing soya bean oil and medium-chain triglycerides, and lipid emulsions of cottonseed oil. The active ingredient may be either dissolved in a pre-mixed emulsion composition or alternatively it may be dissolved in an oil (e.g., soybean oil, safflower oil, cottonseed oil, sesame oil, corn oil or almond oil) and an emulsion formed upon mixing with a phospholipid (e.g., egg phospholipids, soybean phospholipids or soybean lecithin) and water. It will be appreciated that other ingredients may be added, for example glycerol or glucose, to adjust the tonicity of the emulsion. Suitable emulsions will typically contain up to 20% oil, for example, between 5 and 20%. The fat emulsion may comprise fat droplets between 0.1 and 1.0 μm, particularly 0.1 and 0.5 μm, and have a pH in the range of 5.5 to 8.0. For example, the emulsion compositions may be those prepared by mixing a compound of the invention with a lipid emulsions comprising soybean oil or the components thereof (soybean oil, egg phospholipids, glycerol and water). Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as set out above. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions in preferably sterile pharmaceutically acceptable solvents may be nebulized by use of gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device may be attached to a face mask, tent or intermittent positive pressure breathing machine. Solution, suspension or powder compositions may be administered, preferably orally or nasally, from devices which deliver the formulation in an appropriate manner. A drug product intermediate (DPI) is a partly processed material that must undergo further processing steps before it becomes bulk drug product. Compounds of the invention may be formulated into drug product intermediate DPI containing the active ingredient in a higher free energy form than the crystalline form. One reason to use a DPI is to improve oral absorption characteristics due to low solubility, slow dissolution, improved mass transport through the mucus layer adjacent to the epithelial cells, and in some cases, limitations due to biological barriers such as metabolism and transporters. Other reasons may include improved solid state stability and downstream manufacturability. In one embodiment, the drug product intermediate contains a compound of the invention isolated and stabilized in the amorphous state (for example, amorphous solid dispersions (ASDs)). There are many techniques known in the art to manufacture ASD’s that produce material suitable for integration into a bulk drug product, for example, spray dried dispersions (SDD’s), melt extrudates (often referred to as HME’s), co-precipitates, amorphous drug nanoparticles, and nano-adsorbates. In one embodiment amorphous solid dispersions comprise a compound of the invention and a polymer excipient. Other excipients as well as concentrations of said excipients and the compound of the invention are well known in the art and are described in standard textbooks. See, for example, “Amorphous Solid Dispersions Theory and Practice” by Navnit Shah et al. The pharmaceutical composition may, for example, be in a form suitable for oral administration as a tablet, capsule, pill, powder, sustained release formulation, solution or suspension, for parenteral injection as a sterile solution, suspension or emulsion, for topical administration as an ointment or cream or for rectal administration as a suppository. Exemplary parenteral administration forms include solutions or suspensions of active compounds in sterile aqueous solutions, for example, aqueous propylene glycol or dextrose solutions. Such dosage forms may be suitably buffered, if desired. The pharmaceutical composition may be in unit dosage forms suitable for single administration of precise dosages. One of ordinary skill in the art would appreciate that the composition may be formulated in sub-therapeutic dosage such that multiple doses are envisioned. In one embodiment the composition comprises (a therapeutically effective amount of) a compound of Formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. Administration and Dosing The term "treating", "treat" or "treatment" as used herein embraces both preventative, i.e., prophylactic, and palliative treatment, i.e., relieve, alleviate, or slow the progression of the patient’s disease (or condition) or any tissue damage associated with the disease. As used herein, the terms, “subject, “individual” or “patient,” used interchangeably, refer to any animal, including mammals. Mammals according to the invention include canine, feline, bovine, caprine, equine, ovine, porcine, rodents, lagomorphs, primates, humans and the like, and encompass mammals in utero. In an embodiment, humans are suitable subjects. Human subjects may be of any gender and at any stage of development. As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which may include one or more of the following: (1) preventing a condition, disease, or disorder; for example, preventing the condition, disease, or disorder in an individual that may be predisposed to the condition, disease, or disorder but does not yet experience or display the pathology or symptomatology of the disease; (2) inhibiting a condition, disease, or disorder; for example, inhibiting the condition, disease, or disorder in an individual that is experiencing or displaying the pathology or symptomatology of the condition, disease, or disorder [i.e., arresting (or slowing) further development of the pathology or symptomatology or both]; and (3) ameliorating a condition, disease, or disorder; for example, ameliorating the condition, disease, or disorder in an individual that is experiencing or displaying the pathology or symptomatology of the condition, disease, or disorder [i.e., reversing the pathology or symptomatology or both]. Typically, a compound of the invention is administered in an amount effective to treat a condition, disease, or disorder as described herein. The compounds of the invention may be administered as compound in the free form, or alternatively, as a pharmaceutically acceptable salt. For administration and dosing purposes, the compound in free form or pharmaceutically acceptable salt thereof will simply be referred to as the compounds of the invention. The compounds of the invention are administered by any suitable route in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. Administration of the compounds of this invention can be via any method which delivers a compound of this invention systemically and / or locally. The compounds of the invention may be administered orally, rectally, vaginally, parenterally (including, e.g., intravenous, subcutaneous, intramuscular, intravascular or infusion), topically, intranasally, or by inhalation. The compounds of the invention may be administered orally. Oral administration may involve swallowing, so that the compound enters the gastrointestinal tract, or buccal or sublingual administration may be employed by which the compound enters the bloodstream directly from the mouth. In another embodiment, the compounds of the invention may also be administered parenterally, for example directly into the bloodstream, into muscle, or into an internal organ. Suitable means for parenteral administration include intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular and subcutaneous. Suitable devices for parenteral administration include needle (including microneedle) injectors, needle-free injectors, and infusion techniques. In another embodiment, the compounds of the invention may also be administered topically to the skin or mucosa, that is, dermally or transdermally. In another embodiment, the compounds of the invention may also be administered intranasally or by inhalation. In another embodiment, the compounds of the invention may be administered rectally or vaginally. In another embodiment, the compounds of the invention may also be administered directly to the eye or ear. The dosage regimen for the compounds of the invention or compositions containing said compounds is based on a variety of factors, including the type, age, weight, sex and medical condition of the patient; the severity of the condition; the route of administration; and the activity of the particular compound employed. Thus, the dosage regimen may vary widely. In one embodiment, the total daily dose of a compound of the invention is typically from about 0.0001 to about 100 mg / kg (i.e., mg compound of the invention per kg body weight) for the treatment of the indicated conditions discussed herein. In another embodiment, total daily dose of the compound of the invention is from about 0.01 to about 50 mg / kg; and in another embodiment, from about 0.1 to about 50 mg / kg; and in another embodiment, from about 0.5 to about 30 mg / kg. It is not uncommon that the administration of the compounds of the invention will be repeated a plurality of times in a day (typically no greater than 4 times). Multiple doses per day typically may be used to increase the total daily dose, if desired. Methods and Uses Another embodiment of the present invention includes a compound of the present invention for use as a medicament, particularly wherein the medicament is for use in the treatment or prevention of a GIPR-related condition, disease, or disorder, including administering to a mammal, such as a human, in need of such treatment. Another embodiment of the present invention includes use of a compound of the present invention as a medicament, particularly wherein the medicament is for use in the treatment or prevention of a GIPR-related condition, disease, or disorder, including administering to a mammal, such as a human, in need of such treatment. Another embodiment of the present invention includes use of a compound of the present invention in the manufacture of a medicament for treating or preventing a GIPR-related condition, disease, or disorder, including administering to a mammal, such as a human, in need of such treatment a therapeutically effective amount. Another embodiment of the present invention includes a compound of invention for use as a medicament, particularly wherein the medicament is for use in treating or preventing a condition, disease, or disorder selected from diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high- density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug). Another embodiment of the present invention includes use of the compound of invention as a medicament, particularly wherein the medicament is for use in the treatment or prevention of a condition, disease, or disorder selected from diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high- density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug). Another embodiment of the present invention includes use of the compound of invention for the manufacture of a medicament for treating or preventing a condition, disease, or disorder selected from diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug). In some further embodiments of the methods and uses of the present invention described herein, the condition, disease, or disorder that can be treated or prevented in accordance with the present invention is selected from obesity, T2DM, Heart Failure (e.g. HFpEF and HFrEF); CKD; NAFLD, NASH, atherosclerosis, PAD, obstructive sleep apnea, diabetic retinopathy, and diabetic neuropathy. The compound of the invention is a GIPR antagonist. Thus, the present invention further provides a method for modulating (e.g. antagonizing) GIPR (either in vitro or in vivo), comprising contacting (including incubating) the GIPR with the compound of Formula I or a pharmaceutically acceptable salt thereof (such as one selected from Examples 1–229 herein) described herein. In some embodiments, the amount of the compound of the invention used in any one of the methods (or uses) of the present invention is effective in antagonizing GIPR. Stereoisomers The compounds of the present invention may contain asymmetric or chiral centers, and, therefore, exist in two or more stereoisomeric forms. Unless specified otherwise, it is intended that all stereoisomeric forms of the compounds of the present invention as well as mixtures thereof, including racemic mixtures, form part of the present invention. In addition, the present invention embraces all geometric and positional isomers. For example, if a compound of the present invention incorporates a double bond or a fused ring, both the cis- and trans- forms, as well as mixtures, are embraced within the scope of the invention. The pharmaceutically acceptable salts of compounds of the invention may also contain a counterion which is optically active (e.g., D-lactate or L-lysine) or racemic (e.g. DL-tartrate or DL-arginine). Included within the scope of the claimed compounds of the present invention are all stereoisomers, geometric isomers and tautomeric forms of the compounds of the invention, including compounds exhibiting more than one type of isomerism, and mixtures of one or more thereof. Also included are acid addition or base salts wherein the counterion is optically active, for example, D-lactate or L-lysine, or racemic, for example, DL-tartrate or DL-arginine. Tautomerism Where structural isomers are interconvertible via a low energy barrier, tautomeric isomerism (‘tautomerism’) may occur. This may take the form of proton tautomerism in compounds of the invention containing, for example, an imino / amino, keto / enol, or oxime / nitroso group, lactam / lactim or so-called valence tautomerism in compounds which contain an aromatic moiety. It follows that a single compound may exhibit more than one type of isomerism . It must be emphasized that while, for conciseness, the compounds of the invention have been drawn herein in a single tautomeric form, all possible tautomeric forms are included within the scope of the invention. It is possible that the intermediates and compounds of the present invention may exist in different tautomeric forms, and all such forms are embraced within the scope of the invention. The term “tautomer” or “tautomeric form” refers to structural isomers of different energies which are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions by reorganization of some of the bonding electrons. Isotopes The present invention includes all pharmaceutically acceptable isotopically labelled compounds of the invention wherein one or more atoms are replaced by atoms having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes suitable for inclusion in the compounds of the invention (Compound 1 or a pharmaceutically acceptable salt thereof such as L-lysine salt or L-arginine salt of Compound 1) include isotopes of hydrogen, such as2H and3H, carbon, such as11C,13C and14C, chlorine, such as36Cl, fluorine, such as18F, iodine, such as123I,124I and125I, nitrogen, such as13N and15N, oxygen, such as15O,17O and18O, phosphorus, such as32P, and sulphur, such as35S. In some embodiments, the disclosure provides deuterium-labeled (or deuterated) compounds and salts, where the formula and variables of such compounds and salts are each and independently as described herein. “Deuterated” means that at least one of the atoms in the compound is deuterium in an abundance that is greater than the natural abundance of deuterium (typically approximately 0.015%). A skilled artisan recognized that in chemical compounds with a hydrogen atom, the hydrogen atom actually represents a mixture of H and D, with about 0.015% being D. The concentration of the deuterium incorporated into the deuterium-labeled compounds and salt of the invention may be defined by the deuterium enrichment factor. It is understood that one or more deuterium may exchange with hydrogen under physiological conditions. In some embodiments, the deuterium compound is selected from any one of the compounds set forth in Table X-1 shown in the Examples section. In some embodiments, one or more hydrogen atoms on certain metabolic sites on the compounds of the invention are deuterated. In some embodiment, one or more of the deuterium compounds in Table X-1 can be converted to a pharmaceutically acceptable salt thereof such as L-lysine salt or L-arginine salt. Certain isotopically labelled Compound 1 or salt thereof (e.g. L-lysine salt or L-arginine salt of Compound 1), for example, those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotopes tritium, i.e.,3H, and carbon-14, i.e.,14C, are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. Substitution with heavier isotopes such as deuterium, i.e.,2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and hence may be preferred in some circumstances. In some embodiments, the disclosure provides deuterium-labeled (or deuterated) compounds and salts, where the formula and variables of such compounds and salts are each and independently as described herein. “Deuterated” means that at least one of the atoms in the compound is deuterium in an abundance that is greater than the natural abundance of deuterium (typically approximately 0.015%). A skilled artisan recognized that in chemical compounds with a hydrogen atom, the hydrogen atom actually represents a mixture of H and D, with about 0.015% being D. The concentration of the deuterium incorporated into the deuterium-labeled compounds and salt of the invention may be defined by the deuterium enrichment factor. It is understood that one or more deuterium may exchange with hydrogen under physiological conditions. In some embodiments, one or more hydrogen atoms on certain metabolic sites on the compounds of the invention may be deuterated. MetaSite (moldiscovery.com / software / metasite / ) may be helpful in predicting some metabolic sites on the compounds of the invention. Substitution with positron-emitting isotopes, such as11C,18F,15O and13N, can be useful in Positron Emission Tomography (PET) studies for examining substrate receptor occupancy. Isotopically labelled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples and Preparations using an appropriate isotopically labelled reagent in place of the non-labelled reagent previously employed. Pharmaceutically acceptable solvates (including hydrates) in accordance with the invention include those wherein the solvent of crystallization may be isotopically substituted, e.g., D2O, d6-acetone, d6-DMSO. Salts The compounds of the present invention may be isolated and used per se, or when possible, in the form of its pharmaceutically acceptable salt. The term “salts” refers to inorganic and organic salts of a compound of the present invention. These salts can be prepared in situ during the final isolation and purification of a compound, or by separately treating the compound with a suitable organic or inorganic acid or base and isolating the salt thus formed. Pharmaceutically acceptable salts of compounds of the invention may be prepared by methods well known to one skilled in the art, including but not limited to the following procedures (i) by reacting a compound of the invention with the desired acid or base; (ii) by removing an acid- or base-labile protecting group from a suitable precursor of a compound of the invention or by ring-opening a suitable cyclic precursor, for example, a lactone or lactam, using the desired acid or base; or (iii) by converting one salt of a compound of the invention to another. This may be accomplished by reaction with an appropriate acid or base or by means of a suitable ion exchange procedure. These procedures are typically carried out in solution. The resulting salt may precipitate out and be collected by filtration or may be recovered by evaporation of the solvent. Solvates The compounds of the invention may exist in unsolvated and solvated forms. The term ‘solvate’ is used herein to describe a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term ‘hydrate’ is employed when said solvent is water. In addition, the compounds of the invention may also include other solvates of such compounds that are not necessarily pharmaceutically acceptable solvates, which may be useful as intermediates for one or more of the following: 1) preparing Compound 1 or its Lysine salt; 2) purifying compounds of Compound 1 or its Lysine salt; 3) separating Compound 1 or its Lysine salt; or 4) separating diastereomers of Compound 1 or its Lysine salt. A currently accepted classification system for organic hydrates is one that defines isolated site, channel, or metal-ion coordinated hydrates - see Polymorphism in Pharmaceutical Solids by K. R. Morris (Ed. H. G. Brittain, Marcel Dekker, 1995). Isolated site hydrates are ones in which the water molecules are isolated from direct contact with each other by intervening organic molecules. In channel hydrates, the water molecules lie in lattice channels where they are next to other water molecules. In metal-ion coordinated hydrates, the water molecules are bonded to the metal ion. When the solvent or water is tightly bound, the complex may have a well-defined stoichiometry independent of humidity. When, however, the solvent or water is weakly bound, as in channel solvates and hygroscopic compounds, the water / solvent content may be dependent on humidity and drying conditions. In such cases, non-stoichiometry will be the norm. Complexes Also included within the scope of the invention are multi-component complexes (other than salts and solvates) wherein the drug and at least one other component are present in stoichiometric or non-stoichiometric amounts. Complexes of this type include clathrates (drug- host inclusion complexes) and co-crystals. The latter are typically defined as crystalline complexes of neutral molecular constituents which are bound together through non-covalent interactions, but could also be a complex of a neutral molecule with a salt. Co-crystals may be prepared by melt crystallization, by recrystallization from solvents, or by physically grinding the components together – see O. Almarsson and M. J. Zaworotko, Chem. Commun., 17, 1889- 1896 (2004). For a general review of multi-component complexes, see Haleblian, J. Pharm. Sci., 64 (8), 1269-1288 (1975). Metabolites Also included within the scope of the invention are active metabolites of compounds of Formula I (including prodrugs) or their pharmaceutically acceptable salts, that is, compounds formed in vivo upon administration of the drug, often by oxidation or dealkylation. Some examples of metabolites in accordance with the invention include: (i) where the compound of Formula I or its pharmaceutically acceptable salt contains a methyl group, a hydroxymethyl derivative thereof (-CH3 -> -CH2OH) and (ii) where the compound of Formula I or its pharmaceutically acceptable salt contains an alkoxy group, a hydroxy derivative thereof (-OR -> -OH). Also included within the scope of the invention are active metabolites of compounds of the invention, that is, compounds formed in vivo upon administration of the drug, often by oxidation or dealkylation. Some examples of metabolites in accordance with the invention include, but are not limited to, (i) where the compound of the invention contains an alkyl group, a hydroxyalkyl derivative thereof (-CH -> -COH): (ii) where the compound of the invention contains an alkoxy group, a hydroxy derivative thereof (-OR -> -OH); (iii) where the compound of the invention contains a tertiary amino group, a secondary amino derivative thereof (-NRR’-> -NHR or –NHR’); (iv) where the compound of the invention contains a secondary amino group, a primary derivative thereof (-NHR -> -NH2); (v) where the compound of the invention contains a phenyl moiety, a phenol derivative thereof (-Ph -> -PhOH); (vi) where the compound of the invention contains an amide group, a carboxylic acid derivative thereof (-CONH2-> COOH); and (vii) where the compound contains a hydroxy or carboxylic acid group, the compound may be metabolized by conjugation, for example with glucuronic acid to form a glucuronide. Other routes of conjugative metabolism exist. These pathways are frequently known as Phase 2 metabolism and include, for example, sulfation or acetylation. Other functional groups, such as NH groups, may also be subject to conjugation. Solid form The compounds of the invention may exist in a continuum of solid states ranging from fully amorphous to fully crystalline. The term ‘amorphous’ refers to a state in which the material lacks long range order at the molecular level and, depending upon temperature, may exhibit the physical properties of a solid or a liquid. Typically, such materials do not give distinctive X-ray diffraction patterns and, while exhibiting the properties of a solid, are more formally described as a liquid. Upon heating, a change from solid to liquid properties occurs which is characterized by a change of state, typically second order (‘glass transition’). The term ‘crystalline’ refers to a solid phase in which the material has a regular ordered internal structure at the molecular level and gives a distinctive X-ray diffraction pattern with defined peaks. Such materials when heated sufficiently will also exhibit the properties of a liquid, but the change from solid to liquid is characterized by a phase change, typically first order (‘melting point’). The compounds of the invention may also exist in a mesomorphic state (mesophase or liquid crystal) when subjected to suitable conditions. The mesomorphic state is intermediate between the true crystalline state and the true liquid state (either melt or solution) and consists of two dimensional order on the molecular level. Mesomorphism arising as the result of a change in temperature is described as ‘thermotropic’ and that resulting from the addition of a second component, such as water or another solvent, is described as ‘lyotropic’. Compounds that have the potential to form lyotropic mesophases are described as ‘amphiphilic’ and consist of molecules which possess an ionic (such as -COO-Na+, -COO-K+, or -SO3-Na+) or non-ionic (such as -N-N+(CH3)3) polar head group. For more information, see Crystals and the Polarizing Microscope by N. H. Hartshorne and A. Stuart, 4thEdition (Edward Arnold, 1970). Certain compounds of the present invention may exist in more than one crystal form (generally referred to as “polymorphs”). Polymorphs may be prepared by crystallization under various conditions, for example, using different solvents or different solvent mixtures for recrystallization; crystallization at different temperatures; and / or various modes of cooling, ranging from very fast to very slow cooling during crystallization. Polymorphs may also be obtained by heating or melting the compound of the present invention followed by gradual or fast cooling. The presence of polymorphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calorimetry, powder X-ray diffraction or such other techniques. In general the compounds of this invention can be made by processes which include processes analogous to those known in the chemical arts, particularly in light of the description contained herein. Certain processes for the manufacture of the compounds of this invention are provided as further features of the invention and are illustrated by the following reaction schemes. Other processes may be described in the experimental section. Specific synthetic schemes for preparation of the compounds of Formula I or their pharmaceutically acceptable salts are outlined below. Note that tetrazoles are generally a high-energy functional group and care should be taken in the synthesis and handling of tetrazole-containing molecules. Synthesis Compounds of the present invention may be synthesized by synthetic routes that include processes analogous to those well-known in the chemical arts, particularly in light of the description contained herein. The starting materials are generally available from commercial sources or may be prepared using methods well known to those skilled in the art. Many of the compounds used herein are related to, or may be derived from, compounds in which one or more of the scientific interest or commercial need has occurred. Accordingly, such compounds may be one or more of 1) commercially available; 2) reported in the literature or 3) prepared from other commonly available substances by one skilled in the art using materials which have been reported in the literature. For illustrative purposes, a detailed description of the individual reaction steps, see the Examples section below. Those skilled in the art will appreciate that other synthetic routes may be used to synthesize the inventive compounds. Although specific starting materials and reagents are discussed below, other starting materials and reagents may be substituted to provide one or more of a variety of derivatives or reaction conditions. In addition, many of the compounds prepared by the methods described below may be further modified in light of this disclosure using conventional chemistry well known to those skilled in the art. The skilled person will appreciate that the experimental conditions set forth in the schemes that follow are illustrative of suitable conditions for effecting the transformations shown, and that it may be necessary or desirable to vary the precise conditions employed for the preparation of compounds of the invention. It will be further appreciated that it may be necessary or desirable to carry out the transformations in a different order from that described in the schemes, or to modify one or more of the transformations, to provide the desired compound of the invention. In the preparation of compounds of the invention it is noted that some of the preparation methods useful for the preparation of the compounds described herein may require protection of remote functionality (e.g., a primary amine, secondary amine, carboxyl, etc. in a precursor of a compound of the invention). The need for such protection will vary depending on the nature of the remote functionality and the conditions of the preparation methods. The need for such protection is readily determined by one skilled in the art. The use of such protection / deprotection methods is also within the skill in the art. For a general description of protecting groups and their use, see March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure 8th Edition. For example, if a compound contains a amine or carboxylic acid functionality, such functionality may interfere with reactions at other sites of the molecule if left unprotected. Accordingly, such functionalities may be protected by an appropriate protecting group (PG) which may be removed in a subsequent step. Suitable protecting groups for amine and carboxylic acid protection include those protecting groups commonly used in peptide synthesis (such as N-t-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), and 9- fluorenylmethylenoxycarbonyl (Fmoc) for amines and lower alkyl or benzyl esters for carboxylic acids) which are generally not chemically reactive under the reaction conditions described and may typically be removed without chemically altering other functionality in a compound of the invention. Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g.,1H or13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry, or by chromatographic methods such as high- performance liquid chromatography (HPLC) or thin-layer chromatography (TLC). Compounds of invention may be prepared according to the following reaction schemes and accompanying discussion. The reaction schemes described below are intended to provide a general description of the methodology employed in the preparation of the compounds of the present invention. Some of the compounds of the present invention contain a single chiral center with stereochemical designation (R or S) and others will contain two separate chiral centers with stereochemical designation (R or S). It will be apparent to one skilled in the art that most of the synthetic transformations can be conducted in a similar manner whether the materials are enantioenriched or racemic. Moreover, the resolution to the desired optically active material may take place at any desired point in the sequence using well known methods such as described herein and in the chemistry literature. In general, the compounds of this invention may be made by processes described herein and by analogous processes known to those skilled in the art. Certain processes for the manufacture of the compounds of this invention are described in the following reaction schemes. Other processes are described in the experimental section. The schemes and examples provided herein (including the corresponding description) are for illustration only. One skilled in the art will recognize that intermediates and compounds of invention prepared according to the following schemes may be isolated as salts or non-salts depending on the conditions of the reaction, isolation, or purification. One skilled in the art will also recognize that in some instances, additional synthetic steps may be required to protect and deprotect certain functional groups present within the synthetic sequence. One skilled in the art will further recognize that in other instances, certain functional groups may be carried through the synthetic sequences described and then may be transformed into alternate substituents present in compounds of the invention. A detailed description of the individual reaction steps is provided in the Example section below. Those skilled in the art will appreciate that other synthetic routes may be used to synthesize the compounds. Although specific starting materials and reagents are discussed below, other starting materials and reagents can be easily substituted to provide a variety of derivatives and / or reaction conditions. In addition, many of the compounds prepared by the methods described below can be further modified in light of this disclosure using conventional chemistry well known to those skilled in the art. Co-administration The compounds of the invention may be used alone, or in combination with one or more other therapeutic agents. The invention provides any of the uses, methods or compositions as defined herein wherein the compound of the invention, or pharmaceutically acceptable salt thereof, is used in combination with one or more other therapeutic agent discussed herein. The administration of two or more compounds “in combination” means that all of the compounds are administered closely enough in time to affect treatment of the subject. The two or more compounds may be administered simultaneously or sequentially, via the same or different routes of administration, on same or different administration schedules and with or without specific time limits depending on the treatment regimen. Additionally, simultaneous administration may be carried out by mixing the compounds prior to administration or by administering the compounds at the same point in time but as separate dosage forms at the same or different site of administration. Examples of “in combination” include, but are not limited to, “concurrent administration,” “co-administration,” “simultaneous administration,” “sequential administration” and “administered simultaneously”. A compound of the invention and the one or more other therapeutic agents may be administered as a fixed or non-fixed combination of the active ingredients. The term "fixed combination" means a compound of the invention, or a pharmaceutically acceptable salt thereof, and the one or more therapeutic agents, are both administered to a subject simultaneously in a single composition or dosage. The term "non-fixed combination" means that a compound of the invention, or a pharmaceutically acceptable salt thereof, and the one or more therapeutic agents are formulated as separate compositions or dosages such that they may be administered to a subject in need thereof simultaneously or at different times with variable intervening time limits, wherein such administration provides effective levels of the two or more compounds in the body of the subject. The combination agents are administered to a patient (e.g. a mammal or human) in a therapeutically effective amount. By "therapeutically effective amount" it is meant an amount of a compound of the present invention that, when administered alone or in combination with an additional therapeutic agent to a mammal, is effective to treat the desired disease / disorder / condition (e.g., T2DM or obesity). In some embodiments, a compound of this invention may be co-administered with one or more other agents such as Orlistat, TZDs and other insulin-sensitizing agents, FGF21 analogs, Metformin, Omega-3-acid ethyl esters (e.g., Lovaza), Fibrates, HMG CoA-reductase Inhibitors, Ezetimibe, Probucol, Ursodeoxycholic acid, TGR5 agonists, FXR agonists, Vitamin E, Betaine, Pentoxifylline, CB1 antagonists, Carnitine, N-acetylcysteine, Reduced glutathione, lorcaserin, the combination of naltrexone with buproprion, SGLT2 inhibitors (including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, ertugliflozin, ASP-1941, THR1474, TS- 071, ISIS388626 and LX4211 as well as those in WO2010023594), Phentermine, Topiramate, GLP-1 receptor agonists, GIP receptor agonists, GIP receptor inhibitors and / or antagonists, dual GLP-1 receptor / glucagon receptor agonists (e.g., OPK88003, MEDI0382, JNJ-64565111, NN9277, BI 456906), dual GLP-1 receptor / GIP receptor agonists [e.g., Tirzepatide (LY3298176), NN9423, NN9541, HS-20094, SCO-094, VK2735, CT-388, GMA-106, CT-868, HRS9531], dual GLP-1 receptor / glucagon receptor agonists (e.g. DD-01, PB-718, mazdutide, pemvidutide, pegapamodutide, survodutide, LM-008, IBI-362, AZD9550), dual GLP-1 receptor / GLP-2 receptor agonists (e.g. dapiglutide), dual GLP-1 receptor / amylin receptor agonists (e.g. amycretin), cagrilinitide / semaglutide, GLP-1 receptor agonist / GIP receptor antagonist (maridebart cafraglutide), dual GLP-1 receptor / FGF21 receptor agonists (e.g. HEC- 88473, BI 3006337), triple agonists of the GLP-1 receptor / glucagon receptor / GIP receptor (e.g. retatrutide), triple agonists of the GLP-1 receptor / glucagon receptor / FGF21 receptor (e.g. DR10624), NPY2 receptor agonists (e.g. BI 1820237), activin receptor type-2B modulators (e.g. bimagrumab), amylin receptor agonists, GPR75 modulators, delta-5 desaturase inhibitors, orexin 2 receptor modulators, Angiotensin-receptor blockers, an acetyl-CoA carboxylase (ACC) inhibitor, a ketohexokinase (KHK) inhibitor, ASK1 inhibitors, branched-chain alpha-keto acid dehydrogenase kinase inhibitors (BCKDK inhibitors), inhibitors of CCR2 and / or CCR5, PNPLA3 inhibitors, DGAT1 inhibitors, DGAT2 inhibitors, an FGF21 analog, FGF19 analogs, PPAR agonists, FXR agonists, AMPK activators [e.g., ETC-1002 (bempedoic acid)], SCD1 inhibitors or MPO inhibitors. Exemplary GLP-1 receptor agonists include liraglutide, albiglutide, exenatide, lixisenatide, dulaglutide, semaglutide, danuglipron, orforglipron, lotiglipron, PF-06954522, HM15211, LY3298176, Medi-0382, NN-9924, TTP-054, TTP-273, efpeglenatide, CT-996, ECC5004, XW004, XW014, MDR-001, ZT002, KN-056, GL0034, GSBR-1290, noiiglutide, RGT- 075, TTP-273, HRS-7535, GMA-105, TG103, GZR-18, GX-G6, ecnoglutide, PB-119, QLG2065, beinaglutide, those described in WO2018109607, those described in WO2019239319 (PCT / IB2019 / 054867 filed June 11, 2019), and those described in WO2019239371 (PCT / IB2019 / 054961 filed June 13, 2019). Exemplary ACC inhibitors include 4-(4-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1'H- spiro[indazole-5,4'-piperidin]-1'-yl)carbonyl]-6-methoxypyridin-2-yl)benzoic acid, gemcabene, and firsocostat (GS-0976) and phamaceutally acceptable salts thereof. Exemplary FXR agonists include tropifexor (2-[(1R,3R,5S)-3-({5-cyclopropyl-3-[2- (trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3- benzothiazole-6-carboxylic acid), cilofexor (GS-9674), obeticholic acid, LY2562175, Met409, TERN-101 and EDP-305 and pharmaceutically acceptable salts thereof. Exemplary KHK inhibitors include [(1R,5S,6R)-3-{2-[(2S)-2-methylazetidin-1-yl]-6- (trifluoromethyl)pyrimidin-4-yl}-3-azabicyclo[3.1.0]hex-6-yl]acetic acid and pharmaceutically acceptable salts thereof. Exemplary DGAT2 inhibitors include (S)-2-(5-((3-ethoxypyridin-2-yl)oxy)pyridin-3-yl)-N- (tetrahydrofuran-3-yl)pyrimidine-5-carboxamide [including its crystalline solid forms (Form 1 and Form 2)]. See U.S. Patent No.10,071,992. Some exemplary BCKDK inhibitors include those described in US Patent Nos. 11542270 and 11059833, including the following: 5-(5-chloro-4-fluoro 3-methylthiophen-2-yl)-1H-tetrazole; 5-(5-chloro-3-difluoromethylthiophen-2-yl)-1H-tetrazole; 5-(5-fluoro-3-methylthiophen-2-yl)-1H-tetrazole; 5-(5-chloro-3-methylthiophen-2-yl)-1H-tetrazole; 5-(3,5-dichlorothiophen-2-yl)-1H-tetrazole; 5-(4-bromo-3-methylthiophen-2-yl)-1H-tetrazole; 5-(4-bromo-3-ethylthiophen-2-yl)-1H-tetrazole; 5-(4-chloro-3-ethylthiophen-2-yl)-1H-tetrazole; 3-chloro-5-fluorothieno[3,2-b]thiophene-2-carboxylic acid; 3-bromo-5-fluorothieno[3,2- b]thiophene-2-carboxylic acid; 3-(difluoromethyl)-5-fluorothieno[3,2-b]thiophene-2-carboxylic acid; 5,6-difluorothieno[3,2-b]thiophene-2-carboxylic acid; and 3,5-difluorothieno[3,2-b]thiophene-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. Some additional exemplary BCKDK inhibitors include those described in US Patent Application 18 / 060,027, filed November 30, 2022, including the following: 6-fluoro-3-(2,4,6-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid; 6-fluoro-3-(2,4,5-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid; 6-chloro-3-(2,4,5-trifluoro-3-methylphenyl)-1-benzothiophene-2-carboxylic acid; 6-chloro-3-(2,4-difluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid; 3-(6-chloro-2,4-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid; 3-(6-chloro-2,4-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid, ATROP-2; 3-(3-chloro-2,4,5-trifluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid; 3-(4-chloro-2,6-difluoro-3-methoxyphenyl)-6-fluoro-1-benzothiophene-2-carboxylic acid; 6-chloro-3-(2,4,6-trifluoro-3-methoxyphenyl)-1-benzothiophene-2-carboxylic acid; 6-chloro-3-(3-ethyl-2,4,5-trifluorophenyl)-1-benzothiophene-2-carboxylic acid; or ammonium 3-(3-ethyl-2,4,5-trifluorophenyl)-6-fluoro-1-benzothiophene-2-carboxylate; or a pharmaceutically acceptable salt thereof. In some embodiments, a compound of this invention may be co-administered with one or more anti-diabetic agents. Suitable anti-diabetic agents include insulin, metformin, GLP-1 receptor agonists (described herein above), an acetyl-CoA carboxylase (ACC) inhibitor (described herein above), SGLT2 inhibitors (described herein above), monoacylglycerol O- acyltransferase inhibitors, phosphodiesterase (PDE)-10 inhibitors, AMPK activators [e.g., ETC- 1002 (bempedoic acid)], sulfonylureas (e.g., acetohexamide, chlorpropamide, diabinese, glibenclamide, glipizide, glyburide, glimepiride, gliclazide, glipentide, gliquidone, glisolamide, tolazamide, and tolbutamide), meglitinides, α-amylase inhibitors (e.g., tendamistat, trestatin and AL-3688), an α-glucoside hydrolase inhibitor (e.g., acarbose), α-glucosidase inhibitors (e.g., adiposine, camiglibose, emiglitate, miglitol, voglibose, pradimicin-Q, and salbostatin), PPARγ agonists (e.g., balaglitazone, ciglitazone, darglitazone, englitazone, isaglitazone, pioglitazone and rosiglitazone), PPAR α / γ agonists (e.g., CLX-0940, GW-1536, GW-1929, GW-2433, KRP- 297, L-796449, LR-90, MK-0767 and SB-219994), protein tyrosine phosphatase-1B (PTP-1B) inhibitors [e.g., trodusquemine, hyrtiosal extract, and compounds disclosed by Zhang, S. et al., Drug Discovery Today, 12(9 / 10), 373-381 (2007)], SIRT-1 activators (e.g., resveratrol, GSK2245840 or GSK184072), dipeptidyl peptidase IV (DPP-IV) inhibitors (e.g., those in WO2005116014, sitagliptin, vildagliptin, alogliptin, dutogliptin, linagliptin and saxagliptin), insulin secretagogues, fatty acid oxidation inhibitors, A2 antagonists, c-jun amino-terminal kinase (JNK) inhibitors, glucokinase activators (GKa) such as those described in WO2010103437, WO2010103438, WO2010013161, WO2007122482, TTP-399, TTP-355, TTP-547, AZD1656, ARRY403, MK-0599, TAK-329, AZD5658 or GKM-001, insulin, insulin mimetics, glycogen phosphorylase inhibitors (e.g., GSK1362885), VPAC2 receptor agonists, glucagon receptor modulators such as those described in Demong, D.E. et al., Annual Reports in Medicinal Chemistry 2008, 43, 119-137, GPR119 modulators, particularly agonists, such as those described in WO2010140092, WO2010128425, WO2010128414, WO2010106457, Jones, R.M. et al., Annual Reports in Medicinal Chemistry 2009, 44, 149-170 (e.g., MBX-2982, GSK1292263, APD597 and PSN821), FGF21 derivatives or analogs such as those described in Kharitonenkov, A. et al., Current Opinion in Investigational Drugs 2009, 10(4)359-364, TGR5 (also termed GPBAR1) receptor modulators, particularly agonists, such as those described in Zhong, M., Current Topics in Medicinal Chemistry, 2010, 10(4), 386-396 and INT777, GPR40 agonists, such as those described in Medina, J.C., Annual Reports in Medicinal Chemistry, 2008, 43, 75-85, including but not limited to TAK-875, GPR120 modulators, particularly agonists, high-affinity nicotinic acid receptor (HM74A) activators, and SGLT1 inhibitors, such as GSK1614235. A further representative listing of anti-diabetic agents that can be combined with the compounds of the present invention can be found, for example, at page 28, line 35 through page 30, line 19 of WO2011005611. Other antidiabetic agents could include inhibitors or modulators of carnitine palmitoyl transferase enzymes, inhibitors of fructose 1,6-diphosphatase, inhibitors of aldose reductase, mineralocorticoid receptor inhibitors, inhibitors of TORC2, inhibitors of CCR2 and / or CCR5, inhibitors of PKC isoforms (e.g., PKC^^ PKC^, PKC^), inhibitors of fatty acid synthetase, inhibitors of serine palmitoyl transferase, modulators of GPR81, GPR39, GPR43, GPR41, GPR105, Kv1.3, retinol binding protein 4, glucocorticoid receptor, somatostain receptors (e.g., SSTR1, SSTR2, SSTR3 and SSTR5), inhibitors or modulators of PDHK2 or PDHK4, inhibitors of MAP4K4, modulators of IL1 family including IL1beta, and modulators of RXRalpha. In addition suitable anti-diabetic agents include mechanisms listed by Carpino, P.A., Goodwin, B. Expert Opin. Ther. Pat., 2010, 20(12), 1627-51. The compounds of the present invention may be co-administered with anti-heart failure agents such as ACE inhibitors (e.g., captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril), Angiotensin II receptor blockers (e.g., candesartan, losartan, valsartan), Angiotensin-receptor neprilysin inhibitors (sacubitril / valsartan), If channel blocker Ivabradine, Beta-Adrenergic blocking agents (e.g., bisoprolol, metoprolol succinate, carvedilol), Aldosterone antagonists (e.g., spironolactone, eplerenone), hydralazine and isosorbide dinitrate, diuretics (e.g., furosemide, bumetanide, torsemide, chlorothiazide, amiloride, hydrochlorothiazide, Indapamide, Metolazone, Triamterene), or digoxin. The compounds of the present invention may also be co-administered with cholesterol or lipid lowering agents including the following exemplary agents: HMG CoA reductase inhibitors (e.g., pravastatin, pitavastatin, lovastatin, atorvastatin, simvastatin, fluvastatin, NK- 104 (a.k.a. itavastatin, or nisvastatin or nisbastatin) and ZD-4522 (a.k.a. rosuvastatin, or atavastatin or visastatin); squalene synthetase inhibitors; fibrates (e.g., gemfibrozil, pemafibrate, fenofibrate, clofibrate); bile acid sequestrants (such as questran, colestipol, colesevelam); ACAT inhibitors; MTP inhibitors; lipooxygenase inhibitors; cholesterol absorption inhibitors (e.g., ezetimibe); nicotinic acid agents (e.g., niacin, niacor, slo-niacin); omega-3 fatty acids (e.g., epanova, fish oil, eicosapentaenoic acid); cholesteryl ester transfer protein inhibitors (e.g., obicetrapib) and PCSK9 modulators [e.g., alirocumab, evolocumab, bococizumab, ALN- PCS (inclisiran)]. The compounds of the present invention may also be used in combination with antihypertensive agents and such antihypertensive activity is readily determined by those skilled in the art according to standard assays (e.g., blood pressure measurements). Examples of suitable anti-hypertensive agents include: alpha-adrenergic blockers; beta-adrenergic blockers; calcium channel blockers (e.g., diltiazem, verapamil, nifedipine and amlodipine); vasodilators (e.g., hydralazine), diruetics (e.g., chlorothiazide, hydrochlorothiazide, flumethiazide, hydroflumethiazide, bendroflumethiazide, methylchlorothiazide, trichloromethiazide, polythiazide, benzthiazide, ethacrynic acid tricrynafen, chlorthalidone, torsemide, furosemide, musolimine, bumetanide, triamtrenene, amiloride, spironolactone); renin inhibitors; ACE inhibitors (e.g., captopril, zofenopril, fosinopril, enalapril, ceranopril, cilazopril, delapril, pentopril, quinapril, ramipril, lisinopril); AT-1 receptor antagonists (e.g., losartan, irbesartan, valsartan); ET receptor antagonists (e.g., sitaxsentan, atrsentan and compounds disclosed in U.S. Patent Nos.5,612,359 and 6,043,265); Dual ET / AII antagonist (e.g., compounds disclosed in WO 00 / 01389); neutral endopeptidase (NEP) inhibitors; vasopepsidase inhibitors (dual NEP-ACE inhibitors) (e.g., gemopatrilat and nitrates). An exemplary antianginal agent is ivabradine. Examples of suitable calcium channel blockers (L-type or T-type) include diltiazem, verapamil, nifedipine and amlodipine and mybefradil. Examples of suitable cardiac glycosides include digitalis and ouabain. In one embodiment, a compound of invention may be co-administered with one or more diuretics. Examples of suitable diuretics include (a) loop diuretics such as furosemide (such as LASIX™), torsemide (such as DEMADEX™), bemetanide (such as BUMEX™), and ethacrynic acid (such as EDECRIN™); (b) thiazide-type diuretics such as chlorothiazide (such as DIURIL™, ESIDRIX™ or HYDRODIURIL™), hydrochlorothiazide (such as MICROZIDE™ or ORETIC™), benzthiazide, hydroflumethiazide (such as SALURON™), bendroflumethiazide, methychlorthiazide, polythiazide, trichlormethiazide, and indapamide (such as LOZOL™); (c) phthalimidine-type diuretics such as chlorthalidone (such as HYGROTON™), and metolazone (such as ZAROXOLYN™); (d) quinazoline-type diuretics such as quinethazone; and (e) potassium-sparing diuretics such as triamterene (such as DYRENIUM™), and amiloride (such as MIDAMOR™ or MODURETIC™). In another embodiment, a compound of the invention may be co-administered with a loop diuretic. In still another embodiment, the loop diuretic is selected from furosemide and torsemide. In still another embodiment, one or more compounds of Formula I or their pharmaceutically acceptable salts may be co-administered with furosemide. In still another embodiment, one or more compounds of Formula I or their pharmaceutically acceptable salts may be co-administered with torsemide which may optionally be a controlled or modified release form of torsemide. In another embodiment, a compound of the invention may be co-administered with a thiazide-type diuretic. In still another embodiment, the thiazide-type diuretic is selected from the group consisting of chlorothiazide and hydrochlorothiazide. In still another embodiment, one or more compounds of Formula I or their pharmaceutically acceptable salts may be co- administered with chlorothiazide. In still another embodiment, one or more compounds of Formula I or their pharmaceutically acceptable salts may be co-administered with hydrochlorothiazide. In another embodiment, one or more compounds of Formula I or their pharmaceutically acceptable salts may be co-administered with a phthalimidine-type diuretic. In still another embodiment, the phthalimidine-type diuretic is chlorthalidone. Examples of suitable mineralocorticoid receptor antagonists include sprionolactone and eplerenone. Examples of suitable phosphodiesterase inhibitors include: PDE III inhibitors (such as cilostazol); and PDE V inhibitors (such as sildenafil). Those skilled in the art will recognize that the compounds of this invention may also be used in conjunction with other cardiovascular or cerebrovascular treatments including Percutaneous Coronary Intervention (PCI), stenting, drug-eluting stents, stem cell therapy and medical devices such as implanted pacemakers, defibrillators, or cardiac resynchronization therapy. Particularly when provided as a single dosage unit, the potential exists for a chemical interaction between the combined active ingredients. For this reason, when a compound of this invention and a second therapeutic agent are combined in a single dosage unit they may be formulated such that although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized (that is, reduced). For example, one active ingredient may be enteric-coated. By enteric-coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. One of the active ingredients may also be coated with a material that effects a sustained release throughout the gastrointestinal tract and also serves to minimize physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric-coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and / or enteric-release polymer, and the other component is also coated with a polymer such as a low viscosity grade of hydroxypropyl methylcellulose (HPMC) or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component. These as well as other ways of minimizing contact between the components of combination products of the present invention, whether administered in a single dosage form or administered in separate forms but at the same time by the same manner, will be readily apparent to those skilled in the art, once armed with the present disclosure. Another approach may involve the formulation of a combination product in which both active components are combined with a material that effects a sustained release throughout the gastrointestinal tract of both active ingredients. In some embodiments of combination therapy treatment, both the compounds of this invention and the other drug therapies are administered to patients such as mammals (e.g., humans, male or female) by conventional methods. Kits Another aspect of the invention provides kits comprising the compound of the invention or pharmaceutical compositions comprising the compound of the invention. A kit may include, in addition to the compound of the invention or pharmaceutical composition thereof, diagnostic or therapeutic agents. A kit may also include instructions for use in a diagnostic or therapeutic method. In some embodiments, the kit includes the compound or a pharmaceutical composition thereof and a diagnostic agent. In other embodiments, the kit includes the compound or a pharmaceutical composition thereof and one or more therapeutic agents as described in the co- administration section hereinabove. In yet another embodiment, the invention comprises kits that are suitable for use in performing the methods of treatment described herein. In one embodiment, the kit contains a first dosage form comprising one or more of the compounds of the invention in quantities sufficient to carry out the methods of the invention. In another embodiment, the kit comprises one or more compounds of the invention in quantities sufficient to carry out the methods of the invention and a container for the dosage and a container for the dosage. EXAMPLES The following illustrate the synthesis of various compounds of the present invention. Additional compounds within the scope of this invention may be prepared using the methods illustrated in these Examples, either alone or in combination with techniques generally known in the art. All starting materials in these Preparations and Examples are either commercially available or can be prepared by methods known in the art or as described herein. Reactions were performed in air or, when oxygen- or moisture-sensitive reagents or intermediates were employed, under an inert atmosphere (nitrogen or argon). When appropriate, reaction apparatuses were dried under dynamic vacuum using a heat gun, and anhydrous solvents (Sure-SealTMproducts from Aldrich Chemical Company, Milwaukee, Wisconsin or DriSolvTMproducts from EMD Chemicals, Gibbstown, NJ) were employed. In some cases, some commercial solvents may have been passed through columns packed with 4Å molecular sieves, until the following QC standards for water were attained: a) <100 ppm for dichloromethane, toluene, N,N-dimethylformamide, and tetrahydrofuran; b) <180 ppm for methanol, ethanol, 1,4-dioxane, and diisopropylamine. For very sensitive reactions, some solvents may have been further treated with metallic sodium, calcium hydride, or molecular sieves, and distilled just prior to use. Other commercial solvents and reagents were used without further purification. For syntheses referencing procedures in other Examples or Methods, reaction conditions (reaction time and temperature) may vary. Products were generally dried under vacuum before being carried on to further reactions or submitted for biological testing. When indicated, reactions were heated by microwave irradiation using Biotage Initiator or Personal Chemistry Emrys Optimizer microwave instruments. Reaction progress was monitored using thin-layer chromatography (TLC), liquid chromatography-mass spectrometry (LCMS), high-performance liquid chromatography (HPLC), and / or gas chromatography-mass spectrometry (GCMS) analyses. TLC was performed on pre-coated silica gel plates with a fluorescence indicator (254 nm excitation wavelength) and visualized under UV light and / or with I2, KMnO4, CoCl2, phosphomolybdic acid, or ceric ammonium molybdate stains. LCMS data were acquired on an Agilent 1100 Series instrument with a Leap Technologies autosampler, Gemini C18 columns, acetonitrile / water gradients, and either trifluoroacetic acid, formic acid, or ammonium hydroxide modifiers. The column eluent was analyzed using a Waters ZQ mass spectrometer scanning in both positive and negative ion modes from 100 to 1200 Da. Other similar instruments were also used. HPLC data were generally acquired on an Agilent 1100 Series instrument using Gemini or XBridge C18 columns, acetonitrile / water gradients, and either trifluoroacetic acid or ammonium hydroxide modifiers. GCMS data were acquired using a Hewlett Packard 6890 oven with an HP 6890 injector, HP-1 column (12 m x 0.2 mm x 0.33 µm), and helium carrier gas. Samples were analyzed on an HP 5973 mass selective detector, scanning from 50 to 550 Da using electron ionization. Purifications were performed by medium performance liquid chromatography (MPLC) using Isco CombiFlash Companion, AnaLogix IntelliFlash 280, Biotage SP1, or Biotage Isolera One instruments and pre-packed Isco RediSep or Biotage Snap silica cartridges. Chiral purifications were generally performed by chiral supercritical fluid chromatography (SFC) using Berger or Thar instruments; ChiralPAK-AD, -AS, -IC, Chiralcel-OD, or -OJ columns; and CO2mixtures with methanol, ethanol, propan-2-ol, or acetonitrile, alone or modified using trifluoroacetic acid or propan-2-amine. UV detection was used to trigger fraction collection. For syntheses referencing procedures in other Examples or Methods, purifications may vary: in general, solvents and the solvent ratios used for eluents / gradients were chosen to provide appropriate Rfs or retention times. Mass spectrometry data are reported from LCMS analyses. Mass spectrometry (MS) was performed via atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI), electron impact ionization (EI) or electron scatter (ES) ionization sources. Proton nuclear magnetic spectroscopy (1H NMR) chemical shifts are given in parts per million downfield from tetramethylsilane and were recorded on 300, 400, 500, or 600 MHz Varian, Bruker, or Jeol spectrometers. Chemical shifts are expressed in parts per million (ppm, ^) referenced to the deuterated solvent residual peaks (chloroform, 7.26 ppm; CD2HOD, 3.31 ppm; acetonitrile-d2, 1.94 ppm; dimethyl sulfoxide-d5, 2.50 ppm; DHO, 4.79 ppm). The peak shapes are described as follows: s, singlet; d, doublet; t, triplet; q, quartet; quin, quintet; m, multiplet; br s, broad singlet; app, apparent. Analytical SFC data were acquired on a Berger analytical instrument as described above. Optical rotation data were acquired on a PerkinElmer model 343 polarimeter using a 1 dm cell. Silica gel chromatography was performed primarily using medium-pressure Biotage or ISCO systems using columns pre-packaged by various commercial vendors including Biotage and ISCO. Microanalyses were performed by Quantitative Technologies Inc. and were within 0.4% of the calculated values. Unless otherwise noted, chemical reactions were performed at room temperature (about 23 degrees Celsius). Unless noted otherwise, all reactants were obtained commercially without further purifications or were prepared using methods known in the literature. The terms “concentrated,” “evaporated,” and “concentrated in vacuo” refer to the removal of solvent at reduced pressure on a rotary evaporator with a bath temperature less than 60 °C. The abbreviation “min” and “h” stand for “minutes” and “hours” respectively. The term “TLC” refers to thin-layer chromatography, “room temperature or ambient temperature” means a temperature between 18 and 25 °C, “GCMS” refers to gas chromatography–mass spectrometry, “LCMS” refers to liquid chromatography–mass spectrometry, “UPLC” refers to ultra-performance liquid chromatography and “HPLC” refers to high-performance liquid chromatography, “SFC” refers to supercritical fluid chromatography. Hydrogenation may be performed in a Parr Shaker under pressurized hydrogen gas, or in a Thales-nano H-Cube flow hydrogenation apparatus at full hydrogen and a flow rate between 1 and 2 mL / minute at the specified temperature. HPLC, UPLC, LCMS, GCMS, and SFC retention times were measured using the methods noted in the procedures. In some examples, chiral separations were carried out to separate enantiomers or diastereomers of certain compounds of the invention (in some examples, the separated enantiomers are designated as ENANT-1 and ENANT-2, according to their order of elution; similarly, separated diastereomers are designated as DIAST-1 and DIAST-2, according to their order of elution). In some examples, the optical rotation of an enantiomer was measured using a polarimeter. According to its observed rotation data (or its specific rotation data), an enantiomer with a clockwise rotation was designated as the (+)-enantiomer and an enantiomer with a counter-clockwise rotation was designated as the (-)-enantiomer. Racemic compounds are indicated either by the absence of drawn or described stereochemistry, or by the presence of (+ / -) adjacent to the structure; in this latter case, the indicated stereochemistry represents just one of the two enantiomers that make up the racemic mixture. The compounds and intermediates described below were named using the naming convention provided with ACD / ChemSketch 2020.2.1.1, File Version C25H41, Build 121153 (Advanced Chemistry Development, Inc., Toronto, Ontario, Canada). The naming convention provided with ACD / ChemSketch 2020.2.1.1 is well known by those skilled in the art and it is believed that the naming convention provided with ACD / ChemSketch 2020.2.1.1 generally comports with the IUPAC (International Union for Pure and Applied Chemistry) recommendations on Nomenclature of Organic Chemistry and the CAS Index rules. Example 1 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid (Compound 1) Step 1. Synthesis of 1-{[4-(propan-2-yl)phenyl]carbamoyl}-D-proline (C1). 4-Methylmorpholine (20.5 mL, 186 mmol) was added to a 2 °C to 3 °C mixture of D- proline (21.4 g, 186 mmol) in tetrahydrofuran (520 mL). After 2 minutes, 1-isocyanato-4- (propan-2-yl)benzene (25.0 g, 155 mmol) was added over 30 seconds, whereupon stirring was continued for 5 minutes before the reaction mixture was removed from the ice bath and allowed to stir at room temperature. Two hours later, LCMS analysis indicated formation of C1: LCMS m / z 277.4 [M+H]+. Water (500 mL) was added, followed by solid sodium bicarbonate (19.5 g, 233 mmol), yielding a pH of 7 to 8. The resulting mixture was washed with methyl tert-butyl ether (2 x 600 mL); the aqueous layer was then acidified to pH 2 by addition of concentrated hydrochloric acid and stirred for 20 minutes. Filtration, followed by rinsing of the filter cake with water, provided C1 as a white solid. Yield: 39.1 g, 141 mmol, 91%.1H NMR (400 MHz, DMSO- d6) ^ 12.36 (br s, 1H), 8.16 (s, 1H), 7.38 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 4.34 – 4.26 (m, 1H), 3.58 – 3.50 (m, 1H), 3.49 – 3.41 (m, 1H), 2.81 (septet, J = 6.9 Hz, 1H), 2.22 – 2.11 (m, 1H), 1.97 – 1.83 (m, 3H), 1.17 (d, J = 6.9 Hz, 6H). Step 2. Synthesis of (2R)-N2-(4-bromophenyl)-N1-[4-(propan-2-yl)phenyl]pyrrolidine-1,2- dicarboxamide (C3). A mixture of 4-bromoaniline (1.94 g, 11.3 mmol), C1 (3.12 g, 11.3 mmol), and 1-[3- (dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (2.60 g, 13.6 mmol) in dichloromethane (50 mL) was stirred at room temperature for 16 hours, whereupon LCMS analysis indicated conversion to C3: LCMS m / z 430.2 (bromine isotope pattern observed) [M+H]+. The reaction mixture was poured into water and extracted with dichloromethane; the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford C3 as a white solid. Yield: 4.82 g, 11.2 mmol, 99%.1H NMR (400 MHz, chloroform-d) ^ 9.94 (br s, 1H), 7.41 (AB quartet, JAB= 8.9 Hz, Δ^AB= 27.9 Hz, 4H), 7.25 (AB quartet, JAB= 8.5 Hz, Δ^AB= 46.6 Hz, 4H), 6.30 (br s, 1H), 4.74 (br d, J = 8.0 Hz, 1H), 3.55 (ddd, J = 8, 8, 1.9 Hz, 1H), 3.44 – 3.36 (m, 1H), 2.89 (septet, J = 7.0 Hz, 1H), 2.64 (dd, J = 12.6, 6.3 Hz, 1H), 2.29 – 2.07 (m, 2H), 1.89 (tdd, J = 12.4, 8.0, 6.8 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H). Step 3. Synthesis of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid (Compound 1) To a mixture of C3 (1.50 g, 3.49 mmol) and 4-boronobenzoic acid (694 mg, 4.18 mmol) in 1,4-dioxane (22 mL) was added aqueous sodium carbonate solution (2 M; 5.23 mL, 10.5 mmol), followed by mesylate[(di(1-adamantyl)-n-butylphosphine)-2-(2′-amino-1,1′- biphenyl)]palladium(II) (cataCXium®A Pd G3; 127 mg, 0.174 mmol). After the reaction mixture had been degassed for 5 minutes, it was heated at 90 °C overnight and then cooled to room temperature. The pH was adjusted to 4 to 5 via addition of 1 M hydrochloric acid, and the resulting mixture was partitioned between ethyl acetate (200 mL) and water (100 mL); this produced an insoluble solid, which was isolated via filtration and washed with ethyl acetate. This material was triturated with propan-2-ol, first at 70 °C for 5 hours, then at room temperature for 20 hours, whereupon the suspension was filtered and the filter cake was washed with dichloromethane, affording 4'-[(1-{[4-(propan-2-yl)phenyl]carbamoyl}-D- prolyl)amino][1,1'-biphenyl]-4-carboxylic acid (Compound 1) as a white solid. Yield: 435 mg, 0.922 mmol, 26%. LCMS m / z 472.3 [M+H]+.1H NMR (400 MHz, DMSO-d6) ^ 12.90 (br s, 1H), 10.13 (s, 1H), 8.19 (s, 1H), 7.88 (AB quartet, JAB = 8.4 Hz, Δ^AB = 83.3 Hz, 4H), 7.72 (AB quartet, JAB= 9.0 Hz, Δ^AB= 12.2 Hz, 4H), 7.40 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 4.47 (dd, J = 8.3, 3.6 Hz, 1H), 3.70 – 3.60 (m, 1H), 3.56 – 3.47 (m, 1H), 2.80 (septet, J = 6.9 Hz, 1H), 2.26 – 2.12 (m, 1H), 2.10 – 1.87 (m, 3H), 1.16 (d, J = 6.9 Hz, 6H). The combined organic layers from above were washed sequentially with water (2 x 50 mL) and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 5% methanol in dichloromethane), followed by trituration with a mixture of dichloromethane and methanol at room temperature for 20 hours, provided additional 4'-[(1-{[4-(propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid (Compound 1) as a white solid. Yield: 410 mg, 0.869 mmol, 25%; combined yield: 51%. Alternate Synthesis of Compound 1 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid (Compound 1)

[0003] Step 1. Synthesis of tert-butyl 4'-amino[1,1'-biphenyl]-4-carboxylate (C11). To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (20.0 g, 91.3 mmol) in a mixture of 1,4-dioxane (400 mL) and water (100 mL) were added tert-butyl 4- bromobenzoate (25.8 g, 100 mmol) and potassium carbonate (37.8 g, 274 mmol). [1,1’- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (3.34 g, 4.56 mmol) was then added; the reaction mixture was heated at 95 °C for 16 hours, whereupon it was filtered. The filtrate was concentrated under reduced pressure, and the residue was diluted with water (500 mL) and extracted with ethyl acetate (2 x 500 mL). After the combined organic layers had been washed with saturated aqueous sodium chloride solution (2 x 500 mL), they were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 50% ethyl acetate in petroleum ether) provided a solid, which was treated with propan-2-yl acetate (20 mL) and heptane (80 mL) and stirred for 30 minutes before collection of the solid via filtration. The filter cake was washed with heptane (3 x 15 mL) to afford C11 as a pinkish-white solid. Yield: 18.5 g, 68.7 mmol, 75%. LCMS m / z 270.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) ^ 7.88 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 6.66 (d, J = 8.5 Hz, 2H), 5.39 (s, 2H), 1.55 (s, 9H). Step 2. Synthesis of tert-butyl 4'-[(1-{[4-(propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'- biphenyl]-4-carboxylate (C12). 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (3.46 g, 18.0 mmol) was added to a solution of C1 (3.95 g, 14.3 mmol) and C11 (4.05 g, 15.0 mmol) in N,N- dimethylacetamide (38 mL). After 1.5 hours, LCMS analysis indicated the presence of product: LCMS m / z 528.5 [M+H]+. Water (50 mL) was added, and the mixture was stirred for 8 minutes before being filtered; the collected solids were washed with water and stirred in diethyl ether (60 mL) for 10 minutes. Solids were isolated again by filtration, suspended in a solution of methanol in dichloromethane (5%, 50 mL), stirred for 25 minutes, and filtered. Washing of the filter cake with dichloromethane afforded C12 as a white solid. Yield: 5.43 g, 10.3 mmol, 72%.1H NMR (400 MHz, DMSO-d6) ^ 10.14 (s, 1H), 8.19 (s, 1H), 7.94 (d, J = 8.5 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 7.72 (AB quartet, JAB= 8.9 Hz, ΔνAB= 15.6 Hz, 4H), 7.40 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 4.47 (dd, J = 8.2, 3.6 Hz, 1H), 3.69 – 3.60 (m, 1H), 3.56 – 3.47 (m, 1H), 2.79 (septet, J = 6.9 Hz, 1H), 2.25 – 2.13 (m, 1H), 2.10 – 1.88 (m, 3H), 1.56 (s, 9H), 1.16 (d, J = 6.9 Hz, 6H). Step 3. Synthesis of 4'-[(1-{[4-(propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid (Compound 1). Methanesulfonic acid (0.129 mL, 1.99 mmol) was added to a solution of C12 (1.00 g, 1.90 mmol) in 1,1,1,3,3,3-hexafluoropropan-2-ol (10 mL), and the reaction mixture was stirred at room temperature for 15 minutes, whereupon it was concentrated in vacuo. The residue was slurried in diethyl ether for 5 minutes; solids were collected via filtration, washed with diethyl ether, and suspended in propan-2-yl acetate (15 mL). Methanol (2 mL) was added, and the mixture was stirred at room temperature for 3 days. Isolation via filtration, followed by washing of the filter cake with propan-2-yl acetate (3 mL), provided 4'-[(1-{[4-(propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid (Compound 1) as a solid. Yield: 668 mg, 1.42 mmol, 75%. LCMS m / z 472.4 [M+H]+.1H NMR (400 MHz, DMSO-d6) 12.90 (v br s, 1H), 10.13 (s, 1H), 8.19 (s, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 7.72 (AB quartet, JAB = 9.0 Hz, ΔνAB = 12.7 Hz, 4H), 7.40 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 4.47 (dd, J = 8.3, 3.6 Hz, 1H), 3.70 – 3.61 (m, 1H), 3.56 – 3.47 (m, 1H), 2.80 (septet, J = 6.9 Hz, 1H), 2.25 – 2.13 (m, 1H), 2.10 – 1.88 (m, 3H), 1.16 (d, J = 6.9 Hz, 6H). Example 2 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L- Lysine salt (Form 1 of L-lysine salt of Compound 1) Compound 1 (21.3 g 45.2 mmol) was stirred in 1.03 L acetone. A 100 mg / mL aqueous solution of L-lysine (6.60 g, 66.0 ml, 45.2 mmol) was added and the mixture was stirred at room temperature for 24 h. The reaction mixture was then filtered. The filter cake was resuspended in a mixture of 575 mL acetone and 145 mL H2O and stirred at room temperature for 18 h. Then the resulting suspension was filtered and the solid collected was dried under vacuum to afford a white solid 17.8 g (27.6 mmol, 64% yield) LCMS m / z 472.4 [M+H]+The white solid was determined to be crystalline and sesquihydrate (herein designated as Form 1). Acquisition of Powder X-ray Diffraction (PXRD) Data A sample of white solid of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'- biphenyl]-4-carboxylic acid L-Lysine salt prepared according to the method described hereinabove was submitted for PXRD analysis and found to be a crystalline material (which is herein designated as Form 1). Powder X-ray diffraction analysis was conducted using a Bruker AXS D8 Endeavor diffractometer equipped with a Cu radiation source (K-α average). The divergence slit was set at 15 mm continuous illumination. Diffracted radiation was detected by a PSD-Lynx Eye detector, with the detector PSD opening set at 4.10 degrees. The X-ray tube voltage and amperage were set to 40 kV and 40 mA respectively. Data was collected in the Theta-Theta goniometer at the Cu wavelength from 3.0 to 40.0 degrees 2-Theta using a step size of 0.01 degrees and a step time of 1.0 second. The antiscatter screen was set to a fixed distance of 3.0 mm. Samples were rotated at 15 / min during collection. Samples were prepared by placing them in a silicon low background sample holder and rotated during collection. Data were collected using Bruker DIFFRAC Plus software and analysis was performed by EVA diffract plus software. The PXRD data file was not processed prior to peak searching. Using the peak search algorithm in the EVA software, peaks selected with a threshold value of 10 were used to make preliminary peak assignments. To ensure validity, adjustments were manually made; the output of automated assignments was visually checked, and peak positions were adjusted to the peak maximum. Peaks with relative intensity of ≥ 3.0% were generally chosen. Typically, the peaks which were not resolved or were consistent with noise were not selected. A typical error associated with the peak position from PXRD stated in USP up to + / - 0.2° 2-Theta (USP-941). A representative PXRD pattern of Form 1 of L-lysine salt of Compound 1 is shown in FIG.1. A list of PXRD diffraction peaks expressed in terms of the degree 2θ and relative intensities with a relative intensity of ≥ 3.0% from a sample of Form 1 of L-lysine of Compound 1 is provided below. Table 1: PXRD Peaks and Relative Intensities of Form 1 of the L-lysine of Compound 1 Angle (°2θ) Relative Intensity (%) + 0.2º 2Ɵ 7.3 27 10.9 4 11.2 3 13.4 7 14.7 5 16.3 16 16.7 14 17.3 10 17.6 11 17.9 20 18.2 11 18.6 32 18.9 22 19.1 11 19.7 100 20.7 7 21.0 14 21.2 17 21.7 11 21.9 11 22.4 28 22.5 22 22.9 10 23.2 11 23.8 8 24.0 9 24.3 12 24.5 8 24.9 7 25.1 8 25.7 9 26.2 8 26.5 11 26.7 14 27.0 16 27.5 10 28.4 19 29.8 12 29.9 12 30.4 9 31.0 8 31.8 7 32.2 9 34.9 9 38.3 7 39.0 8 Single Crystal X-Ray Analysis. A sample of white solid of L-Lysine salt of Compound 1 was added to 2 mL of 1:1 EtOH / water (v / v) to form a slurry. The slurry was then heated to 40°C for approximately 10 minutes, and then centrifuge filtered. The filtrate (i.e., a solution of L-Lysine salt of Compound 1 dissolved in 1:1 EtOH / water) was transferred to a 2 mL glass vial (and holes were poked in the septum of the of the vial cap and a needle was left in the cap) and the solution was subject to slow evaporation at room temperature for about one day, which resulted in crystals. A crystal (Form 1) was characterized by single crystal X-ray diffraction analysis which confirmed sesquihydrate stoichiometry. Data collection was performed on a Bruker D8 Venture diffractometer with rotating copper anode (Cu Ka (1.54178 Å)) at room temperature (298 K) on a representative crystal. Data collection consisted of omega and phi scans. The structure was solved by intrinsic phasing using SHELX software suite (SHELXTL, Version 5.1, Bruker AXS, 1997) (SHELXTL, Version 5.1, Bruker AXS, 1997) in the monoclinic space group P21. The structure was subsequently refined by the full-matrix least squares method. All non-hydrogen atoms were found and refined using anisotropic displacement parameters using OLEX2 software (OLEX2, Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H., (2009). J. Appl. Cryst., 42, 339-341.). After the initial single crystal X-ray diffraction analysis, an updated analysis was conducted. For both analyses, the hydrogen atoms located on N1A, N1B, N3A, N3B, N4A, N5A, and O9 were found from the Fourier difference map and refined with distances restrained. The remaining hydrogen atoms were placed in calculated positions and allowed to ride on their carrier atoms. The final refinement included isotropic displacement parameters for all hydrogen atoms. The N4BA / N4BB segment was treated as disordered with a population ratio of approximately 60:40 and refined with the appropriate restraints. Analysis of the absolute structure using likelihood methods (See R.W.W. Hooft et al. J. Appl. Cryst. (2008).41.96-103) was performed using PLATON (See A.L. Spek, J. Appl. Cryst. 2003, 36, 7-13). The final R-index was 6.2% for both the initial and the updated analyses. A final difference Fourier revealed no missing or misplaced electron density. The refined structure was plotted using the SHELXTL plotting package (SHELXTL, Version 5.1, Bruker AXS, 1997) (see e.g. FIG.2 and FIG.14, which shows the full asymmetric unit diagram with anisotropic displacement parameters drawn at 50% probability; and FIG.3 and FIG.15, which shows partial asymmetric unit with representative labeling scheme, where both figures were prepared using Mercury software (MERCURY, C.F. Macrae, P.R. Edington, P. McCabe, E. Pidcock, G.P. Shields, R. Taylor, M. Towler and J. van de Streek, J. Appl. Cryst.39, 453-457, 2006.)). According to the refined structure, Form 1 is a sesquihydrate of L-lysine salt of Compound 1. The initial and the updated analyses differ mainly in the placement of hydrogen atoms on O7. Other changes are primarily associated with the subsequent refinement. Pertinent crystal, data collection and refinement are summarized in Table 2 and 2A. Atomic coordinates, bond lengths, bond angles and displacement parameters are listed in Tables 3 to 6 (for the initial analysis and Tables 3A to 6A respectively. Table 2: Crystal data and refinement for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – initial analysis. Empirical formula C34H46N5O7.5Formula weight 644.76 Temperature 298 K Crystal system monoclinic Space group P21a = 7.6335(5) Å α = 90° Unit Cell Dimensions b = 48.606(3) Å β = 92.206(3) ° c = 9.0437(5) Å γ = 90° Volume 3353.0(4) Å3Z 4 Density (calculated) 1.277 mg / m3Absorption coefficient 0.743 mm-1F(000) 1380.0 Crystal size 0.183 × 0.06 × 0.029 mm3Radiation CuKα (λ = 1.54178 Å) 2Θ range for data collection 7.274 to 157.492° Index ranges -8 ≤ h ≤ 9, -61 ≤ k ≤ 61, -9 ≤ l ≤ 9 Reflections collected 36397 Independent reflections 10946 [Rint = 0.0636, Rsigma = 0.0707] Data / restraints / parameters 10946 / 28 / 920 Goodness-of-fit on F21.008 Final R indexes [I>=2σ (I)] R1 = 0.0617, wR2 = 0.1513 Final R indexes [all data] R1 = 0.1063, wR2 = 0.1800 Largest diff. peak / hole 0.47 / -0.27 e Å-3Flack parameter -0.21(16) Table 3: Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – initial analysis. U(eq) is defined as one-third of the trace of the orthogonalized Uijtensor. Atom x y z U(eq) O1A 3145(6) 4625.0(9) 1418(5) 56.9(12) O2A 5287(7) 4334.6(11) 1962(7) 84.1(17) O3A -7414(7) 3007.6(11) 2822(7) 78.5(17) O4A -4052(7) 2326.5(9) 4907(6) 63.2(13) N1A -4864(8) 2887.4(10) 4074(7) 53.3(15) N2A -6387(7) 2341.6(10) 3278(7) 56.3(15) N3A -4295(9) 2011.1(12) 3031(8) 69.1(17) C1A 3714(9) 4390.9(13) 1868(7) 49.4(16) C2A 2391(8) 4176.1(12) 2261(7) 48.5(16) C3A 620(9) 4208.9(13) 1925(8) 54.2(17) C4A -598(9) 4007.7(13) 2258(8) 56.5(18) C5A -41(8) 3762.3(12) 2962(7) 47.7(16) C6A 1741(9) 3733.8(13) 3318(8) 56.0(18) C7A 2913(9) 3938.2(13) 2974(8) 56.5(18) C8A -1322(9) 3538.8(12) 3251(8) 49.8(17) C9A -2931(9) 3523.4(13) 2527(8) 55.1(18) C10A -4154(9) 3316.3(13) 2737(8) 53.7(18) C11A -3741(9) 3111.5(12) 3763(8) 51.2(18) C12A -2119(9) 3122.1(14) 4527(9) 60.0(19) C13A -945(10) 3330.0(13) 4263(9) 58.5(18) C14A -6551(10) 2846.6(14) 3573(8) 54.4(18) C15A -7272(8) 2566.6(13) 4040(8) 54.4(17) C16A -9182(10) 2526.3(16) 3599(10) 70(2) C17A -9139(11) 2404.8(17) 2052(11) 81(3) C18A -7530(10) 2212.6(16) 2140(10) 72(2) C19A -4858(10) 2231.2(14) 3815(9) 55.5(18) C20A -2818(9) 1835.6(13) 3333(9) 57.5(19) C21A -2498(11) 1637.1(16) 2275(10) 76(2) C22A -1123(12) 1453.2(17) 2498(12) 82(3) C23A -75(12) 1457.8(18) 3746(13) 83(3) Atom x y z U(eq) C24A -415(12) 1655.9(19) 4786(13) 92(3) C25A -1770(11) 1843.9(16) 4614(11) 73(2) C26A 1441(14) 1262(2) 3948(18) 130(5) C27A 1284(14) 1067(2) 5142(13) 118(4) C28A 3146(13) 1379(3) 3676(17) 136(5) O1B 155(7) 712.5(10) -1189(7) 74.0(15) O2B -1951(6) 447.3(9) -2192(5) 59.6(12) O3B -12319(7) 2090.2(10) -696(7) 78.1(16) O4B -9320(7) 2787.6(9) -2788(6) 61.9(12) N1B -9922(8) 2237.0(11) -1912(7) 61.9(16) N2B -11391(7) 2773.9(11) -1048(6) 57.8(15) N3B -9258(9) 3103.8(13) -931(7) 68.7(17) C1B -1375(9) 675.5(14) -1659(8) 50.8(17) C2B -2648(8) 909.2(13) -1655(7) 47.9(16) C3B -4442(8) 863.8(13) -1726(8) 50.5(17) C4B -5614(9) 1080.8(12) -1668(8) 54.4(17) C5B -5036(9) 1352.6(12) -1625(8) 50.2(17) C6B -3237(9) 1396.6(13) -1610(9) 62(2) C7B -2058(9) 1177.9(13) -1589(8) 55.7(17) C8B -6296(8) 1584.4(12) -1629(8) 48.6(16) C9B -7798(9) 1576.1(13) -831(8) 56.3(18) C10B -9022(9) 1785.8(13) -883(8) 56.5(18) C11B -8761(9) 2014.8(12) -1760(8) 55.1(18) C12B -7224(9) 2025.0(13) -2544(9) 62.4(19) C13B -6014(9) 1820.2(13) -2484(9) 62(2) C14B -11555(10) 2269.8(14) -1397(9) 58.3(18) C15B -12399(9) 2548.6(13) -1806(9) 59.7(18) C16B -14225(9) 2583.4(17) -1234(10) 72(2) C17B -13916(10) 2704.9(17) 311(11) 78(2) C18B -12377(10) 2901.5(15) 144(10) 71(2) C19B -9944(9) 2884.9(13) -1664(9) 54.0(18) C20B -7834(9) 3274.1(14) -1332(8) 57.1(19) Atom x y z U(eq) C21B -7439(10) 3494.0(17) -407(9) 71(2) C22B -6091(10) 3672.5(16) -701(9) 67(2) C23B -5080(10) 3638.4(16) -1937(9) 65(2) C24B -5499(11) 3415.8(16) -2837(10) 79(2) C25B -6871(11) 3234.4(17) -2553(10) 77(2) C26B -3567(12) 3831.0(19) -2265(12) 89(3) C27B -3656(17) 3934(2) -3810(14) 127(4) C28B -1841(12) 3704(3) -1871(13) 115(4) O5A -10666(7) 178.7(11) 1632(6) 66.6(14) O6A -9371(7) 355.7(16) 3672(7) 107(2) N4A -7930(7) 263.6(11) -36(6) 50.9(14) N5A -2652(8) 453.1(15) 4712(8) 68.0(18) C29A -9403(11) 276.5(17) 2324(9) 65(2) C30A -7626(8) 294.7(14) 1594(8) 51.9(17) C31A -6534(8) 544.7(14) 1967(9) 59.6(19) C32A -4601(9) 510.4(16) 1730(8) 61.8(19) C33A -3480(10) 733.3(17) 2494(9) 73(2) C34A -3415(10) 717.7(18) 4166(9) 71(2) O5B -4579(9) 4649.9(17) 6850(9) 117(2) O6B -5098(8) 5008.6(15) 5472(8) 96(2) N4BA -2276(11) 4987(2) 4062(11) 65(4) N4BB -2840(20) 4767(4) 3420(30) 78(9) N5B 2500(9) 4680.3(14) 8365(8) 67.1(17) C29B -4311(11) 4799.4(18) 5755(10) 67(2) C30B -2731(11) 4713.6(19) 4878(13) 85(3) C31B -1027(18) 4668(5) 5966(17) 199(9) C32B 597(16) 4602(3) 5408(15) 133(4) C33B 1342(14) 4390.9(19) 6317(13) 98(3) C34B 1566(13) 4418(2) 7961(11) 90(3) O7 -2693(12) 4627.2(19) -208(10) 126(3) O8 -5061(6) 5115.0(10) 1673(7) 72.4(15) O9 318(6) 4954.1(10) 2021(6) 66.8(14) Table 4: Bond Lengths for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – initial analysis Atom Atom Length / Å Atom Atom Length / Å O1A C1A 1.279(8) N3B C20B 1.424(9) O2A C1A 1.231(8) C1B C2B 1.495(9) O3A C14A 1.214(9) C2B C3B 1.386(9) O4A C19A 1.233(9) C2B C7B 1.382(9) N1A C11A 1.421(8) C3B C4B 1.385(9) N1A C14A 1.363(9) C4B C5B 1.393(9) N2A C15A 1.471(8) C5B C6B 1.389(9) N2A C18A 1.465(10) C5B C8B 1.481(9) N2A C19A 1.357(9) C6B C7B 1.393(10) N3A C19A 1.363(9) C8B C9B 1.379(9) N3A C20A 1.432(9) C8B C13B 1.404(9) C1A C2A 1.504(9) C9B C10B 1.382(9) C2A C3A 1.383(9) C10B C11B 1.386(9) C2A C7A 1.376(9) C11B C12B 1.395(10) C3A C4A 1.391(9) C12B C13B 1.357(9) C4A C5A 1.410(9) C14B C15B 1.539(10) C5A C6A 1.392(9) C15B C16B 1.515(10) C5A C8A 1.492(9) C16B C17B 1.527(12) C6A C7A 1.380(9) C17B C18B 1.526(11) C8A C9A 1.371(10) C20B C21B 1.384(11) C8A C13A 1.389(10) C20B C25B 1.364(11) C9A C10A 1.391(9) C21B C22B 1.380(11) C10A C11A 1.389(10) C22B C23B 1.392(11) C11A C12A 1.396(10) C23B C24B 1.384(11) C12A C13A 1.377(10) C23B C26B 1.525(11) C14A C15A 1.533(9) C24B C25B 1.400(11) C15A C16A 1.509(10) C26B C27B 1.483(15) C16A C17A 1.520(12) C26B C28B 1.486(14) C17A C18A 1.543(11) O5A C29A 1.225(9) C20A C21A 1.387(11) O6A C29A 1.278(10) C20A C25A 1.383(11) N4A C30A 1.491(9) Atom Atom Length / Å Atom Atom Length / Å C21A C22A 1.387(12) N5A C34A 1.489(11) C22A C23A 1.358(13) C29A C30A 1.534(10) C23A C24A 1.378(14) C30A C31A 1.505(9) C23A C26A 1.504(13) C31A C32A 1.508(10) C24A C25A 1.384(12) C32A C33A 1.529(11) C26A C27A 1.444(15) C33A C34A 1.513(12) C26A C28A 1.450(15) O5B C29B 1.251(10) O1B C1B 1.241(8) O6B C29B 1.203(10) O2B C1B 1.281(8) N4BA C30B 1.564(14) O3B C14B 1.238(9) N4BB C30B 1.35(2) O4B C19B 1.233(8) N5B C34B 1.497(11) N1B C11B 1.400(9) C29B C30B 1.527(12) N1B C14B 1.357(9) C30B C31B 1.616(18) N2B C15B 1.490(9) C31B C32B 1.393(17) N2B C18B 1.476(9) C32B C33B 1.421(15) N2B C19B 1.367(9) C33B C34B 1.496(15) N3B C19B 1.348(9)

[0004] Table 5: Bond Angles for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ C14A N1A C11A 128.0(6) C4B C3B C2B 121.0(6) C18A N2A C15A 112.1(6) C3B C4B C5B 121.3(6) C19A N2A C15A 122.0(6) C4B C5B C8B 121.1(6) C19A N2A C18A 124.3(6) C6B C5B C4B 117.3(6) C19A N3A C20A 129.1(7) C6B C5B C8B 121.6(5) O1A C1A C2A 118.0(6) C5B C6B C7B 121.3(6) O2A C1A O1A 122.5(6) C2B C7B C6B 120.8(6) O2A C1A C2A 119.4(6) C9B C8B C5B 122.0(6) C3A C2A C1A 121.8(6) C9B C8B C13B 117.4(6) C7A C2A C1A 120.6(6) C13B C8B C5B 120.6(6) C7A C2A C3A 117.6(6) C8B C9B C10B 122.4(6) C2A C3A C4A 121.8(6) C9B C10B C11B 120.0(6) C3A C4A C5A 120.0(6) C10B C11B N1B 124.8(6) C4A C5A C8A 120.4(6) C10B C11B C12B 117.5(6) C6A C5A C4A 117.6(6) C12B C11B N1B 117.7(6) C6A C5A C8A 121.9(6) C13B C12B C11B 122.6(6) C7A C6A C5A 120.8(6) C12B C13B C8B 120.2(6) C2A C7A C6A 122.2(6) O3B C14B N1B 123.4(6) C9A C8A C5A 122.5(6) O3B C14B C15B 122.9(6) C9A C8A C13A 115.7(6) N1B C14B C15B 113.7(6) C13A C8A C5A 121.8(6) N2B C15B C14B 109.4(6) C8A C9A C10A 124.6(6) N2B C15B C16B 103.1(6) C11A C10A C9A 118.3(7) C16B C15B C14B 113.5(6) C10A C11A N1A 123.9(7) C15B C16B C17B 104.1(6) C10A C11A C12A 118.6(6) C18B C17B C16B 104.1(7) C12A C11A N1A 117.5(6) N2B C18B C17B 103.0(6) C13A C12A C11A 120.8(7) O4B C19B N2B 121.9(6) C12A C13A C8A 122.0(7) O4B C19B N3B 123.6(6) O3A C14A N1A 125.3(6) N3B C19B N2B 114.5(6) O3A C14A C15A 122.2(7) C21B C20B N3B 116.5(6) N1A C14A C15A 112.5(6) C25B C20B N3B 124.3(7) Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ N2A C15A C14A 110.8(5) C25B C20B C21B 119.2(7) N2A C15A C16A 103.7(6) C22B C21B C20B 121.0(7) C16A C15A C14A 113.3(6) C21B C22B C23B 121.4(7) C15A C16A C17A 103.8(6) C22B C23B C26B 122.0(7) C16A C17A C18A 103.5(7) C24B C23B C22B 116.2(7) N2A C18A C17A 103.2(6) C24B C23B C26B 121.7(7) O4A C19A N2A 122.3(6) C23B C24B C25B 122.8(7) O4A C19A N3A 123.7(7) C20B C25B C24B 119.3(7) N2A C19A N3A 114.1(7) C27B C26B C23B 112.5(9) C21A C20A N3A 116.2(8) C27B C26B C28B 112.0(9) C25A C20A N3A 124.6(7) C28B C26B C23B 111.7(8) C25A C20A C21A 119.1(7) O5A C29A O6A 126.1(7) C20A C21A C22A 120.0(9) O5A C29A C30A 119.6(7) C23A C22A C21A 121.9(9) O6A C29A C30A 114.1(7) C22A C23A C24A 117.3(8) N4A C30A C29A 108.2(6) C22A C23A C26A 121.1(10) N4A C30A C31A 111.5(6) C24A C23A C26A 121.6(12) C31A C30A C29A 116.2(6) C23A C24A C25A 123.0(10) C30A C31A C32A 114.5(6) C20A C25A C24A 118.7(8) C31A C32A C33A 113.0(6) C27A C26A C23A 114.8(9) C34A C33A C32A 114.4(7) C27A C26A C28A 119.0(11) N5A C34A C33A 111.8(7) C28A C26A C23A 115.0(9) O5B C29B C30B 114.1(9) C14B N1B C11B 130.0(6) O6B C29B O5B 124.3(8) C18B N2B C15B 112.1(5) O6B C29B C30B 121.2(8) C19B N2B C15B 120.9(6) N4BA C30B C31B 102.5(10) C19B N2B C18B 125.1(6) N4BB C30B C29B 115.9(12) C19B N3B C20B 128.2(6) N4BB C30B C31B 130.0(12) O1B C1B O2B 124.0(6) C29B C30B N4BA 102.0(7) O1B C1B C2B 119.5(6) C29B C30B C31B 110.8(9) O2B C1B C2B 116.5(6) C32B C31B C30B 121.2(12) C3B C2B C1B 121.3(6) C31B C32B C33B 107.3(15) C7B C2B C1B 120.5(6) C32B C33B C34B 122.6(10) Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ C7B C2B C3B 118.2(6) C33B C34B N5B 110.7(7) Table 6: Anisotropic Displacement Parameters (Å2×103) for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – initial analysis. The Anisotropic displacement factor exponent takes the form: -2 π2[h2a*2U11+ 2 h k a* b* U12+…]. Atom U11 U22 U33 U23 U13 U12 O1A 52(3) 49(2) 69(3) 7(2) 1(2) -2(2) O2A 46(3) 73(3) 133(5) 18(3) 4(3) 2(2) O3A 60(3) 60(3) 115(5) 21(3) 2(3) 2(3) O4A 72(3) 54(3) 63(3) -5(3) -10(3) 0(2) N1A 62(4) 40(3) 58(4) 4(3) 2(3) -2(3) N2A 55(4) 51(3) 62(4) -3(3) -11(3) 5(3) N3A 78(4) 55(3) 73(5) -10(3) -9(4) 18(3) C1A 47(4) 51(4) 49(4) -2(3) 1(3) -2(3) C2A 48(4) 49(4) 48(4) -4(3) 5(3) 0(3) C3A 51(4) 48(3) 63(5) 10(3) -1(3) 7(3) C4A 47(4) 48(4) 74(5) 7(3) -1(4) -2(3) C5A 39(4) 48(3) 56(4) 3(3) 1(3) 2(3) C6A 55(4) 49(4) 64(5) 12(3) 0(4) 6(3) C7A 43(4) 56(4) 70(5) -1(4) -5(3) 5(3) C8A 49(4) 44(3) 56(5) 1(3) 4(3) 7(3) C9A 57(5) 48(4) 60(5) 9(3) 0(4) 7(3) C10A 51(4) 47(3) 62(5) 12(3) -2(3) -1(3) C11A 50(4) 40(3) 64(5) -3(3) 6(4) 1(3) C12A 59(5) 58(4) 63(5) 17(4) 7(4) 9(3) C13A 52(4) 54(4) 69(5) -1(4) 0(4) 3(3) C14A 54(4) 51(4) 58(5) 0(4) 7(4) 5(3) C15A 60(4) 49(3) 55(5) -2(3) 12(3) 0(3) C16A 59(5) 60(4) 90(6) 6(4) 13(4) -1(4) C17A 66(5) 70(5) 104(8) 1(5) -19(5) 4(4) C18A 70(5) 66(4) 77(6) -8(4) -13(4) 2(4) Atom U11U22U33U23U13U12C19A 64(5) 50(4) 52(5) 4(4) 2(4) -5(4) C20A 57(4) 49(4) 67(5) 6(4) 2(4) 4(3) C21A 84(6) 66(5) 79(6) -6(4) 11(5) 5(4) C22A 85(6) 69(5) 94(7) 6(5) 26(6) 18(5) C23A 71(6) 66(5) 114(8) 6(6) 18(6) 9(4) C24A 74(6) 94(7) 106(8) 13(6) -19(5) 2(5) C25A 69(5) 58(4) 90(7) -3(4) -8(5) 6(4) C26A 85(7) 93(7) 214(14) 54(8) 41(8) 29(6) C27A 89(7) 137(9) 127(9) 58(8) -1(6) 34(6) C28A 66(6) 141(10) 204(14) 33(9) 28(7) 17(6) O1B 53(3) 61(3) 107(5) 3(3) -12(3) 5(2) O2B 66(3) 52(3) 60(3) -4(2) -2(2) 5(2) O3B 64(3) 57(3) 114(5) 8(3) 6(3) -1(3) O4B 76(3) 50(2) 59(3) -4(2) 7(3) 1(2) N1B 62(4) 46(3) 77(5) 4(3) 6(3) 9(3) N2B 62(4) 53(3) 59(4) -4(3) 8(3) 5(3) N3B 78(4) 67(4) 62(4) -12(3) 18(3) -11(3) C1B 50(4) 50(4) 52(5) 5(3) -2(3) 4(3) C2B 48(4) 48(3) 47(4) -1(3) -7(3) 1(3) C3B 49(4) 43(3) 59(5) 3(3) -5(3) -1(3) C4B 46(4) 44(3) 73(5) 7(3) -6(3) -4(3) C5B 47(4) 48(3) 55(5) 4(3) -7(3) 0(3) C6B 50(4) 46(4) 89(6) -10(4) -4(4) -9(3) C7B 49(4) 51(4) 68(5) -4(3) -3(3) -5(3) C8B 46(4) 40(3) 59(5) 0(3) -2(3) -2(3) C9B 59(4) 43(3) 67(5) 6(3) 1(4) 1(3) C10B 54(4) 54(4) 62(5) -1(3) 4(3) -2(3) C11B 64(4) 42(3) 60(5) 1(3) -2(4) -2(3) C12B 63(4) 43(3) 81(6) 13(3) 8(4) 2(3) C13B 51(4) 54(4) 82(6) 15(4) 6(4) -2(3) C14B 61(5) 47(4) 66(5) -6(4) -13(4) 4(3) C15B 64(4) 50(4) 65(5) -5(3) -11(4) 2(3) Atom U11U22U33U23U13U12C16B 53(4) 68(4) 95(7) -1(5) -5(4) 9(4) C17B 65(5) 73(5) 96(7) -5(5) 17(5) -2(4) C18B 76(5) 64(4) 75(6) -12(4) 15(4) 3(4) C19B 58(4) 43(3) 61(5) 2(3) 1(4) 4(3) C20B 64(5) 55(4) 53(5) 2(3) 6(4) 2(3) C21B 70(5) 84(5) 58(5) -13(4) -2(4) -2(4) C22B 71(5) 64(4) 67(6) -10(4) -4(4) -8(4) C23B 65(5) 66(5) 64(5) -4(4) 5(4) -7(4) C24B 80(5) 73(5) 88(7) -14(5) 32(5) -10(4) C25B 85(6) 77(5) 69(6) -19(4) 18(5) -13(4) C26B 79(6) 89(6) 101(8) 8(6) 8(5) -17(5) C27B 133(10) 112(8) 135(11) 32(8) 12(8) -22(7) C28B 64(6) 151(10) 129(9) 18(8) -12(6) -19(6) O5A 49(3) 83(3) 68(4) 0(3) 4(3) -10(3) O6A 67(4) 178(7) 76(5) -46(5) 17(3) -23(4) N4A 43(3) 59(3) 51(4) 2(3) 1(3) 2(3) N5A 47(4) 95(5) 61(5) -21(4) -3(3) -4(3) C29A 55(5) 87(5) 55(6) -9(4) 9(4) -1(4) C30A 44(4) 57(4) 54(5) -1(3) -1(3) 5(3) C31A 40(4) 65(4) 73(5) -6(4) -3(3) -6(3) C32A 52(4) 87(5) 47(5) -7(4) 4(3) -5(4) C33A 57(4) 85(5) 76(7) -3(5) 3(4) -12(4) C34A 54(4) 88(5) 70(6) -12(5) -6(4) -5(4) O5B 100(5) 136(6) 117(6) 44(5) 44(4) 18(4) O6B 68(4) 112(5) 111(5) 26(4) 19(3) 27(4) N4BA 50(5) 83(7) 61(7) -23(5) 3(5) 0(5) N4BB 52(11) 60(12) 120(20) -7(12) -28(12) 6(9) N5B 72(4) 72(4) 56(5) 7(3) -3(3) 12(3) C29B 63(5) 79(5) 60(6) -14(4) 9(4) -7(4) C30B 77(6) 90(6) 90(8) -18(6) 19(5) -34(5) C31B 126(11) 340(20) 130(12) -124(15) -14(9) 65(14) C32B 115(9) 166(12) 118(10) -15(9) -3(8) 41(9) Atom U11U22U33U23U13U12C33B 104(7) 73(6) 114(10) -6(6) -22(6) -9(5) C34B 94(6) 94(6) 80(7) 9(5) 5(5) -14(5) O7 117(6) 123(6) 139(7) 22(5) 19(5) -17(5) O8 54(3) 61(3) 104(4) 2(3) 21(3) -3(2) O9 51(3) 58(3) 92(4) 2(3) 19(3) -4(2) Table 2A: Crystal data and refinement for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – updated analysis. Empirical formula C34H46N5O7.5Formula weight 644.76 Temperature 298 K Crystal system monoclinic Space group P21a = 7.6335(5) Å α = 90° Unit Cell Dimensions b = 48.606(3) Å β = 92.206(3) ° c = 9.0437(5) Å γ = 90° Volume 3353.0(4) Å3Z 4 Density (calculated) 1.277 mg / m3Absorption coefficient 0.743 mm-1F(000) 1380 Crystal size 0.183 × 0.06 × 0.029 mm3Radiation CuKα (λ = 1.54178 Å) 2Θ range for data collection 7.274 to 157.492° Index ranges -8 ≤ h ≤ 9, -61 ≤ k ≤ 61, -9 ≤ l ≤ 9 Reflections collected 36397 Independent reflections 10946 [Rint = 0.0636, Rsigma = 0.0707] Data / restraints / parameters 10946 / 33 / 915 Goodness-of-fit on F21.007 Final R indexes [I>=2σ (I)] R1 = 0.0606, wR2 = 0.1512 Final R indexes [all data] R1 = 0.1049, wR2 = 0.1799 Largest diff. peak / hole 0.59 / -0.26 Flack parameter -0.20(16) Table 3A: Fractional Atomic Coordinates (×104) and Equivalent Isotropic Displacement Parameters (Å2×103) for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – updated analysis. U(eq) is defined as one-third of the trace of the orthogonalized Uijtensor Atom x y z U(eq) O1A 13145(6) 4625.0(9) 1419(5) 57.8(12) O2A 15286(7) 4334.5(11) 1959(7) 85.3(18) O3A 2587(7) 3008.1(11) 2823(7) 79.4(17) O4A 5948(7) 2326.5(9) 4903(6) 64.4(13) N1A 5137(8) 2887.3(10) 4075(7) 53.9(15) N2A 3614(7) 2341.7(10) 3277(7) 56.9(15) N3A 5712(9) 2012.2(12) 3032(8) 69.6(17) C1A 13712(9) 4391.0(13) 1868(7) 50.2(16) C2A 12393(8) 4176.0(12) 2261(7) 49.1(16) C3A 10620(9) 4208.8(13) 1923(8) 55.3(17) C4A 9403(9) 4007.2(13) 2255(8) 56.9(18) C5A 9958(8) 3762.4(12) 2964(7) 48.2(16) C6A 11739(9) 3734.1(13) 3318(8) 56.7(18) C7A 12914(9) 3938.5(13) 2975(8) 57.1(18) C8A 8681(9) 3539.0(12) 3251(8) 50.4(17) C9A 7070(9) 3523.0(13) 2527(8) 55.9(18) C10A 5846(9) 3316.6(13) 2737(8) 54.9(18) C11A 6260(9) 3111.5(12) 3764(8) 52.1(18) C12A 7878(9) 3122.3(14) 4526(9) 60.6(19) C13A 9054(10) 3330.6(13) 4263(9) 59.1(18) C14A 3449(10) 2847.0(14) 3573(8) 55.3(18) C15A 2729(8) 2566.6(13) 4040(8) 55.6(17) C16A 817(10) 2526.8(15) 3597(10) 70(2) C17A 862(11) 2404.8(17) 2051(11) 82(3) C18A 2472(10) 2213.0(16) 2141(10) 72(2) C19A 5143(10) 2230.9(14) 3810(9) 55.9(18) C20A 7184(9) 1835.8(13) 3336(9) 58.4(19) C21A 7504(11) 1637.2(16) 2276(10) 77(2) C22A 8876(12) 1453.6(17) 2499(12) 82(3) C23A 9927(12) 1457.6(18) 3746(13) 84(3) C24A 9587(12) 1656.7(19) 4784(13) 92(3) C25A 8230(11) 1844.4(16) 4610(11) 73(2) C26A 11431(14) 1261(2) 3937(18) 130(5) C27A 11288(14) 1067(2) 5141(13) 118(4) C28A 13145(13) 1378(3) 3681(17) 136(5) O1B 10157(7) 712.5(10) 8808(7) 74.8(15) O2B 8050(6) 447.4(9) 7810(5) 60.7(12) O3B -2320(7) 2090.7(10) 9304(7) 79.5(16) O4B 680(6) 2787.8(9) 7211(6) 62.7(12) N1B 79(8) 2236.8(11) 8086(7) 62.8(16) N2B -1392(7) 2773.8(11) 8951(6) 58.7(15) N3B 743(9) 3103.7(13) 9067(7) 69.7(17) C1B 8627(9) 675.5(13) 8343(8) 51.4(17) C2B 7353(8) 909.1(13) 8345(7) 48.5(16) C3B 5559(8) 864.3(13) 8274(8) 51.5(17) C4B 4388(9) 1080.8(12) 8330(8) 55.1(18) C5B 4965(8) 1352.3(12) 8375(8) 50.8(17) C6B 6764(9) 1396.6(13) 8390(9) 63(2) C7B 7943(9) 1178.2(13) 8410(8) 55.9(17) C8B 3705(8) 1584.7(12) 8371(8) 49.3(16) C9B 2202(9) 1575.8(13) 9169(8) 57.1(18) C10B 980(9) 1786.3(13) 9120(8) 57.1(18) C11B 1238(9) 2014.8(12) 8240(8) 55.8(18) C12B 2773(9) 2024.9(13) 7457(9) 63.3(19) C13B 3986(9) 1819.9(13) 7516(9) 63(2) C14B -1554(10) 2270.0(14) 8602(9) 59.4(18) C15B -2398(9) 2549.0(13) 8195(9) 60.2(18) C16B -4220(9) 2583.8(17) 8769(10) 73(2) C17B -3917(10) 2705.3(17) 10309(10) 78(2) C18B -2380(10) 2901.5(15) 10142(10) 72(2) C19B 59(9) 2885.2(13) 8337(9) 54.7(18) C20B 2165(9) 3274.5(14) 8667(8) 57.5(19) C21B 2561(10) 3494.1(17) 9593(9) 72(2) C22B 3907(10) 3673.1(16) 9298(9) 68(2) C23B 4920(10) 3639.0(16) 8062(9) 66(2) C24B 4500(11) 3415.8(16) 7164(10) 81(3) C25B 3129(11) 3234.1(17) 7449(10) 78(2) C26B 6434(12) 3831.2(19) 7739(12) 89(3) C27B 6352(17) 3933(2) 6192(14) 129(4) C28B 8157(12) 3705(3) 8124(13) 116(4) O5A -662(7) 178.6(11) 1635(6) 67.8(14) O6A 625(7) 356.3(16) 3673(7) 108(2) N4A 2072(7) 263.7(11) -36(6) 51.5(14) N5A 7351(8) 453.2(15) 4711(8) 68.3(17) C29A 596(11) 276.8(17) 2321(9) 66(2) C30A 2370(8) 294.1(13) 1590(8) 52.7(17) C31A 3478(8) 545.4(14) 1966(9) 60.6(19) C32A 5388(8) 510.5(16) 1732(8) 62.9(19) C33A 6517(10) 733.5(17) 2493(9) 74(2) C34A 6585(10) 717.5(18) 4166(9) 72(2) O5B 5424(9) 4650.8(17) 6849(9) 118(2) O6B 4904(8) 5008.2(15) 5471(8) 98(2) N4BA 7722(11) 4987(2) 4060(11) 63(4) N4BB 7130(20) 4768(4) 3460(30) 89(9) N5B 12501(9) 4680.6(14) 8368(8) 68.3(17) C29B 5693(10) 4798.9(18) 5759(10) 68(2) C30B 7287(11) 4712(2) 4901(12) 86(3) C31B 8912(16) 4669(5) 5963(15) 201(9) C32B 10621(15) 4601(3) 5402(15) 136(5) C33B 11341(14) 4390.3(19) 6320(13) 97(3) C34B 11566(13) 4419(2) 7963(11) 90(3) O7 7289(9) 4626.4(12) -213(8) 127(3) O8 4940(6) 5114.6(9) 1673(6) 73.4(15) O9 318(6) 4954.1(10) 2020(6) 67.8(14) Table 4A: Bond Lengths for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – updated analysis Atom Atom Length / Å Atom Atom Length / Å O1A C1A 1.278(8) N3B C20B 1.424(9) O2A C1A 1.232(8) C1B C2B 1.495(9) O3A C14A 1.214(9) C2B C3B 1.386(9) O4A C19A 1.235(9) C2B C7B 1.384(9) N1A C11A 1.421(8) C3B C4B 1.383(9) N1A C14A 1.364(9) C4B C5B 1.391(9) N2A C15A 1.471(8) C5B C6B 1.389(9) N2A C18A 1.462(10) C5B C8B 1.483(8) N2A C19A 1.357(9) C6B C7B 1.391(9) N3A C19A 1.356(9) C8B C9B 1.380(9) N3A C20A 1.431(9) C8B C13B 1.401(9) C1A C2A 1.503(9) C9B C10B 1.384(9) C2A C3A 1.385(9) C10B C11B 1.385(9) C2A C7A 1.374(9) C11B C12B 1.393(10) Atom Atom Length / Å Atom Atom Length / Å C3A C4A 1.391(9) C12B C13B 1.360(9) C4A C5A 1.409(9) C14B C15B 1.540(9) C5A C6A 1.391(9) C15B C16B 1.513(10) C5A C8A 1.489(9) C16B C17B 1.522(12) C6A C7A 1.382(9) C17B C18B 1.524(11) C8A C9A 1.373(10) C20B C21B 1.383(11) C8A C13A 1.387(9) C20B C25B 1.362(11) C9A C10A 1.389(9) C21B C22B 1.380(11) C10A C11A 1.390(9) C22B C23B 1.393(11) C11A C12A 1.392(10) C23B C24B 1.385(11) C12A C13A 1.380(10) C23B C26B 1.523(11) C14A C15A 1.535(9) C24B C25B 1.401(11) C15A C16A 1.511(10) C26B C27B 1.483(15) C16A C17A 1.520(12) C26B C28B 1.482(14) C17A C18A 1.542(11) O5A C29A 1.220(9) C20A C21A 1.388(11) O6A C29A 1.282(10) C20A C25A 1.378(11) N4A C30A 1.486(9) C21A C22A 1.385(12) N5A C34A 1.487(11) C22A C23A 1.359(13) C29A C30A 1.532(10) C23A C24A 1.379(13) C30A C31A 1.517(9) C23A C26A 1.499(13) C31A C32A 1.491(9) C24A C25A 1.385(12) C32A C33A 1.532(11) C26A C27A 1.446(15) C33A C34A 1.514(12) Atom Atom Length / Å Atom Atom Length / Å C26A C28A 1.454(15) O5B C29B 1.244(10) O1B C1B 1.239(8) O6B C29B 1.206(10) O2B C1B 1.280(8) N4BA C30B 1.580(14) O3B C14B 1.238(9) N4BB C30B 1.33(3) O4B C19B 1.234(8) N5B C34B 1.497(11) N1B C11B 1.399(9) C29B C30B 1.527(12) N1B C14B 1.357(9) C30B C31B 1.553(13) N2B C15B 1.487(9) C31B C32B 1.456(12) N2B C18B 1.476(9) C32B C33B 1.415(15) N2B C19B 1.370(9) C33B C34B 1.496(14) N3B C19B 1.345(9) Table 5A: Bond Angles for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – updated analysis Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ C14A N1A C11A 127.9(6) C4B C3B C2B 121.2(6) C18A N2A C15A 112.0(6) C3B C4B C5B 121.2(6) C19A N2A C15A 122.2(6) C4B C5B C8B 121.2(6) C19A N2A C18A 124.2(6) C6B C5B C4B 117.3(6) C19A N3A C20A 129.4(7) C6B C5B C8B 121.5(5) O1A C1A C2A 118.2(6) C5B C6B C7B 121.3(6) O2A C1A O1A 122.5(6) C2B C7B C6B 120.8(6) O2A C1A C2A 119.3(6) C9B C8B C5B 121.8(6) C3A C2A C1A 121.7(6) C9B C8B C13B 117.5(6) C7A C2A C1A 120.7(6) C13B C8B C5B 120.6(6) C7A C2A C3A 117.6(6) C8B C9B C10B 122.2(6) Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ C2A C3A C4A 121.7(6) C9B C10B C11B 120.0(6) C3A C4A C5A 120.1(6) C10B C11B N1B 124.9(6) C4A C5A C8A 120.5(6) C10B C11B C12B 117.5(6) C6A C5A C4A 117.5(6) C12B C11B N1B 117.6(6) C6A C5A C8A 121.9(6) C13B C12B C11B 122.6(6) C7A C6A C5A 121.0(6) C12B C13B C8B 120.1(6) C2A C7A C6A 122.0(6) O3B C14B N1B 123.4(6) C9A C8A C5A 122.6(6) O3B C14B C15B 122.8(6) C9A C8A C13A 115.5(6) N1B C14B C15B 113.8(6) C13A C8A C5A 121.9(6) N2B C15B C14B 109.5(6) C8A C9A C10A 124.8(6) N2B C15B C16B 103.0(6) C9A C10A C11A 118.2(7) C16B C15B C14B 113.5(6) C10A C11A N1A 124.0(7) C15B C16B C17B 104.3(6) C10A C11A C12A 118.6(6) C18B C17B C16B 104.1(7) C12A C11A N1A 117.5(6) N2B C18B C17B 103.1(6) C13A C12A C11A 120.9(7) O4B C19B N2B 121.7(6) C12A C13A C8A 122.1(7) O4B C19B N3B 123.6(6) O3A C14A N1A 125.4(6) N3B C19B N2B 114.7(6) O3A C14A C15A 122.3(7) C21B C20B N3B 116.6(6) N1A C14A C15A 112.4(6) C25B C20B N3B 124.2(7) N2A C15A C14A 110.8(5) C25B C20B C21B 119.2(7) N2A C15A C16A 103.7(6) C22B C21B C20B 121.1(7) C16A C15A C14A 113.2(6) C21B C22B C23B 121.3(7) C15A C16A C17A 103.8(6) C22B C23B C26B 122.0(7) C16A C17A C18A 103.5(7) C24B C23B C22B 116.1(7) N2A C18A C17A 103.3(6) C24B C23B C26B 121.9(7) O4A C19A N2A 122.0(6) C23B C24B C25B 122.9(7) O4A C19A N3A 123.4(7) C20B C25B C24B 119.2(7) Atom Atom Atom Angle / ˚ Atom Atom Atom Angle / ˚ N2A C19A N3A 114.5(7) C27B C26B C23B 112.5(9) C21A C20A N3A 116.2(8) C27B C26B C28B 111.4(9) C25A C20A N3A 124.6(7) C28B C26B C23B 111.9(8) C25A C20A C21A 119.1(7) O5A C29A O6A 126.0(7) C20A C21A C22A 120.0(9) O5A C29A C30A 119.6(7) C23A C22A C21A 122.0(9) O6A C29A C30A 114.3(7) C22A C23A C24A 117.0(8) N4A C30A C29A 108.5(6) C22A C23A C26A 120.7(10) N4A C30A C31A 111.4(6) C24A C23A C26A 122.2(12) C31A C30A C29A 116.2(6) C23A C24A C25A 123.0(9) C30A C31A C32A 114.6(6) C20A C25A C24A 118.8(8) C31A C32A C33A 113.1(6) C27A C26A C23A 115.0(9) C34A C33A C32A 114.2(7) C27A C26A C28A 118.0(11) N5A C34A C33A 111.9(7) C28A C26A C23A 114.9(9) O5B C29B C30B 113.7(9) C14B N1B C11B 130.0(6) O6B C29B O5B 124.2(8) C18B N2B C15B 112.0(5) O6B C29B C30B 121.7(8) C19B N2B C15B 121.1(6) N4BA C30B C31B 103.5(11) C19B N2B C18B 125.0(6) N4BB C30B C29B 113.5(12) C19B N3B C20B 128.4(6) N4BB C30B C31B 132.2(12) O1B C1B O2B 124.0(6) C29B C30B N4BA 101.4(7) O1B C1B C2B 119.6(6) C29B C30B C31B 110.8(8) O2B C1B C2B 116.4(6) C32B C31B C30B 121.3(11) C3B C2B C1B 121.5(6) C31B C32B C33B 107.1(13) C7B C2B C1B 120.5(6) C32B C33B C34B 122.9(10) C7B C2B C3B 118.0(6) C33B C34B N5B 110.9(7) Table 6A: Anisotropic Displacement Parameters (Å2×103) for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) – updated analysis. The Anisotropic displacement factor exponent takes the form: -2 π2[h2a*2U11+ 2 h k a* b* U12+…]. Atom U11 U22 U33 U23 U13 U12 O1A 53(3) 50(2) 71(3) 7(2) 1(2) -2(2) O2A 47(3) 74(3) 135(5) 19(3) 5(3) 1(2) O3A 61(3) 62(3) 115(5) 22(3) 2(3) 2(3) O4A 73(3) 55(3) 64(3) -4(3) -10(3) 0(2) N1A 62(4) 40(3) 59(4) 4(3) 2(3) -2(3) N2A 56(4) 51(3) 63(4) -3(3) -11(3) 5(3) N3A 76(4) 57(4) 74(5) -12(3) -13(4) 18(3) C1A 48(4) 52(4) 51(4) -2(3) 2(3) -2(3) C2A 49(4) 50(4) 49(4) -4(3) 5(3) 0(3) C3A 52(4) 49(3) 64(5) 10(3) -2(3) 7(3) C4A 49(4) 49(4) 73(5) 7(3) 0(4) -1(3) C5A 40(4) 48(3) 56(4) 3(3) 2(3) 3(3) C6A 57(4) 49(4) 64(5) 13(3) 0(4) 5(3) C7A 43(4) 56(4) 72(5) -1(4) -6(3) 5(3) C8A 49(4) 45(3) 57(5) 1(3) 3(3) 8(3) C9A 58(5) 49(4) 60(5) 10(3) 1(4) 6(3) C10A 53(4) 48(3) 63(5) 11(3) -2(3) -1(3) C11A 51(4) 39(3) 66(5) -3(3) 6(4) 2(3) C12A 59(5) 58(4) 65(5) 16(4) 6(4) 9(3) C13A 52(4) 54(4) 71(5) -1(4) 1(4) 3(3) C14A 56(4) 53(4) 58(5) 0(4) 7(4) 5(3) C15A 61(4) 49(3) 57(5) -2(3) 13(3) 0(3) C16A 61(5) 60(4) 90(6) 6(4) 13(4) -1(4) C17A 68(5) 71(5) 106(8) 2(5) -18(5) 4(4) C18A 71(5) 66(4) 77(6) -8(4) -13(4) 2(4) C19A 65(5) 50(4) 52(5) 3(4) 2(4) -6(4) Atom U11 U22 U33 U23 U13 U12 C20A 58(4) 50(4) 68(5) 7(4) 1(4) 3(3) C21A 85(6) 66(5) 80(6) -6(4) 12(5) 5(4) C22A 85(6) 68(5) 95(7) 6(5) 26(6) 18(5) C23A 70(6) 67(5) 117(8) 7(6) 18(6) 8(4) C24A 74(6) 95(7) 105(8) 12(6) -19(5) 2(5) C25A 70(5) 60(4) 89(7) -3(4) -8(5) 7(4) C26A 88(7) 93(7) 213(14) 53(8) 42(8) 29(6) C27A 91(7) 135(9) 126(9) 57(8) 1(6) 33(6) C28A 66(6) 143(10) 202(14) 29(9) 29(7) 17(6) O1B 52(3) 62(3) 109(5) 2(3) -12(3) 4(2) O2B 67(3) 53(3) 62(3) -4(2) -2(2) 7(2) O3B 65(3) 57(3) 117(5) 8(3) 8(3) -1(3) O4B 77(3) 51(2) 61(3) -4(2) 8(3) 1(2) N1B 63(4) 47(3) 78(4) 4(3) 6(3) 9(3) N2B 63(4) 54(3) 59(4) -4(3) 7(3) 5(3) N3B 80(4) 68(4) 63(4) -11(3) 18(3) -11(3) C1B 52(5) 49(4) 52(5) 4(3) -1(3) 3(3) C2B 49(4) 49(3) 47(4) 0(3) -8(3) 1(3) C3B 50(4) 44(3) 60(5) 3(3) -5(3) -2(3) C4B 46(4) 44(3) 74(5) 8(3) -6(3) -3(3) C5B 48(4) 49(3) 55(5) 4(3) -6(3) 0(3) C6B 51(4) 47(4) 90(6) -10(4) -4(4) -9(3) C7B 49(4) 51(4) 67(5) -4(3) -3(3) -5(3) C8B 47(4) 40(3) 61(5) 0(3) -2(3) -2(3) C9B 60(4) 44(3) 67(5) 6(3) 2(4) 2(3) C10B 55(4) 54(4) 63(5) 0(3) 4(3) -2(3) C11B 65(4) 42(3) 60(5) 1(3) -2(4) -2(3) C12B 64(4) 43(3) 83(6) 13(3) 8(4) 2(3) Atom U11 U22 U33 U23 U13 U12 C13B 52(4) 55(4) 82(6) 14(4) 7(4) -2(3) C14B 61(5) 47(4) 68(5) -6(4) -11(4) 4(3) C15B 63(4) 50(4) 66(5) -4(3) -12(4) 2(3) C16B 55(4) 68(4) 96(7) -1(5) -5(4) 10(4) C17B 66(5) 73(5) 96(7) -5(5) 17(5) -2(4) C18B 76(5) 65(4) 75(6) -11(4) 14(4) 4(4) C19B 59(4) 43(3) 62(5) 1(3) 2(4) 4(3) C20B 64(5) 55(4) 54(5) 2(3) 6(4) 1(3) C21B 71(5) 85(5) 59(5) -12(4) -2(4) -1(4) C22B 71(5) 65(4) 68(6) -11(4) -5(4) -9(4) C23B 66(5) 67(5) 65(5) -4(4) 6(4) -6(4) C24B 81(6) 75(5) 88(7) -15(5) 32(5) -11(4) C25B 86(6) 78(5) 71(6) -19(4) 19(5) -12(4) C26B 77(6) 89(6) 101(7) 8(5) 7(5) -17(5) C27B 138(10) 113(8) 138(11) 34(8) 13(8) -24(7) C28B 67(6) 150(10) 129(9) 17(8) -12(6) -20(6) O5A 50(3) 84(3) 70(4) -1(3) 4(3) -10(3) O6A 68(4) 181(7) 77(5) -47(4) 17(3) -24(4) N4A 43(3) 60(3) 51(4) 2(3) 1(3) 2(3) N5A 47(4) 96(5) 62(5) -21(4) -3(3) -4(3) C29A 55(5) 87(5) 56(6) -9(4) 9(4) -2(4) C30A 44(4) 58(4) 56(5) -1(3) 0(3) 6(3) C31A 42(4) 65(4) 74(5) -6(4) -2(3) -6(3) C32A 53(4) 88(5) 48(5) -7(4) 3(3) -6(4) C33A 58(4) 86(5) 77(6) -3(4) 4(4) -13(4) C34A 56(5) 89(5) 70(6) -12(5) -6(4) -4(4) O5B 102(5) 137(6) 117(6) 45(5) 45(4) 19(4) O6B 69(4) 114(5) 111(5) 24(4) 19(3) 26(4) Atom U11 U22 U33 U23 U13 U12 N4BA 49(5) 82(7) 60(7) -22(5) 3(5) 0(5) N4BB 53(11) 60(12) 150(30) -15(13) -39(13) 8(9) N5B 73(4) 74(4) 58(5) 8(3) -2(3) 12(3) C29B 63(5) 78(5) 62(6) -13(4) 10(4) -5(4) C30B 79(6) 96(6) 84(7) -15(6) 13(5) -36(5) C31B 128(11) 340(20) 132(12) -121(15) -19(9) 64(14) C32B 116(9) 171(12) 121(10) -19(10) -4(8) 43(9) C33B 102(7) 74(6) 114(9) -4(6) -23(6) -7(5) C34B 94(6) 96(6) 81(7) 11(5) 4(5) -14(5) O7 110(5) 133(6) 138(7) 27(5) 12(5) -24(4) O8 55(3) 62(3) 105(4) 1(3) 21(3) -4(2) O9 52(3) 58(3) 95(4) 1(3) 19(3) -4(2) Raman Spectroscopy Raman spectra were collected using a Thermo Scientific iS50 FT-Raman accessory attached to the FT-IR bench. A CaF2beamsplitter is utilized in the FT-Raman configuration. The spectrometer was equipped with a 1064 nm diode laser and a room temperature InGaAs detector. Samples were analyzed in glass NMR tubes. The spectra were collected using 0.5 W of laser power and 512 co-added scans. The collection range was 3700-200 cm-1. The Form 1 of L-lysine salt of Compound 1 (sesquihydrate) spectra were recorded using 2 cm-1resolution, and Happ-Genzel apodization was utilized for all of the spectra. Multiple spectra were recorded and a representative spectrum is shown in FIG.8. The variability in the peak positions with this experimental configuration is within ±2^cm-1. Peaks were picked using the automatic peak analysis function in ACD / Spectrus Processor software (2023.2.0). Peaks were picked using a noise factor of 0.3 and a minimum peak level of 3% maximum intensity. To ensure validity, the output of automated assignments was visually checked. Where a peak was present but not selected by the automatic peak analysis function, the peak(s) were manually selected. If a peak was selected by the automatic peak analysis function but was poorly resolved, or if the peak was not placed at the peak maximum, the peak was deleted. Typically, the peaks which were not resolved or were consistent with noise were not selected. Table Raman-1 lists the peak position (cm-1) and relative intensity for the observed spectrum shown in FIG.8. The variability in the peak positions with this experimental configuration is within ±2^cm-1. Table Raman-1: Raman peak list for Form 1 of L-lysine salt of Compound 1 (sesquihydrate). Peak position (cm-1)Relative intensity (%)422 7 630 5 730 4 809 4 830 4 852 8 891 5 1137 9 1189 9 1203 13 1250 9 1284 37 1356 7 1381 11 1418 4 1440 4 1525 6 1542 6 1604 100 1636 9 1696 7 2870 4 2933 6 2945 7 2964 6 3005 4 3055 6 3071 6 Solid State NMR 13C solid-state NMR (ssNMR) analysis was conducted on a CPMAS probe positioned into a Bruker-BioSpin Avance NEO 500 MHz (1H frequency) NMR spectrometer. Form 1 of L- lysine salt of Compound 1 (sesquihydrate) was packed into a ZrO2 rotor. A magic angle spinning rate of 15 kHz was used. Spectra were collected at ambient temperature (temperature uncontrolled). 13C ssNMR spectra were collected using a proton decoupled cross-polarization magic angle spinning (CPMAS) experiment. A phase modulated proton decoupling field of 80-100 kHz was applied during spectral acquisition. The cross-polarization contact time was set to 2 ms and the recycle delay to 3.5 s for Form 1 of L-lysine salt of Compound 1 (sesquihydrate). The number of scans was adjusted to obtain an adequate signal to noise ratio. The13C chemical shift scale was referenced using a13C MAS experiment on an external standard of crystalline adamantane, setting its up-field resonance to 29.5 ppm. Automatic peak picking was performed using Bruker-BioSpin TopSpin version 4.1 software. Generally, a threshold value of 5% relative intensity was used for preliminary peak selection. The output of the automated peak picking was visually checked to ensure validity and adjustments were manually made if necessary. Although specific solid-state NMR peak values are reported herein there does exist a range for these peak values due to differences in instruments, samples, and sample preparation. This is common practice in the art of solid-state NMR because of the variation inherent in peak positions. A typical variability for the chemical shift x-axis value is on the order of plus or minus 0.2 ppm for a crystalline solid and plus or minus 0.5 ppm for an amorphous solid. The solid-state NMR peak heights reported herein are relative intensities. Solid-state NMR intensities can vary depending on the actual setup of the experimental parameters and the thermal history of the sample. A representative observed13C ssNMR spectrum for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) is shown in FIG.9. The peaks marked by hashes are spinning side bands. Table C13NMR-1 shows the13C ssNMR peak list for the observed13C ssNMR spectrum for Form 1 of L-lysine salt of Compound 1 (sesquihydrate) as shown in FIG.9. A typical variability for the chemical shift x-axis value is on the order of plus or minus 0.2 ppm for a crystalline solid and plus or minus 0.5 ppm for an amorphous solid. Table C13NMR-1:13C ssNMR peak list for Form 1 of L-lysine salt of Compound 1 (sesquihydrate). 13C Chemical Shift (ppm) Relative Intensity (%) 175.1 36 174.7 32 174.1 23 169.6 41 Example 3. 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid L-Lysine salt (Form 2 of L-lysine salt of Compound 1) Compound 1 (574.2 mg) was added to 10 mL of methanol to form a slurry. To the slurry, 1.8 mL of aqueous L-lysine solution (0.68M, 1.05 equivalents) was added to form a mixture. The mixture was heated to approximately 55°C and stirred for approximately 12 hours. Solids were isolated by vacuum filtration and rinsed with methanol. Solids were dried at ambient conditions. The solids were determined to crystalline and anhydrous (designated herein as Form 2 of L-lysine salt of Compound 1). Differential scanning calorimetry (DSC) analysis of Form 2 of L-lysine salt of Compound 1 DSC measurements were performed with a Discovery DSC (TA instruments) equipped with a refrigerated cooling accessory. The cell constant was determined using indium and temperature calibration was performed using indium and tin as standards. All the measurements were done under continuous dry nitrogen purge (50 mL / min). Approximately 1-5 mg of solid sample was weighed into a Tzero aluminum pan, sealed non-hermetically and heated from -50 °C to 260 °C at 10 °C / min heating rate. The experimental data were analyzed using commercially available software (TA Universal Analysis 2000 / Trios software, TA Instruments). A reprentative differential scanning calorimetry thermogram of Form 2 is shown in FIG. 4. As can be seen in FIG.4, no thermal events are observed until approximately 219 °C. Thus, Form 2 of L-lysine salt of Compound 1 was determined to be anhydrous. Those skilled in the art would understand that endotherm onsets can be significantly impacted by factors such as crystallinity, presence of impurities, instrument parameters (e.g. ramp rate, sample mass), chemical degradation which is occurring in parallel with another event such as melting, etc. Thus, the onset temperature of about 219 °C may be significantly impacted by certain factors, which may cause variations, for example, of ± 10 °C. Acquisition of Powder X-ray Diffraction (PXRD) Data A sample of Form 2 of L-Lysine salt of Compound 1 prepared according to the method described hereinabove was submitted for PXRD analysis and found to be a crystalline material. Powder X-ray diffraction analysis was conducted using a Bruker AXS D8 Endeavor diffractometer equipped with a Cu radiation source. The divergence slit was set at 11 mm continuous illumination. Diffracted radiation was detected by a PSD-Lynx Eye detector, with the detector PSD opening set at 4.1 degrees. The X-ray tube voltage and amperage were set to 40 kV and 40 mA respectively. Data was collected in the Theta-Theta goniometer at the Cu wavelength from 3.0 to 40.0 degrees 2-Theta using a step size of 0.02 degrees and a step time of 0.4 second. The antiscatter screen was set to a fixed distance of 3.0 mm. Samples were rotated at 15 / min during collection. Samples were prepared by placing them in a silicon low background sample holder and rotated during collection. Data were collected using Bruker DIFFRAC Plus software and analysis was performed by EVA diffract plus software. The PXRD data file was not processed prior to peak searching. Using the peak search algorithm in the EVA software, peaks selected with a threshold value of 10 were used to make preliminary peak assignments. To ensure validity, adjustments were manually made; the output of automated assignments was visually checked, and peak positions were adjusted to the peak maximum. Peaks with relative intensity of ≥ 3.0% were generally chosen. Typically, the peaks which were not resolved or were consistent with noise were not selected. A typical error associated with the peak position from PXRD stated in USP up to + / - 0.2° 2-Theta (USP-941). A representative PXRD pattern of Form 2 of L-lysine salt of Compound 1 is shown in FIG.5. A list of PXRD diffraction peaks expressed in terms of the degree 2θ and relative intensities with a relative intensity of ≥ 3.0% from a sample of Form 2 of L-lysine salt of Compound 1 is provided below. Table 7: PXRD Peaks and Relative Intensities of Form 2 of L-lysine salt of Compound 1 Angle (°2θ) Relative Intensity (%) + 0.2º 2Ɵ 4.4 68 5.9 13 7.4 22 8.8 23 10.3 21 13.2 13 14.7 24 17.6 23 18.3 100 19.2 48 22.2 24 26.6 33 32.9 15 35.8 10 Raman Spectroscopy Raman spectra were collected using a Thermo Scientific iS50 FT-Raman accessory attached to the FT-IR bench. A CaF2beamsplitter is utilized in the FT-Raman configuration. The spectrometer was equipped with a 1064 nm diode laser and a room temperature InGaAs detector. Samples were analyzed in glass NMR tubes. The spectra were collected using 0.4 W of laser power and 512 co-added scans. The collection range was 3700-200 cm-1. The Form 2 of L-Lysine salt of Compound 1 spectra were recorded using 2 cm-1resolution, and Happ- Genzel apodization was utilized for all of the spectra. Multiple spectra were recorded and a representative spectrum is shown in FIG.10. The variability in the peak positions with this experimental configuration is within ±2^cm-1. Peaks were picked using the automatic peak analysis function in ACD / Spectrus Processor software (2023.2.0). Peaks were picked using a noise factor of 0.3 and a minimum peak level of 3% maximum intensity. To ensure validity, the output of automated assignments was visually checked. Where a peak was present but not selected by the automatic peak analysis function, the peak(s) were manually selected. If a peak was selected by the automatic peak analysis function but was poorly resolved, or if the peak was not placed at the peak maximum, the peak was deleted. Typically, the peaks which were not resolved or were consistent with noise were not selected. Table Raman-2 lists the peak position (cm-1) and relative intensity for the observed spectrum shown in FIG.10. The variability in the peak positions with this experimental configuration is within ±2^cm-1. Table Raman-2: Raman peak list for Form 2 of L-lysine salt of Compound 1 Peak position (cm-1) Relative intensity (%) 410 7 448 4 630 12 642 6 716 5 724 5 729 5 746 3 759 3 788 3 805 4 823 5 829 5 845 16 863 4 908 9 927 8 961 3 975 3 1017 3 1041 5 1059 5 1081 4 1139 11 1179 9 1185 10 1196 11 1211 7 1251 11 1271 18 1283 38 1306 9 1357 5 1396 12 1417 6 1450 9 1462 6 1518 7 1535 4 1606 100 1644 8 1666 14 1684 3 2882 14 2911 14 2927 14 2942 14 2947 14 2962 16 2976 15 2985 13 3019 8 Solid State NMR13C solid-state NMR (ssNMR) analysis was conducted on a CPMAS probe positioned into a Bruker-BioSpin Avance NEO 500 MHz (1H frequency) NMR spectrometer. Material was packed into a ZrO2 rotor. A magic angle spinning rate of 15 kHz was used. Spectra were collected at ambient temperature (temperature uncontrolled). 13C ssNMR spectra were collected using a proton decoupled cross-polarization magic angle spinning (CPMAS) experiment. A phase modulated proton decoupling field of 80-100 kHz was applied during spectral acquisition. The cross-polarization contact time was set to 2 ms and the recycle delay to 3.5 s for Form 2 of L-lysine salt of Compound 1. The number of scans was adjusted to obtain an adequate signal to noise ratio. The13C chemical shift scale was referenced using a13C MAS experiment on an external standard of crystalline adamantane, setting its up-field resonance to 29.5 ppm. Automatic peak picking was performed using Bruker-BioSpin TopSpin version 4.1 software. Generally, a threshold value of 5% relative intensity was used for preliminary peak selection. The output of the automated peak picking was visually checked to ensure validity and adjustments were manually made if necessary. Although specific solid-state NMR peak values are reported herein there does exist a range for these peak values due to differences in instruments, samples, and sample preparation. This is common practice in the art of solid-state NMR because of the variation inherent in peak positions. A typical variability for the chemical shift x-axis value is on the order of plus or minus 0.2 ppm for a crystalline solid and plus or minus 0.5 ppm for an amorphous solid. The solid-state NMR peak heights reported herein are relative intensities. Solid-state NMR intensities can vary depending on the actual setup of the experimental parameters and the thermal history of the sample. A representative13C ssNMR spectrum for Form 2 of L-lysine salt of Compound 1 is shown in FIG.11. The peaks marked by hashes are spinning side bands. Table C13NMR-2 shows the13C ssNMR peak list for the observed13C ssNMR spectrum for Form 2 of L-lysine salt of Compound 1 as shown in FIG.11. A typical variability for the chemical shift x-axis value is on the order of plus or minus 0.2 ppm for a crystalline solid and plus or minus 0.5 ppm for an amorphous solid. Table C13NMR-2:13C ssNMR peak list for Form 2 of L-lysine salt of Compound 1. 13C Chemical Shift (ppm) Relative Intensity (%) 177.4 14 175.0 19 173.4 19 157.1 10 155.9 11 140.7 27 137.4 46 136.3 25 133.9 11 130.5 11 127.3 100 124.8 11 122.7 12 120.9 35 119.8 24 59.4 31 56.3 13 50.1 13 49.0 16 41.6 7 40.7 5 34.8 5 32.2 64 28.8 11 27.8 28 26.3 47 22.9 27 Example 4. 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4- carboxylic acid L-arginine salt (Form 1 of L-arginine salt of Compound 1) Compound 1 (50.0 g) was added to a mixture of isopropanol (210 mL) and water (90 mL). Then L-arginine (17.1 g) was added. The resulting mixture was stirred and heated to 70 °C to attain full dissolution. Then isopropanol (700 mL) was added over 4 hours. The mixture was cooled to 65 °C. Seeds of Form 1 of L-arginine salt of Compound 1 (1000 mg) were added. The resulting slurry was then cooled from 65 °C to 20 °C at 0.15 °C / min. The product (52.25 g, 95% yield) was isolated by filtration, washed with IPA (150 mL) and dried under vacuum at 50 °C (the product can also be used as seeding material used in another preparation of Form 1 of L-arginine salt of Compound 1). Preparation of Seeds of Form 1 of L-arginine salt of Compound 1 A slurry was prepared by adding approximately 29 mg PF-07976016 (free acid) to 2 mL methanol. The slurry was stirred at 50 °C for several minutes. Approximately 62 uL of aqueous L-arginine (0.99 M) was added to the slurry. The slurry was observed to thin considerably. The resulting slurry was stirred at 55 °C for several minutes, then allowed to cool to ambient and stirred for up to 72 hours. The resulting solids were isolated by centrifuge filtration. Differential scanning calorimetry (DSC) analysis of Form 1 of L- arginine salt of Compound 1 DSC measurements were performed with a DSC 2500 (TA instruments) equipped with a refrigerated cooling accessory. The cell constant was determined using indium and temperature calibration was performed using indium and tin as standards. All the measurements were done under continuous dry nitrogen purge (50 mL / min). Approximately 1-5 mg of solid sample was weighed into a Tzero aluminum pan, sealed non-hermetically and heated from 0 °C to 250 °C at 10 °C / min heating rate. The experimental data were analyzed using commercially available software (TA Universal Analysis 2000 / Trios software, TA Instruments). A reprentative differential scanning calorimetry thermogram of Form 1 of L-arginine salt of Compound 1 is shown in FIG.6. As can be seen in FIG.6, no thermal events are observed until approximately 221 °C. Thus, Form 1 of L-arginine salt of Compound 1 was determined to be anhydrous. Those skilled in the art would understand that endotherm onsets can be significantly impacted by factors such as crystallinity, presence of impurities, instrument parameters (e.g. ramp rate, sample mass), chemical degradation which is occurring in parallel with another event such as melting, etc. Thus, the onset temperature of about 221 °C may be significantly impacted by certain factors, which may cause variations, for example, of ± 10 °C. Acquisition of Powder X-ray Diffraction (PXRD) Data A sample of Form 1 of L-arginine salt of Compound 1 prepared according to the method described hereinabove was submitted for PXRD analysis and found to be a crystalline material. Powder X-ray diffraction analysis was conducted using a Bruker AXS D8 Endeavor diffractometer equipped with a Cu radiation source. The divergence slit was set at 15 mm continuous illumination. Diffracted radiation was detected by a PSD-Lynx Eye detector, with the detector PSD opening set at 4.1 degrees. The X-ray tube voltage and amperage were set to 40 kV and 40 mA respectively. In addition, the energy dispersive detector, a nickel filter was used to screen out unwanted wavelengths. Data was collected in the Theta-Theta goniometer at the Cu wavelength from 3.0 to 40.0 degrees 2-Theta using a step size of 0.01 degrees and a step time of 1.0 second. The antiscatter screen was set to a fixed distance of 3.0 mm. Samples were rotated at 15 / min during collection. Samples were prepared by placing them in a silicon low background sample holder and rotated during collection. Data were collected using Bruker DIFFRAC Plus software and analysis was performed by EVA diffract plus software. Data were collected using Bruker DIFFRAC Plus software and analysis was performed by EVA diffract plus software. Data analysis was performed by EVA diffract plus software. The PXRD data file was not processed prior to peak searching. Using the peak search algorithm in the EVA software, peaks selected with a threshold value of 10 were used to make preliminary peak assignments. To ensure validity, adjustments were manually made; the output of automated assignments was visually checked, and peak positions were adjusted to the peak maximum. Peaks with relative intensity of ≥ 3.0% were generally chosen. Typically, the peaks which were not resolved or were consistent with noise were not selected. A typical error associated with the peak position from PXRD stated in USP up to + / - 0.2° 2-Theta (USP-941). A representative PXRD pattern of Form 1 of L-arginine salt of Compound 1 is shown in FIG.7. A list of PXRD diffraction peaks expressed in terms of the degree 2θ and relative intensities with a relative intensity of ≥ 3.0% from a sample of Form 1 of L-arginine salt of Compound 1 is provided below. Table 8: PXRD Peaks and Relative Intensities of Form 1 of L-arginine salt of Compound 1 Angle (°2θ) Relative Intensity (%) + 0.2º 2Ɵ 3.7 4 7.3 92 11.0 4 13.5 4 14.6 17 16.0 17 16.7 7 17.2 21 17.6 34 18.3 41 18.6 35 20.0 100 20.4 12 21.0 53 21.7 30 22.0 15 22.4 12 23.4 20 24.2 11 24.6 11 25.3 14 25.8 8 26.5 7 27.6 8 28.3 21 29.4 14 30.6 13 31.1 7 33.3 10 37.1 10 38.5 9 39.1 9 Raman Spectroscopy Raman spectra were collected using a Thermo Scientific iS50 FT-Raman accessory attached to the FT-IR bench. A CaF2beamsplitter is utilized in the FT-Raman configuration. The spectrometer was equipped with a 1064 nm diode laser and a room temperature InGaAs detector. Samples were analyzed in glass NMR tubes. The spectra were collected using 0.5 W of laser power and 512 co-added scans. The collection range was 3700-200 cm-1. The Form 1 of L-arginine salt of Compound 1 spectra were recorded using 2 cm-1resolution, and Happ- Genzel apodization was utilized for all of the spectra. Multiple spectra were recorded and a representative spectrum is shown in FIG.12. The variability in the peak positions with this experimental configuration is within ±2^cm-1. Peaks were picked using the automatic peak analysis function in ACD / Spectrus Processor software (2023.2.0). Peaks were picked using a noise factor of 0.3 and a minimum peak level of 3% maximum intensity. To ensure validity, the output of automated assignments was visually checked. Where a peak was present but not selected by the automatic peak analysis function, the peak(s) were manually selected. If a peak was selected by the automatic peak analysis function but was poorly resolved, or if the peak was not placed at the peak maximum, the peak was deleted. Typically, the peaks which were not resolved or were consistent with noise were not selected. Table Raman-3 lists the peak position (cm-1) and relative intensity for the observed spectrum shown in FIG.12. The variability in the peak positions with this experimental configuration is within ±2^cm-1. Table Raman-3: Raman peak list for Form 1 of L-arginine salt of Compound 1. Peak position (cm-1) Relative intensity (%) 248 3 417 10 458 3 632 7 730 6 809 4 830 6 844 10 891 5 926 5 1050 3 1139 11 1178 8 1186 10 1199 18 1253 13 1270 22 1279 42 1291 20 1305 15 1336 3 1354 7 1388 14 1417 4 1440 5 1461 4 1522 8 1536 6 1545 6 1602 100 1611 78 1637 10 1694 7 2873 7 2892 5 2939 9 2974 7 2985 8 3020 5 3049 7 3067 9 Solid State NMR 13C solid-state NMR (ssNMR) analysis was conducted on a CPMAS probe positioned into a Bruker-BioSpin Avance NEO 500 MHz (1H frequency) NMR spectrometer. Form 1 of L- arginine salt of Compound 1 was packed into a ZrO2 rotor. A magic angle spinning rate of 15 kHz was used. Spectra were collected at ambient temperature (temperature uncontrolled). 13C ssNMR spectra were collected using a proton decoupled cross-polarization magic angle spinning (CPMAS) experiment. A phase modulated proton decoupling field of 80-100 kHz was applied during spectral acquisition. The cross-polarization contact time was set to 2 ms and the recycle delay to 3.5 s for Form 1 of L-arginine salt of Compound 1. The number of scans was adjusted to obtain an adequate signal to noise ratio. The13C chemical shift scale was referenced using a13C MAS experiment on an external standard of crystalline adamantane, setting its up-field resonance to 29.5 ppm. Automatic peak picking was performed using Bruker-BioSpin TopSpin version 4.1 software. Generally, a threshold value of 5% relative intensity was used for preliminary peak selection. The output of the automated peak picking was visually checked to ensure validity and adjustments were manually made if necessary. Although specific solid-state NMR peak values are reported herein there does exist a range for these peak values due to differences in instruments, samples, and sample preparation. This is common practice in the art of solid-state NMR because of the variation inherent in peak positions. A typical variability for the chemical shift x-axis value is on the order of plus or minus 0.2 ppm for a crystalline solid and plus or minus 0.5 ppm for an amorphous solid. The solid-state NMR peak heights reported herein are relative intensities. Solid-state NMR intensities can vary depending on the actual setup of the experimental parameters and the thermal history of the sample. A representative observed13C ssNMR spectrum for Form 1 of L-arginine salt of Compound 1 is shown in FIG.13. The peaks marked by hashes are spinning side bands. Table C13NMR-3 shows the13C ssNMR peak list for the observed13C ssNMR spectrum for Form 1 of L-arginine salt of Compound 1 as shown in FIG.13. A typical variability for the chemical shift x-axis value is on the order of plus or minus 0.2 ppm for a crystalline solid and plus or minus 0.5 ppm for an amorphous solid. Table C13NMR-3:13C ssNMR peak list for Form 1 of L-arginine salt of Compound 1. 13C Chemical Shift (ppm) Relative Intensity (%) 176.8 17 176.3 30 174.6 23 174.0 27 171.0 21 170.2 38 160.2 15 157.6 18 155.9 49 143.6 57 140.7 39 140.2 37 139.5 35 138.6 44 138.2 50 136.4 31 135.9 25 135.6 22 133.2 40 132.4 30 128.6 55 128.1 68 126.2 100 125.3 28 119.9 82 119.4 80 119.0 64 118.1 21 61.0 74 54.6 22 53.3 14 46.3 69 40.9 31 40.3 21 34.4 43 33.4 39 29.4 22 27.8 39 26.9 46 26.3 89 26.0 77 24.9 91 24.6 90 23.5 24 Prophetic deuterated analogs (PDAs) of certain compounds of the invention Example X-1: Some Prophetic deuterated analogs (PDA) of Compound 1 The compounds provided in Table X-1 are some prophetic deuterated analogs (PDA) of Compound 1. The Formula (X-A) is a generic formula of deuterated Compound 1, wherein Y1a, Y1b, Y2, Y3, Y4a, Y4b, Y5a, Y5b, Y5c, Y6a, Y6b, Y6c, Y7a, Y7b, Y8a, Y8b, Y9a, Y9b, Y10a, Y10b, Y11aand Y11b, Y12a, Y12b, Y13aand Y13bare each independently H or D (deuterium) and wherein at least one of them is D. The deuterated analogs of Compound 1 in Table X-1 can be predicted based on the metabolic profile of Compound 1, with MetaSite (moldiscovery.com / software / metasite / ). Y1a, Y1b, Y2, Y3, Y4a, Y4b,Y5a, Y5b, Y5c, Y6a, Y6b, Y6c, Y7a, Y7b, Y8a, Y8b, Y9a, Y9b, Y10a, Y10b, Y11a, Y11b, Y12a, Y12b, Y13aand Y13bare predicted metabolized positions based on MetaSite predictions.

[0005] Table X-1. PDA # Y1aY2Y3Y4aY5aY6aY7aY8aY9aY10a- Y11a- Y12a- Y13a- - -Y4b-Y5c-Y6c- - - Y10bY11bY12bY13bY1bY7bY8bY9bXA-1 D H H H H H H H H H H H H XA-2 H D H H H H H H H H H H H XA-3 H H D H H H H H H H H H H XA-4 H H H D H H H H H H H H H XA-5 H H H H D H H H H H H H H XA-6 H H H H H H D H H H H H H XA-7 H H H H H H H D H H H H H XA-8 H H H H H H H H D H H H H XA-9 H H H H H H H H H D H H H XA-10 H H H D H H H H H H D H H XA-11 H H H H H H H H H H H D H XA-12 H H H H H H H H H H H H D XA-13 D D H H H H H H H H H H H XA-14 D H D H H H H H H H H H H XA-15 H D D H H H H H H H H H H XA-16 H D H H D H H H H H H H H XA-17 H H H H D D H H H H H H H XA-18 H D H H D D H H H H H H H The prophetic deuterated analogs (PDA) of Compound 1 in Table X-1 can also form a pharmaceutically acceptable salt thereof, for example, L-lysine salt or L-arginine salt thereof. Example AA. Functional In Vitro GIPR Antagonist Potency Assay The functional in vitro antagonist potency for test compounds was determined by monitoring intracellular cyclic adenosine monophosphate (cAMP) levels in Chinese hamster ovary (CHO)-K1 cells stably expressing the human Glucose-dependent Insulinotropic Polypeptide Receptor (hGIPR). Following agonist activation, hGIPR associates with the G- protein complex causing the Gαs subunit to exchange bound guanosine diphosphate (GDP) for guanosine triphosphate (GTP), followed by dissociation of the Gαs-GTP complex. The activated Gαs subunit can couple to downstream effectors to regulate the levels of second messengers or cAMP within the cell. Thereby, determination of intracellular cAMP levels allows for pharmacological characterization. Intracellular cAMP levels are quantitated using a homogenous assay utilizing the Homogeneous Time Resolved Fluorescence (HTRF) technology from Perkin Elmer. The method is a competitive immunoassay between native cAMP produced by the cells and cAMP labelled with the acceptor dye, d2. The two entities compete for binding to a monoclonal anti-cAMP antibody labeled with cryptate. The specific signal is inversely proportional to the concentration of cAMP in the cells. Test compounds were solubilized to a concentration of 30 mM in 100% dimethyl sulfoxide (DMSO). An 11-point dilution series using 1 in 3.162-fold serial dilutions was created in 100% DMSO with a top concentration of 8 mM. The serially diluted compound was spotted with an Echo Acoustic liquid handler (Beckman Coulter) into a 384-well assay plate (Corning, Cat No.3824) at 50 nL / well with duplicate points at each concentration, at a 200x final assay concentration (FAC). The final compound concentration range in the assay was 40 µM to 400 pM, with a final DMSO concentration of 0.5%. Frozen assay-ready vials (at 1x107cells / vial) of CHO-K1 cells stably expressing the Gs- coupled human GIPR receptor (Eurofins, DiscoverX, Cat No.95-0146C2) were thawed, counted, and resuspended in assay buffer consisting of Hank’s Balanced Salt Solution (HBSS, Lonza Cat No.10-527) containing 20 mM (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, Lonza, Cat No.17-737E), 0.1% bovine serum albumin (BSA, Sigma, Cat No. A7979), and 200 µM 3-isobutyl-1-methylxanthine (IBMX, Sigma, Cat No. I5879) at a density of 4x105cells / mL. Cells were added to assay plate (5 μL / well of 4x105cells / mL stock for 2,000 cells / well final) containing 50 nL of 200x FAC test compound, and incubated at 37oC (95% O2: 5% CO2) for 2 hours, with micro-clime lids (Labcyte, Cat No. LLS-0310). Following the 2-hour cell and compound incubation, a stimulation mix comprised of hGIPR agonist human glucose- dependent insulinotropic polypeptide (hGIP, full length, Sigma Cat No. G2269) in assay buffer / 0.1% DMSO was added to the assay plate (5 µL / well) at an estimated EC80FAC (based on previous hGIP agonist curves) and incubated for another 30 minutes with micro-clime lids at 37oC (95% O2: 5% CO2), after which intracellular cAMP levels were quantified as per Perkin Elmer’s protocol (5 μL of d2 and then 5 μL cryptate, incubated for 1 hour at room temperature). Emission spectra of samples were measured on a Pherastar plate reader (BMG Labtech Inc) using a HTRF protocol (excitation, 320 nm; emission, 665 nm / 620 nm). hGIP EC50was determined daily by incubating cells (5 μL / well of 4x105cells / mL stock, for 2,000 cells / well final) with 50 nL 100% DMSO for 2 hours at 37oC (95% O2: 5% CO2), with a micro-clime lid. Following the 2-hour cell and DMSO incubation, a hGIP concentration response curve at 2x FAC (12-point curve using 1 in 3 serial dilutions, with triplicate points at each concentration, 100 nM final top concentration) in assay buffer / 1% DMSO was added (5 µL / well) and incubated for a further 30 minutes with a micro-clime lid at 37oC (95% O2: 5% CO2), after which intracellular cAMP levels were quantified and samples measured as described previously. Experiments passed quality control if the agonist concentration used for stimulation fell between the on-the-day EC50-EC90. Data were analyzed using the ratio of fluorescence intensity at 620 and 665 nm for each well, extrapolated from the cAMP standard curve to express data as nanomolar (nM) cAMP for each well. Data expressed as nM cAMP were then normalized to control wells using ActivityBase (IDBS data management software). Zero percent effect (ZPE) was defined as nM cAMP generated from the hGIP stimulation mix, while 100% effect, or one hundred percent effect (HPE), was defined as nM cAMP generated from the combined effects of hGIP simulation mix + antagonism by 80 μM of (-)-3-(6-(2-methyl-1-(4'-(trifluoromethyl)biphenyl-4- yl)propylamino)nicotinamido)propanoic acid as GIPR antagonist. The concentration and % effect values for each compound were plotted by ActivityBase using a four-parameter logistic dose response equation, and the concentration required for 50% inhibition (IC50) was determined. Table AA-1 lists biological activities (IC50values) and compound names for tested compounds. Table AA-1. Biological activity and Compound name hGIPR hGIPR antagonist Test antagonist IC50Compound Name Compound IC50 (nM)1replicate count 4'-[(1-{[4-(propan-2-yl)phenyl]carbamoyl}-D- Compound 1 4.1 14 prolyl)amino][1,1'-biphenyl]-4-carboxylic acid 1. Values represent the geometric mean 2. Values include the overall geometric mean of multiple forms (including salts) tested Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application for all purposes. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A compound that is 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'- biphenyl]-4-carboxylic acid lysine salt.

2. A crystalline form of the compound of claim 1.

3. A hydrate form of the compound of claim 1.

4. A crystalline form of the compound of claim 1, wherein the crystalline form is anhydrous.

5. A compound that is 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'- biphenyl]-4-carboxylic acid lysine salt, sesquihydrate.

6. An amorphous form of the compound of claim 1.

7. The compound of any one of claims 1 to 6 wherein the 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid lysine salt is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt.

8. The compound of claim 1, wherein the compound is a sesquihydrate crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L- lysine salt (“Form 1 of L-lysine salt of Compound 1”), wherein Form 1 has a powder X-ray diffraction pattern (PXRD) comprising at least one peaks in terms of 2θ, selected from those at 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º.

9. The compound of claim 8, wherein Form 1 of L-lysine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, selected from those at 7.3 + 0.2º, 16.7 + 0.2º, 17.9 + 0.2º, 18.6 + 0.2º, and 19.7 + 0.2º.

10. The compound of claim 8 or 9, wherein Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), selected from those at the position of 1284 ± 2 cm-1, 1604± 2 cm-1, and 1636 ± 2 cm-1.

11. The compound of any one of claims 8 to 10, wherein Form 1 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising at least two peaks, in terms ofwavenumbers (cm-1), selected from those at the position of 1284 ± 2 cm-1, 1604± 2 cm-1, and 1636 ± 2 cm-1.

12. The compound of any one of claims 8 to 11, wherein Form 1 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising two peaks, in terms of chemical shifts, at 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm.

13. The compound of any one of claims 8 to 12, wherein Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising at least three peaks, in terms of chemical shifts, selected from those at 24.5 ± 0.2 ppm, 47.1± 0.2 ppm, 131.3 ± 0.2 ppm, and 169.6 ± 0.2 ppm.

14. The compound of claim 1, wherein the compound is an anhydrous crystalline form of 4'- [(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-lysine salt (“Form 2 of L-lysine salt of Compound 1”), wherein Form 2 has a powder X-ray diffraction pattern (PXRD) comprising at least one peak, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, and 10.3+ 0.2º.

15. The compound of claim 14, wherein Form 2 of L-lysine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, selected from those at 4.4 + 0.2º, 5.9 + 0.2º, 8.8 + 0.2º, 10.3+ 0.2º, and 18.3+ 0.2º.

16. The compound of claim 14 or 15, wherein Form 2 of L-lysine salt of Compound 1 has a differential scanning calorimetry trace comprising an endotherm having an onset at about 219.9 + 10.0 ºC.

17. The compound of any one of claims 14 to 16, wherein Form 2 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising two peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1283 ± 2 cm-1, 1606 ± 2 cm-1, and 1666 ± 2 cm-1.

18. The compound of any one of claims 14 to 17, wherein Form 2 of L-lysine salt of Compound 1 has an FT-Raman spectrum comprising peaks, in terms of wavenumbers (cm-1), at the position of 1283 ± 2 cm-1, 1606 ± 2 cm-1, and 1666 ± 2 cm-1.

19. The compound of any one of claims 14 to 18, wherein Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemicalshifts, selected from those at 32.2 ± 0.2 ppm, 120.9 ± 0.2 ppm, 127.3 ± 0.2 ppm, and 177.4 ± 0.2 ppm.

20. The compound of any one of claims 14 to 19, wherein Form 2 of L-lysine salt of Compound 1 has a13C ssNMR spectrum comprising at least two peaks, in terms of chemical shifts, selected from those at 32.2 ± 0.2 ppm, 120.9 ± 0.2 ppm, 127.3 ± 0.2 ppm, and 177.4 ± 0.2 ppm.

21. A compound that is 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'- biphenyl]-4-carboxylic acid arginine salt.

22. A crystalline form of the compound of claim 21.

23. A crystalline form of the compound of claim 21 or 22, wherein the crystalline form is anhydrous.

24. An amorphous form of the compound of claim 21.

25. The compound of any one of claims 21 to 24 wherein the 4'-[(1-{[4-(Propan-2- yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid arginine salt is 4'-[(1-{[4- (Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L-arginine salt.

26. The compound of claim 21, wherein the compound is an anhydrous crystalline form of 4'-[(1-{[4-(Propan-2-yl)phenyl]carbamoyl}-D-prolyl)amino][1,1'-biphenyl]-4-carboxylic acid L- arginine salt (“Form 1 of L-arginine salt of Compound 1”), wherein Form 1 has a powder X-ray diffraction pattern (PXRD) comprising at least one peak, in terms of 2θ, at 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º.

27. The compound of claim 26, wherein Form 1 of L-arginine salt of Compound 1 has a PXRD comprising at least two peaks, in terms of 2θ, at 7.3 + 0.2º, 14.6 + 0.2º, 17.6 + 0.2º, 18.3 + 0.2º, and 20.0 + 0.2º.

28. The compound of claim 26 or 27, wherein Form 1 of L-arginine salt of Compound 1 has differential scanning calorimetry trace comprising an endotherm having an onset at about 221.2 + 10.0 ºC.

29. The compound of any one of claims 26 to 28, wherein Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising at least one peak, in terms of wavenumbers (cm-1), selected from those at the position of 1279 ± 2 cm-1, 1602 ± 2 cm-1, and 1611 ± 2 cm-1.

30. The compound of any one of claims 26 to 29, wherein Form 1 of L-arginine salt of Compound 1 has an FT-Raman spectrum comprising at least two peaks, in terms of wavenumbers (cm-1), selected from those at the position of 1279 ± 2 cm-1, 1602 ± 2 cm-1, and 1611 ± 2 cm-1.

31. The compound of any one of claims 26 to 30, wherein Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising at least one peak, in terms of chemical shifts, selected from those at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm.

32. The compound of any one of claims 26 to 31, wherein Form 1 of L-arginine salt of Compound 1 has a13C ssNMR spectrum comprising at least two peaks, in terms of chemical shifts, selected from those at 46.3 ± 0.2 ppm, 138.2 ± 0.2 ppm, 140.1 ± 0.2 ppm, and 176.3 ± 0.2 ppm.

33. A pharmaceutical composition comprising a compound of any one of claims 1 to 32 and a pharmaceutically acceptable excipient. 34 A method for treating or preventing a condition, disease, or disorder in a patient comprising administering to the patient a compound of any one of claims 1 to 32, wherein the condition, disease, or disorder is selected from the group consisting of diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth- onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition- related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes),weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), overweight, excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug); or a method for weight management of a human comprising administering to the human a compound of any one of claims 1 to 32.

35. Use of a compound of any one of claims 1 to 32 for treating or preventing a condition, disease, or disorder, or use of a compound of any one of claims 1 to 32 in manufacturing a medicament for treating or preventing a condition, disease, or disorder, wherein the condition, disease, or disorder is selected from the group consisting of diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamicobesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), overweight, excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug); or use of a compound of any one of claims 1 to 32 for weight management (e.g. chronic weight management); or use of a compound of any one of claims 1 to 20 in manufacturing a medicament for weight management (e.g. chronic weight management).

36. A compound of any one of claims 1 to 32 for use in a method for treating or preventing a condition, disease, or disorder in a patient, wherein the condition, disease, or disorder is selected from the group consisting of diabetes [e.g. Type 1 diabetes mellitus (T1D), Type 2 diabetes mellitus (T2DM), including pre-diabetes], idiopathic T1D (Type 1b), latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease [e.g., acute kidneydisorder, tubular dysfunction, proinflammatory changes to the proximal tubules, or chronic kidney disease (CKD)], diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea [e.g. obstructive sleep apnea (OSA)], obesity (including hypothalamic obesity and monogenic obesity) and related comorbidities (e.g., osteoarthritis and urine incontinence), eating disorders (including binge eating syndrome, bulimia nervosa, and syndromic obesity such as Prader-Willi and Bardet-Biedl syndromes), weight gain such as weight gain caused by use of other agents (e.g., caused by use of steroids and / or antipsychotics, or caused by treatment of depression, or caused by use of agents on cognitive function), overweight, excessive sugar craving, dyslipidemia [including hyperlipidemia, hypertriglyceridemia, increased total cholesterol, high LDL (low-density lipoprotein) cholesterol, and low HDL (high-density lipoprotein) cholesterol], hyperinsulinemia, nonalcoholic fatty liver disease [NAFLD, including related diseases such as steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma], cardiovascular disease, atherosclerosis (including coronary artery disease), peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, heart failure [e.g. congestive heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF)], myocardial infarction (e.g. necrosis and apoptosis), stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post- prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, osteoarthritis, Parkinson’s disease, left ventricular hypertrophy, peripheral arterial disease (PAD), macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, Alzheimer’s Disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, Crohn’s disease, colitis, irritable bowel syndrome, polycystic ovary syndrome (PCOS), and addiction (e.g., addition to alcohol, nicotine, and / or drug); or a compound of any one of claims 1 to 32 for use in a method for weight management (e.g. chronic weight management) of a human.

37. A method for modulating a glucose-dependent insulinotropic polypeptide receptor (GIPR) comprising contacting the GIPR with a compound of any one of clams 1 to 32.

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