A mixing and kneading machine (1) for continual compounding comprises a screw shaft (3) rotating in a casing (2) and simultaneously moving axially translationally. To sustainably enhance the efficiency of the machine as regards its material thruput per unit of time the screw shaft (3) comprises at least four groups of radial screw vanes (4a, 4b, 4c, 4d) evenly distributed circumferentially, each group consisting of a plurality of screw vanes in axial sequence. The outer diameter (Da) of the screw shaft ranges from 400 to 800 millimeters. The rotary speed of the screw shaft (3) ranges from 30 to 80 rpm. A mixing and kneading machine (1) engineered as such is particularly suitable for compounding an anodic mass in the production of electrodes—anodes—for the aluminum industry.

A treatment element to treat material in a multi-shaft worm machine has an outer contour with at least one outer contour portion, the associated evolute of which is a quantity of at least three points, each of the points lying outside the longitudinal axis and within the outer radius of the treatment element and two respective adjacent points having a spacing from one another, which is less than half the core radius. The treatment element ensures high flexibility during the adjustment of shear and/or extensional flows on the material to be treated.

This invention is directed to a stirring apparatus comprising: a plurality of blades having between a 5° to 180° twist along the length of their axis attached perpendicularly to a shaft so that a downward fluid flow is created when the shaft is rotated by a rotary drive; and, a plurality of standards attached to the plurality of blades separating the plurality of blades and arranged parallel to the shaft and rotated between 0° and 25° relative to a plane defined by the blades and the standards so that an inward fluid flow is created when the shaft is rotated and a bottom blade connected to the standards.

Provided are a fluid agitation apparatus using a structure which is simple in shape and short in a fluid passage direction without a movable part so as to produce a sufficient effect from the viewpoint of reducing temperature fluctuation, and a thermostatic apparatus using the fluid agitation apparatus. The fluid agitation apparatus is installed in a fluid passage and includes, in an order from an upstream side thereof: a dividing part for dividing a flow of a fluid into a plurality of flows; a circumvolving part for circumvolving the fluid about an axis in a flow direction of the fluid; and an accelerating part for increasing a flow rate of the fluid.

A dissolution generator includes: an upright housing; a screen assembly extending across an interior of the housing, and configured to support a column of powder thereabove; a spray nozzle disposed below the screen assembly and directed towards the screen assembly; and a pressure mechanism disposed above the screen assembly, and configured to apply a substantially constant downward pressure.

A seal ring is provided which allows the interior of a cylinder 1 of a screw extruder to be maintained at elevated temperature and elevated pressure, thus suppressing a variation in the pressure in the cylinder 1. In a special seal ring 300 attached to a screw shaft 7 in the cylinder of the screw extruder so as to be rotatable integrally with the screw shaft 7, thus restraining a material to be treated from being fed from upstream to downstream in the cylinder, a lead groove 317 extending in an axial direction of the shaft 7 is formed in an outer circumferential surface 316 opposing with a predetermined gap to an inner circumferential surface 1a of the cylinder. The lead groove 317 serves to disturb the flow of the material to be treated passing between the outer circumferential surface 316 and the inner wall surface 1a of the cylinder 1 to complex the flow. This stabilizes feeding resistance to suppress a variation in the pressure in the cylinder 1.

The present invention discloses a high intensity ultrasonic treatment method and apparatus that is used in conjunction with an existing commercial dough or batter mixer to enhance the rheological, aeration and textural properties of the dough or batter. This change in properties is a result of the phenomenon of acoustic cavitation induced in the dough or batter by treatment with high intensity ultrasonic waves. The present invention discloses a mixing bowl (20) of an existing mixer system that is preloaded with dough or batter, the bowl (20) is located at the center of an ultrasonic bath tank (101) filled with a working fluid. The effect of ultra-sonic waves with power levels above 1 kW can be observed over the entire or partial mixing period of the dough or batter. The ultra-sonic waves of the present invention are generated by a plurality of ultrasonic wave generators (104A, 104B) and piezoelectric transducers (1) mounted on a stainless steel tank (101). The electrical energy received in each transducer (1) will be converted into appropriate mechanical expansion and contractions in the piezoelectric ceramics of the transducer (1) thus leading to pressure waves being transmitted to the dough or batter to be mixed. The generation and transmission of high intensity ultrasonic waves to the dough or batter affects its rheological, aeration and textural properties.

A mixing silo for free-flowing finely divided solid materials, in particular for powdered, fibrous and/or granular mixed material, especially polymer granules, specifically suited for mixing polymer granules, having an excellent mixing quality and at the same time a simplified and improved suitability for washing out in order to avoid cross contamination. The mixing silo may be used for homogenizing possibly inhomogeneous polymer granule batches in the form of a stream of product from a process producing polymer granules.

An improved dual-shaft preconditioner (10) of simplified design is provided giving increased moisturization and partial cooking of food or feed ingredients. The preconditioner (10) includes an elongated, tapered housing (12) presenting a pair of side-by-side, communicating housing sections (58, 60), with a corresponding pair of converging shafts (20, 22) within the sections (58, 60) and having a series of elongated, outwardly extending mixing elements (24, 26) secured to the shafts (20, 22). The preconditioner (10) is designed for use in a system including a downstream processing device, such as an extruder (146).

Provided is a stirrer including a stirring section formed of a plurality of wire members and a handle section to which ends of the respective wire members are mounted, which is capable of preventing, with a simple configuration, liquid such as water from entering inside the handle section from gaps between a mounting part of the handle section and root parts of the respective wire members. The stirrer includes: a stirring section including a plurality of wire members; a fitting body including one or both of grooves and through-holes into which ends of the respective wire members are fitted; and a handle section including a mounting recess to which the fitting body is fitted and fixed under a state in which the ends of the respective wire members are fitted into the one or both of grooves and through-holes.

An agitator, particularly for abrasive media includes a support disk to which agitator blades are connected substantially perpendicular to the support disk. The blades are arranged substantially in a radial direction. The support disk also includes a hub that receives an agitator shaft which is preferably motor-driven. The trailing faces of the blades of the agitator and/or the area of the blade connections to the support disk are designed to largely prevent vortex shedding. This is accomplished by implementing a specific geometry for the agitator blades, the support disk, and the connection of the blades to the support disk.

A measuring device comprising at least one mixer structure to receive a fiber suspension sample from at least one process part. Each mixer structure is provided with a measuring unit, a feeding valve for feeding feed liquid into a sample line for pushing the sample in the sample line towards the measuring unit, a mixing valve structure for feeding dilution liquid into the mixer structure The mixer structure mixes the flowing sample and the dilution liquid with one another in order to reduce the consistency of the sample. The measuring device measures from the first part of the mixed sample one property of the fiber suspension and the measuring device measures from the second part of the mixed sample a further property.

The present invention generally relates to multiple emulsions, and to methods and apparatuses for making multiple emulsions. A multiple emulsion generally describes larger droplets that contain one or more smaller droplets therein. The larger droplets may be suspended in a third fluid in some cases. These can be useful for encapsulating species such as pharmaceutical agents, cells, chemicals, or the like. In some cases, one or more of the droplets can change form, for instance, to become solidified to form a microcapsule, a liposome, a polymerosome, or a colloidosome. Multiple emulsions can be formed in one step in certain embodiments, with generally precise repeatability, and can be tailored to include one, two, three, or more inner droplets within a single outer droplet (which droplets may all be nested in some cases).

A compact portable blender system features a base unit. A base unit top surface features a recess having an “L” shaped locking slot and a motor with a drive gear. A base unit bottom surface features a removable power supply. The base unit features a power charger, a removable cord, a cord storage cavity, a power switch, and a power indicator. The system features a blending container. A blending blade unit is located on a container bottom. A blade drive gear located on a blending blade unit bottom and a blending blade is located on a blending blade unit top. The blending blade unit features a locking tab located on a blending blade unit side wall. The system features a container lid having an aperture. The container lid features a cover located over the aperture on a container lid top.

The present invention relates to the field of organic chemistry and in particular to organic free radicals used as polarizing agents in the technique of Dynamic Nuclear Polarization (DNP), which involves transferring the polarization of electron spins to the nuclei of a compound whose Nuclear Magnetic Resonance (NMR) is being observed. It concerns Dinitroxide-type Biradical polarizing agents characterized by a rigid linkage between the aminoxyl groups of said nitroxide units. This particular structure enables, at low temperatures and high fields, optimal transfer of polarization and optimal enhancement of NMR/MAS signals of the polarized nuclei of the compound studied.

This disclosure is directed to pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. The compounds may bind to and antagonize receptor α2B, α1B or α2A. The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption, or to regulate blood glucose level, increase insulin secretion and treat diseases or conditions that are, or are expected to be, responsive to an increase in insulin production. The compounds may also be used to treat diseases or conditions that are expected to be responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular, renal disorders or type 2 diabetes is particularly described.

Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed.

A method of synthesizing a crystalline molecular sieve having an MSE framework type comprises crystallizing a reaction mixture comprising a source of water, a source of an oxide of a tetravalent element, Y, selected from at least one of silicon, tin, titanium, vanadium, and germanium, optionally a source of a trivalent element, X, a source of an alkali or alkaline earth metal, M, and a source of organic dications, Q, such as 3-hydroxy-1-(4-(1-methylpiperidin-1-ium-1-yl)butyl)quinuclidin-1-ium, 3-hydroxy-1-(5-(1-methylpiperidin-1-ium-1-yl)pentyl)quinuclidin-1-ium, 1,1'-(butane-1,4-diyl)bis(1-methylpiperidin-1-ium), 1,1'-(pentane-1,5-diyl)bis(1-methylpiperidin-1-ium), 1,1'-(hexane-1,6-diyl)bis(1-methylpiperidin-1-ium), and 1,1'-((3as,6as)-octahydropentalene-2,5-diyl)bis(1-methylpiperidin-1-ium).

There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein Ring A represents a partially saturated heteroaryl group, an aryl group or a heteroaryl group,RB represents a C4-18 alkyl group, a C3-8 cycloalkyl group, a partially saturated aryl group, an aryl group, or the following formula (II): wherein V represents the formula —CR11R12—, —CO—, —CO—O—, or —CO—NH—,W represents a single bond or a C1-3 alkylene group, andRing B represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a partially saturated heteroaryl group, a saturated heterocyclyl group, an aryl group, or a heteroaryl group,Y represents a nitrogen atom or the formula N+(RF),RF represents a C1-4 alkyl group, andm and n, which may be the same or different, each represent an integer of 0 or 1.

The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.

A process for preparing the compound of the following formula (E): wherein Bn represents a benzyl group, and tBu represents a tert-butyl group, the process including: (a) subjecting the following compound (B) to trifluoroacetylation, wherein tBu represents a tert-butyl group to produce the following compound (C): wherein tBu represents a tert-butyl group, and TFA represents a trifluoroacetyl group; (b) reacting the compound (C) with benzyloxyamine in the presence of a hydroxyl group activating agent to produce the following compound (D): wherein Bn represents a benzyl group, tBu represents a tert-butyl group, and TFA represents a trifluoroacetyl group; and (c) subjecting the compound (D) to detrifluoroacetylation.

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

A description is given of N-(1,2,5-oxadiazol-3-yl)pyridinecarboxamides of the general formula (I) as herbicides. R in this formula (I) stands for radicals such as hydrogen, organic radicals, and other radicals such as halogen. W stands for a substituted pyridyl radical.

The present invention is directed to ethanamine compounds, pharmaceutical compositions comprising the same, and methods of treating depression by administering the ethanamine compound.

The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods.

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.

The present invention relates, inter alia, to metal complexes having improved solubility, to processes for the preparaion of the metal complexes, to devices comprising these metal complexes and to the use of the metal complexes.

A method of manufacturing an anhydrous copper complex of formula C12H10CICuN2O4 and methods of treating neuromuscular and other diseases, including but not limited to fibromyalgia, multiple sclerosis, muscular dystrophy, rheumatoid arthritis, pain, fatigue, sleeplessness, loss of fine motor control, speech loss, inflexibility, Alzheimer's, dementia, amyotrophic lateral sclerosis, depression, lyme disease, lyme disease co-infection, gastroparesis (GP), myopathy, chronic inflammation and/or incontinence. The anhydrous copper complex preferably is administered in a pharmaceutical and/or dietary supplement composition of the invention.

This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

This disclosure is directed to fused tetracyclic pyrido[4,3-b>]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

Compounds are described herein useful for treating diseases and conditions by modulation of one or more alpha adrenergic receptor. The compounds can include a naphthalene, a quinoline, a benzoimidazole or an isoquinoline as a core structure. Methods of making, using and formulating these compounds are described.

The present disclosure relates to Oxime-Substituted Quinoxaline-Type Piperidine Compounds, such as those of Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R20, R21, Q, Y1, Z, A, B, and a are as defined herein; compositions comprising an effective amount of an Oxime-Substituted Quinoxaline-Type Piperidine Compound, and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of an Oxime-Substituted Quinoxaline-Type Piperidine Compound.

The present invention is directed to a compound of Formula (I) and to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

The present invention features compounds having the Formula (Ia) and (Ib) (e.g., a compound of any of Formulas ((Ia-2)-(Ia-21)), including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, pharmaceutically acceptable salts, and compositions thereof. The invention also features methods for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient by administering an effective amount of a compound of Formula (Ia) or (Ib). The invention also features a method for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient that includes administering to a patient in need thereof an effective amount of a compound of Formula (IIa) or (IIb) (e.g., a compound of any of Formulas ((IIa-2)-(IIa-6)). The compounds described herein (e.g., a compound of Formulas (Ia), (Ib), (IIa), or (IIb)) can also be used as anticonvulsants.

The present invention generally relates to use of compounds and compositions as a chemosensitizers and/or radiosensitizers and/or inhibitors of PNKP phosphatase activity. The present invention provides pharmaceutical combinations and/or a pharmaceutically acceptable salt thereof, kits containing such compounds and/composition and methods of using such compounds and/or compositions.

The present invention relates to compounds of Formula I or II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which relates to mophinan compounds useful as μ, δ and/or κ receptor opioid compounds and pharmaceuticals containing same that may be useful for mediating analgesia, combating drug addiction, alcohol addiction, drug overdose, mental illness, bladder dysfunctions, neurogenic bladder, interstitial cystitis, urinary incontinence, premature ejaculation, inflammatory pain, peripherally mediated and neuropathic pain, cough, lung edema, diarrhea, cardiac disorders, cardioprotection, depression, and cognitive, respiratory, diarrhea, irritable bowel syndrome and gastro-intestinal disorders, immunomodulation, and anti-tumor agents.

The present invention provides a process for the synthesis of substituted phenoxymethylpropionic acid and related compounds. The compounds are useful for inhibiting the formation of AGEs (Advanced Glycation End Products).

Disclosed are solid forms of 8-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-6-(trifluoromethyl)-imidazo[1,2-a]pyridine-2-carboxamide (Compound 1). Methods for the preparation of solid forms of Compound 1 and for the conversion of one solid form of Compound 1 into another are disclosed. Disclosed are nematocidal compositions comprising a nematocidally effective amount of a solid form of Compound 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers. Compositions comprising a mixture of a solid form of Compound 1 and at least one other nematicide, insecticide and/or fungicide are also disclosed.Also disclosed are methods for protecting a plant from nematodes comprising applying to the plant, or portion, or seed thereof, or to the growing medium of the plant, a nematocidally effective amount of Compound 1 comprising the polymorph Form A.

The present invention provides compounds having the general structural formula (I), and pharmaceutically acceptable derivatives thereof, as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases involving abnormal or excessive fibrosis.

The invention is directed to novel substituted benzylamino quinolines, compounds comprising substituted benzylamino quinolines, methods of making substituted benzylamino quinolines, the use of substituted benzylamino quinolines for treating or preventing a variety of conditions or diseases associated with lipoprotein metabolism, and the use of substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors.

The invention provides novel substituted amino azaheterocyclic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Cyanine dye compounds having a substituted methine moiety that are nucleic acid stains, particularly for fluorescent staining of RNA, including compounds having the formula where R1 is a C1-C6 alkyl, sulfoalkyl, carboxyalkyl or C1-C6 alkoxy; each R2 is independently selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkoxy, fused benzo, trifluoromethyl, amino, sulfo, carboxy and halogen, that is optionally further substituted; at least one of R3, R4, and R5 is an alkyl, aryl, heteroaryl, cyclic, or heterocyclic moiety that is optionally substituted by alkyl, amino, aminoalkyl, carboxy, nitro, or halogen; and the remaining R3, R4 or R5 are hydrogen; X is S, O, or Se; and D is a substituted or unsubstituted pyridinium, quinolinium or benzazolium moiety.

Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.

There are provided compounds of formula (I), wherein R1, R6, R8, Q2, Q3, Q3a, Q4, L and A have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a member of the MAPEG family is desired and/or required, and particularly in the treatment of inflammation and/or cancer.

The present invention relates to the use of selective adenosine A1 agonists, in particular the dicyanopyridines of formula (I), for the treatment and/or prophylaxis of glaucoma and ocular hypertension as well as the their use for the production of a medicament for the treatment and/or prophylaxis of glaucoma and ocular hypertension.

The disclosure relates to BAX activators and therapeutic uses relates thereto. In certain embodiments, the disclosure relates to methods of treating or preventing cancer, such as lung cancer, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or pharmaceutically acceptable salt to a subject in need thereof.

This invention relates to a method of preparing a benzoimidazole derivative at high purity and high yield so as to enable the production of the benzoimidazole derivative compound as an antagonist against a vanilloid reactor-1, and particularly to a method of preparing a benzoimidazole derivative at high purity and high yield, wherein the benzoimidazole derivative is synthesized using a novel intermediate, namely, benzaldehyde, and thereby the preparation process is simple so that it can be applied to production.

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, R4, Y and Z have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.

A platinum complex of a formula (I): whereR1 and R2 are each fluoroalkyl,X is C—H or nitrogen, andL1 is a bidentate, nitrogen-containing heteroaromatic ligand.

Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.