Patent Publication Number: US-2006014788-A1

Title: Self-emulsifying formulations of cholesteryl ester transfer protein inhibitors

Description:
FIELD OF THE INVENTION  
      This invention relates to encapsulated formulations of cholesterol ester transfer protein (CETP) inhibitors for use in mammals, especially humans, which for mutations provide increased concentrations of CETP inhibitors for absorption, hence higher bioavailability.  
     BACKGROUND OF THE INVENTION  
      CETP inhibitors, as a class, are characterized by high binding activity. Such CETP inhibitors are generally hydrophobic, however, with the consequence that they have extremely low aqueous solubility and have low oral bioavailability. Such compounds have generally proven to be difficult to formulate for oral administration such that high bioavailabilities are achieved.  
      Atherosclerosis and its associated coronary artery disease (CAD) is the leading cause of death in the industrialized world. Despite attempts to modify secondary risk factors (smoking, obesity, lack of exercise) and treatment of dyslipidemia with dietary modification and drug therapy, coronary heart disease (CHD) remains the most common cause of death in the U.S., where cardiovascular disease accounts for 44% of all deaths, with 53% of these associated with atherosclerotic coronary heart disease.  
      Risk for development of this condition has been shown to be strongly correlated with certain plasma lipid levels. While elevated LDL-cholesterol may be the most recognized form of dyslipidemia, it is by no means the only significant lipid-associated contributor to CHD. Low HDL-cholesterol is also a known risk factor for CHD (Gordon, D. J., et al.,: “High-density Lipoprotein Cholesterol and Cardiovascular Disease”, Circulation, (1989), 79: 8-15).  
      High LDL-cholesterol and triglyceride levels are positively correlated, while high levels of HDL-cholesterol are negatively correlated, with the risk for developing cardiovascular diseases. Thus, dyslipidemia is not a unitary risk profile for CHD but may be comprised of one or more lipid aberrations.  
      Among the many factors controlling plasma levels of these disease dependent principles, cholesteryl ester transfer protein (CETP) activity affects all three. The role of this 70,000 dalton plasma glycoprotein found in a number of animal species, including humans, is to transfer cholesteryl ester and triglyceride between lipoprotein particles, including high density lipoproteins (HDL), low density lipoproteins (LDL), very low density lipoproteins (VLDL), and chylomicrons. The net result of CETP activity is a lowering of HDL cholesterol and an increase in LDL cholesterol. This effect on lipoprotein profile is believed to be pro-atherogenic, especially in subjects whose lipid profile constitutes an increased risk for CHD.  
      No wholly satisfactory HDL-elevating therapies exist. Niacin can significantly increase HDL, but has serious toleration issues that reduce compliance. Fibrates and the HMG CoA reductase inhibitors raise HDL-cholesterol only modestly (˜10-12%). As a result, there is a significant unmet medical need for a well-tolerated agent that can significantly elevate plasma HDL levels, thereby reversing or slowing the progression of atherosclerosis.  
      CETP inhibitors have been developed that inhibit CETP activity, and thus, if present in the blood, should result in higher HDL cholesterol levels and lower LDL cholesterol levels. To be effective, such CETP inhibitors must be absorbed into the blood. Oral dosing of CETP inhibitors is preferred because to be effective such CETP inhibitors must be taken on a regular basis, such as daily. Accordingly, it is preferred that patients be able to take CETP inhibitors by oral dosing rather than by injection.  
      However, it has proven to be difficult to formulate CETP inhibitors for oral administration such that therapeutic blood levels are achieved. CETP inhibitors, in general, possess a number of characteristics that render them poorly bioavailable when dosed orally in a conventional manner. CETP inhibitors tend to be quite hydrophobic and extremely water insoluble, with solubility in aqueous solution of usually less than about 10 μg/ml and typically less than 1 μg/ml. Often the aqueous solubility of CETP inhibitors is less than 0.1 μg/ml. Indeed, the solubility of some CETP inhibitors is so low that it is in fact difficult to measure. Accordingly, when CETP inhibitors are dosed orally, concentrations of CETP inhibitor in the aqueous environment of the gastrointestinal tract tend to be extremely low, resulting in poor absorption from the GI tract to blood. The hydrophobicity of CETP inhibitors not only leads to low equilibrium aqueous solubility but also tends to make the drugs poorly wetting and slow to dissolve, further reducing their tendency to dissolve and be absorbed from the gastrointestinal tract. This combination of characteristics has resulted in the bioavailability for orally dosed conventional crystalline or amorphous forms of CETP inhibitors generally to be quite low, often having absolute bioavailabilities of less than 1%.  
      Various attempts have been made to improve the aqueous concentration of CETP inhibitors, but generally have met with limited success. Conventional methods of formulation do not provide sufficient solubilities and thus poor oral bioavailabilities have been obtained. Pre-dissolving CETP inhibitors in hydrophilic solvents such as acetone or PEG followed by delivery as a solution have failed due to inadequate solubility in the solvent or precipitation upon dilution into the aqueous medium . Suspensions of crystalline drug do not provide sufficient concentrations of drug in solution due to very low aqueous solubilities and therefore yield inadequate blood levels.  
      One approach that has been disclosed to formulate CETP inhibitors is the formation of CETP solutions in lipids. Solutions in medium chain triglycerides have been of value either as oral solutions or encapsulated in softgels. However, the solubility (65 mg/mL or less) for some of the most potent and useful CETP inhibitors known to the inventors has limited the dose to 30 mg in a reasonable sized softgel. The efficacious dose is expected to be several multiples of this and therefore may require administration of more than 2 softgels per day.  
      It has also been found that it is necessary to administer triglyceride solutions with food in order to achieve efficacious blood levels of CETP inhibitors. Food effects of 20-30× have been observed in man for some CETP inhibitors, with considerable variability between patients. The food effect is the ratio of plasma AUC values measured for administration of drug with a meal vs. administration in the fasted state. In addition, there is minimal CETP inhibition in the absence of food due to low fasted plasma exposure. As a result, labeling would need to indicate administration with food. This strong dependence of exposure on food could compromise the effectiveness of this medication in the treatment of atherosclerosis if there is a lack of compliance with labeling instructions.  
      Therefore, there remains a need to develop oral formulations of CETP inhibitors that would reduce the food effect substantially, primarily by improving fasted exposure, thereby minimizing patient-to-patient variability in clinical outcome. An increase in the dose per capsule would also be a desirable improvement.  
      Lack of mixing between oil formulations and the aqueous environment of the GI tract is known to lead to variable gastric emptying and thus variable absorption. A frequent means of increasing fasted bioavailability of hydrophobic drugs is to use a surfactant or combination of surfactants to produce an emulsion, which, if of sufficiently small particle size can lead to enhanced absorption of the drug. Lipid solutions containing surfactants that spontaneously form emulsions when mixed with an aqueous medium are referred to in the literature as self-emulsifying drug delivery systems (SEDDS) (S. Charman, et. al., Pharm Res., vol. 9, 87 (1992)). They are isotropic mixtures of oil, typically medium chain triglycerides, and non-ionic emulsifier that yield fine emulsions when gently mixed with aqueous fluid, such as in the stomach and intestine, and have the appropriate polarity for fast drug release (C. W. Pouton, Adv. Drug Deliv. Rev, vol. 25, 47 (1997); P. P. Constantinides, Pharm. Res., vol. 12, 1561 (1995); A. Humberstone and W. Charman, Adv. Drug Del. Rev., vol 25, 103 (1997)). Early SEDDS were defined as forming an emulsion with particle size below 5 microns (S. Charman, et. al., Pharm Res., vol. 9, 87 (1992)) and utilized MIGLYOL® and a single surfactant, Tagat TO, which has an HLB (hydrophilic-lipophilic balance) of 10, to form a emulsion with a droplet size of 3 microns. Tagat is not available for human use as are other excipients with the appropriate properties.  
      Much of the effort in both the open and patent literature has been invested in formulations of cyclosporin. A formulation of cyclosporin that was found to increase bioavailability by in situ generation of an emulsion utilized long chain triglyceride, a polyglycolyzed glyceride, and ethanol and was marketed as Sandimmune® (Cavanak (Sandoz)). See U.S. Pat. No. 4,388,307 (1983). This had the disadvantage of considerable variability in oral bioavailability and PK profile. Subsequently, a self-microemulsifying system was developed (Meinzer, (Sandoz) WO 93/20833; Ritschel, Clin. Transplant., vol. 10, 364 (1996)) using polyethoxylated hydrogenated castor oil (Cremophor® RH40), corn oil mono-, di- and triglycerides, propylene glycol and ethanol. This softgel formulation, marketed as Neoral®, reduced variability in exposure and also reduced the moderate food effect (Mueller, Pharm . Res. vol 11, 151 (1994)).  
      Lipophilic solvents have been used in place of ethanol or propylene glycol which will not migrate to the shell and affect shell integrity and/or volatilize and thus impact on the concentration in the fill and on solubility. Triacetin has been used as a lipophilic cosolvent for cyclosporin microemulsion preconcentrates with a long chain triglyceride and high HLB surfactant (Hong (Chong Kun Dang Corp.) WO 99/000002). It has also been used alone and in a mixture with propylene glycol dicaprylate/dicaprate and a high HLB surfactant for ketoprofen and related anti-inflammatory acids (Shelley and Wei (Scherer) WO 95/31979A).  
      U.S. Pat. No. 5,993,858 discloses the use of an oil, high HLB surfactant, cosurfactant and triacetin as cosolvent for self-emulsifying formulations of hydrophobic drugs. Propylene carbonate has also been used as a lipophilic solvent for cyclosporin self-emulsifying systems (Woo (Novartis) WO 97/48410 and U.S. Pat. No. 5,958,876 (1999)). Use of ethyl lactate as a cosolvent for cyclosporin formulations, including clinical evaluation, has also been reported (WO 00/40219).  
     SUMMARY OF THE INVENTION  
      This invention provides pharmaceutical compositions that are liquid solutions, suspensions, and (oil-in-water) emulsions of CETP inhibitors, said solutions being orally administrable. The solutions or dispersions may be administered, for example, as fill in encapsulated dosage forms such as hard or soft gelatin capsules. The CETP inhibitors can be dissolved or dispersed in a variety of lipophilic vehicles, as further described and discussed below, such as digestible oils, solvents and surfactants, including mixtures of any two or more of the aforementioned vehicles.  
      Reference to a compositional component such as a “digestible oil”, to a “surfactant” and so forth, shall be understood as including mixtures of such components such as mixtures of digestible oils and surfactants.  
      In a first embodiment, the CETP inhibitor is dissolved or dispersed in a digestible oil such as a medium chain triglyceride oil or a mixture of digestible oils.  
      In a second embodiment, the CETP inhibitor is dissolved or dispersed in a digestible oil with one or more high HLB surfactants. The aforementioned solution or dispersion containing a high HLB surfactant or surfactant mixture may optionally contain one or more low HLB surfactants.  
      In a third embodiment, the CETP inhibitor is dissolved in a pharmaceutically acceptable lipophilic solvent optionally containing a digestible oil or digestible oil mixture. The CETP inhibitor solvent solution or dispersion or solvent/digestible oil solution or dispersion may optionally contain one or more high HLB surfactants and/or one or more low HLB surfactants.  
      The presence of one or more surfactants can, upon contacting the pharmaceutical composition with water, yield an emulsion that is either preformed by mixing with an aqueous phase or that is generated in vivo by contacting the aqueous fluids of the gastrointestinal tract. Formation of an emulsion can improve fasted bioavailability and thus reduce the food effect in man (i.e., the effect of food upon absorption and/or bioavailability of a drug). It can also allow the oil to be consumed as a beverage in addition to being administered in capsules. Use of surfactants to provide an emulsion can also be of value for increasing exposures in toxicology species. Combination of a digestible oil with a cosolvent can have the advantage of higher solubility and thus a higher dose in a given volume of formulation than is obtainable with the digestible oil alone. It is advantageous for bioavailability to have the entire dose dissolved. The presence of a third component in any of the above embodiments may also improve miscibility between the first two components.  
      Thus, in a first embodiment, the invention provides an orally administrable pharmaceutical composition comprising a CETP inhibitor and a lipophilic vehicle selected from a digestible oil, a lipophilic solvent (also referred to herein as a “cosolvent”, whether or not another solvent is in fact present), a lipophilic surfactant, and mixtures of any two or more thereof. Preferred embodiments include a CETP inhibitor and: (1) the combination of a pharmaceutically acceptable digestible oil and a surfactant; (2) the combination of a pharmaceutically acceptable digestible oil and a lipophilic solvent which is miscible therewith; and (3) the combination of a pharmaceutically acceptable digestible oil, a lipophilic solvent, and a surfactant.  
      In a particularly preferred embodiment, the invention provides a composition of matter for increasing the oral bioavailability of a CETP inhibitor. The composition comprises: 
      1. a CETP inhibitor;     2. a cosolvent;     3. a surfactant having an HLB of from 1 to not more than 8;     4. a surfactant having an HLB of over 8 up to 20; and     5. optionally, a digestible oil.    

      In such formulations, all of the excipients are pharmaceutically acceptable. The above composition is sometimes referred to herein as a “pre-concentrate”, in reference to its function of forming a stable emulsion when gently mixed with water or other aqueous medium, usually gastrointestinal fluids. It is also referred to herein as a “fill”, referring to its utility as a fill for a softgel capsule.  
      Reference herein is frequently made to a softgel as a preferred dosage form for use with this invention, “softgel” being an abbreviation for soft gelatin capsules. It is understood that when reference is made to the term “softgel” alone, it shall be understood that the invention applies equally to all types of gelatin and non-gelatin capsules, regardless of hardness, softness, and so forth.  
      A cosolvent means a solvent in which the CETP inhibitor of interest is highly soluble, having, for any given CETP inhibitor, a solubility of at least 150 mg/mL.  
      As noted above, and as discussed further below, a digestible oil can form a part of the pre-concentrate. If no other component of the pre-concentrate is capable of functioning as an emulsifiable oily phase, a digestible oil can be included as the oil which acts as a solvent for the CETP inhibitor and which disperses to form the (emulsifiable) oil droplet phase once the pre-concentrate has been added to water. Some surfactants can serve a dual function, however, i.e., that of acting as a surfactant and also as a solvent and an oily vehicle for forming an oil-in-water emulsion. In the event such a surfactant is employed, and, depending on the amount used, a digestible oil may be required in less of an amount, or not required at all.  
      The pre-concentrate can be self-emulsifying or self-microemulsifying.  
      The term “self-emulsifying” refers to a formulation which, when diluted by a factor of at least 100 by water or other aqueous medium and gently mixed, yields an opaque, stable oil/water emulsion with a mean droplet diameter less than about 5 microns, but greater than 100 nm, and which is generally polydisperse. Such an emulsion is stable for at least several (i.e., for at least 6) hours, meaning there is no visibly detectable phase separation and that there is no visibly detectable crystallization of CETP inhibitor.  
      The term “self-microemulsifying” refers to a pre-concentrate which, upon at least 100× dilution with an aqueous medium and gentle mixing, yields a non-opaque, stable oil/water emulsion with an average droplet size of about 1 micron or less, said average particle size preferably being less than 100 nm. The particle size is primarily unimodal. Most preferably the emulsion is transparent and has a unimodal particle size distribution with a mean diameter less than 50 nm as determined, for example, by dynamic light scattering. The microemulsion is thermodynamically stable and without any indication of crystallization of CETP inhibitor.  
      “Gentle mixing” as used above is understood in the art to refer to the formation of an emulsion by gentle hand (or machine) mixing, such as by repeated inversions on a standard laboratory mixing machine. High shear mixing is not required to form the emulsion. Such pre-concentrates generally emulsify nearly spontaneously when introduced into the human (or other animal) gastrointestinal tract.  
      The term “CETP inhibitor” implies any such compound that is sparingly or poorly water soluble. Generally, and as mentioned above, such compounds exhibit an aqueous solubility (e.g., in water) of less than about 10 μg/mL measured at about 22° C. and at a physiologically relevant pH of from 1 through 8.  
      Combinations of 2 surfactants, one being a low HLB surfactant with an HLB of 1 to 8, the other being a high HLB surfactant with a higher HLB of over 8 to 20, preferably 9 to 20, can be employed to create the right conditions for efficient emulsification. The HLB, an acronym for “hydrophobic-lipophilic balance”, is a rating scale which can range from 1-20 for non-ionic surfactants. The higher the HLB, the more hydrophilic the surfactant. Hydrophilic surfactants (HLB ca. 8 -20), when used alone, provide fine emulsions which are, advantageously, more likely to empty uniformly from the stomach and provide a much higher surface area for absorption. Disadvantageously, however, limited miscibility of such high HLB surfactants with oils can limit their effectiveness, and thus a low HLB, lipophilic surfactant (HLB ca. 1-8) is also included. This combination of surfactants can also provide superior emulsification. A combination of a medium chain triglyceride (such as Miglyol® 812), Polysorbate 80 (HLB 15) and medium chain mono/diglycerides (Capmul® MCM, HLB=6) was found to be as efficient as Miglyol® 812 and a surfactant with an HLB of 10 (Labrafac® CM). N. H. Shah et al. Int. J. Pharm., vol 106, 15 (1994). The advantages of using combinations of high and low HLB surfactants for self-emulsifying systems, including promotion of lipolysis, have been demonstrated by Lacy, U.S. Pat. No. 6,096,338.  
    
    
     DETAILED DESCRIPTION  
      Suitable digestible oils, which can be used alone as the vehicle or in a vehicle which includes a digestible oil as part of a mixture, include medium chain triglycerides (MCT, C6-C12) and long chain triglycerides (LCT, C14-C20) and mixtures of mono-, di-, and triglycerides, or lipophilic derivatives of fatty acids such as esters with alkyl alcohols. Examples of preferred MCT&#39;s include fractionated coconut oils, such as Miglyol® 812 which is a 56% caprylic (C8) and 36% capric (C10) triglyceride, Miglyol® 810 (68% C8 and 28% C10), Neobee® M5, Captex® 300, Captex® 355, and Crodamol® GTCC. The Miglyols are supplied by Condea Vista Inc. (Huls), Neobee® by Stepan Europe, Voreppe, France, Captex® by Abitec Corp., and Crodamol® by Croda Corp. Examples of LCTs include vegetable oils such as soybean, safflower, corn, olive, cottonseed, arachis, sunflowerseed, palm, or rapeseed. Examples of fatty acid esters of alkyl alcohols include ethyl oleate and glyceryl monooleate. Of the digestible oils MCT&#39;s are preferred, and Miglyol® 812 is most preferred.  
      The vehicle may also be a pharmaceutically acceptable solvent, for use alone, or as a cosolvent in a mixture. Suitable solvents include any solvent that is used to increase solubility of the CETP inhibitor in the formulation in order to allow delivery of the desired dose per dosing unit. It is not generally possible to predict the solubility of CETP inhibitors in the individual solvents, but such can be easily determined by “trial runs”. Suitable solvents include triacetin (1,2,3-propanetriyl triacetate or glyceryl triacetate available from Eastman Chemical Corp.) or other polyol esters of fatty acids, trialkyl citrate esters, propylene carbonate, dimethylisosorbide, ethyl lactate, N-methyl pyrrolidones, transcutol, glycofurol, peppermint oil, 1,2-propylene glycol, ethanol, and polyethylene glycols. Preferred as solvents are triacetin, propylene carbonate (Huntsman Corp.), transcutol (Gattefosse), ethyl lactate (Purac, Lincolnshire, Nebr.) and dimethylisosorbide (sold under the registered trademark ARLASOLVE DMI, ICI Americas). A hydrophilic solvent is more likely to migrate to the capsule shell and soften the shell, and, if volatile, its concentration in the composition can be reduced, but with a potential negative impact on active component (CETP inhibitor) solubility. More preferred are the lipophilic solvents triacetin, ethyl lactate and propylene carbonate. Most preferred is triacetin.  
      Hydrophilic surfactants having an HLB of 8-20, preferably having an HLB greater than 10, are particularly effective at reducing emulsion droplet particle size. Suitable choices include nonionic surfactants such as polyoxyethylene 20 sorbitan monooleate, polysorbate 80, sold under the trademark TWEEN 80, available commercially from ICI; polyoxyethylene 20 sorbitan monolaurate (Polysorbate 20, TWEEN 20); polyethylene (40 or 60) hydrogenated castor oil (available under the registered trademarks CREMOPHOR® RH40 and RH60 from BASF); polyoxyethylene (35) castor oil (CREMOPHOR® EL); polyethylene (60) hydrogenated castor oil (Nikkol® HCO-60); alpha tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS); glyceryl PEG 8 caprylate/caprate (available commercially under the registered trademark LABRASOL® from Gattefosse); PEG 32 glyceryl laurate (sold commercially under the registered trademark GELUCIRE® 44/14 by Gattefosse), polyoxyethylene fatty acid esters (availble commercially under the registered trademark MYRJ from ICI), polyoxyethylene fatty acid ethers (available commercially under the registered trademark BRIJ from ICI). Preferred are Polysorbate 80, CREMOPHOR® RH40 (BASF), and Vitamin E TPGS (Eastman). Most preferred are Polysorbate 80 and CREMOPHOR® RH40.  
      Lipophilic surfactants having an HLB of less than 8 are useful for achieving a balance of polarity to provide a stable emulsion, and have also been used to reverse the lipolysis inhibitory effect of hydrophilic surfactants. Suitable lipophilic surfactants include mono and diglycerides of capric and caprylic acid under the following registered trademarks: Capmul® MCM, MCM 8, and MCM 10, available commercially from Abitec; and lmwitor® 988, 742 or 308, available commercially from Condea Vista; polyoxyethylene 6 apricot kernel oil, available under the registered trademark Labrafil® M 1944 CS from Gattefosse; polyoxyethylene corn oil, available commercially as Labrafil® M 2125; propylene glycol monolaurate, available commercially as Lauroglycol from Gattefosse; propylene glycol dicaprylate/caprate available commercially as Captex® 200 from Abitec or Miglyol® 840 from Condea Vista, polyglyceryl oleate available commercially as Plurol oleique from Gattefosse, sorbitan esters of fatty acids (e.g. Span® 20, Crill® 1, Crill® 4, available commercially from ICI and Croda), and glyceryl monooleate (Maisine, Peceol). Preferred from this class are Capmul® MCM (Abitec Corp.) and Labrafil® M1944 CS (Gattefosse). Most preferred is Capmul® MCM.  
      In addition to the main liquid formulation ingredients previously noted, other stabilizing additives, as conventionally known in the art of softgel formulation, can be introduced to the fill as needed, usually in relatively small quantities, such as antioxidants (BHA, BHT, tocopherol, propyl gallate, etc.) and other preservatives such as benzyl alcohol or parabens.  
      The composition can be formulated as a fill encapsulated in a soft gelatin capsule, a hard gelatin capsule with an appropriate seal, a non-gelatin capsule such as a hydroxypropyl methylcellulose capsule or an oral liquid or emulsion by methods commonly employed in the art. The fill is prepared by mixing the excipients and CETP inhibitor with heating if required.  
      The ratio of CETP inhibitor, digestible oil, cosolvent, and surfactants depends upon the efficiency of emulsification and the solubility, and the solubility depends on the dose per capsule that is desired. A self-emulsifying formulation is generally useful if the primary goals are to deliver a high dose per softgel (at least 60 mg) with, generally, a much lower food effect than with an oil solution alone. In general, softgel preconcentrates having solubilities of CETP inhibitor of at least 140 mg/mL in the preconcentrate, and thus requiring higher amounts of cosolvent and lower levels of surfactants and oil, are preferred.  
      In general, the following ranges, in weight percent, of the components for a self-emulsifying formulation of CETP inhibitors are:  
      1-50% CETP inhibitor  
      5-60% cosolvent  
      5-75% high HLB surfactant  
      5-75% low HLB surfactant  
      Preferred ranges which have advantageously low food effects include those stated immediately below:  
      1-33% CETP inhibitor  
      0-30% digestible oil  
      15-55% cosolvent  
      5-40% high HLB surfactant  
      10-50% low HLB surfactant  
      More preferred ranges include  
      1-25% CETP inhibitor  
      10-25% digestible oil  
      20-35% cosolvent  
      10-30% high HLB surfactant  
      15-35% low HLB surfactant  
      If a specific goal is a minimal food effect, then a self-microemulsifying formulation is advantageous. Such formulations generally require relatively high levels of surfactants and a reduced amount of cosolvent. These formulations can, however, result in lower solubilities and, accordingly, a lower dose per capsule. These formulations have been found to increase fasted exposure.  
      General ranges, in weight percent, for the components for a self-microemulsifying formulation of CETP inhibitors are  
      1-40% CETP inhibitor  
      5-65% digestible oil  
      5-60% cosolvent  
      10-75% high HLB surfactant  
      5-75% low HLB surfactant  
      Preferred ranges include those which follow  
      1-20% CETP inhibitor  
      5-30% digestible oil  
      5-45% cosolvent  
      30-55%, high HLB surfactant  
      10-40%, low HLB surfactant  
      Specific examples of preferred formulations include:  
      A composition comprising  
      a compound which is [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester; or a compound which is [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester; or a compound which is [2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester  
      a cosolvent;  
      a high HLB surfactant;  
      a low HLB surfactant; and  
      optionally, a digestible oil.  
      A more preferred composition is that noted immediately above, wherein  
      said cosolvent is triacetin or ethyl lactate;  
      said high HLB surfactant comprises polysorbate 80 or a polyethylene hydrogenated castor oil;  
      said low HLB surfactant comprises a mixture of mono- and diglycerides of capric and caprylic acids;  
      said digestible oil comprises a medium chain triglyceride, wherein each of the three hydrocarbon chains therein is predominantly C6-C12.  
      A more specific preferred composition is that noted immediately above, which comprises, by weight:  
      5 -25% of said CETP inhibitor;  
      10-25% of said digestible oil;  
      20-35% of said cosolvent:  
      10-35% of said high HLB surfactant; and  
      10-35% of said low HLB surfactant;  
      A still more specific preferred embodiment is that noted immediately above which comprises, by weight:  
      8-12% of [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester  
      10-20% of said digestible oil;  
      25-35% of said cosolvent which comprises triacetin:  
      10-30% of said high HLB surfactant which comprises polysorbate 80; and  
      15-35% of said low HLB surfactant which comprises a mixture of medium chain mono- and di-glycerides.  
      Another still more specific preferred embodiment is one, which comprises, by weight:  
      8-12% of [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;  
      10-20% of said digestible oil;  
      25-35% of said cosolvent which comprises triacetin;  
      10-30% of said high HLB surfactant which comprises a polyethylene (40) hydrogenated castor oil;  
      15-35% of said low HLB surfactant, which comprises a mixture of medium chain mono- and di-glycerides.  
      Another still more specific preferred embodiment is one which comprises, by weight 8-25% of [2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;  
      10-25% of digestible oil;  
      20-35% of said cosolvent which comprises triacetin;  
      10-30% of said high HLB surfactant which comprises polysorbate 80; and  
      15-35% of said low HLB surfactant which comprises a mixture of medium chain mono- and di-glycerides.  
      As indicated by the broadest range above, the digestible oil may be optionally omitted in order to further increase the amount of cosolvent and, therefore, solubility of the CETP inhibitor in the pre-concentrate.  
      In addition to the main softgel capsule ingredients previously noted, other stabilizing additives, as conventionally known in the art of softgel formulation, can be introduced to the fill as needed, usually in relatively small quantities, such as antioxidants (BHA, BHT, tocopherol, propyl gallate, etc.) and other preservatives such as benzyl alcohol or parabens.  
      The composition can be formulated as a fill encapsulated in a soft gelatin capsule, a hard gelatin capsule with an appropriate seal, a non-gelatin capsule such as a hydroxypropyl methylcellulose capsule or an oral liquid or emulsion by methods commonly employed in the art. The fill is prepared by mixing the excipients and CETP inhibitor with heating if required.  
      Preferred embodiments comprise a CETP inhibitor with:  
      (a) solubility less than 10 μg/ml;  
      (b) c log P greater than 5; and/or (c) dose greater than 10 mg, preferably at least 30 mg.  
      The invention is not limited by any particular structure or group of CETP inhibitors. Rather, the invention has general applicability to CETP inhibitors as a class, the class tending to be composed of compounds having low solubility. Compounds which may be the subject of the invention may be found in a number of patents and published applications, including DE 19741400 A1; DE 19741399 A1; WO 9914215 A1; WO 9914174; DE 19709125 A1; DE 19704244 A1; DE 19704243 A1; EP 818448 A1; WO 9804528 A2; DE 19627431 A1; DE 19627430 A1; DE 19627419 A1; EP 796846 A1; DE 19832159; DE 818197; DE 19741051; WO 9941237 A1; WO 9914204 A1; WO 9835937 A1; JP 11049743; WO 200018721; WO 200018723; WO 200018724; WO 200017164; WO 200017165; WO 200017166; EP 992496; and EP 987251, all of which are hereby incorporated by reference in their entirety.  
      Oral delivery of many CETP inhibitors is particularly difficult because their aqueous solubility is usually extremely low, typically being less than 2 μg/ml, often being less than 0.1 μg/ml. Such low solubilities are a direct consequence of the particular structural characteristics of species that bind to CETP and thus act as CETP inhibitors. This low solubility is primarily due to the hydrophobic nature of CETP inhibitors. Log P, defined as the base 10 logarithm of the ratio of the drug concentration in octanol to the drug concentration in water in a partitioning experiment, is a widely accepted measure of hydrophobicity. In general, Log P values for CETP inhibitors are greater than 4 and are often greater than 5 to 7. This property may also be calculated from the structure of the molecule and is designated “cLog P.”. The calculation of cLog P values from chemical structures is given in Leo, A. J.; “Calculating log P from structures”, Chem. Rev. 1993, 93, 1281. Thus, the hydrophobic and insoluble nature of CETP inhibitors as a class pose a particular challenge for oral delivery. Achieving therapeutic drug levels in the blood by oral dosing of practical quantities of drug generally requires a large enhancement in drug concentrations in the gastrointestinal fluid and a resulting large enhancement in bioavailability.  
      The formulations of this invention will be administered in such an amount that an effective dose of the CETP inhibitor of interest is administered to the patient. The amount of CETP inhibitor will generally be known or determined by the attending physician. Thus the amount or volume of preconcentrate administered will be determined by the amount of CETP inhibitor prescribed and/or otherwise desired as a dose and the solubility of the CETP in the preconcentrate. In general, an effective dose for most CETP inhibitors is in the range of from 5 to 500 mg, preferably 10-300 mg, more preferablly 10-200 mg per day, in single or divided doses. The compositions of the invention are pre-concentrates for emulsification which are generally administered orally, in soft or hard gelatin capsules, gelatin encapsulation technology being well known to the pharmaceutical arts. Such pre-concentrates can also be administered in aqueous oral emulsions by adding the pre-concentrate to water or other aqueous liquid (e.g., soda). They can be mixed with an aqueous liquid and sold as pre-formed emulsions, or added to food such as ice cream.  
      Turning now to the chemical structures of specific CETP inhibitors, one class of CETP inhibitors that finds utility with the present invention consists of oxy substituted 4-carboxyamino-2-methyl-1,2,3,4-tetrahydroquinolines having the Formula I  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds; 
 
 wherein R I-1 , is hydrogen, Y I , W I —X I , WI—Y I ; 
 
 wherein W I  is a carbonyl, thiocarbonyl, sulfinyl or sulfonyl; 
 
 X I  is —O—Y I , —S—Y I , —N(H)—Y, or —N—(Y I ) 2 ; 
 
      wherein Y I  for each occurrence is independently Z I  or a fully saturated, partially unsaturated or fully unsaturated one to ten membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with Z I ;  
      wherein Z I  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or, a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said Z I  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxyl, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxyl, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      R I-3  is hydrogen or Q I ;  
      wherein Q I  is a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V I ;  
      wherein V I  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said V I  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carbamoyl, mono-N— or di-N,N—(C 1 -C 6 ) alkylcarbamoyl, carboxyl, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxyl, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituents are also optionally substituted with from one to nine fluorines;  
      R I-4  is Q I-1  or V 1-I ,  
      wherein Q I-1  is a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with  
      V I-1 ;  
      wherein V I-1 is a partially saturated, fully saturated or fully unsaturated three to six membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen;  
      wherein said V I-1  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, nitro, cyano, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-substituted with oxo, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      wherein either R I-3  must contain V I  or R I-4  must contain V I-4 ; and R I-5 , R I-6 , R I-7  and R I-8 are each independently hydrogen, hydroxy or oxy wherein said oxy is substituted with T I  or a partially saturated, fully saturated or fully unsaturated one to twelve membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with T I ;  
      wherein T I  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said T I  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines.  
      Compounds of Formula I are disclosed in commonly assigned pending U.S. patent application Ser. No. 09/390,731, the complete disclosure of which is herein incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from one of the following compounds of Formula I: 
      [2R,4S]4-[(3,5-dichloro-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-dinitro-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(2,6-dichloro-pyridin-4-ylmethyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester,     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-ethoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid 2,2,2-trifluoro-ethylester;     [2R,4S]4-[(3,5-bis-trfluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester;     [2R,4S] 4 -[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-6-trifluoromethoxy-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester,     [2R,4S](3,5-bis-trifluoromethyl-benzyl)-(1-butyryl-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid methyl ester;     [2R,4S](3,5-bis-trifluoromethyl-benzyl)-(1-butyl-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid methyl ester;     [2R,4S](3,5-bis-trifluoromethyl-benzyl)-[1-(2-ethyl-butyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-carbamic acid methyl ester, hydrochloride    

      Another class of CETP inhibitors that finds utility with the present invention consists of 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines, having the Formula II  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds; 
      wherein R II-1 , is hydrogen, Y II , W II —X II , W II —Y II ;     wherein W II  is a carbonyl, thiocarbonyl, sulfinyl or sulfonyl;     X II  is —O—Y II , —S—Y II , —N(H)—Y II , or —N—(Y II ) 2 ;    

      wherein Y II  for each occurrence is independently Z II  or a fully saturated, partially unsaturated or fully unsaturated one to ten membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with Z II ;  
      Z II  is a partially saturated, fully saturated or fully unsaturated three to twelve membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said Z II  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl is also optionally substituted with from one to nine fluorines;  
      R II-3  is hydrogen or Q II ;  
      wherein Q II  is a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V II ;  
      wherein V II  is a partially saturated, fully saturated or fully unsaturated three to twelve membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or, a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said V II  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxamoyl, mono-N— or di-N,N—(C 1 -C 6 ) alkylcarboxamoyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino or said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituents are optionally substituted with from one to nine fluorines;  
      R II-4  is Q II-1  or V II-1 ,  
      wherein Q II-1  a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V II-1 ;  
      wherein V II-1  is a partially saturated, fully saturated or fully unsaturated three to six membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen;  
      wherein said V II-1  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, nitro, cyano, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-substituted with oxo, said (C 1 -C 6 )alkyl substituent is optionally substituted with from one to nine fluorines;  
      wherein either R II-3  must contain V II  or R II-4  must contain V II-1 ; and R II-5 , R II-6 , R II-7  and R II-8  are each independently hydrogen, a bond, nitro or halo wherein said bond is substituted with T II , or a partially saturated, fully saturated or fully unsaturated (C 1 -C 12 ) straight or branched carbon chain wherein carbon may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen wherein said carbon atoms are optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon is optionally mono-substituted with T II ;  
      wherein T II  is a partially saturated, fully saturated or fully unsaturated three to twelve membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or, a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said T II  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      provided that at least one of substituents R II-5 , R II-6 , R II-7  and R II-8  is not hydrogen and is not linked to the quinoline moiety through oxy.  
      Compounds of Formula II are disclosed in commonly assigned pending U.S. Pat. No. 6,147,090 the complete disclosure of which is herein incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from one of the following compounds of Formula II: 
      [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-7-chloro-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-chloro-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2,6,7-trimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester     [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-diethyl-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-ethyl-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester.     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester.    

      Another class of CETP inhibitors that finds utility with the present invention consists of annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines, having the Formula III  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds; 
      wherein R III-1  is hydrogen, Y III , W III —X III , W III —Y III ;     wherein W III  is a carbonyl, thiocarbonyl, sulfinyl or sulfonyl;     X III  is —O—Y III , —S—Y III , —N(H)—Y III  or —N—(Y III ) 2 ;    

      Y III  for each occurrence is independently Z III  or a fully saturated, partially unsaturated or fully unsaturated one to ten membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with Z III ;  
      wherein Z III  is a partially saturated, fully saturated or fully unsaturated three to twelve membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said Z III  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl optionally substituted with from one to nine fluorines;  
      R III-3  is hydrogen or Q III ;  
      wherein Q III  is a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V III ;  
      wherein V III  is a partially saturated, fully saturated or fully unsaturated three to twelve membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said V III  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxamoyl, mono-N— or di-N,N—(C 1 -C 6 ) alkylcarboxamoyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino or said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl are optionally substituted with from one to nine fluorines;  
      R III-4  is Q III-1  or V III-1 ;  
      wherein Q III-1  a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with  
      V III-1 ;  
      wherein V III-1  is a partially saturated, fully saturated or fully unsaturated three to six membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen;  
      wherein said V III-1  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, nitro, cyano, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-substituted with oxo, said (C 1 -C 6 )alkyl substituent optionally having from one to nine fluorines;  
      wherein either R III-3  must contain V III  or R III-4  must contain V III-1 ; and R III-5  and R III-6 , or R III-6  and R III-7 , and/or R III-7  and R III-8  are taken together and form at least one four to eight membered ring that is partially saturated or fully unsaturated optionally having one to three heteroatoms independently selected from nitrogen, sulfur and oxygen;  
      wherein said ring or rings formed by R III-5  and R III-6 , or R III-6  and R III-7 , and/or R III-7  and R III-8  are optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkylsulfonyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent optionally having from one to nine fluorines;  
      provided that the R III-5 , R III-6 , R III-7  and/or R III-8 , as the case may be, that do not form at least one ring are each independently hydrogen, halo, (C 1 -C 6 )alkoxy or (C 1 -C 6 )alkyl, said (C 1 -C 6 )alkyl optionally having from one to nine fluorines.  
      Compounds of Formula IIII are disclosed in commonly assigned pending U.S. Pat. No. 6,147,089 the complete disclosure of which is herein incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from one of the following compounds of Formula III: 
      [2R, 4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-2,3,4,6,7,8-hexahydro-cyclopenta[g]quinoline-1-carboxylic acid ethyl ester;     [6R, 8S]8-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-methyl-3,6,7,8-tetrahydro-1H-2-thia-5-aza-cyclopenta[b]naphthalene-5-carboxylic acid ethylester;     [6R, 8S]8-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-methyl-3,6,7,8-tetrahydro-2H-furo[2,3-g]quinoline-5-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-3,4,6,8-tetrahydro-2H-furo[3,4-g]quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-3,4,6,7,8,9-hexahydro-2H-benzo[g]quinoline-1-carboxylic acid propyl ester;     [7R,9S]9-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-7-methyl-1,2,3,7,8,9-hexahydro-6-aza-cyclopenta[a]naphthalene-6-carboxylic acid ethyl ester; and     [6S,8R]6-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-8-methyl-1,2,3,6,7,8-hexahydro-9-aza-cyclopenta[a]naphthalene-9-carboxylic acid ethyl ester.    

      Another class of CETP inhibitors that finds utility with the present invention consists of 4-carboxyamino-2-substituted-1,2,3,4,-tetrahydroquinolines, having the Formula IV  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds; 
 
 wherein R IV-1  is hydrogen, Y IV-1 , W IV —X IV  or W IV —Y IV ; 
 
 wherein W IV  is a carbonyl, thiocarbonyl, sulfinyl or sulfonyl; 
 
 X IV  is —O—Y IV , —S—Y IV , —N(H)—Y IV  or —N—(Y IV ) 2 ; 
 
      wherein Y IV  for each occurrence is independently Z IV  or a fully saturated, partially unsaturated or fully unsaturated one to ten membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with Z IV ;  
      wherein Z IV  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said Z IV  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      R IV-2  is a partially saturated, fully saturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen wherein said carbon atoms are optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with oxo, said carbon is optionally mono-substituted with hydroxy, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo; or said R IV-2  is a partially saturated, fully saturated or fully unsaturated three to seven membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen, wherein said R IV-2  ring is optionally attached through (C 1 -C 4 )alkyl;  
      wherein said R IV-2  ring is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, oxo or (C 1 -C 6 )alkyloxycarbonyl;  
      with the proviso that R IV-2  is not methyl;  
      R IV-3  is hydrogen or Q IV ;  
      wherein Q IV  is a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V IV ;  
      wherein V IV  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said V IV  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxamoyl, mono-N— or di-N,N—(C 1 -C 6 ) alkylcarboxamoyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituents are also optionally substituted with from one to nine fluorines;  
      R IV-4  is Q IV-1  or V IV-1 ;  
      wherein Q IV-1  a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with  
      V IV-1 ;  
      wherein V IV-1  is a partially saturated, fully saturated or fully unsaturated three to six membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen;  
      wherein said V IV-1  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, nitro, cyano, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-substituted with oxo, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      wherein either R IV-3  must contain V IV  or R IV-4  must contain V IV-1 ;  
      R IV-5 , R IV-6 , R IV-7  and R IV-8  are each independently hydrogen, a bond, nitro or halo wherein said bond is substituted with T IV  or a partially saturated, fully saturated or fully unsaturated (C 1 -C 12 ) straight or branched carbon chain wherein carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen wherein said carbon atoms are optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon is optionally mono-substituted with T IV ;  
      wherein T IV  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or, a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said T IV  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines; and  
      wherein R IV-5  and R IV-6  or R IV-6  and R IV-7  and/or R IV-7  and R IV-6  may also be taken together and can form at least one four to eight membered ring that is partially saturated or fully unsaturated optionally having one to three heteroatoms independently selected from nitrogen, sulfur and oxygen;  
      wherein said ring or rings formed by R IV-5  and R IV-6 , or R IV-6  and R IV-7 , and/or R IV-7  and R IV-8  are optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkylsulfonyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      with the proviso that when R IV-2  is carboxyl or (C 1 -C 4 )alkylcarboxyl, then R IV-1  is not hydrogen.  
      Compounds of Formula IV are disclosed in commonly assigned pending U.S. Pat. No. 6,197,786 the complete disclosure of which is herein incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from one of the following compounds of Formula IV: 
      [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-isopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-chloro-2-cyclopropyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]2-cyclopropyl-4-[(3,5-dichloro-benzyl)-methoxycarbonyl-amino]-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester;     [2R,4R]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinaline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclobutyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester,     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methoxymethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid 2-hydroxy-ethyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester; and     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester.    

      Another class of CETP inhibitors that finds utility with the present invention consists of 4-amino substituted-2-substituted-1,2,3,4,-tetrahydroquinolines, having the Formula V  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds; 
 
 wherein R V-1  is Y V , W V —X V  or W V —Y V ; 
 
 wherein W V  is a carbonyl, thiocarbonyl, sulfinyl or sulfonyl; 
 
 X V  is —O—Y V , —S—Y V , —N(H)—Y V  or —N—(Y V ) 2 ; 
 
      wherein Y V  for each occurrence is independently Z V  or a fully saturated, partially unsaturated or fully unsaturated one to ten membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with Z V ;  
      wherein Z V  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said Z V  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      R V-2  is a partially saturated, fully saturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen wherein said carbon atoms are optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with oxo, said carbon is optionally mono-substituted with hydroxy, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo; or said R V-2  is a partially saturated, fully saturated or fully unsaturated three to seven membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen, wherein said R V-2  ring is optionally attached through (C 1 -C 4 )alkyl;  
      wherein said R V-2  ring is optionally mono-, di- or tri-substituted independently with halo, (C 2 -C 6 )alkenyl, (C 1 -C 6 ) alkyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, oxo or (C 1 -C 6 )alkyloxycarbonyl;  
      R V-3  is hydrogen or Q V ;  
      wherein Q V  is a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons, other than the connecting carbon, may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V V ;  
      wherein V V  is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said V V  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxamoyl, mono-N— or di-N,N—(C 1 -C 6 ) alkylcarboxamoyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl or (C 2 -C 6 )alkenyl substituents are also optionally substituted with from one to nine fluorines;  
      R V-4  is cyano, formyl, W V-1 Q V-1 , W V-1 V V-1 , (C 1 -C 4 )alkylene V V-1  or V V-2 ;  
      wherein W V-1  is carbonyl, thiocarbonyl, SO or SO 2 ,  
      wherein Q V-1  a fully saturated, partially unsaturated or fully unsaturated one to six membered straight or branched carbon chain wherein the carbons may optionally be replaced with one heteroatom selected from oxygen, sulfur and nitrogen and said carbon is optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono-, or di-substituted with oxo, and said carbon chain is optionally mono-substituted with V V-1 ;  
      wherein V V-1  is a partially saturated, fully saturated or fully unsaturated three to six membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said V V-1  substituent is optionally mono-, di-, tri-, or tetra-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy, oxo, amino, nitro, cyano, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-substituted with oxo, said (C 1 -C 6 )alkyl substituent is also optionally substituted with from one to nine fluorines;  
      wherein V V-2  is a partially saturated, fully saturated or fully unsaturated five to seven membered ring containing one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;  
      wherein said V V-2  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 2 )alkyl, (C 1 -C 2 )alkoxy, hydroxy, or oxo wherein said (C 1 -C 2 )alkyl optionally has from one to five fluorines; and  
      wherein R V-4  does not include oxycarbonyl linked directly to the C 4  nitrogen;  
      wherein either R V-3  must contain V V  or R V-4  must contain V V-1 ;  
      R V-5 , R V-6 , R V-7  and R V-8  are independently hydrogen, a bond, nitro or halo wherein said bond is substituted with T V  or a partially saturated, fully saturated or fully unsaturated (C 1 -Cl 2 ) straight or branched carbon chain wherein carbon may optionally be replaced with one or two heteroatoms selected independently from oxygen, sulfur and nitrogen, wherein said carbon atoms are optionally mono-, di- or tri-substituted independently with halo, said carbon is optionally mono-substituted with hydroxy, said carbon is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, said nitrogen is optionally mono- or di-substituted with oxo, and said carbon chain is optionally mono-substituted with T V ;  
      wherein T V  is a partially saturated, fully saturated or fully unsaturated three to twelve membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen;  
      wherein said T V  substituent is optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent also optionally has from one to nine fluorines;  
      wherein R V-5  and R V-6 , or R V-6  and R V-7 , and/or R V-7  and R V-8  may also be taken together and can form at least one ring that is a partially saturated or fully unsaturated four to eight membered ring optionally having one to three heteroatoms independently selected from nitrogen, sulfur and oxygen;  
      wherein said rings formed by R V-5  and R V-6 , or R V-6  and RV 7 , and/or R V-7  and R V-8  are optionally mono-, di- or tri-substituted independently with halo, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkylsulfonyl, (C 2 -C 6 )alkenyl, hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino wherein said (C 1 -C 6 )alkyl substituent is optionally mono-, di- or tri-substituted independently with hydroxy, (C 1 -C 6 )alkoxy, (C 1 -C 4 )alkylthio, amino, nitro, cyano, oxo, carboxy, (C 1 -C 6 )alkyloxycarbonyl, mono-N— or di-N,N—(C 1 -C 6 )alkylamino, said (C 1 -C 6 )alkyl substituent also optionally has from one to nine fluorines.  
      Compounds of Formula V are disclosed in commonly assigned pending U.S. Pat. No. 6,140,343 the complete disclosure of which is herein incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from one of the following compounds of Formula V: 
      [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester;     [2S,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester;     [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester,     [2S,4S]4-[1-(3,5-bis-trifluoromethyl-benzyl)-ureido]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2S,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methoxymethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2S,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester;     [2S,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester,     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2S,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2S,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester;     [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-formyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester; and     [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester.    

      Another class of CETP inhibitors that finds utility with the present invention consists of cycloalkano-pyridines having the Formula VI  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds; 
 
 in which 
 
      A VI  denotes an aryl containing 6 to 10 carbon atoms, which is optionally substituted with up to five identical or different substituents in the form of a halogen, nitro, hydroxyl, trifluoromethyl, trifluoromethoxy or a straight-chain or branched alkyl, acyl, hydroxyalkyl or alkoxy containing up to 7 carbon atoms each, or in the form of a group according to the formula —BNR VI-3 R VI-4 , wherein  
      R VI-3  and R VI-4  are identical or different and denote a hydrogen, phenyl or a straight-chain or branched alkyl containing up to 6 carbon atoms,  
      D VI  denotes an aryl containing 6 to 10 carbon atoms, which is optionally substituted with a phenyl, nitro, halogen, trifluoromethyl or trifluoromethoxy, or a radical according to the formula R VI-5 -L VI ,  
                 
 
 or R VI-9 -T VI -V VI -X Vi , wherein 
 
      R VI-5 , R VI-6  and R VI-9  denote, independently from one another, a cycloalkyl containing 3 to 6 carbon atoms, or an aryl containing 6 to 10 carbon atom or a 5- to 7-membered, optionally benzo-condensed, saturated or unsaturated, mono-, bi- or tricyclic heterocycle containing up to 4 heteroatoms from the series of S, N and/or O, wherein the rings are optionally substituted, in the case of the nitrogen-containing rings also via the N function, with up to five identical or different substituents in the form of a halogen, trifluoromethyl, nitro, hydroxyl, cyano, carboxyl, trifluoromethoxy, a straight-chain or branched acyl, alkyl, alkylthio, alkylalkoxy, alkoxy or alkoxycarbonyl containing up to 6 carbon atoms each, an aryl or trifluoromethyl-substituted aryl containing 6 to 10 carbon atoms each, or an optionally benzo-condensed, aromatic 5- to 7-membered heterocycle containing up to 3 heteoatoms from the series of S, N and/or O, and/or in the form of a group according to the formula BOR VI-10 , —SR VI-11 , —SO 2 R VI-12  or BNR VI-13 R VI-14 , wherein  
      R VI-10 , R VI-11  and R VI-12  denote, independently from one another, an aryl containing 6 to 10 carbon atoms, which is in turn substituted with up to two identical or different substituents in the form of a phenyl, halogen or a straight-chain or branched alkyl containing up to 6 carbon atoms, R VI-13  and R VI-14  are identical or different and have the meaning of R VI-3  and R VI-4  given above, or  
      R VI-5  and/or R VI-6  denote a radical according to the formula  
                 
 
      R VI-7  denotes a hydrogen or halogen, and  
      R VI-8  denotes a hydrogen, halogen, azido, trifluoromethyl, hydroxyl, trifluoromethoxy, a straight-chain or branched alkoxy or alkyl containing up to 6 carbon atoms each, or a radical according to the formula
 
—NR VI-15 R VI-16 ,
 
 wherein 
 
      R VI-15  and R VI-16  are identical or different and have the meaning of R VI-3  and R VI-4  given above, or  
      R VI-7  and R VI-8  together form a radical according to the formula ═O or ═NR VI-17 , wherein  
      R VI-17  denotes a hydrogen or a straight-chain or branched alkyl, alkoxy or acyl containing up to 6 carbon atoms each,  
      L VI  denotes a straight-chain or branched alkylene or alkenylene chain containing up to 8 carbon atoms each, which are optionally substituted with up to two hydroxyl groups,  
      T VI  and X VI  are identical or different and denote a straight-chain or branched alkylene chain containing up to 8 carbon atoms, or  
      T VI  or X VI  denotes a bond,  
      V VI  denotes an oxygen or sulfur atom or an BNR VI-18  group, wherein  
      R VI-18  denotes a hydrogen or a straight-chain or branched alkyl containing up to 6 carbon atoms or a phenyl,  
      E VI  denotes a cycloalkyl containing 3 to 8 carbon atoms, or a straight-chain or branched alkyl containing up to 8 carbon atoms, which is optionally substituted with a cycloalkyl containing 3 to 8 carbon atoms or a hydroxyl, or a phenyl, which is optionally substituted with a halogen or trifluoromethyl,  
      R VI-1  and R VI-2  together form a straight-chain or branched alkylene chain containing up to 7 carbon atoms, which must be substituted with a carbonyl group and/or a radical according to the formula  
                 
 
 wherein 
 
      a and b are identical or different and denote a number equaling 1, 2 or 3,  
      R VI-19  denotes a hydrogen atom, a cycloalkyl containing 3 to 7 carbon atoms, a straight-chain or branched silylalkyl containing up to 8 carbon atoms, or a straight-chain or branched alkyl containing up to 8 carbon atoms, which is optionally substituted with a hydroxyl, a straight-chain or a branched alkoxy containing up to 6 carbon atoms or a phenyl, which may in turn be substituted with a halogen, nitro, trifluoromethyl, trifluoromethoxy or phenyl or tetrazole-substituted phenyl, and an alkyl that is optionally substituted with a group according to the formula BOR VI-22 , wherein  
      R VI-22  denotes a straight-chain or branched acyl containing up to 4 carbon atoms or benzyl, or  
      R VI-19  denotes a straight-chain or branched acyl containing up to 20 carbon atoms or benzoyl, which is optionally substituted with a halogen, trifluoromethyl, nitro or trifluoromethoxy, or a straight-chain or branched fluoroacyl containing up to 8 carbon atoms,  
      R VI-20  and R VI-21  are identical or different and denote a hydrogen, phenyl or a straight-chain or branched alkyl containing up to 6 carbon atoms, or  
      R VI-20  and R VI-21  together form a 3- to 6-membered carbocyclic ring, and a the carbocyclic rings formed are optionally substituted, optionally also geminally, with up to six identical or different substituents in the form of trifluoromethyl, hydroxyl, nitrile, halogen, carboxyl, nitro, azido, cyano, cycloalkyl or cycloalkyloxy containing 3 to 7 carbon atoms each, a straight-chain or branched alkoxycarbonyl, alkoxy or alkylthio containing up to 6 carbon atoms each, or a straight-chain or branched alkyl containing up to 6 carbon atoms, which is in turn substituted with up to two identical or different substituents in the form of a hydroxyl, benzyloxy, trifluoromethyl, benzoyl, a straight-chain or branched alkoxy, oxyacyl or carboxyl containing up to 4 carbon atoms each and/or a phenyl, which may in turn be substituted with a halogen, trifluoromethyl or trifluoromethoxy, and/or the carbocyclic rings formed are optionally substituted, also geminally, with up to five identical or different substituents in the form of a phenyl, benzoyl, thiophenyl or sulfonylbenzyl, which in turn are optionally substituted with a halogen, trifluoromethyl, trifluoromethoxy or nitro, and/or optionally in the form of a radical according to the formula  
                 
 
 wherein 
 
      c is a number equaling 1, 2, 3 or 4,  
      d is a number equaling 0 or 1,  
      R VI-23  and R VI-24  are identical or different and denote a hydrogen, cycloalkyl containing 3 to 6 carbon atoms, a straight-chain or branched alkyl containing up to 6 carbon atoms, benzyl or phenyl, which is optionally substituted with up to two identical or different substituents in the form of halogen, trifluoromethyl, cyano, phenyl or nitro, and/or the carbocyclic rings formed are optionally substituted with a spiro-linked radical according to the formula  
                 
 
 wherein 
 
      W VI  denotes either an oxygen atom or a sulfur atom,  
      Y VI  and Y= VI  together form a 2- to 6-membered straight-chain or branched alkylene chain,  
      e is a number equaling 1, 2, 3, 4, 5, 6 or 7,  
      f is a number equaling 1 or 2,  
      R VI-25 , R VI-26 , R VI-27 , R VI-28 , R VI-29 , R VI-30  and R VI-31  are identical or different and denote a hydrogen, trifluoromethyl, phenyl, halogen or a straight-chain or branched alkyl or alkoxy containing up to 6 carbon atoms each, or  
      R VI-25  and R VI-26  or R VI-27  and R VI-28  each together denote a straight-chain or branched alkyl chain containing up to 6 carbon atoms or  
      R VI-25  and R VI-26  or R VI-27  and R VI-28  each together form a radical according to the formula  
                 
 
 wherein 
 
      W VI  has the meaning given above,  
      g is a number equaling 1, 2, 3, 4, 5, 6 or 7,  
      R VI-32  and R VI-33  together form a 3- to 7-membered heterocycle, which contains an oxygen or sulfur atom or a group according to the formula SO, SO 2  or BNR VI-34 , wherein  
      R VI-34  denotes a hydrogen atom, a phenyl, benzyl, or a straight-chain or branched alkyl containing up to 4 carbon atoms, and salts and N oxides thereof, with the exception of 5(6H)-quinolones, 3-benzoyl-7,8-dihydro-2,7,7-trimethyl-4-phenyl.  
      Compounds of Formula VI are disclosed in European Patent Application No. EP 818448 A1, U.S. Pat. No. 6,207,671 and U.S. Pat. No. 6,064,148 the complete disclosures of which are herein incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from one of the following compounds of Formula VI: 
      2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-3-(4-trifluoromethylbenzoyl)-4,6,7,8-tetrahydro-1H-quinolin-5-one;     2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-3-(4-trifluoromethylbenzoyl)-7,8-dihydro-6H-quinolin-5-one;     [2-cyclopentyl-4-(4-fluorophenyl)-5-hydroxy-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl]-(4-trifluoromethylphenyl)-methanone;     [5-(t-butyldimethylsilanyloxy)-2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl]-(4-trifluoromethylphenyl)-methanone;     [5-(t-butyldimethylsilanyloxy)-2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl]-(4-trifluoromethylphenyl)-methanol;     5-(t-butyldimethylsilanyloxy)-2-cyclopentyl-4-(4-fluorophenyl)-3-[fluoro-(4-trifluoromethylphenyl)-methyl]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline;     2-cyclopentyl-4-(4-fluorophenyl)-3-[fluoro-(4-trifluoromethylphenyl)-methyl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol.    

      Another class of CETP inhibitors that finds utility with the present invention consists of substituted-pyridines having the Formula VII  
                 
 
 or a pharmaceutically acceptable salt or tautomer thereof, 
 
 wherein 
 
      R VII-2  and R VII-6  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, fluorinated alkyl, fluorinated aralkyl, chlorofluorinated alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, alkoxyalkyl, and alkoxycarbonyl; provided that at least one of R VII-2  and R VII-6  is fluorinated alkyl, chlorofluorinated alkyl or alkoxyalkyl;  
      R VII-3  is selected from the group consisting of hydroxy, amido, arylcarbonyl, heteroarylcarbonyl, hydroxymethyl —CHO, 
 
 —CO 2 R VII-7 , wherein R VII-7  is selected from the group consisting of hydrogen, alkyl and cyanoalkyl; and  
                 
 
      wherein R VII-15a  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy and heterocyclyloxy, and  
      R VII-6a  is selected from the group consisting of alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, aryl, heteroaryl, and heterocyclyl, arylalkoxy, trialkylsilyloxy;  
      R VII-4  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, hetereoarylalkenyl, heterocyclylalkenyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkanoyloxy, alkenoyloxy, alkynoyloxy, aryloyloxy, heteroaroyloxy, heterocyclyloyloxy, alkoxycarbonyl, alkenoxycarbonyl, alkynoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocyclyloxycarbonyl, thio, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclythioalkenyl, alkylamino, alkenylamino, alkynylamino, arylamino, heteroarylamino, heterocyclylamino, aryldialkylamino, diarylamino, diheteroarylamino, alkylarylamino, alkylheteroarylamino, arylheteroarylamino, trialkylsilyl, trialkenylsilyl, triarylsilyl, —CO(O)N(R VII-8a RVII- 8 b), wherein R VII-81  and R VII-8b  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, —SO 2 R VII-9 , wherein R VII-9  is selected from the group consisting of hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, —OP(O)(OR VII-10a ) (OR VII-10b ), wherein R VII-10a  and R VII-10b  are independently selected from the group consisting of hydrogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and —OP(S) (OR VII-11a ) (OR VII-11b ), wherein R VII-11a  and R VII-11b  are independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
      R VII-5  is selected from the group consisting of hydrogen, hydroxy, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkylcarbonyloxyalkyl, alkenylcarbonyloxyalkyl, alkynylcarbonyloxyalkyl, arylcarbonyloxyalkyl, heteroarylcarbonyloxyalkyl, heterocyclylcarbonyloxyalkyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkylthioalkyl, cycloalkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, alkoxyalkyl, alkenoxyalkyl, alkynoxylalkyl, aryloxyalkyl, heteroaryloxyalkyl, heterocyclyloxyalkyl, alkoxyalkenyl, alkenoxyalkenyl, alkynoxyalkenyl, aryloxyalkenyl, heteroaryloxyalkenyl, heterocyclyloxyalkenyl, cyano, hydroxymethyl, —CO 2 R VII-14 , wherein R VII-14  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
                 
 
      wherein R VII-15b  is selected from the group consisting of hydroxy, hydrogen, halogen, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio, heterocyclylthio, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, aroyloxy, and alkylsulfonyloxy, and  
      R VII-16b  is selected form the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, arylalkoxy, and trialkylsilyloxy;  
                 
 
      wherein R VII-17  and R VII-18  are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
                 
 
      wherein R- VII-19  is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, —SR VII-20 , —OR VII-21 , and BR VII-22 CO 2 R VII-23 , wherein  
      R VII-20  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aminoaryl, aminoheteroaryl, aminoheterocyclyl, alkylheteroarylamino, arylheteroarylamino,  
      R VII-21  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl,  
      R VII-22  is selected from the group consisting of alkylene or arylene, and  
      R VII-23  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                 
 
      wherein R VII-24  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aralkyl, aralkenyl, and aralkynyl;  
                 
 
      wherein R VII-25  is heterocyclylidenyl;  
                 
 
      wherein R VII-26  and R VII-27  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                 
 
      wherein R VII-28  and R VII-29  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                 
 
      wherein R VII-30  and R VII-31  are independently alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, and heterocyclyloxy; and  
                 
 
      wherein R VII-32  and R VII-33  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                 
 
      wherein R VII-36  is selected from the group consisting of alkyl, alkenyl, aryl, heteroaryl and heterocyclyl;  
                 
 
      wherein R VII-37  and R VII-38  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl;  
                 
 
      wherein R VII-39  is selected from the group consisting of hydrogen, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio and heterocyclylthio, and  
      R VII-40  is selected from the group consisting of haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, haloheterocyclyl, cycloalkyl, cycloalkenyl, heterocyclylalkoxy, heterocyclylalkenoxy, heterocyclylalkynoxy, alkylthio, alkenylthio, alkynylthio, arylthio, heteroarylthio and heterocyclylthio;
 
—N═R VII-41 ,
 
      wherein R VII-41  is heterocyclylidenyl;  
                 
 
      wherein R VII-42  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl, and  
      R VII-43  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, and haloheterocyclyl;  
                 
 
      wherein R VII-44  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;
 
—N═S═O;
 
—N═C═S;
 
—N═C═O;
 
—N 3 ;
 
—SR VII-45 
 
      wherein R VII-45  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl, haloheterocyclyl, heterocyclyl, cycloalkylalkyl, cycloalkenylalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkylalkenyl, cycloalkenylalkenyl, aralkenyl, heteroarylalkenyl, heterocyclylalkenyl, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyi,heteroarylthioalkyl, heterocyclylthioalkyl, alkylthioalkenyl, alkenylthioalkenyl, alkynylthioalkenyl, arylthioalkenyl, heteroarylthioalkenyl, heterocyclylthioalkenyl, aminocarbonylalkyl, aminocarbonylalkenyl, aminocarbonylalkynyl, aminocarbonylaryl, aminocarbonylheteroaryl, and aminocarbonylheterocyclyl,
 
—SR VII-45 , and —CH 2 R VII-47 ,
 
      wherein R VII-46  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
      R VII-47  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl; and  
                 
 
      wherein R VII-48  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl, and  
      R VII-49  is selected from the group consisting of alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy, heterocyclyloxy, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl and haloheterocyclyl;  
                 
 
      wherein R VII-50  is selected from the group consisting of hydrogen, alkyl, cycloaikyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, alkoxy, alkenoxy, alkynoxy, aryloxy, heteroaryloxy and heterocyclyloxy;  
                 
 
      wherein R VII-51  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, haloheteroaryl and haloheterocyclyl; and  
                 
 
      wherein R VII-53  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl;  
      provided that when R VII-5  is selected from the group consisting of heterocyclylalkyl and heterocyclylalkenyl, the heterocyclyl radical of the corresponding heterocyclylalkyl or heterocyclylalkenyl is other than δ-lactone; and  
      provided that when R VII-4  is aryl, heteroaryl or heterocyclyl, and one of R VII-2  and R VII-6  is trifluoromethyl, then the other of R VII-2  and R VII-6  is difluoromethyl.  
      Compounds of Formula VII are disclosed in WO 9941237-A1, the complete disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula VII: 
      Dimethyl 5,5-dithiobis[2-difluoromethyl-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridine-carboxylate].    

      Another class of CETP inhibitors that finds utility with the present invention consists of substituted pyridines having the Formula VIII  
                 
 
 or a pharmaceutically acceptable salt, enantiomers, or stereoisomers thereof, in which 
 
      A VIII  stands for aryl with 6 to 10 carbon atoms, which is optionally substituted up to 3 times in an identical manner or differently by halogen, hydroxy, trifluoromethyl, trifluoromethoxy, or by straight-chain or branched alkyl, acyl, or alkoxy with up to 7 carbon atoms each, or by a group of the formula
 
—NR VIII-1 R VIII-2 , wherein
 
      R VIII-1  and R VIII-2  are identical or different and denote hydrogen, phenyl, or straight-chain or branched alkyl with up to 6 carbon atoms,  
      D VIII  stands for straight-chain or branched alkyl with up to 8 carbon atoms, which is substituted by hydroxy,  
      E VIII  and L VIII  are either identical or different and stand for straight-chain or branched alkyl with up to 8 carbon atoms, which is optionally substituted by cycloalkyl with 3 to 8 carbon atoms, or stands for cycloalkyl with 3 to 8 carbon atoms, or  
      E VIII  has the above-mentioned meaning and  
      L VIII  in this case stands for aryl with 6 to 10 carbon atoms, which is optionally substituted up to 3 times in an identical manner or differently by halogen, hydroxy, trifluoromethyl, trifluoromethoxy, or by straight-chain or branched alkyl, acyl, or alkoxy with up to 7 carbon atoms each, or by a group of the formula
 
—NR VIII-3 R VIII-4 , wherein
 
      R VIII-3  and R VIII-4  are identical or different and have the meaning given above for R VIII-1  and R VIII-2 , or  
      E VIII  stands for straight-chain or branched alkyl with up to 8 carbon atoms, or stands for aryl with 6 to 10 carbon atoms, which is optionally substituted up to 3 times in an identical manner or differently by halogen, hydroxy, trifluoromethyl, trifluoromethoxy, or by straight-chain or branched alkyl, acyl, or alkoxy with up to 7 carbon atoms each, or by a group of the formula
 
—NR VIII-5 R VIII-6 , wherein
 
      R VIII-5  and R VIII-6  are identical or different and have the meaning given above for R VIII-1  and R VIII-2 , and  
      L VIII  in this case stands for straight-chain or branched alkoxy with up to 8 carbon atoms or for cycloalkyloxy with 3 to 8 carbon atoms,  
      T VIII  stands for a radical of the formula  
                 
 
      R VIII-7  and R VIII-8  are identical or different and denote cycloalkyl with 3 to 8 carbon atoms, or aryl with 6 to 10 carbon atoms, or denote a 5- to 7-member aromatic, optionally benzo-condensed, heterocyclic compound with up to 3 heteroatoms from the series S, N and/or O, which are optionally substituted up to 3 times in an identical manner or differently by trifluoromethyl, trifluoromethoxy, halogen, hydroxy, carboxyl, by straight-chain or branched alkyl, acyl, alkoxy, or alkoxycarbonyl with up to 6 carbon atoms each, or by phenyl, phenoxy, or thiophenyl, which can in turn be substituted by halogen, trifluoromethyl, or trifluoromethoxy, and/or the rings are substituted by a group of the formula
 
—NR VIII-11 R VIII-12 , wherein
 
      R VIII-11  and R VIII-12  are identical or different and have the meaning given above for R VIII-1  and R VIII-2 ,  
      X VIII  denotes a straight or branched alkyl chain or alkenyl chain with 2 to 10 carbon atoms each, which are optionally substituted up to 2 times by hydroxy,  
      R VIII-9  denotes hydrogen, and  
      R VIII-10  denotes hydrogen, halogen, azido, trifluoromethyl, hydroxy, mercapto, trifluoromethoxy, straight-chain or branched alkoxy with up to 5 carbon atoms, or a radical of the formula
 
—NR VIII-13 R VIII-14 , wherein
 
      R VIII-13  and R VIII-14  are identical or different and have the meaning given above for R VIII-1  and R VIII-2 , or  
      R VIII-9  and Rvil- 10  form a carbonyl group together with the carbon atom.  
      Compounds of Formula VIII are disclosed in WO 9804528, the complete disclosure of which is incorporated by reference.  
      Another class of CETP inhibitors that finds utility with the present invention consists of substituted 1,2,4-triazoles having the Formula IX  
                 
 
 or a pharmaceutically acceptable salt or tautomer thereof; 
 
      wherein R IX-1  is selected from higher alkyl, higher alkenyl, higher alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkylthioalkyl, arylthioalkyl, and cycloalkylalkyl;  
      wherein R IX-2  is selected from aryl, heteroaryl, cycloalkyl, and cycloalkenyl,  
      wherein  
      R IX-2  is optionally substituted at a substitutable position with one or more radicals independently selected from alkyl, haloalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkoxy, halo, aryloxy, aralkyloxy, aryl, aralkyl, aminosulfonyl, amino, monoalkylamino and dialkylamino; and  
      wherein R IX-3  is selected from hydrido, —SH and halo;  
      provided RIX 2  cannot be phenyl or 4-methylphenyl when R IX-1  is higher alkyl and when R IX-3  is BSH.  
      Compounds of Formula IX are disclosed in WO 9914204, the complete disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula IX: 
      2,4-dihydro-4-(3-methoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-fluorophenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-methylphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3-chlorophenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-methoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3-methylphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     4-cyclohexyl-2,4-dihydro-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3-pyridyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-ethoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2,6-dimethylphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(4-phenoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     4-(1,3-benzodioxol-5-yl)-2,4-dihydro-5-tridecyl-3H-1,2,4-triazole-3-thione;     4-(2-chlorophenyl)-2,4-dihydro-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(4-methoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-5-tridecyl-4-(3-trifluoromethylphenyl)-3H-1,2,4-triazole-3-thione;     2,4-dihydro-5-tridecyl-4-(3-fluorophenyl)-3H-1,2,4-triazole-3-thione;     4-(3-chloro-4-methylphenyl)-2.4-dihydro-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-methylthiophenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     4-(4-benzyloxyphenyl)-2,4-dihydro-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-naphthyl)-5-tridecyl-3H-1,2,4triazole-3-thione;     2,4-dihydro-5-tridecyl-4-(4-trifluoromethylphenyl)-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(1-naphthyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3-methylthiophenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(4-methylthiophenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3,4-dimethoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2,5-dimethoxyphenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(2-methoxy-5-chlorophenyl)-5-tridecyl-3H-1,2,4-triazole-3-thione;     4-(4-aminosulfonylphenyl)-2,4-dihydro-5-tridecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-5-dodecyl-4-(3-methoxyphenyl)-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3-methoxyphenyl)-5-tetradecyl-3H-1,2,4-triazole-3-thione;     2,4-dihydro-4-(3-methoxyphenyl)-5-undecyl-3H-1,2,4-triazole-3-thione; and     2,4-dihydro-(4-methoxyphenyl)-5-pentadecyl-3H-1,2,4-triazole-3-thione.    

      Another class of CETP inhibitors that finds utility with the present invention consists of hetero-tetrahydroquinolines having the Formula X  
                 
 
 and pharmaceutically acceptable salts, enantiomers, or stereoisomers or N-oxides of said compounds; 
 
 in which 
 
      A X  represents cycloalkyl with 3 to 8 carbon atoms or a 5 to 7-membered, saturated, partially saturated or unsaturated, optionally benzo-condensed heterocyclic ring containing up to 3 heteroatoms from the series comprising S, N and/or O, that in case of a saturated heterocyclic ring is bonded to a nitrogen function, optionally bridged over it, and in which the aromatic systems mentioned above are optionally substituted up to 5-times in an identical or different substituents in the form of halogen, nitro, hydroxy, trifluoromethyl, trifluoromethoxy or by a straight-chain or branched alkyl, acyl, hydroxyalkyl or alkoxy each having up to 7 carbon atoms or by a group of the formula BNR X-3 R X-4 ,  
      in which  
      R X-3  and R X-4  are identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,  
      or  
      A X  represents a radical of the formula  
                 
 
      D X  represents an aryl having 6 to 10 carbon atoms, that is optionally substituted by phenyl, nitro, halogen, trifluormethyl or trifluormethoxy, or it represents a radical of the formula  
                 
 
 in which 
 
      R X-5 , R X-6  and R X-9  independently of one another denote cycloalkyl having 3 to 6 carbon atoms, or an aryl having 6 to 10 carbon atoms or a 5- to 7-membered aromatic, optionally benzo-condensed saturated or unsaturated, mono-, bi-, or tricyclic heterocyclic ring from the series consisting of S, N and/or O, in which the rings are substituted, optionally, in case of the nitrogen containing aromatic rings via the N function, with up to 5 identical or different substituents in the form of halogen, trifluoromethyl, nitro, hydroxy, cyano, carbonyl, trifluoromethoxy, straight straight-chain or branched acyl, alkyl, alkylthio, alkylalkoxy, alkoxy, or alkoxycarbonyl each having up to 6 carbon atoms, by aryl or trifluoromethyl-substituted aryl each having 6 to 10 carbon atoms or by an, optionally benzo-condensed, aromatic 5- to 7-membered heterocyclic ring having up to 3 heteroatoms from the series consisting of S, N, and/or O, and/or substituted by a group of the formula BOR X-10 , —SR X-11 , SO 2 R X-12  or BNR X-13 R X-14 .  
      in which  
      R X-10 , R X-11  and R X-12  independently from each other denote aryl having 6 to 10 carbon atoms, which is in turn substituted with up to 2 identical or different substituents in the form of phenyl, halogen or a straight-chain or branched alkyl having up to 6 carbon atoms,  
      R X-13  and R X-14  are identical or different and have the meaning of R X-3  and R X-4  indicated above,  
      or  
      R X-5  and/or R X-6  denote a radical of the formula  
                 
 
      R X-7  denotes hydrogen or halogen, and  
      R X-8  denotes hydrogen, halogen, azido, trifluoromethyl, hydroxy, trifluoromethoxy, straight-chain or branched alkoxy or alkyl having up to 6 carbon atoms or a radical of the formula
 
BNR X-15 R X-16 ,
 
 in which 
 
      R X-15  and R X-16  are identical or different and have the meaning of R X-3  and R X-4  indicated above,  
      or  
      R X-7  and R X-8  together form a radical of the formula ═O or ═NR X-17 ,  
      in which  
      R X-17  denotes hydrogen or straight chain or branched alkyl, alkoxy or acyl having up to 6 carbon atoms,  
      L X  denotes a straight chain or branched alkylene or alkenylene chain having up to 8 carbon atoms, that are optionally substituted with up to 2 hydroxy groups,  
      T X  and X X  are identical or different and denote a straight chain or branched alkylene chain with up to 8 carbon atoms  
      or  
      T X  or X X  denotes a bond,  
      V X  represents an oxygen or sulfur atom or an BNR X-18 -group, in which  
      R X-18  denotes hydrogen or straight chain or branched alkyl with up to 6 carbon atoms or phenyl,  
      E X  represents cycloalkyl with 3 to 8 carbon atoms, or straight chain or branched alkyl with up to 8 carbon atoms, that is optionally substituted by cycloalkyl with 3 to 8 carbon atoms or hydroxy, or represents a phenyl, that is optionally substituted by halogen or trifluoromethyl,  
      R X-1  and R X-2  together form a straight-chain or branched alkylene chain with up to 7 carbon atoms, that must be substituted by carbonyl group and/or by a radical with the formula  
                 
 
 in which a and b are identical or different and denote a number equaling 1,2, or 3, 
 
      R X-19  denotes hydrogen, cycloalkyl with 3 up to 7 carbon atoms, straight chain or branched silylalkyl with up to 8 carbon atoms or straight chain or branched alkyl with up to 8 carbon atoms, that are optionally substituted by hydroxyl, straight chain or branched alkoxy with up to 6 carbon atoms or by phenyl, which in turn might be substituted by halogen, nitro, trifluormethyl, trifluoromethoxy or by phenyl or by tetrazole-substituted phenyl, and alkyl, optionally be substituted by a group with the formula BOR X-22 ,  
      in which  
      R X-22  denotes a straight chain or branched acyl with up to 4 carbon atoms or benzyl,  
      or  
      R X-19  denotes straight chain or branched acyl with up to 20 carbon atoms or benzoyl, that is optionally substituted by halogen , trifluoromethyl, nitro or trifluoromethoxy, or it denotes straight chain or branched fluoroacyl with up to 8 carbon atoms and 9 fluorine atoms,  
      R X-20  and R X-21  are identical or different and denote hydrogen, phenyl or straight chain or branched alkyl with up to 6 carbon atoms,  
      or  
      R X-20  and R X-21  together form a 3- to 6-membered carbocyclic ring, and the carbocyclic rings formed are optionally substituted, optionally also geminally, with up to six identical or different substituents in the form of triflouromethyl, hydroxy, nitrile, halogen, carboxyl, nitro, azido, cyano, cycloalkyl or cycloalkyloxy with 3 to 7 carbon atoms each, by straight chain or branched alkoxycarbonyl, alkoxy or alkylthio with up to 6 carbon atoms each or by straight chain or branched alkyl with up to 6 carbon atoms, which in turn is substituted with up to 2 identically or differently by hydroxyl, benzyloxy, trifluoromethyl, benzoyl, straight chain or branched alkoxy, oxyacyl or carbonyl with up to 4 carbon atoms each and/or phenyl, which may in turn be substituted with a halogen, trifuoromethyl or trifluoromethoxy, and/or the formed carbocyclic rings are optionally substituted, also geminally, with up to 5 identical or different substituents in the form of phenyl, benzoyl, thiophenyl or sulfonylbenzyl, which in turn are optionally substituted by halogen, trifluoromethyl, trifluoromethoxy or nitro, and/or optionally are substituted by a radical with the formula  
                 
 
 in which 
 
      c denotes a number equaling 1, 2, 3, or 4,  
      d denotes a number equaling 0 or 1,  
      R X-23  and R X-24  are identical or different and denote hydrogen, cycloalkyl with 3 to 6 carbon atoms, straight chain or branched alkyl with up to 6 carbon atoms, benzyl or phenyl, that is optionally substituted with up to 2 identically or differently by halogen, trifluoromethyl, cyano, phenyl or nitro, and/or the formed carbocyclic rings are substituted optionally by a spiro-linked radical with the formula  
                 
 
 in which 
 
      W X  denotes either an oxygen or a sulfur atom  
      Y X  and Y′ X  together form a 2 to 6 membered straight chain or branched alkylene chain,  
      e denotes a number equaling 1, 2, 3, 4, 5, 6, or 7,  
     
         
          f denotes a number equaling 1 or 2,  
       
    
      R X-25 , R X-26 , R X-27 , R X-28 , R X-29 , R X-30  and R X-31  are identical or different and denote hydrogen, trifluoromethyl, phenyl, halogen or straight chain or branched alkyl or alkoxy with up to 6 carbon atoms each,  
      or  
      R X-25  and R X-26  or R X-27  and R X-28  respectively form together a straight chain or branched alkyl chain with up to 6 carbon atoms,  
      or  
      R X-25  and R X-26  or R X-27  and R X-28  each together form a radical with the formula  
                 
 
 in which 
 
      W X  has the meaning given above,  
      g denotes a number equaling 1, 2, 3, 4, 5, 6, or 7,  
      R X-32  and R X-33  form together a 3- to 7-membered heterocycle, which contains an oxygen or sulfur atom or a group with the formula SO, SO 2  or —NR X-34 ,  
      in which  
      R X-34  denotes hydrogen, phenyl, benzyl or straight or branched alkyl with up to 4 carbon atoms.  
      Compounds of Formula X are disclosed in WO 9914215, the complete disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula X: 
      2-cyclopentyl-5-hydroxy-7,7-dimethyl-4-(3-thienyl)-3-(4-trifluoromethylbenxoyl)-5,6,7,8-tetrahydroquinoline;     2-cyclopentyl-3-[fluoro-(4-trifluoromethylphenyl)methyl]-5-hydroxy-7,7-dimethyl-4-(3-thienyl)-5,6,7,8-tetrahydroquinoline; and     2-cyclopentyl-5-hydroxy-7,7-dimethyl-4-(3-thienyl)-3-(trifluoromethylbenxyl)-5,6,7,8-tetrahydroquinoiine.    

      Another class of CETP inhibitors that finds utility with the present invention consists of substituted tetrahydro naphthalines and analogous compound having the Formula XI  
                 
 
      and stereoisomers, stereoisomer mixtures, and salts thereof, in which  
      A XI  stands for cycloalkyl with 3 to 8 carbon atoms, or stands for aryl with 6 to 10 carbon atoms, or stands for a 5- to 7-membered, saturated, partially unsaturated or unsaturated, possibly benzocondensated, heterocycle with up to 4 heteroatoms from the series S, N and/or O, where aryl and the heterocyclic ring systems mentioned above are substituted up to 5-fold, identical or different, by cyano, halogen, nitro, carboxyl, hydroxy, trifluoromethyl, trifluoro-methoxy, or by straight-chain or branched alkyl, acyl, hydroxyalkyl, alkylthio, alkoxycarbonyl, oxyalkoxycarbonyl or alkoxy each with up to 7 carbon atoms, or by a group of the formula
 
—NR XI-3 R XI-4 ,
 
 in which 
 
      R XI-3  and R XI-4  are identical or different and denote hydrogen, phenyl, or straight-chain or branched alkyl with up to 6 carbon atoms  
      D XI  stands for a radical of the formula  
                 
 
 in which 
 
      R XI-5 , R XI-6  and R XI-9 , independent of each other, denote cycloalkyl with 3 to 6 carbon atoms, or denote aryl with 6 to 10 carbon atoms, or denote a 5- to 7-membered, possibly benzocondensated, saturated or unsaturated, mono-, bi- or tricyclic heterocycle with up to 4 heteroatoms of the series S, N and/or O, where the cycles are possibly substitutedCin the case of the nitrogen-containing rings also via the N-functionCup to 5-fold, identical or different, by halogen, trifluoromethyl. nitro, hydroxy, cyano, carboxyl, trifluoromethoxy, straight-chain or branched acyl, alkyl, alkylthio, alkylalkoxy, alkoxy or alkoxycarbonyl with up to 6 carbon atoms each. by aryl or trifluoromethyl substituted aryl with 6 to 10 carbon atoms each, or by a possibly benzocondensated aromatic 5- to 7-membered heterocycle with up to 3 heteroatoms of the series S, N and/or O, and/or are substituted by a group of the formula
 
OR XI-10 , —SR XI-11  , —SO 2 R XI-12  or —NR XI-13 R XI-14 ,
 
 in which 
 
      R XI-10 , R XI-11  and R XI-12 , independent of each other, denote aryl with 6 to 10 carbon atoms, which itself is substituted up to 2-fold, identical or different, by phenyl, halogen. or by straight-chain or branched alkyl with up to 6 carbon atoms,  
      R XI-13  and R XI-14  are identical or different and have the meaning given above for R XI-3  and R XI-4 ,  
      or  
      R XI-5  and/or R XI-6  denote a radical of the formula  
                 
 
      R XI-7  denotes hydrogen, halogen or methyl,  
      and  
      R XI-8  denotes hydrogen, halogen, azido, trifluoromethyl, hydroxy, trifluoromethoxy, straight-chain or branched alkoxy or alkyl with up to 6 carbon atoms each, or a radical of the formula —NR XI-15 R XI-16 ,  
      in which  
      R XI-15  and R XI-16  are identical or different and have the meaning given above for R XI-3  and R XI-4 ,  
      or  
      R XI-7  and R XI-8  together form a radical of the formula ═O or ═NR XI-17 , in which  
      R XI-17  denotes hydrogen orstraight-chain or branched alkyl, alkoxy or acyl with up to 6 carbon atoms each,  
      L XI  denotes a straight-chain or branched alkylene- or alkenylene chain with up to 8 carbon atoms each, which is possibly substituted up to 2-fold by hydroxy,  
      T XI  and X XI  are identical or different and denote a straight-chain or branched alkylene chain with up to 8 carbon atoms,  
      or  
      T XI  and X XI  denotes a bond,  
      V XI  stands for an oxygen- or sulfur atom or for an —NR XI-18  group,  
      in which  
      R XI-18  denotes hydrogen or straight-chain or branched alkyl with up to 6 carbon atoms, or phenyl,  
      E XI  stands for cycloalkyl with 3 to 8 carbon atoms, or stands for straight-chain or branched alkyl with up to 8 carbon atoms, which is possibly substituted by cycloalkyl with 3 to 8 carbon atoms or hydroxy, or stands for phenyl, which is possibly substituted by halogen or trifluoromethyl,  
      R XI-1  and R XI-2  together form a straight-chain or branched alkylene chain with up to 7 carbon atoms, which must be substituted by a carbonyl group and/or by a radical of the f0ormula  
                 
 
 in which 
 
      a and b are identical or different and denote a number 1, 2 or 3  
      R XI-19  denotes hydrogen, cycloalkyl with 3 to 7 carbon atoms, straight-chain or branched silylalkyl with up to 8 carbon atoms, or straight-chain or branched alkyl with up to 8 carbon atoms, which is possibly substituted by hydroxy, straight-chain or branched alkoxy with up to 6 carbon atoms, or by phenyl, which itself can be substituted by halogen, nitro, trifluoromethyl, trifluoromethoxy or by phenyl substituted by phenyl or tetrazol, and alkyl is possibly substituted by a group of the formula —OR XI-22,    
      in which  
      R XI-22  denotes straight-chain or branched acyl with up to 4 carbon atoms, or benzyl,  
      or  
      R XI-19  denotes straight-chain or branched acyl with up to 20 carbon atoms or benzoyl, which is possibly substituted by halogen, trifluoromethyl, nitro or trifluoromethoxy, or denotes straight-chain or branched fluoroacyl with up to 8 carbon atoms and 9 fluorine atoms,  
      R XI-20  and R XI-21  are identical or different, denoting hydrogen, phenyl or straight-chain or branched alkyl with up to 6 carbon atoms,  
      or  
      R XI-20  and R XI-21  together form a 3- to 6-membered carbocycle, and, possibly also geminally, the alkylene chain formed by R XI-1  and R XI-2 , is possibly substituted up to 6-fold, identical or different, by trifluoromethyl, hydroxy, nitrile, halogen, carboxyl, nitro, azido, cyano, cycloalkyl or cycloalkyloxy with 3 to 7 carbon atoms each, by straight-chain or branched alkoxycarbonyl, alkoxy or alkoxythio with up to 6 carbon atoms each, or by straight-chain or branched alkyl with up to 6 carbon atoms, which itself is substituted up to 2-fold, identical or different. by hydroxyl, benzyloxy, trifluoromethyl, benzoyl, straight-chain or branched alkoxy, oxyacyl or carboxyl with up to 4 carbon atoms each, and/or phenyl-which itself can be substituted by halogen, trifluoromethyl or trifluoromethoxy, and/or the alkylene chain formed by R XI-1  and R XI-2  is substituted, also geminally, possibly up to 5-fold, identical or different, by phenyl, benzoyl, thiophenyl or sulfobenzyl -which themselves are possibly substituted by halogen, trifluoromethyl, trifluoromethoxy or nitro, and/or the alkylene chain formed by R XI-1  and R XI-2  is possibly substituted by a radical of the formula  
                 
 
 in which 
 
      c denotes a number 1, 2, 3 or 4,  
      d denotes a number 0 or 1,  
      R XI-23  and R XI-24  are identical or different and denote hydrogen, cycloalkyl with 3 to 6 carbon atoms, straight-chain or branched alkyl with up to 6 carbon atoms, benzyl or phenyl, which is possibly substituted up to 2-fold. identical or different, by halogen, trifluoromethyl, cyano, phenyl or nitro, and/or the alkylene chain formed by R XI-1  and R XI-2  is possibly substituted by a spiro-jointed radical of the formula  
                 
 
 in which 
 
      W XI  denotes either an oxygen or a sulfur atom,  
      Y XI  and Y′ XI  together form a 2- to 6-membered straight-chain or branched alkylene chain,  
      e is a number 1, 2, 3, 4, 5, 6 or 7,  
      f denotes a number 1 or 2,  
      R XI-25 , R XI-26 , R XI-27 , R XI-28 , R XI-29 , R XI-30  and R XI-31  are identical or different and denote hydrogen, trifluoromethyl, phenyl, halogen, or straight-chain or branched alkyl or alkoxy with up to 6 carbon atoms each,  
      or  
      R XI-25  and R XI-26  or R XI-27  and R XI-28  together form a straight-chain or branched alkyl chain with up to 6 carbon atoms,  
      or  
      R 25  and R XI-26  or R XI-27  and R XI-28  together form a radical of the formula  
                 
 
 in which 
 
      W XI  has the meaning given above,  
      g is a number 1, 2, 3, 4, 5, 6 or 7,  
      R XI-32  and R XI-33  together form a 3- to 7-membered heterocycle that contains an oxygen- or sulfur atom or a group of the formula SO, SO 2  or —NR XI-34 ,  
      in which  
      R XI-34  denotes hydrogen, phenyl, benzyl, or straight-chain or branched alkyl with up to 4 carbon atoms.  
      Compounds of Formula XI are disclosed in WO 9914174, the complete disclosure of which is incorporated by reference.  
      Another class of CETP inhibitors that finds utility with the present invention consists of 2-aryl-substituted pyridines having the Formula (XII)  
                 
 
 or pharmaceutically acceptable salts, enantiomers, or stereoisomers of said compounds, 
 
 in which 
 
      A XII  and E XII  are identical or different and stand for aryl with 6 to 10 carbon atoms which is possibly substituted, up to 5-fold identical or different, by halogen, hydroxy, trifluoromethyl, trifluoromethoxy, nitro or by straight-chain or branched alkyl, acyl, hydroxy alkyl or alkoxy with up to 7 carbon atoms each, or by a group of the formula —NR XII-1 R XII-2 ,  
      where  
      R XII-1  and R XII-2  are identical or different and are meant to be hydrogen, phenyl or straight-chain or branched alkyl with up to 6 carbon atoms,  
      D XII  stands for straight-chain or branched alkyl with up to 8 carbon atoms, which is substituted by hydroxy,  
      L XII  stands for cycloalkyl with 3 to 8 carbon atoms or for straight-chain or branched alkyl with up to 8 carbon atoms, which is possibly substituted by cycloalkyl with 3 to 8 carbon atoms, or by hydroxy,  
      T XII  stands for a radical of the formula R XII-3 —X XII  — or  
                 
 
 where 
 
      R XII-3  and R XII-4  are identical or different and are meant to be cycloalkyl with 3 to 8 carbon atoms, or aryl with 6 to 10 carbon atoms, or a 5- to 7-membered aromatic, possibly benzocondensated heterocycle with up to 3 heteroatoms from the series S, N and/or O, which are possibly substituted. up to 3-fold identical or different, by trifluoromethyl, trifluoromethoxy, halogen, hydroxy, carboxyl, nitro, by straight-chain or branched alkyl, acyl, alkoxy or alkoxycarbonyl with up to 6 carbon atoms each or by phenyl, phenoxy or phenylthio which in turn can be substituted by halogen. trifluoromethyl or trifluoromethoxy, and/or where the cycles are possibly substituted by a group of the formula —NR XII-7 R XII-8 ,  
      where  
      R XII-7  and R XII-8  are identical or different and have the meaning of R XII-1  and R XII-2  given above,  
      X XII  is a straight-chain or branched alkyl or alkenyl with 2 to 10 carbon atoms each, possibly substituted up to 2-fold by hydroxy or halogen,  
      R XII-5  stands for hydrogen,  
      and  
      R XII  means to be hydrogen, halogen, mercapto, azido, trifluoromethyl, hydroxy, trifluoromethoxy, straight-chain or branched alkoxy with up to 5 carbon atoms, or a radical of the formula BNR XII-9 R XII-10 ,  
      where  
      R XII-9  and R XII-10  are identical or different and have the meaning of R XII-1  and R XII-2  given above,  
      or  
      R XII-5  and R XII-6 , together with the carbon atom, form a carbonyl group.  
      Compounds of Formula XII are disclosed in EP 796846-A1, U.S. Pat. No. 6,127,383 and U.S. Pat. No. 5,925,645 the complete disclosures of which are incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula XII: 
      4,6-bis-(p-fluorophenyl)-2-isopropyl-3-[(p-trifluoromethylphenyl)-(fluoro)-methyl]-5-(1-hydroxyethyl)pyridine;     2,4-bis-(4-fluorophenyl)-6-isopropyl-5-[4-(trifluoromethylphenyl)-fluoromethyl]-3-hydroxymethyl)pyridine; and     2,4-bis-(4-fluorophenyl)-6-isopropyl-5-[2-(3-trifluoromethylphenyl)vinyl]-3-hydroxymethyl)pyridine.    

      Another class of CETP inhibitors that finds utility with the present invention consists of compounds having the Formula (XIII)  
                 
 
 or pharmaceutically acceptable salts, enantiomers, stereoisomers, hydrates, or solvates of said compounds, in which 
 
      R XIII  is a straight chain or branched C 1-10  alkyl; straight chain or branched C 2-10  alkenyl; halogenated C 1-4  lower alkyl; C 3-10  cycloalkyl that may be substituted; C 5-8  cycloalkenyl that may be substituted; C 3-10  cycloalkyl C 1-10  alkyl that may be substituted; aryl that may be substituted; aralkyl that may be substituted; or a 5- or 6-membered heterocyclic group having 1 to 3 nitrogen atoms, oxygen atoms or sulfur atoms that may be substituted,  
      X XIII-1 , X XIII-2 , X XIII-3  X XIII-4  may be the same or different and are a hydrogen atom; halogen atom; C 1-4  lower alkyl; halogenated C 1-4  lower alkyl; C 1-4  lower alkoxy; cyano group; nitro group; acyl; or aryl, respectively;  
      Y XIII  is —CO—; or BSO 2 —; and  
      Z XIII  is a hydrogen atom; or mercapto protective group.  
      Compounds of Formula XIII are disclosed in WO 98/35937, the complete disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula XIII: 
      N,N′-(dithiodi-2,1-phenylene)bis[2,2-dimethyl-propanamide];     N,N′-(dithiodi-2,1-phenylene)bis[1-methyl-cyclohexanecarboxamide];     N,N′-(dithiodi-2,1-phenylene)bis[1-(3-methylbutyl)-cyclopentanecarboxamide];     N,N′-(dithiodi-2,1-phenylene)bis[1-(3-methylbutyl)-cyclohexanecarboxamide];     N,N′-(dithiodi-2,1-phenylene)bis[1-(2-ethylbutyl)-cyclohexanecarboxamide];     N,N′-(dithiodi-2,1-phenylene)bis-tricyclo[3.3.1.1 3,7 ]decane-1-carboxamide;     propanethioic acid, 2-methyl-,S-[2[[[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino]phenyl]ester;     propanethioic acid, 2,2-dimethyl-, S-[2-[[[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino]phenyl]ester; and     ethanethioic acid, S-[2-[[[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino]phenyl]ester.    

      Another class of CETP inhibitors that finds utility with the present invention consists of polycyclic aryl and heteroaryl tertiary-heteroalkylamines having the Formula XIV  
                 
 
 and pharmaceutically acceptable forms thereof, wherein: 
 
      n XIV  is an integer selected from 0 through 5;  
      R XIV-1  is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;  
      X XIV  is selected from the group consisting of O, H, F, S, S(O),NH, N(OH), N(alkyl), and N(alkoxy);  
      R XIV-16  is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy, dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, dialkoxyphosphonoalkyl, trialkylsilyl, and a spacer selected from the group consisting of a covalent single bond and a linear spacer moiety having from 1 through 4 contiguous atoms linked to the point of bonding of an aromatic substituent selected from the group consisting of R XIV-4 , R XIV-8  R XIV-9 , and R XIV-13  to form a heterocyclyl ring having from 5 through 10 contiguous members with the provisos that said spacer moiety is other than a covalent single bond when R XIV-2  is alkyl and there is no R XIV-16  wherein X is H or F;  
      D XIV-1 , D XIV-2 , J XIV-1 , J XIV-2  and K XIV-1  are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D XIV-1 , D XIV-2 , J XIV-1 , J XIV-2  and K XIV-1  is a covalent bond, no more than one of D XIV-1 , D XIV-2 , J XIV-1 , J XIV-2  and K XIV-1  is O, no more than one of D XIV-1 , D XIV-2 , J XIV-1 , J XIV-2  and K XIV-1  is S, one of D XIV-1 , D XVI-2 , J XIV-1 , J XIV-2  and K XVI-1  must be a covalent bond when two of D XIV-1 , D XIV-2 , J XIV-1 , J XIV-2  and K XIV-1  are O and S, and no more than four of D XIV-1 , D XIV-2 , J XIV-1 , J XIV-2  and K XIV-1  are N;  
      D XIV-3 , D XVI-4 , J XIV-3 , J XIV-4  and K XIV-2  are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D XIV-3 , D XIV-4 , J XIV-3 , J XIV-4  and K XIV-2  is a covalent bond, no more than one of D XIV-3 , D XIV-4 , J XIV-3 , J XIV-4  and K XIV-2  is O, no more than one of D XIV-3 , D XIV-4 , J XIV-3 , J XIV-4  and K XIV-2  is S, one of D XIV-3 . D XIV-4 , J XIV-3 , J XIV-4  and K XIV-2  must be a covalent bond when two of D XIV-3 , D XIV-4 , J XIV-3 , J XIV-4  and K XIV-2  are 0 and S, and no more than four of D XIV-3 , D XIV-4  J XIV-3 , J XIV-4  and K XIV-2  and K XIV-2  are N;  
      R XIV-2  is independently selected from the group consisting of hydrido, hydroxy, hydroxyalkyl, amino, aminoalkyl, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, aloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl;  
      R XIV-2  and R XIV-3  are taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 6 contiguous atoms to form a rng selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;  
      R XIV-3  is selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, amino, alkylamino, dialkylamino, acyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, heteroarylthio, aralkylthio, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aroyl, heteroaroyl, aralkylthioalkyl, heteroaralkylthioalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl;  
      Y XIV  is selected from a group consisting of acovalent single bond, (C(R XIV-14 ) 2 ) qXIV  wherein  qXIV  is an integer selected from 1 and 2 and (CH(R XIV-14 )) gXIV —W XIV —(CH(R XIV-14 )) pXIV  wherein  gXIV  and  pXIV  are integers independently selected from 0 and 1;  
      R XIV-14  is independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, a spacer selected from a moiety having a chain length of 3 to 6 atoms connected to the point of bonding selected from the group consisting of R XIV-9  and R XIV-13  to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members and a heterocyclyl ring having from 5 through 8 contiguous members and a spacer selected from a moiety having a chain length of 2 to 5 atoms connected to the point of bonding selected from the group consisting of R XIV-4  and R XIV-8  to form a heterocyclyl having from 5 through 8 contiguous members with the proviso that, when Y XIV  is a covalent bond, an R XIV-14  substituent is not attached to Y XIV ;  
      R XIV-14  and R XIV-14 , when bonded to the different atoms, are taken together to form a group selected from the group consisting of a covalent bond, alkylene, haloalkylene, and a spacer selected from a group consisting of a moiety having a chain length of 2 to 5 atoms connected to form a ring selected from the group of a saturated cycloalkyl having from 5 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;  
      R XIV-14  and R XIV-14 , when bonded to the same atom are taken together to form a group selected from the group consisting of oxo, thiono, alkylene, haloalkylene, and a spacer selected from the group consisting of a moiety having a chain length of 3 to 7 atoms connected to form a ring selected from the group consisting of a cycloalkyl having from 4 through 8 contiguous members, a cycloalkenyl having from 4 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;  
      W XIV  is selected from the group consisting of O, C(O), C(S), C(O)N(R XIV-14 ), C(S)N(R XIV-14 ), (R XIV-14 )NC(O), (R XIV-14 )NC(S), S, S(O), S(O) 2 , S(O) 2 N(R XIV-14 ), (R XIV-   14 )NS(O) 2 , and N(R XIV-14 ) with the proviso that R XIV-14  is selected from other than halo and cyano;  
      Z XIV  is independently selected from a group consisting of a covalent single bond, (C(R XIV-15 ) 2 ) qXIV-2  wherein  qXIV-2  is an integer selected from 1 and 2, (CH(R XIV-15 )) jXIV —(CH(R XIV-15 )) kXIV  wherein  jXIV  and  kXIV  are integers independently selected from 0 and 1 with the proviso that, when Z XIV  is a covalent single bond, an R XIV-15  substituent is not attached to Z XIV ;  
      R XIV-15  is independently selected, when Z XIV  is (C(R XIV-15 ) 2 ) qXIV  wherein  qXIV  is an integer selected from 1 and 2, from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, a spacer selected from a moiety having a chain length of 3 to 6 atoms connected to the point of bonding selected from the group consisting of R XIV-4  and R XIV-8  to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members and a heterocyclyl ring having from 5 through 8 contiguous members, and a spacer selected from a moiety having a chain length of 2 to 5 atoms connected to the point of bonding selected from the group consisting of R XIV-9  and R XIV-13  to form a heterocyclyl having from 5 through 8 contiguous members;  
      R XIV-15  and R XIV-15 , when bonded to the different atoms, are taken together to form a group selected from the group consisting of a covalent bond, alkylene, haloalkylene, and a spacer selected from a group consisting of a moiety having a chain length of 2 to 5 atoms connected to form a ring selected from the group of a saturated cycloalkyl having from 5 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;  
      R XIV-15  and R XIV-15 , when bonded to the same atom are taken together to form a group selected from the group consisting of oxo, thiono, alkylene, haloalkylene, and a spacer selected from the group consisting of a moiety having a chain length of 3 to 7 atoms connected to form a ring selected from the group consisting of a cycloalkyl having from 4 through 8 contiguous members, a cycloalkenyl having from 4 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;  
      R XIV-15  is independently selected, when Z XIV  is (CH(R XIV-15 )) jXIV —W—(CH(R XIV-15 )) kXIV  wherein  jXIV  and  kXIV  are integers independently selected from 0 and 1, from the group consisting of hydrido, halo, cyano, aryloxy, carboxyl, acyl, aroyl, heteroaroyl, hydroxyalkyl, heteroaryloxyalkyl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfonylalkyl, alkylsulfinylalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, a spacer selected from a linear moiety having a chain length of 3 to 6 atoms connected to the point of bonding selected from the group consisting of R XIV-4  and R XIV-8  to form a ring selected from the group consisting of a cycloalkeriyl ring having from 5 through 8 contiguous members and a heterocyclyl ring having from 5 through 8 contiguous members, and a spacer selected from a linear moiety having a chain length of 2 to 5 atoms connected to the point of bonding selected from the group consisting of R XIV-13  and R XIV-13  to form a heterocyclyl ring having from 5 through 8 contiguous members;  
      R XIV-4 , R XIV-5 , R XIV-6 , R XIV-7 , R XIV-8 , R XIV-9 , R XIV-10 , R XIV-11 , R XIV-12 , and R XIV-13  are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamido, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl; haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyaikyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the proviso that there are one to five non-hydrido ring substituents R XIV-4 , R XIV-5 , R XIV-6 , R XIV-7 , and R XIV-8  present, that there are one to five non-hydrido ring substituents R XIV-9 , R XIV-10 , R XIV-11 , R XIV-12 , and R XIV-13  present, and R XIV-4 , R XIV-5 , R XIV-6 , R XIV-7 , R XIV-8 , R XIV-9 , R XIV-10 , R XIV-11 , R XIV-12 , and R XIV-13  are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;  
      RN XIV-4  and R XIV-5 , R XIV-5  and R XIV-6 , R XIV-6  and R XIV-7 , R XIV-7  and R XIV-8 , R XIV-8  and R XIV-9 , R XIV-9  and R XIV-10 , R XIV-10  and R XIV-11 , R XIV-11  and R XIV-12 , and R XIV-12  and R XIV-13  are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R XIV-4  and R XIV-5 , R XIV-5  and R XIV-4 , R XIV-6  and R XIV-7  and R XIV-7  and R XIV-8  are used at the same time and that no more than one of the group consisting of spacer pairs R XIV-9  and R XIV-10 , R XIV-10  and R XIV-11 , R XIV-11  and R XIV-12 , and R XIV-12  and R XIV-13  are used at the same time;  
      R XIV-4  and R XIV-9 , R XIV-4  and R XIV-13 , R XIV-8  and R XIV-9 , and R XIV-8  and R XIV-13  are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear moiety wherein said linear moiety forms a ring selected from the group consisting of a partially saturated heterocyclyl ring having from 5 through 8 contiguous members and a heteroaryl ring having from 5 through 6 contiguous members with the proviso that no more than one of the group consisting of spacer pairs R XIV-4  and R XIV-9 , R XIV-4  and R XIV-13 , R XIV-8  and R XIV-9 , and R XIV-8  and R XIV-13  is used at the same time.  
      Compounds of Formula XIV are disclosed in WO 00/18721, the entire disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula XIV: 
      3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-cyclopropylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-(2-furyl)phenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-methlylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3,5-dimethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-t-butylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]1,1,1-trifluoro-2-propanol;     3-[[3-(3-methylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(phenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl ][3-[[3-(trifluoromethoxy)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanoi;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3-(trifluoromethyl)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3,5-dimethylphenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyi]methyl][3-[[3-(trifluoromethylthio)-phenyl]methoxy]phenyl]amino]-1,1,-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3,5-difluorophenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[cyclohexylmethoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-difluoromethoxyphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(pentafluoroethymethyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-cyclopropylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-(2-furyl)phenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyllamino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-methylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4chloro-3ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[3-(pentafluoroethyl)-phenyI]methyl]amino]-,1,1,1-trifluoro-2-propanol;     3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3,5-dimethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-t-butylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-methylphenoxy)phenyl][[3-pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[3-(pentafluoroethyl)phenyl]-methylamino]-1,1,1-trifluoro-2-propanol;     3-[[3-(phenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[3-(pentafluoroethyl)phenyl]-methylamino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3-(trifluoromethoxy)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3-(trifluoromethyl)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3,5-dimethylphenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3-(trifluoromethylthio)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3,5-difluorophenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[cyclohexylmethoxy]phenyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-difluoromethoxyphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[3-(pentafluoroethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-cyclopropylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-(2-furyl)phenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-methylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifiuoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[3-(heptafluoropropyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3,5-dimethylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-ethylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-t-butylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-methylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(phenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3-(trifluoromethoxy)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3-(trifluoromethyl)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3,5-dimethylphenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3-(trifluoromethylthio)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3,5-difluorophenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[cyclohexylmethoxy]phenyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-difluoromethoxyphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[3-(heptafluoropropyl)-phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-cyclopropylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-(2-furyl)phenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-methylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[2-fluoro-5-(trifluoro-methyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3,5-dimethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-ethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-t-butylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-methylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(phenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethoxy)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethyl)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3,5-dimethylphenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethylthio)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3,5-difluorophenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[cyclohexylmethoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-difluoromethoxyphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-cyclopropylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-(2-furyl)phenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][[2-fluoro-4(trifluoromethyi)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-methylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[2-fluoro-4-(trifluoro-methyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3,5-dimethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-ethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-t-butylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-methylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(phenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethoxy)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethyl)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3,5-dimethylphenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethylthio)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3,5-difluorophenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[cyclohexylmethoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-difluoromethoxy-4-pyridyfoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-difluoromethoxyphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol; and     3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[2-fluoro-4-(trifluoro-methyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol.    

      Another class of CETP inhibitors that finds utility with the present invention consists of substitued N-Aliphatic-N-Aromatic tertiary-Heteroalkylamines having the Formula XV  
                 
 
 and pharmaceutically acceptable forms thereof, wherein: 
 
      n XV  is an integer selected from 1 through 2;  
      A XV  and Q XV  are independently selected from the group consisting of  
                 
 
      with the provisos that one of A XV  and Q XV  must be AQ-1 and that one of A XV  and Q XV  must be selected from the group consisting of AQ-2 and —CH 2 (CR XV-37 R XV-38 ) vXV —(CR XV-33 R XV-34 ) uXV —T XV —(CR XV-35 R XV-36 ) xXV —H;  
      T XV  is selected from the group consisting of a single covalent bond, O, S, S(O), S(O) 2 , C(R XV-33 )═C(R XV-35 ), and  
      C≡C;  
       vXV  is an integer selected from 0 through 1 with the proviso that  vXV  is 1 when any one of R XV-33 , R XV-34 , R XV-35  and R XV-36  is aryl or heteroaryl;  
       uXV  and  wXV  are integers independently selected from 0 through 6;  
      A XV-1  is C(R XV-30 );  
      D XV-1 , D XV-2 , J XV-1 , J XV-2 , and K XV-1  are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D XV-1 , D XV-29  J XV-1 , J XV-2 , and K XV-1  is a covalent bond, no more than one of D XV-1 , D XV-2 , J XV-1 , J XV-2 , and K XV-1  is O,no more than one of D XV-1 , D XV-2 , J XV-1 , J XV-2 , and K XV-1 , is S, one of D XV-1 , D XV-2 , J XV-1 , J XV-2 , and K XV-1  must be a covalent bond when two of D XV-1 , D XV-2 , J XV-1 , J XV-2 , and K XV-1  are O and S, and no more than four of D XV-1 , D XV-2 , J XV-1 , J XV-2 , and K XV-1  are N;  
      B XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3 , J XV-4 , and K XV-2  are independently selected from the group consisting of C, C(R XV-30 ), N, O, S and a covalent bond with the provisos that no more than 5 of B XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3 , J XV-4 , and K XV-2  are a covalent bond, no more than two of B XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3 , J XV-4 , and KXV-2 are O, no more than two of BXV XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3,  J XV-4 , and K XV-2  are S, no more than two of B XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3 , J XV-4 , and K XV-2  are simultaneously O and S, and no more than two of B XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3 , J XV-4 , and K XV-2  are N;  
      B XV-1  and D XV-3 , D XV-3  and J XV-3 , J XV-3  and K XV-2 , K XV-2  and J XV-4 , J XV-4  and D XV-4,  and D XV-4  and B XV-2  are independently selected to form an in-ring spacer pair wherein said  
      spacer pair is selected from the group consisting of C(R XV-33 )═C(R XV-35 ) and N═N with the provisos that AQ-2 must be a ring of at least five contiguous members, that no more than two of the group of said spacer pairs are simultaneously C(R XV-33 )═C(R XV-35 ) and that no more than one of the group of said spacer pairs can be N═N unless the other spacer pairs are other than C(R XV-33 )═C(R XV-35 ), N, and S;  
      R XV-1  is selected from the group consisting of haloalkyl and haloalkoxymethyl;  
      R XV-2  is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl and heteroaryl;  
      R XV-3  is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl;  
      Y XV  is selected from the group consisting of a covalent single bond, (CH 2 ) q  wherein q is an integer selected from 1 through 2 and (CH 2 ) j —O—(CH 2 ) k  wherein j and k are integers independently selected from 0 through 1;  
      Z XV  is selected from the group consisting of covalent single bond, (CH2) q  wherein q is an integer selected from 1 through 2, and (CH 2 ) j —O—(CH 2 ) k  wherein j and k are integers independently selected from 0 through 1;  
      R XV-4 , R XV-8 , R XV-9  and R XV-13  are independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl;  
      R XV-30  is selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl with the proviso that R XV-30  is selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;  
      R XV-30 , when bonded to A XV-1 , is taken together to form an intra-ring linear spacer connecting the A XV-1 -carbon at the point of attachment of R XV-30  to the point of bonding of a group selected from the group consisting of R XV-10  R XV-11 , R XV-12 , R XV-31 , and R XV-32  wherein said intra-ring linear spacer is selected from the group consisting of a covalent single bond and a spacer moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 10 contiguous members, a cycloalkenyl having from 5 through 10 contiguous members, and a heterocyclyl having from 5 through 10 contiguous members;  
      R XV-30 , when bonded to A XV-1,  is taken together to form an intra-ring branched spacer connecting the A XV-1 -carbon at the point of attachment of R XV-30  to the points of bonding of each member of any one of substituent pairs selected from the group consisting of subsitituent pairs R XV-10  and R XV-11 , R XV-10  and R XV-31 , R XV-10  and R XV-32 , R XV-10  and R XV-12 , R XV-11  and R XV-31 , R XV-11  and R XV-32 , R XV-11  and R XV-12 , R XV-31  and R XV-32 , R XV-31  and R XV-12 , and R XV-32  and R XV-12  and wherein said intra-ring branched spacer is selected to form two rings selected from the group consisting of cycloalkyl having from 3 through 10 contiguous members, cycloalkenyl having from 5 through 10 contiguous members, and heterocyclyl having from 5 through 10 contiguous members;  
      R XV-4 , R XV-5 , R XV-6 , R XV-7 , R XV-8 , R XV-9 , R XV-10 , R XV-11 , R XV-12 , R XV-13 , R XV-31 , R XV-32 , R XV-33 , R XV-34 , R XV-35 , and R XV-36  are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, alkylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the provisos that R XV-4 , R XV-5 , R XV-6 , R XV-7 , R XV-8 , R XV-9 , R XV-10 , R XV-11 , R XV-12 , R XV-13 , R XV-31 , R XV-32 , R XV-33 , R XV-34 , R XV-35 , and R XV-36  are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen, that no more than three of the R XV-33  and R XV-34 substituents are simultaneously selected from other than the group consisting of hydrido and halo, and that no more than three of the R XV-35  and R XV-36  substituents are simultaneously selected from other than the group consisting of hydrido and halo;  
      R XV-9 , R XV-10 , R XV-11 , R XV-12 , R XV-13 , R XV-31 , and R XV-32  are independently selected to be oxo with the provisos that B XV-1 , B XV-2 , D XV-3 , D XV-4 , J XV-3 , J XV-4 , and K XV-2  are independently selected from the group consisting of C and S, no more than two of R XV-9 . R XV-10 , R XV-11 , R XV-12 , R XV-13 , R XV-31 , and R XV-32  are simultaneously oxo, and that R XV-9 , R XV-10 , R XV-11 , R XV-12 , R XV-13 , R XV-31 , and R XV-32  are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;  
      R XV-4  and R XV-5 , R XV-5  and R XV-6 , R XV-6  and R XV-7 , R XV-7  and R XV-8 , R XV-9  and R XV-10 , R XV-10  and R XV-11 , R XV-11  and R XV-31 , R XV-31  and R XV-32 , R XV-32  and R XV-12 , and R XV-12  and R XV-13  are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R XV-4  and R XV-5 , R XV-5  and R XV-6 , R XV-6  and R XV-7 , R XV-7  and R XV-8  is used at the same time and that no more than one of the group consisting of spacer pairs R XV-9  and R XV-10 , R XV-10  and R XV-11 , R XV-hd 11  and R XV-31 , R XV-31  and R XV-32 , R XV-32  and R XV-12 , and R XV-12  and R XV-13  are used at the same time;  
      R XV-9  and R XV-11 , R XV-9  and R XV-12 , R XV-9  and R XV-13 , R XV-9  and R XV-31 , R XV-9  and R XV-32 , R XV-10  and R XV-12 , R XV-10  and R XV-13 , R XV-10  and R XV-31 , R XV-10  and R XV-32 , R XV-11  and R XV-12 , R XV-11  and R XV-13 , R XV-11  and R XV-32 , R XV-12  and R XV-31 , R XV-13  and R XV-31 , and R XV-13  and R XV-32  are independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 3 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, a saturated heterocyclyl having from 5 through 8 contiguous members and a partially saturated heterocyclyl having from 5 through 8 contiguous members with the provisos that no more than one of said group of spacer pairs is used at the same time;  
      R XV-37  and R XV-38  are independently selected from the group consisting of hydrido, alkoxy, alkoxyalkyl, hydroxy, amino, thio, halo, haloalkyl, alkylamino, alkylthio, alkylthioalkyl, cyano, alkyl, alkenyl, haloalkoxy, and haloalkoxyalkyl.  
      Compounds of Formula XV are disclosed in WO 00/18723, the entire disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula XV: 
      3-[[3-(4-chloro-3-ethylphenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][(3-trifiuoromethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexylmethyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl]](3-pentafluoroethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl](cyclohexylmethyl]amino]-1,1,1-trifiuoro-2-propanol:     3-[[3-(3-isopropylphenoxy)phenyl](cyclopentylmethyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-isopropylphenoxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl](cyclopropylmethy)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][(3-pentafluoroethyl) cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][(3-trifluoromethoxy) cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(2,3-dichlorophenoxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phennyl](cyclopropylmethyl)amino]-1,1,1-triflouro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][(3-trifluoromethyl)cyclohexyi-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(4-fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy]phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy)phenyl](cyclopropylmethyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy]phenyl][(3-trifluoromethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethoxybenzyloxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)-cyclohexylmethyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl](cyclohexylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl](cyclopentylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl](cyclopropylmethyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl][(3-trifluoromethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl][(3-pentafluoroethyl)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl][(3-trifluoromethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[3-(3-trifluoromethylbenzyloxy)phenyl][3-(1,1,2,2-tetrafluoroethoxy)cyclohexyl-methyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](cyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](4-methylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl]phenyl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-cyclohexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl]phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifloromethyl)phenyl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-isopropoxycyclohexyl)-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl](3-cyclopentyloxycyclohexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl]phenyl]methyl](3-cyclopentyloxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl](3-cyclopentyloxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3-cyclopentyloxycyclohexyl)-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-isopropoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-cyclopentyloxycyclohexyl)-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-phenoxycyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-trifluoromethylcyclohexyl)amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl][3-(4-chloro-3-ethylphenoxy)cyclo-hexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl][3-(1,1,2,2-tetrafluoroethoxy)cyclo-hexyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pyrid-6-yl]methyl](3-pentafluoroethylcyclohexyl)-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(2-trifluoromethyl)pydd-6-yl]methyl](3-trifluoromethoxycyclohexyl)-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl][3-(4chloro-3-ethylphenoxy)propyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)propyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)propyl]-amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-propyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2,-difluropropyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2-difluropropyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2 ,2,-difluropropyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(4-chloro-3-ethylphenoxy)-2,2,-difluropropyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethyl)phenyl]methyl][3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-pentafluoroethyl)phenyl]methyl][3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[(3-trifluoromethoxy)phenyl]methyl][3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol;     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl])3-(isopropoxy)propyl]amino]-1,1,1-trifluoro-2-propanol; and     3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-(phenoxy)propyl]amino]-1,1,1-trifluoro-2-propanol.    

      Another class of CETP inhibitors that finds utility with the present invention consists of (R)-chiral halogenated 1-substituted amino-(n+1)-alkanols having the Formula XVI  
                 
 
 and pharmaceutically acceptable forms thereof, wherein: 
 
      n XVI  is an integer selected from 1 through 4;  
      X XVI  is oxy;  
      R XVI-1  is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxymethyl, and haloalkenyloxymethyl with the proviso that R XVI-1  has a higher Cahn-lngold-Prelog stereochemical system ranking than both R XVI-2  and (CHR XVI-3 ) n —N(A XVI )Q XVI  wherein A XVI  is Formula XVI-(II) and Q is Formula XVI-(III);  
                 
 
      R XVI-16  is selected from the group consisting of hydrido, alkyl, acyl, aroyl, heteroaroyl, trialkylsilyl, and a spacer selected from the group consisting of a covalent single bond and a linear spacer moiety having a chain length of 1 to 4 atoms linked to the point of bonding of any aromatic substituent selected from the group consisting of R XVI-4 , R XVI-8 , R XVI-9 , and R XVI-13  to form a heterocyclyl ring having from 5 through 10 contiguous members;  
      D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  are independently selected from the group consisting of C, N. O, S and covalent bond with the provisos that no more than one of D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  is a covalent bond, no more than one D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  is be O, no more than one of D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  is S, one of D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  must be a covalent bond when two of D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  are O and S, and no more than four of D XVI-1 , D XVI-2 , J XVI-1 , J XVI-2  and K XVI-1  is N;  
      D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  are independently selected from the group consisting of C, N. O, S and covalent bond with the provisos that no more than one is a covalent bond, no more than one of D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  is O, no more than one of D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  is S, no more than two of D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  is 0 and S, one of D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  must be a covalent bond when two of D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  are O and S, and no more than four of D XVI-3 , D XVI-4 , J XVI-3 , J XVI-4  and K XVI-2  are N;  
      R XVI-2  is selected from the group consisting of hydrido, aryl, aralkyl, alkyl, alkenyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, halocycloalkyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, dicyanoalkyl, and carboalkoxycyanoalkyl, with the proviso that R XVI-2  has a lower Cahn-lngold-Prelog system ranking than both R XVI-1  and (CHR XVI-3 ) n —N(A XVi )Q XVI ;  
      R XVI-3  is selected from the group consisting of hydrido, hydroxy, cyano, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, heteroaryl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl, with the provisos that (CHR XVI-3 ) n —N(A XVI )Q XVI  has a lower Cahn-lngold-Prelog stereochemical system ranking than R XVI-1  and a higher Cahn-lngold-Prelog stereochemical system ranking than R XVI-2 ;  
      Y XVI  is selected from a group consisting of a covalent single bond, (C(R XVI-14 ) 2 ) q  wherein q is an integer selected from 1 and 2 and (CH(R XVI-14 )) g —W XVI —(CH(R XVI-14 )) p  wherein g and p are integers independently selected from 0 and 1;  
      R XVI-14  is selected from the group consisting of hydrido, hydroxy, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;  
      Z XVI  is selected from a group consisting of a covalent single bond, (C(R XVI-15 ) 2 ) q , wherein q is an integer selected from 1 and 2, and (CH(R XVI-15 )) j —W XVI —(CH(R XVI-15 )) k  wherein j and k are integers independently selected from 0 and 1;  
      W XVI  is selected from the group consisting of O, C(O), C(S),C(O)N(R XVI-14 ), C(S)N(R XVI-14 ), (R XVI-14 )NC(O), (R XVI-14  )NC(S), S, S(O), S(O) 2 , S(O) 2 N(R XVI-14 ), (R XVI-14 )NS(O) 2 , and N(R XVI-14 ) with the proviso that R XVI-14  is other than cyano;  
      R XVI-15  is selected, from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;  
      R XVI-4 , R XVI-5 , R XVI-6 , R XVI-7 , R XVI-8 , R XVI-9 , R XVI-10 , R XVI-11 , R XVI-12 , and R XVI-13  are independently selected from the group consisting of hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroaralkyl, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl, amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the proviso that R XVI-4 , R XVI-5 , R XVI-6 , R XVI-7 , R XVI-8 , R XVI-9 , R XVI-10 , R XVI-11 , R XVI-12 , and R XVI-13  are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;  
      R XVI-4  and R XVI-5 , R XVI-5  and R XVI-6 , R XVI-6  and R XVI-7 , R XVI-7  and R XVI-8 , R XVI-9  and R XVI-10 , R XVI-10  and R XVI-11 , R XVI-11  and R XVI-12 , and R XVI-12  and R XVI-13  are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R XVI-4  and R XVI-5 , R XVI-5  and R XVI-4 , R XVI-6  and R XVI-7 , and R XVI-7  and R XVI-8  is used at the same time and that no more than one of the group consisting of spacer pairs R XVI-9  and R XVI-10 , R XVI-10  and R XVI-11 , R XVI-   11  and R XVI-12 , and R XVI-12  and R XVI-13  can be used at the same time;  
      R XVI-4  and R XVI-9 , R XVI-4  and R XVI-13 , R XVI-8  and R XVI-9 , and R XVI-8  and R XVI-13  is independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear moiety wherein said linear moiety forms a ring selected from the group consisting of a partially saturated heterocyclyl ring having from 5 through 8 contiguous members and a heteroaryl ring having from 5 through 6 contiguous members with the proviso that no more than one of the group consisting of spacer pairs R XVI-4  and R XVI-9 , R XVI-4  and R XVI-13 , R XVI-8  and R XVI-9 , and R XVI-8  and R XVI-13  is used at the same time.  
      Compounds of Formula XVI are disclosed in WO 00/18724, the entire disclosure of which is incorporated by reference.  
      In a preferred embodiment, the CETP inhibitor is selected from the following compounds of Formula XVI: 
      (2R)-3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-isopropylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-cyclopropylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-(2-furyl)phenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-methylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2RY3-[[3-(3,5-dimethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-t-butylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol:     (2R)-3-[[3-(3-methylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(phenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(1,1,2,2,-tetrafluoroethoxy)phenyl]methyl][3-[[3-(trifluoromethoxy)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3-(trifluoro-methyl)phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3,5-dimethylphenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3-(trifluoromethylthio)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[[3,5-difluorophenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl][3-[cyclohexylmethoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanoi;     (2R)-3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-difluoromethoxyphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(3-trifuoromethylthio)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-isopropylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-cyclopropylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-(2-furyl)phenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-fluorophenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyi]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-methylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][ [3-(pentafluoroethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3,5-dimethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-t-butylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)- 3 -[[3-(3-methylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(phenoxy)phenyl][[3(pentafluoroethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3-(trifluoromethoxy)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3-(trifiuoromethyl)-phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3,5-dimethylphenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3-(trifluoromethylthio)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[[3,5-difluorophenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(pentafluoroethyl)phenyl]methyl][3-[cyclohexylmethoxy]phenyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-difluoromethoxyphenoxy)phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[3-(pentafluoroethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[3-(pentafluoroethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-isopropylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-cyclopropylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-(2-furyl)phenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2,3-dichlorophenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-fluorophenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-methylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][ [3-(heptafluoropropyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3,5-dimethylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-ethylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-t-butylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-methylphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(phenoxy)phenyl][[3-(heptafluoropropyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3-(trifluoromethoxy)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3-(trifluoromethyl)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3,5-dimethylphenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3-(trifluoromethylthio)phenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[[3,5-difluorophenyl]methoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(heptafluoropropyl)phenyl]methyl][3-[cyclohexylmethoxy]phenyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-difluoromethoxyphenoxy)phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[3-(heptafluoropropyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[3-(heptafluoropropyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-isopropylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-cyclopropylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-(2-furyl)phenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2,3-dichlorophenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-fluorophenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-3-propanol;     (2R)-3-[[3-(4-methylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[2-fluoro-5-(trifluoro-methyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3,5-dimethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-ethylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-t-butylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-methylphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(phenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(N,N-dimethylamino,phenoxy]phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethoxy)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-3-propanol;     (2R)-3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethyl)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol; po 9  (2R)-3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3,5-dimethylphenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethylthio)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[[3,5-difluorophenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-5-(trifluoromethyl)phenyl]methyl][3-[cyclohexylmethoxyl-phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-difluoromethoxy-4-pyridyloxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-trifluoromethyl-4-pyridyloxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-difluoromethoxyphenoxy)phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[2-fluoro-5-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[2-fluoro-5-(trifluoro-methyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-trifluoromethoxyphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-isopropylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]1-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-cyclopropylphenoxy)phenyl][[2-flouro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-(2-furyl)phenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2,3-dichlorophenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-fluorophenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-methylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-fluoro-5-bromophenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(1,1,2,2-tetrafluoroethoxy)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(pentafluoroethyl)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3,5-dimethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]-methyl]aminol-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-ethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-t-butylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-methylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(5,6,7,8-tetrahydro-2-naphthoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(phenoxy)phenyl][[2-fluoro-4(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-[3-(N,N-dimethylamino)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethoxy)phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (3R)-3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3,5-dimethylphenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3-(trifluoromethylthio)-phenyl]methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[[3,5-difluorophenyl]-methoxy]phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[2-fluoro-4-(trifluoromethyl)phenyl]methyl][3-[cyclohexylmethoxy]-phenyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-difluoromethoxy-4pyridyloxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(2-trifluoromethyl-4-pyridyfoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[3-(3-difluoromethoxyphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol;     (2R)-3-[[[3-(3-trifluoromethylthio)phenoxy]phenyl][[2-fluoro-4-(trifluoromethyl)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol; and     (2R)-3-[[3-(4-chloro-3-trifluoromethylphenoxy)phenyl][[2-fluoro-4-(trifluoromethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol.    

      Another class of CETP inhibitors that finds utility with the present invention consists of quinolines of Formula XVII  
                 
 
 and pharmaceutically acceptable forms thereof, wherein: 
 
      A XVII  denotes an aryl containing 6 to 10 carbon atoms, which is optionally substituted with up to five identical or different substituents in the form of a halogen, nitro, hydroxyl, trifluoromethyl, trifluoromethoxy or a straight-chain or branched alkyl, acyl, hydroxyalkyl or alkoxy containing up to 7 carbon atoms each, or in the form of a group according to the formula —NR XVII-4 R XVII-5 , wherein  
      R XVII-4  and R XVII-5  are identical or different and denote a hydrogen, phenyl or a straight-chain or branched alkyl containing up to 6 carbon atoms,  
      D XVII  denotes an aryl containing 6 to 10 carbon atoms, which is optionally substituted with a phenyl, nitro, halogen, trifluoromethyl or trifluoromethoxy, or a radical according to the formula  
                 
 
 wherein 
 
      R XVII-6 , R XVII-7 , R XVII-10  denote, independently from one another, a cycloalkyl containing 3 to 6 carbon atoms, or an aryl containing 6 to 10 carbon atom or a 5- to 7-membered, optionally benzo-condensed, saturated or unsaturated, mono-, bi- or tricyclic heterocycle containing up to 4 heteroatoms from the series of S, N and/or O, wherein the rings are optionally substituted, in the case of the nitrogen-containing rings also via the N function, with up to five identical or different substituents in the form of a halogen, trifluoromethyl, nitro, hydroxyl, cyano, carboxyl, trifluoromethoxy, a straight-chain or branched acyl, alkyl, alkylthio, alkylalkoxy, alkoxy or alkoxycarbonyl containing up to 6 carbon atoms each, an aryl or trifluoromethyl-substituted aryl containing 6 to 10 carbon atoms each, or an optionally benzo-condensed, aromatic 5- to 7-membered heterocycle containing up to 3 heteoatoms from the series of S, N and/or O, and/or in the form of a group according to the formula —OR XVII-11 , —SR XVII-12 , —SO 2 R XVII-13 , or —NR XVII-14 R XVII-15 ;  
      R XVII-11 , R XVII-12 , and R XVII-13  denote, independently from one another, an aryl containing 6 to 10 carbon atoms, which is in turn substituted with up to two identical or different substituents in the form of a phenyl, halogen or a straight-chain or branched alkyl containing up to 6 carbon atoms,  
      R XVII-14  and R XVII-15  are identical or different and have the meaning of R XVII-14  and R XVII-5  given above, or  
      R XVII-6  and/or R XVII-7  denote a radical according to the formula  
                 
 
      R XVII-8  denotes a hydrogen or halogen, and  
      R XVII-9  denotes a hydrogen, halogen, azido, trifluoromethyl, hydroxyl, trifluoromethoxy, a straight-chain or branched alkoxy or alkyl containing up to 6 carbon atoms each, or a radical according to the formula NR XVI-16 R XVII-17 ;  
      R XVII-16  and R XVII-17  are identical or different and have the meaning of R XVII-4  and R XVII-5  above; or  
      R XVII-8  and R XVII-9  together form a radical according to the formula ═O or ═NR XVII-18 ;  
      R XVII-18  denotes a hydrogen or a straight-chain or branched alkyl, alkoxy or acyl containing up to 6 carbon atoms each;  
      L XVII  denotes a straight-chain or branched alkylene or alkenylene chain containing up to 8 carbon atoms each, which are optionally substituted with up to two hydroxyl groups;  
      T XVII  and X XVII  are identical or different and denote a straight-chain or branched alkylene chain containing up to 8 carbon atoms; or  
      T XVII  and X XVII  denotes a bond;  
      V XVII  denotes an oxygen or sulfur atom or —NR XVII-19 ;  
      R XVII-19  denotes a hydrogen or a straight-chain or branched alkyl containing up to 6 carbon atoms or a phenyl;  
      E XVII  denotes a cycloalkyl containing 3 to 8 carbon atoms, or a straight-chain or branched alkyl containing up to 8 carbon atoms, which is optionally substituted with a cycloalkyl containing 3 to 8 carbon atoms or a hydroxyl, or a phenyl, which is optionally substituted with a halogen or trifluoromethyl;  
      R XVII-1  and R XVII-2  are identical or different and denote a cycloalkyl containing 3 to 8 carbon atoms, hydrogen, nitro, halogen, trifluoromethyl, trifluoromethoxy, carboxy, hydroxy, cyano, a straight-chain or branched acyl, alkoxycarbonyl or alkoxy with up to 6 carbon atoms, or NR XVII-20 R XVII-21 ;  
      R XVII- 20 and R XVII-21  are identical or different and denote hydrogen, phenyl, or a straight-chain or branched alkyl with up to 6 carbon atoms; and or  
      R XVII-1  and/or R XVII-2 are straight-chain or branched alkyl with up to 6 carbon atoms, optionally substituted with halogen, trifluoromethoxy, hydroxy, or a straight-chain or branched alkoxy with up to 4 carbon atoms, aryl containing 6-10 carbon atoms optionally substituted with up to five of the same or different substituents selected from halogen, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, nitro, straight-chain or branched alkyl, acyl, hydroxyalkyl, alkoxy with up to 7 carbon atoms and NR XVII-22 R XVII-23 ;  
      R XVII-22  and R XVII-23  are identical or different and denote hydrogen, phenyl or a straight-chain or branched akyl up to 6 carbon atoms; and/or  
      R XVII-1  and R XVII-2  taken together form a straight-chain or branched alkene or alkane with up to 6 carbon atoms optionally substituted with halogen, trifluoromethyl, hydroxy or straight-chain or branched alkoxy with up to 5 carbon atoms;  
      Rx XVII-3  denotes hydrogen, a straight-chain or branched acyl with up to 20 carbon atoms, a benzoyl optionally substituted with halogen, trifluoromethyl, nitro or trifluoromethoxy, a straight-chained or branched fluoroacyl with up to 8 carbon atoms and 7 fluoro atoms, a cycloalkyl with 3 to 7 carbon atoms, a straight chained or branched alkyl with up to 8 carbon atoms optionally substituted with hydroxyl, a straight-chained or branched alkoxy with up to 6 carbon atoms optionally substituted with phenyl which may in turn be substituted with halogen, nitro, trifluoromethyl, trifluoromethoxy, or phenyl or a tetrazol substitued phenyl, and/or an alkyl that is optionally substituted with a group according to the formula —OR XVII-24 ;  
      R XVII-24  is a straight-chained or branched acyl with up to 4 carbon atoms or benzyl.  
      Compounds of Formula XVII are disclosed in WO 98/39299, the entire disclosure is incorporated by reference.  
      Another class of CETP inhibitors that finds utility with the present invention consists of 4-Phenyltetrahydroquinolines of Formula XVIII  
                 
 
 N oxides thereof, and pharmaceutically acceptable forms thereof, wherein: 
 
      A XVIII  denotes a phenyl optionally substituted with up to two identical or different substituents in the form of halogen, trifluoromethyl or a straight-chain or branched alkyl or alkoxy containing up to three carbon atoms;  
      D XVIII  denotes the formula  
                 
 
      R XVIII-5  and R XVIII-6  are taken together to form ═O; or  
      R XVIII-5  denotes hydrogen and R XVIII-6  denotes halogen or hydrogen; or  
      R XVIII-5  and R XVIII-6  denote hydrogen;  
      R XVIII-7  and R XVIII-8  are identical or different and denote phenyl, naphthyl, benzothiazolyl, quinolinyl, pyrimidyl or pyridyl with up to four identical or different substituents in the form of halogen, trifluoromethyl, nitro, cyano, trifluoromethoxy, —SO 2 —CH 3  or NR XVIII-9 R XVIII-10 ;  
      R XVIII-9  and R XVIII-10  are identical or different and denote hydrogen or a straight-chained or branched alkyl of up to three carbon atoms;  
      E XVIII  denotes a cycloalkyl of from three to six carbon atoms or a straight-chained or branched alkyl of up to eight carbon atoms;  
      R XVIII-1  denotes hydroxy;  
      R XVIII-2  denotes hydrogen or methyl;  
      R XVIII-3  and R XVIII-4  are identical or different and denote straight-chained or branched alkyl of up to three carbon atoms; or  
      R XVIII-3  and R XVIII-4  taken together form an alkenylene made up of between two and four carbon atoms.  
      Compounds of Formula XVIII are disclosed in WO 99/15504, the entire disclosure of which is incorporated by reference.  
      Emulsion pre-concentrates of CETP inhibitors, formulated as described above, are encapsulated in soft gelatin capsules, or are encapsulated in hard gelatin or non-gelatin capsules. If encapsulated in hard gelatin or non-gelatin capsules, it is preferred that the seam between the two capsule shell pieces be sealed, for example with a strip of gelatin, to prevent leakage. Encapsulation in soft-gelatin is well-known and is described in “The Theory and Practice of Industrial Pharmacy”, by L. Lachman, H. Lieberman, and J. Kanig, Lea and Febiger, publisher, 3 rd  Edition, 1986.  
      The invention is further disclosed and described in the following examples, which are illustrative as opposed to limiting. In the examples, “mgA” is an abbreviation for “milligrams of active drug”, the weight being expressed in mg of the non-salt, free acid or base. Other commonly employed and understood abbreviations have been employed: Me, methyl; Cmpd, Compound; In the examples, the following shorthand notation means the corresponding structure listed and/or named below: 
 
 Compound A—[2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, with a Clog P of 7.45 and having the following structure:  
                 
 
 Compound B, Propanethioic acid, 2-methyl-, S-[2-[[[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino]phenyl]ester with a Clog P of 7.15 having the structure:  
                 
 
 Compound C, (S,S)-4′-(4-fluorophenyl)-3′-[fluoro[4-(trifluoromethyl)phenyl]methyl]-5′,8′-dihydro-2′-(1-methylethyl)-spiro[cyclobutane-1,7′(6′H)-quinolin]-5′-ol, with a Clog P of 8.93 and having the following structure:  
                 
 
 Compound D [2R,4S]4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, with a Clog P of 6.52 and the following structure:  
                 
 
 Compound E—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, with a Clog P of 7.76 and having the following structure:  
                 
 
 Compound F—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester, having a Clog P of 7.98 and having the following structure:  
                 
 
 Compound G—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, having a Clog P of 7.58 and having the following structure:  
                 
 
 Compound H—[2S, 4R]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, having a Clog P of 7.58 and having the following structure:  
                 
 
 Compound I—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, having a Clog P of 6,92 and having the following structure:  
                 
 
 Compound J [2S, 4R]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-2,3,4,6,7,8-hexahydro-cyclopenta[g]quinoline-1-carboxylic acid ethyl ester, having a Clog P of 7.05 and having the following structure:  
                 
 
 Compound K—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, having a Clog P of 6.92 and having the following structure:  
                 
 
 Compound L—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, having a Clog P of 6.92 and having the following structure:  
                 
 
 Compound M—[2R, 4S]4-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester, having a Clog P of 6.56 and having the following structure:  
                 
 
 Compound N—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-formyl-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid propyl ester, having a Clog P of 6.33 and having the following structure:  
                 
 
 Compound O—[2R, 4S]4-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, having a Clog P of 5.68 and having the following structure:  
                 
 
 Compound P—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-formyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, having a Clog P of 5.97and having the following structure:  
                 
 
 Compound Q—[2R, 4S]4-[(3,5-Bis-trifluoromethyl-benzyl)-formyl-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, having a Clog P of 5.45 and having the following structure:  
                 
 
     EXAMPLE 1  
      This Example (and Examples 2 through 5) illustrates making a composition according to the invention and using it to make softgel capsules containing it.  
      Capmul® MCM was heated to 55° C. and mixed. To a 2 liter glass beaker was added 277 gm of Miglyol® 812, 510 gm of triacetin, 318 gm of Polysorbate 80, and 442 gm of Capmul® MCM. After stirring for one hour, this solution was added to 161 gm Compound A and the resulting mixture stirred at ambient temperature for 8 hours with scraping of walls as needed. It was then filtered to remove gross particulates. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 1.  
      The above 100 mgA/mL fill was encapsulated into #10 oval and #5 oval softgels to provide fill volumes of 0.6 mL and 0.3 mL respectively. The doses per softgel are therefore 60 mgA and 30 mgA, respectively. The shell was prepared from gelatin, glycerin, and water.  
                           TABLE 1                                   Ingredient   mg/g                                                    Compound A   94           Miglyol ® 812   162           Triacetin   299           Polysorbate 80   186           Capmul ® MCM   259                      
 
     EXAMPLE 2  
      Capmul® MCM was heated to 55° C. and mixed. Cremophor® RH40 was also heated to 65° C. with stirring. Then 539 g of Miglyol 812, 998 g of triacetin, 608 g of Cremophor® RH40, and 860 g of Capmul® MCM were combined and mixed for 20 min. To this mixture was then added 312 gm of Compound D and the resulting mixture stirred at ambient temperature for 3 hours with scraping of walls as needed. It was then filtered to remove gross particulates. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 2.  
      The above 100 mgA/mL fill was encapsulated into #2 and #5 oval softgels to provide fill volumes of 0.1 mL and 0.3 mL, respectively. The doses per softgel were therefore 10 and 30 mgA, respectively. The shell was prepared from gelatin, glycerin, and water.  
                           TABLE 2                                   Ingredient   mg/g                                                    Compound D   94           Miglyol 812   163           Triacetin   301           Cremophor RH40   183           Capmul MCM   259                      
 
     EXAMPLE 3  
      Capmul® MCM was heated to 55° C. and mixed. Alpha-tocopheryl polyethyleneglycol 1000 succinate (TPGS) was also heated to 55° C. with stirring. Then 264 gm of Miglyol® 812, 333 gm of propylene carbonate, 103 gm of TPGS, and 562 gm of Capmul® MCM were combined and mixed for 1 hr. This mixture was then added to 130.4 gm of Compound A and the resulting mixture stirred at ambient temperature for 8 hours with scraping of walls as needed. It was then filtered to remove gross particulates. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 3.  
      The above 100 mgA/mL fill was encapsulated into #11 oblong softgels to provide a fill volume of 0.6 mL. The dose per softgel is therefore 60 mgA. The shell was prepared from gelatin, glycerin, and water.  
                           TABLE 3                                   Ingredient   mg/g                                                    Compound A   94           Miglyol ® 812   164           Propylene carbonate   207           Alpha-tocopheryl   185           polyethyleneglycol 1000           succinate           Capmul ® MCM   350                      
 
     EXAMPLE 4  
      Capmul® MCM was heated to 55° C. and mixed. Then 264 gm of Miglyol® 812, 333 gm of propylene carbonate, 303 gm of Polysorbate 80 and 562 gm of Capmul® MCM were combined and mixed for 1 hr. This mixture was then added to 130.5 gm of Compound A and the resulting mixture stirred at ambient temperature for 8 hours with scraping of walls as needed. It was then filtered to remove gross particulates. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 4.  
      The above 100 mgA/mL fill was encapsulated into #11 oblong softgels to provide a fill volume of 0.6 mL. The dose per softgel is therefore 60 mgA. The shell was prepared from gelatin, glycerin, and water.  
                           TABLE 4                                   Ingredient   mg/g                                                    Compound A   95           Miglyol ® 812   163           Propylene carbonate   206           Polysorbate 80   188           Capmul ® MCM   348                      
 
     EXAMPLE 5  
      Capmul® MCM was heated to 55° C. and mixed. Then 271 gm of Miglyol® 812, 250 gm of triacetin, 779 gm of Polysorbate 80 and 217 gm of Capmul® MCM were combined and mixed for 20 min. This mixture was then added to 75.7 gm of COMPOUND A and the resulting mixture stirred at ambient temperature for 8 hours with scraping of walls as needed. It was filtered to remove gross particulates. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 5.  
      The above 50 mgA/mL fill was encapsulated into #11 oblong softgels to provide a fill volume of 0.6 mL. The dose per softgel is therefore 30 mgA. The shell was prepared from gelatin, glycerin, and water.  
                           TABLE 5                                   Ingredient   mg/g                                                    Compound A   48           Miglyol ® 812   170           Triacetin   157           Polysorbate 80   489           Capmul ® MCM   136                      
 
     EXAMPLE 6  
      This Example (and Example 7) illustrates the composition of fills according to the invention. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 6. This fill was prepared at a concentration of 50 mgA/mL in a manner similar to that described in Examples 1-5 but at a small volume for dog PK studies. It could be prepared at a larger scale for encapsulation into #11 oblong softgels to provide a fill volume of 0.6 mL and a dose of 30 mgA.  
                           TABLE 6                                   Composition   mg/g                                                    Compound A   48           Miglyol ® 812   143           Triacetin   143           Cremophor ® RH 40   381           Capmul ® MCM   286                      
 
     EXAMPLE 7  
      The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 7. The fill was prepared at a concentration of 150 mgA/mL in a manner similar to that described in Examples 1-5, but at a small volume for dog PK studies. It could be prepared at a larger scale for encapsulation into #11 oblong softgels to provide a fill volume of 0.6 mL and a dose of 90 mgA.  
                                                   Composition   mg/g                                                    Compound A   142           Miglyol ® 812   86           Ethyl lactate   429           Cremophor ® RH 40   257           Capmul ® MCM   86                      
 
     EXAMPLE 8  
      To 80.1 g of Compound A was added 1451 gm Miglyol® 812. The resulting mixture was stirred at ambient temperature for 8 hours with scraping of walls as needed. It was filtered to remove gross particulates. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 8.  
      The above 50 mgA/mL fill was encapsulated into #11 oblong and #4 oval softgels to provide fill volumes of 0.6 mL and 0.2 ml, respectively. The doses per sofgel were therefore 30 and 10 mgA, respectively. The shell was prepared from gelatin, glycerin, and water.  
                           TABLE 8                                   Ingredient   mg/g                                                    Compound A   52           Miglyol ® 812   948                      
 
     EXAMPLE 9  
      This example describes the determination of solubility of CETP inhibitors in excipients and emulsion preconcentrates and also an initial assessment of emulsion quality (Table 9a-9d).  
      The solubility of CETP inhibitors in excipients and in formulations was determined by adding an excess of compound to the medium in question. The mixture was agitated by rotation over a period of days at ambient temperature until the concentration in solution had reached an equilibrium as judged by similar measurements for consecutive time points. Concentrations were measured by filtration of aliquots with a PTFE syringe filter and assay by HPLC as described in Example 11.  
      For CETP inhibitors where quantities were limited, an estimate of solubility was obtained by addition of vehicle to a known quantity of the compound and mixing in an ultrasonicator bath for 90 minutes, followed by overnight equilibration at ambient temperature. Addition of vehicle was repeated until a solution was achieved.  
      The extent of emulsification was determined by mixing the preconcentrate and water in a ratio of 1:100 and 1:10 by gentle inversion (5×), visual inspection, and examination under an optical microscope, using a polarizing filter to check for the appearance of crystals. Droplet size determined by this approach is expressed as the upper limit for the average droplet size, since submicron droplets cannot be detected by this method.  
      The results in Table 9a show that the solubility of Compound A in Miglyol® 812 is only sufficient for a 50 mgA/mL fill (30 mgA in a 0.6 mL softgel), while cosolvents such as triacetin and propylene carbonate provide ca. 4× higher solubility and those such as ethyl lactate and dimethyl isosorbide nearly double those levels. Solubility and emulsification data for preconcentrate solutions of Compound A is shown in Table 9c. Use of propylene carbonate and triacetin as cosolvents allow solubilities suffcient in some cases for a 100 mgA/mL self-emulsifying fill. (e.g., Formulations M, O, Q, and R, see Table 9c)  
      Higher levels of surfactants are often required to yield self-microemulsifying formulations and in these cases solubilities only permit in general a 50 mgA/mL fill using triacetin as the cosolvent (e.g. Formulation EE, Y, and PP). Use of propylene carbonate or ethyl lactate as cosolvent can permit a 1 00mgA/mL fill (e.g., Formulations A, B, XX, YY, and ZZ) that has sufficient surfactant to yield microemulsions. However, triacetin has the advantage of good precedence in oral dosage forms (and has GRAS status). Dynamic light scattering was utilized to further characterize the sub-micron particle size distribution for microemulsions as described in Example 10.  
      The solubility in ethyl lactate permits a self-emulsifying 150 mgA/mL fill to be prepared (e.g Formulation WW). However, the solubilities of emulsion preconcentrates shown in Table 9a and 9c cannot reliably be predicted based on the solubilities of the components alone. This is exemplified by formulation WW (Table 9c), which exhibits considerably greater solubility than the corresponding formulation using dimethyl isosorbide (Formulation AAA), although the opposite would have been predicted based on solubilities in the individual cosolvents. Also, lack of data for excipients that are solids at room temperature also hinders prediction.  
      All of the emulsions prepared from these formulations exhibited good physical stability, i.e. there was no sign of crystallization or change in particle size based on microscopic examination after standing overnight at ambient temperature.  
      Results obtained for other CETP inhibitors are shown in Tables 9b and 9d. In case of Compound D (Table 9b), the average emulsion particle size is &lt;5 microns.  
               TABLE 9a                          Equilibrium Solubility Data for Compound A in Oils, Solvents, and       Surfactants                                         Solubility           Vehicle   HLB   (mgA/ml)                                             Water       &lt;0.00004           Oleic acid       8.5           Maisine 35-1   4   9           Peceol   3   10           Olive oil       17           Plurol Oleique CC 497   6   17           Cremophor ® EL       20           Polysorbate 80 (Tween 80)   15   23           Labrafil ® M 1944   4   26           Labrafil ® M 2125   4   27           Tagat TO (Polyoxyethylene   11   32           glycerol trioleate)           Pluronic ® L-44       36           Capmul ® MCM   6   41           Labrasol ®   14   41           Miglyol ® 812       65           Lauroglycol FCC   4   70           Glycofurol       99           Caprylic acid       145           Transcutol P       174           Propylene carbonate       227           Triacetin       235           Triethyl citrate       240           peppermint oil       266           Ethyl lactate       400           Dimethylisosorbide       439           N-methyl-2-pyrrolidone       813                      
 
     
       
         
           
               
             
               
                 TABLE 9b 
               
             
            
               
                   
               
               
                   
               
               
                 Equilibrium Solubility Data for Other CETP inhibitors 
               
            
           
           
               
               
            
               
                   
                 Solubility (mgA/ml) 
               
            
           
           
               
               
               
            
               
                 Vehicle 
                 Compound D 
                 Compound E 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Olive oil 
                 13 
                 39 
               
               
                 Olive oil/Cremophor ® EL 80/20 
                 14 
               
               
                 Cremophor ® EL 
                 18 
               
               
                 Miglyol ® 812/Cremophor ® EL 
                 51 
               
               
                 80/20 
               
               
                 Capmul ® MCM 
                 58 
               
               
                 Miglyol ® 812 
                 61 
                 167 
               
               
                 Miglyol ®/propylene 
                 208 
                 394 
               
               
                 carbonate/Cremophor ® EL 
               
               
                 (60/20/20) 
               
               
                 Triacetin 
                 239 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9c 
               
             
            
               
                   
               
               
                   
               
               
                 Solubility and emulsification data for Compound A in preconcentrates* 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Ave Droplet 
               
               
                   
                   
                   
                 Size (μ) 
               
               
                 Formul. 
                 Composition (% v/v) 
                 Solubility 
                 (1:100 
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 Miglyol ® 812 
                 Cosolvent* 
                 Surfactants 
                 (mgA/mL) 
                 dilution) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                 Vitamin E TPGS/ 
                   
                   
               
               
                   
                   
                   
                 Capmul ® MCM 
               
               
                 A 
                 20 
                 20 P.C. 
                 20/40 
                 145 
                 &lt;1 
               
               
                 H 
                 20 
                 20 triacetin 
                 20/40 
                 113 
                 &lt;2 
               
               
                 I 
                 20 
                 30 P.C. 
                 20/30 
                 189 
                 &lt;2 
               
               
                 S 
                 10 
                 30 triacetin 
                 20/40 
                 131 
                 &lt;5 
               
               
                   
                   
                   
                 Polysorbate 80/ 
               
               
                   
                   
                   
                 Capmul ® MCM 
               
               
                 B 
                 20 
                 20 P.C. 
                 20/40 
                 142 
                 &lt;5 
               
               
                 O 
                 20 
                 30 triacetin 
                 20/30 
                 141 
                 &lt;2 
               
               
                 EE 
                 20 
                 15 triacetin 
                 50/15 
                 64 
                 &lt;1 
               
               
                   
                   
                   
                 Vitamin E TPGS/ 
               
               
                   
                   
                   
                 Labrafil ® M 1944 
               
               
                   
                   
                   
                 CS 
               
               
                 C 
                 20 
                 20 P.C. 
                 20/40 
                 114 
                 &lt;1 
               
               
                 Q 
                 10 
                 40 triacetin 
                 20/30 
                 142 
                 &lt;2 
               
               
                   
                   
                   
                 Gelucire ® 44/14/ 
               
               
                   
                   
                   
                 Capmul ® MCM 
               
               
                 D 
                 20 
                 20 P.C. 
                 20/40 
                 151 
                 &lt;5 
               
               
                   
                   
                   
                 Cremophor ® RH40/ 
               
               
                   
                   
                   
                 Capmul ® MCM 
               
               
                 E 
                 20 
                 20 P.C. 
                 20/40 
                 147 
                 &lt;1 
               
               
                 M 
                 20 
                 30 triacetin 
                 20/30 
                 145 
                 &lt;1 
               
               
                 R 
                 20 
                 30 triacetin 
                 35/15 
                 122 
                 &lt;1 
               
               
                 SS 
                 0 
                 28 triacetin 
                 30/42 
                 108 
                 &lt;1 
               
               
                 PP 
                 17 
                 13 triacetin 
                 39/31 
                 77 
                 &lt;1 
               
               
                 Y 
                 20 
                 10 triacetin 
                 50/20 
                 67 
                 &lt;1 
               
               
                 WW 
                 11 
                 50 
                 29/10 
                 203 
                 &lt;2 
               
               
                   
                   
                 ethyl lactate 
               
               
                 XX 
                 11 
                 40 
                 29/20 
                 159 
                 &lt;1 
               
               
                   
                   
                 ethyl lactate 
               
               
                 YY 
                 16 
                 35 
                 39/10 
                 142 
                 &lt;1 
               
               
                   
                   
                 ethyl lactate 
               
               
                 ZZ 
                 22 
                 29 
                 19/30 
                 145 
                 &lt;1 
               
               
                   
                   
                 ethyl lactate 
               
               
                 AAA 
                 11 
                 47 
                 31/11 
                 157 
                 &lt;1 
               
               
                   
                   
                 dimethyl 
               
               
                   
                   
                 isosorbide 
               
               
                   
               
               
                   *P.C. = propylene carbonate    
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9d 
               
             
            
               
                   
               
               
                   
               
               
                 Solubility and emulsification data for other CETP Inhibitor preconcentrates 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Ave Droplet 
               
               
                   
                   
                   
                 Size (μ) 
               
               
                   
                 Composition (% v/v) 
                 Solubility 
                 (1:100 
               
            
           
           
               
               
               
               
               
               
            
               
                 Compound 
                 Miglyol ® 812 
                 Triacetin 
                 Surfactants 
                 (mgA/mL) 
                 dilution) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                 Polysorbate 80/ 
                   
                   
               
               
                   
                   
                   
                 Capmul ® MCM 
               
               
                 Compound B* 
                 20 
                 30 
                 20/30 
                 ≧100 
                 &lt;5 
               
               
                 Compound C* 
                 6 
                 55 
                 15/24 
                 ≧30 
                 &lt;5 
               
               
                 Compound E 
                 22 
                 27 
                 20/31 
                 308 
                 &lt;2 
               
               
                   
                   
                   
                 Cremophor ® 
               
               
                   
                   
                   
                 RH40/ 
               
               
                   
                   
                   
                 Capmul ® MCM 
               
               
                 Compound D 
                 20 
                 30 
                 20/30 
                 172 
                 &lt;5 
               
               
                   
               
               
                   *Amorphous solids    
               
            
           
         
       
     
     EXAMPLE 10  
      Preliminary particle size analysis data has been obtained on selected formulations using a dynamic light scattering particle size analyzer (ZetaPals, Brookhaven Instruments, Inc.) for measurement of sub-micron particle distribution. The formulation solutions were diluted 1:100 in HPLC-grade water (previously filtered through a 0.22 μm syringe filter). The resulting mixture was gently inverted five times to create the emulsion. Each emulsion sample was then analyzed at a temperature of 37° C. Triplicate measurements were made at each time point (0, 30 min).  
      The results shown in Table 10 confirm that formulations O, Q and R are self-emulsifying formulations with a mean particle size above 100 nm. Formulations such as A and B have mean particle sizes in the microemulsion range but with significant populations of larger particles and are slightly turbid. Formulation EE is very slightly turbid with a trace of larger particles. Use of Cremophor® RH 40 as the high HLB surfactant yielded formulations Y, PP, XX, and ZZ that form transparent microemulsions with all particles smaller than ca. 100 nm, as is the case for Neoral®. Only formulation Y showed a stable unimodal distribution that did not change, even with stirring.  
               TABLE 10a                          Dynamic Light Scattering Particle Size Analysis of Emulsions from       Compound A Self-Emulsifying Formulations*                                 Pre-concentrate   Mean Diam.   Distribution #                                       Form.   Composition (% v/v)   (nm)   Peak 1   Peak 2   Peak 3                                             A   Miglyol ® 812/propylene   78.6   22    73   349           carbonate/Vitamin E-           TPGS/Capmul ® MCM           (20/20/20/40)       B   Miglyol ® 812/propylene   45.3   33   217           carbonate/Polysorbate 80/Capmul ®           MCM (20/20/20/40)       C   Miglyol ® 812/   21.6   17    38   (197)           propylene carbonate/Vitamin E-           TPGS/Labrafil M ® 1944 CS           (20/20/20/40)       O   Miglyol ® 812/Triacetin/   256.6   257           Polysorbate 80/Capmul ® MCM           (20/30/20/30)       Q   Miglyol ® 812Triacetin/   440.9   259   537           Vitamin E-TPGS/           Labrafil M ® 1944 CS           (10/40/20/30)       R   Miglyol ® 812/Triacetin/   245.2   245           Cremophor ® RH40/           Capmul MCM           (20/30/35/15)       X   Neoral ®/propylene carbonate   19.0   11    29           (90:10)       Y   Miglyol ® 812/Triacetin/   22.3   22           Cremophor ® RH40/           Capmul ® MCM           (20/10/50/20)       EE   Miglyol ® 812/Triacetin/   19.6   13    64   (220)           Polysorbate 80/Capmul ® MCM           (20/15/50/15)       PP   Miglyol ® 812/Triacetin/   27.1   27           Cremophor ® RH40/           Capmul ® MCM           (17/13/39/31)       SS   Triacetin/Cremophor ® RH40/   32.4   26   (116)           Capmul ® MCM (28/30/42)       WW   Miglyol ® 812/Ethyl lactate/   293.8   324           Cremophor ® RH40/           Capmul ® MCM           (11/50/29/10)       XX   Miglyol ® 812/Ethyl lactate/   24.9   22   (107)           Cremophor ® RH40/           Capmul ® MCM           (11/40/29/20)       YY   Miglyol ® 812/Ethyl lactate/   31.5   28   (135)           Cremophor ® RH40/           Capmul ® MCM           (16/35/39/10)       ZZ   Miglyol ® 812/Ethyl lactate/   36.3   34   (103)           Cremophor ® RH40/           Capmul ® MCM           (22/29/19/30)           Neoral ®   27.4   27    (65)                   # Parentheses indicate trace levels.            *Measured immediately after preparation unless indicated otherwise             
 
     
       
         
           
               
             
               
                 TABLE 10b 
               
             
            
               
                   
               
               
                   
               
               
                 Dynamic Light Scattering Particle Size Analysis of 
               
               
                 Emulsions prepared for Other Compounds 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Pre-Concentrate 
                 Mean Diam. 
               
               
                   
                 Conc. 
                 Composition 
                 (nm)# 
               
            
           
           
               
               
               
               
               
            
               
                 Cmpd. 
                 (mg/mL) 
                 (% v/v) 
                 Initial* 
                 30 min.* 
               
               
                   
               
               
                 D 
                 100 
                 Miglyol ® 812/Triacetin/ 
                 — 
                 182 ± 17 
               
               
                   
                   
                 Cremophor ® RH40/ 
                   
                  (3) 
               
               
                   
                   
                 Capmul ® MCM 
               
               
                   
                   
                 (20/30/20/30) 
               
               
                 E 
                 100 
                 Miglyol ® 812/Triacetin/ 
                 181 
                 175 
               
               
                   
                   
                 Polysorbate 80/Capmul ® 
               
               
                   
                   
                 MCM (22/27/20/31) 
               
               
                 E 
                 200 
                 Miglyol ® 812/Triacetin/ 
                 239 ± 17 
                 251 ± 45 
               
               
                   
                   
                 Polysorbate 80/Capmul ® 
                  (4) 
                  (4) 
               
               
                   
                   
                 MCM (22/27/20/31) 
               
               
                   
               
               
                   #Number of samples in parentheses    
               
               
                   *Time after preparation of emulsion    
               
            
           
         
       
     
     EXAMPLE 11  
      The fills prepared in the above examples were hand-filled into hydrophobic softgel shells and heat sealed, and then placed on stability under accelerated conditions in sealed HPDE bottles with child-resistant caps. The fills were assayed at intervals by dilution of aliquots into acetonitrile and gradient HPLC analysis on a Water Symmetry C-8 column (3.9×150 mm, 5 micron) at 30° C. at a flow rate of 1 mL/min. The mobile phase program was a 25 minute gradient from 100% A to 50% A/50% B (A=400/300/300/0.8 v/v DI H 2 O/Acetonitrile/2-Propanol/Phosphoric Acid and B=2-Propanol), followed by a 5 minute hold at this condition and a 10 minute gradient to the initial condition. The detection method was UV absorbance at 210 nm.  
      There was no impurity formed at ≧0.1% peak area vs. parent for any formulation in Table 11. There was no sign of crystallization in the fill under any condition based on microscopic examination. There was also no indication of seal leakage.  
      Disintegration times in water at 37° C. were less than 15 min for Formulations A, B, and O after storage under accelerated conditions for 6 weeks.  
      Formulation O softgels of Compound A manufactured by machine have been shown to be stable for 9 months under accelerated conditions. Formulation M softgels of Compound D have been shown to be stable for 6 months under accelerated conditions.  
               TABLE 11                          Accelerated Stability data for selected formulations of Compound A in hand-filled soft gels                         Assay of Fill       Test   Assay of Fill Potency                                         Formulation #   A   B   C   E   M   O               Initial   100.6 ± 0.6    99.4 ± 0.7   101.3 ± 0.8   102.0 ± 0.1   101.6 ± 0.2   102.6 ± 0.6       1 Week        5° C./75% RH   101.8 ± 0.8    99.5 ± 2.3    99.1 ± 0.4   101.5 ± 0.4       30° C./60% RH   100.8 ± 0.6    98.8 ± 0.6   100.5 ± 0.7   101.1 ± 0.1       40° C./75% RH   101.4 ± 0.5    98.6 ± 1.4    99.7 ± 0.5   102.6 ± 0.1       3 Week OR   *   *       4 Week        5° C./75% RH    99.9 ± 0.4    99.0 ± 0.3    99.3 ± 1.0   100.5 ± 0.6   100.6 ± 0.5   101.1 ± 0.6       30° C./60% RH   100.7 ± 0.8    98.4 ± 0.7   100.0 ± 0.6    99.9 ± 0.5   100.3 ± 0.6   101.4 ± 1.3       40° C./75% RH   101.3 ± 0.3   100.7 ± 1.0   101.8 ± 0.5   102.3 ± 0.4   102.9 ± 0.6   101.7 ± 0.2       6 Week        5° C./75% RH   100.7 ± 0.8   100.7 ± 0.1    98.4 ± 0.3   100.0 ± 0.3   101.2 ± 0.5   101.9 ± 0.2       30° C./60% RH   100.4 ± 0.8   100.5 ± 0.4   101.1 ± 0.6   101.1 ± 0.2   101.6 ± 0.6   101.9 ± 0.8       40° C./75% RH   102.4 ± 0.7   102.1 ± 1.0   102.5 ± 0.4   102.7 ± 0.7   101.6 ± 0.5   101.9 ± 0.9                 *4 Week time point.             
 
     EXAMPLE 12  
      Fills were prepared as described in above examples and then encapsulated in #00 hard gelatin capsules. Male Beagle dogs (n=6) between the ages of 2-5 and weighing 6-12 kg were dosed with capsules followed by 50 mL of water. Dogs were also dosed with 30 mgA Miglyol® 812 softgels and aqueous, crystalline drug suspension. The dogs were either fasted or fed just prior to dosing with 14 g of dry dog food and 8 gm olive oil. The same set of dogs were used for all formulations, except where indicated. Blood samples were obtained from the jugular vein of each dog at 0, 0.5, 1,2, 3,4, 6, 8 and 12 hr and analyzed by acidifying the plasma, solid phase extraction, and analysis by LC/MS/MS with a lower limit of quantitation of 25 ng/mL.  
      The results, in Table 12a and 12b are shown in terms of Area Under the Curve (AUC), Cmax, the maximum concentration of drug measured in the plasma, and Tmax, the time in hours it took to reach Cmax. Unless otherwise indicated, results are for the fasted state. Miglyol® softgels have a very low fasted exposure and thus a high food effect. The fasted exposure is higher than that for crystalline suspension, while the fed exposure using this high oil meal is the same. Thus Miglyol softgels provide a lower food effect than crystalline drug. At the same dose of 90 mgA, formulations such as A, O, and C that include surfactants and cosolvent have much higher fasted exposures and only a ca. 3× food effect. The fed exposures are also higher than for Miglyol® 812 softgels and crystalline drug. Poorer fasted exposure was obtained for Formulation WW, which contains a high level of ethyl lactate as a cosolvent.  
      The transparent self-microemulsifying formulations EE and PP at a dose of mgA have a food effect of only 2.2-2.4. For the stable, monodisperse microemulsion Y there is a much higher fasted exposure at 30 mgA than for the self-emulsifying formulation O. The fasted exposure for Y was the same as the fed, i.e. there was no food effect.  
      Similar results were obtained for formulation M for Compound D (Table 12b) as were observed for the same formulation of Compound A.  
               TABLE 12a                          Pharmacokinetic results of Compound A Formulations in dogs                                                 Formulation       Conc.                           Composition       (mg/   Dose   AUC 0-12 h   Cmax   Tmax       #   (v/v)   n*   mL)   (mg)   (μg * h/mL)   (μg/mL)   (hr)                                                         Miglyol ® 812 soft gels   4   50   90   3.0 ± 2.0   0.77 ± 0.48   2.0           Fed               6   50   90   0.6 ± 0.3    0.2 ± 0.14   3.7           Crystalline drug   6 #     —   90   0.16 ± 0.14   0.04 ± 0.11   1.3           suspension in           0.1% Polysorbate 80/           0.5% methyl cellulose           Fed   6   —   90   2.9 ± 1.3   0.98 ± 0.53   2.7       A   Miglyol ® 812/Propylene   6   100   90   2.7 ± 0.9   0.67 ± 0.17   1.2           carbonate/Vitamin E-           TPGS/Capmul ® MCM           (20/20/20/40)           Fed   5   100   90   9.6 ± 3.4   2.49 ± 1.30   1.4       B   Miglyol ® 812/Propylene   6   100   90   2.3 ± 0.5   0.73 ± 0.16   1.8           carbonate/Polysorbate           80/Capmul  ®MCM           (20/20/20/40)       C   Miglyol ® 812/propylene   5   80   90   3.4 ± 1.3    1.2 ± 0.41   1.2           carbonate/           Vitamin E-TPGS/           Labrafil ® M 1944           (20/20/20/40)           Fed   6   80   90   9.3 ± 3.5   4.31 ± 1.89   1.0       I   Miglyol ® 812/Propylene   6   125   90   1.6 ± 0.5   0.61 ± 0.27   0.9           carbonate/Vitamin E-           TPGS/Capmul ® MCM           (20/30/20/30)       J   Miglyol ® 812/Propylene   6   125   90   2.0 ± 0.8   0.71 ± 0.36   1.7           carbonate/Vitamin E-           TPGS (20/40/40)       M   Miglyol ® 812/Triacetin/   5   100   90   2.6 ± 1.2   0.73 ± 0.26   1.2           Cremophor  ®RH40/           Capmul  ®MCM           (20/30/20/30)       O   Miglyol ® 812/Triacetin/   6   100   90   2.7 ± 0.7   0.97 ± 0.36   1.2           Polysorbate 80/Capmul ®           MCM (20/30/20/30)           Fed   4   100   90   8.5 ± 3.6   2.7 ± 1.0   1.5               6   100   30   1.1 ± 0.5   0.37 ± 0.22   1.0       Q   Miglyol ® 812/Triacetin/   5**   100   90   2.9 ± 0.8   1.1 ± 0.2   1.0           Vitamin E-TPGS/           Labrafil ® M 1944           (10/40/20/30)       R   Miglyol ® 812/Triacetin/   6   100   90   2.8 ± 1.2   1.0 ± 0.4   1.0           Cremophor ® RH40/           Capmul ® MCM           (20/30/35/15)               6   50   90   4.0 ± 1.3   1.1 ± 0.4   1.5       X   Neoral ®/propylene   3   50   90   2.4 ± 1.9   0.67 ± 0.23   1.3           carbonate           (90:10)       Y   Miglyol ® 812/Triacetin/   6   50   90   4.6 ± 1.4   1.35 ± 0.26   1.7           Cremophor ® RH40/           Capmul ® MCM           (20/10/50/20)               4**   50   30   4.6 ± 2.0   1.32 ± 0.60   2.0           Fed   5   50   30   4.7 ± 1.1   1.94 ± 0.74   1.0       EE   Miglyol ® 812/Triacetin/   6   50   90   2.7 ± 1.5   0.86 ± 0.31   1.3           Polysorbate 80/           Capmul ® MCM           (20/15/50/15)           Fed   5   50   30   1.7 ± 0.3   0.64 ± 0.21   1.0               6   50   30   3.8 ± 1.2   1.6 ± 0.6   1.0       PP   Miglyol ® 812/Triacetin/   5   50   30   1.6 ± 0.6   0.61 ± 0.18   1.2           Cremophor ® RH40/           Capmul ® MCM           (17/13/39/31)           Fed   5   50   30   3.8 ± 0.8   1.55 ± 0.38   1.4       SS   Triacetin/Cremophor ®   6   75   90   1.9 ± 1.7   0.44 ± 0.26   1.3           RH40/Capmul ® MCM           (28/30/42)           Fed   4   75   90   7.3 ± 1.3   1.8 ± 0.5   1.5       WW   Miglyol ® 812/Ethyl   5   150   90   1.5 ± 0.7   0.54 ± 0.17   0.9           lactate/Cremophor           ® RH40/Capmul ® MCM           (11/50/29/10)                 *n &lt; 6 due to emesis.            **Due to emesis and outlier            #Different set of dogs             
 
     
       
         
           
               
             
               
                 TABLE 12b 
               
             
            
               
                   
               
               
                   
               
               
                 Pharmacokinetic results for Other Compounds in dogs 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Formulation 
                   
                 Conc. 
                 Dose 
                 AUG 0-tlast #   
                 Cmax 
                 Tmax 
               
               
                 Cmpd 
                 Composition 
                 n 
                 (mg/mL) 
                 (mg) 
                 (μg*h/mL) 
                 (μg/mL) 
                 (hr) 
               
               
                   
               
               
                 D* 
                 Miglyol ® 812/ 
                 3* 
                 100 
                 90 
                 3.45 ± 0.96 
                 0.86 ± 0.31 
                 1.7 
               
               
                   
                 Triacetin/ 
               
               
                   
                 Cremophor ® RH40/ 
               
               
                   
                 Capmul ® MCM 
               
               
                   
                 (20/30/20/30) 
               
               
                   
                 Fed 
                 4* 
                 100 
                 90 
                 4.84 ± 1.23 
                 1.20 ± 0.41 
                 1.5 
               
               
                 E 
                 Miglyol ® 
                 4** 
                 100 
                 60 
                 2.90 ± 0.67 
                 0.20 ± 0.14 
                 1.5 
               
               
                   
                 812/Triacetin/ 
               
               
                   
                 Polysorbate 
               
               
                   
                 80/Capmul ® MCM 
               
               
                   
                 (22/27/20/31) 
               
               
                   
               
               
                   *Emesis in 1 fasted dog (data not included) and in 4 fed dogs (included); dosed with 50 mL water.    
               
               
                   **Emesis in 3 dogs (included), dosed with 10 mL water. Different set of dogs from those receiving Compound D.    
               
               
                     # Tlast = 24 hr for Compound D and 48 hr for Compound E.    
               
            
           
         
       
     
     EXAMPLE 13  
      This example further illustrates the determination of equilibrium solubilities of CETP inhibitors in vehicles. For experimental methods, see Example 9.  
      The solubility of crystalline CETP inhibitors in representative vehicles was determined by adding an excess of compound to the vehicle in question. The mixture was agitated by rotation over a period of days at ambient temperature until the concentration in solution had reached equilibrium as judged by similar measurements for consecutive time points. Concentrations were measured by filtration of aliquots with a PTFE syringe filter and assayed by HPLC.  
      The concentrations of CETP inhibitor in each vehicle were assayed at intervals by dilution of aliquots into acetonitrile and gradient HPLC analysis on a Water Symmetry C-8 column (3.9×150 mm, 5 micron) at 30° C. at a flow rate of 1 mL/min. The mobile phase program was a 25 minute gradient from 100% A to 50% A/50% B (A =400/300/300/0.8 v/v DI H 2 O/Acetonitrile/2-Propanol/Phosphoric Acid and B=2-Propanol), followed by a 5 minute hold at this condition and a 10 minute gradient to the initial condition. The detection method was UV absorbance at 210 nm.  
      The results of the equilibrium solubility studies are given in Tables 13a-13c.  
               TABLE 13a                          Equilibrium Solubilities of Compound A in Triglyceride/surfactant(s)                                 Solubility               (mgA/ml)           Vehicle   Cmpd A                       Miglyol ® 812/Capmul ® MCM (80/20)   74           Miglyol ® 812/Capmul ® MCM/Polysorbate 80   58           (40/40/20)           Miglyol ® 812/Capmul ® MCM/Polysorbate 80   63           (20/60/20)           Miglyol ® 812/Tagat ® TO (80/20)   58           Miglyol ® 812/Labrafil ® M 1944 (80/20)   59           Miglyol ® 812/Labrafil ® M 2125 (80/20)   57           Miglyol ® 812/Labrasol ® (80/20)   69           Miglyol ® 812/Cremophor ® EL 80/20   68           Olive oil/Capmul ® MCM (80/20)   23                      
 
     
       
         
           
               
             
               
                 TABLE 13b 
               
             
            
               
                   
               
               
                   
               
               
                 Equilibrium Solubility of Compound A in Triglyceride/solvent 
               
            
           
           
               
               
               
            
               
                   
                   
                 Solubility 
               
               
                   
                 Vehicle 
                 (mgA/ml) 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 Miglyol ® 812/triacetin (90/10)* 
                 106 
               
               
                   
                 Miglyol ® 812/Peppermint oil (90/10) 
                 79 
               
               
                   
                 Miglyol ® 812/Peppermint oil (80/20) 
                 93 
               
               
                   
                 Olive oil/Peppermint oil (90/10) 
                 25 
               
               
                   
                   
               
               
                   
                   *Not completely miscible    
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13c 
               
             
            
               
                   
               
               
                   
               
               
                 Equilibrium Solubility of Compound A in Miglyol/Solvent/surfactant 
               
            
           
           
               
               
            
               
                   
                 Solubility 
               
               
                 Vehicle 
                 (mgA/ml) 
               
               
                   
               
            
           
           
               
               
            
               
                 Miglyol ® 812/Propylene carbonate/Cremophor ® EL 
                   
               
               
                 72/8/20 
                 108 
               
               
                 60/20/20 
                 146 
               
               
                 55/25/20 
                 158 
               
               
                 40/40/20 
                 209 
               
               
                 30/50/20 
                 228 
               
               
                 Miglyol ® 812/Ethyl lactate/Cremophor ® EL 
               
               
                 72/8/20 
                 94 
               
               
                 70/10/20 
                 99 
               
               
                 65/15/20 
                 120 
               
               
                 60/20/20 
                 143 
               
               
                 50/30/20 
                 196 
               
               
                 40/40/20 
                 221 
               
               
                 30/50/20 
                 256 
               
               
                 Miglyol ® 812/Triacetin/Cremophor ® EL 
               
               
                 72/8/20 
                 94 
               
               
                 65/15/20 
                 111 
               
               
                 60/20/20 
                 133 
               
               
                 50/30/20 
                 158 
               
               
                 40/40/20 
                 183 
               
               
                 30/50/20 
                 198 
               
               
                 Miglyol ® 812/Peppermint Oil/Cremophor ® EL (72/8/20) 
                 72 
               
               
                 Miglyol ® 812/EtOH/Cremophor ® EL (76/4/20) 
                 89 
               
               
                 Miglyol ® 812/Ethyl lactate/Tagat ® TO (72/8/20) 
                 87 
               
               
                 Miglyol ® 812/Ethyl lactate/Labrasol ® (72/8/20) 
                 98 
               
               
                 Miglyol ® 812/Propylene carbonate/Tagat ® TO (72/8/20) 
                 111 
               
               
                 Miglyo ® 812/Propylene carbonate/Labrasol ® (72/8/20) 
                 116 
               
               
                   
               
            
           
         
       
     
     EXAMPLE 14  
      For CETP inhibitors where quantities were limited or the samples were amorphous solids, an estimate of solubility was obtained by addition of vehicle to a known quantity of the compound and mixing in an ultrasonicator bath for 90 minutes, followed by overnight equilibration at ambient temperature. Addition of vehicle was repeated until a solution was achieved. From the total volume of vehicle added to solubilize the CETP inhibitor compound, the solubility value, or so-called microsolubility, was calculated by the equation:
 
Weight of sample (mgA)/vehicle volume (mL)=Microsolubility (mgA/mL)
 
      The microsolubility values for CETP inhibitors in various vehicles are given in Tables 14a-14c.  
               TABLE 14a                          Microsolubility Data for Crystalline Compounds                             Solubility               (mg/mL)                                 Solvent   Cmpd A   Cmpd B                                             Crodamol ® GTCC   &lt;75   &lt;20           Miglyol ® 810   &lt;100           Long chain triglycerides   &lt;75   &lt;100           (soy, peanut, corn, safflower, sesame)           Cotton oil   &lt;75           Olive oil       &lt;100           Capmul ® MCM       &lt;100           PEG 400       &lt;100           Crodamol ® GTCC/Capmul ® MCM/       &lt;100           Polysorbate 80 (40/40/20)           Linoleic acid   &lt;60           Incromega ® TG2671   &lt;75           propylene glycol   &lt;75           Glycerin   &lt;75           mineral oil   &lt;75                      
 
     
       
         
           
               
             
               
                 TABLE 14b 
               
             
            
               
                   
               
               
                   
               
               
                 Microsolubilities of amorphous compounds (mg/mL) 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Cmpd F 
                 Cmpd G 
                 Cmpd H 
                 Cmpd I 
                 Cmpd J 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Miglyol ® 812 
                 &lt;100 
                   
                   
                   
                   
               
               
                 Crodamol ® GTCC 
                   
                   
                 &gt;300 
                 &gt;20 
                 &gt;100 
               
               
                 Corn, Safflower, 
                   
                   
                 &gt;300 
                 &lt;20 
                 &gt;100 
               
               
                 Soybean oils 
               
               
                 Peanut oil 
                   
                   
                   
                 &lt;20 
                 &gt;100 
               
               
                 Olive oil 
                 303 
                 &gt;300 
                 &gt;300 
                 &lt;20 
                 &gt;100 
               
               
                 Sesame oil 
                   
                 &gt;300 
                   
                 &lt;20 
                 &gt;100 
               
               
                 Cremophor ® EL 
                   
                 &gt;300 
                 &lt;160 
               
               
                 Capmul ® MCM 
                   
                   
                 &gt;300 
                 &gt;20 
                 &gt;100 
               
               
                 PEG 400 
                   
                   
                 &lt;160 
                 &lt;20 
                 50-100 
               
               
                 Corn 
                   
                   
                   
                 &gt;20 
               
               
                 oil/Polysorbate 80 
               
               
                 (80/20) 
               
               
                 Corn oil/Labrafil 
                   
                   
                   
                 &lt;20 
               
               
                 (80/20) 
               
               
                 Crodamol ® 
                   
                 &gt;300 
                   
                 &gt;20 
                 &gt;100 
               
               
                 GTCC/Capmul ® 
               
               
                 MCM/Polysorbate 
               
               
                 80 (40/40/20) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14c 
               
             
            
               
                   
               
               
                   
               
               
                 Microsolubilities of amorphous compounds (mg/mL) 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Olive oil 
                 Safflower oil 
                 Miglyol ® 812 
                 Capmul ® MCM 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                 Cmpd L 
                 &lt;300 
                 &gt;300 
                 &gt;300 
                 &gt;300 
               
               
                 Cmpd M 
                 &lt;300 
                 &lt;300 
                 &gt;300 
                 &gt;300 
               
               
                 Cmpd A 
                 &gt;300 
                 &gt;300 
                 &gt;300 
                 &gt;300 
               
               
                 Cmpd N 
                 &gt;300 
                 &gt;300 
                 &gt;300 
                 &gt;300 
               
               
                 Cmpd O 
                 &lt;300 
                 &lt;300 
                 &gt;300 
                 &gt;300 
               
               
                 Cmpd P 
                 &gt;300 
                 &lt;300 
                 &gt;300 
                 &gt;300 
               
               
                 Cmpd Q 
                 &lt;300 
                 &lt;300 
                 &gt;300 
                 &gt;300 
               
               
                   
               
            
           
         
       
     
     EXAMPLE 15  
      To 1.41 mL of Miglyol® 812, 0.471 mL of propylene carbonate and 0.471 mL of Cremophor® EL was added 900 mg of Compound E. The resulting mixture was stirred at ambient temperature for 20 minutes with scraping of the container walls as needed. It was then probe sonicated for 30 seconds with occasional mixing to completely dissolve the drug, and then stirred for 20 minutes at ambient temperature. The amounts (in mg) of each component in the oil solution per gram of solution are set forth in Table 15.  
                           TABLE 15                                   Ingredient   mg/g                          Compound E   275           Miglyol ® 812   406           Propylene carbonate   166           Cremophor ® EL   153                      
 
 An emulsion was prepared by combining 1 volume of oil solution with an equal volume of de-ionized water. This mixture was stirred for 10 minutes and then vortex mixed for 1 minute to yield an emulsion with an average particle size less than 10 microns. The emulsion is then stirred continuously to maintain homogeneity. No chemical degradation based on HPLC analysis or crystallization based on microscopic examination was detected in the oil or emulsion after storage for 24 hr. 
 
     EXAMPLE 16  
      Capmul® MCM was heated to 55° C. and mixed. Cremophor® RH40 was also heated to 65° C. with stirring. Then 2.70 g of triacetin, 2.71 g of Cremophor® RH40, and 3.60 g of Capmul® MCM were combined and mixed for 20 min. To this mixture was then added 1.01 gm of Compound A and the resulting mixture stirred at ambient temperature for 3 hours with scraping of walls as needed. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 16a.  
                           TABLE 16a                                   Ingredient   mg/g                          Cmpd A   100           Triacetin   270           Cremophor ® RH40   270           Capmul ® MCM   360                      
 
     EXAMPLE 17  
      To 495 mg of Miglyol® 812, 203 mg of propylene carbonate and 187 mg of Cremophor® EL was added 115 mg of Compound A. The resulting mixture was stirred at ambient temperature for 20 minutes with scraping of the container walls as needed. It was then probe sonicated for 3 minutes with occasional mixing to completely dissolve the drug, and then stirred for 20 minutes at ambient temperature. The amounts (in mg) of each component in the oil solution per gram of solution are set forth in Table 17a.  
                           TABLE 17a                                   Ingredient   mg/g                          Cmpd A   115           Miglyol ® 812   495           Propylene carbonate   203           Cremophor ® EL   187                      
 
 An emulsion was prepared by combining 1 volume of oil solution with an equal volume of de-ionized water. This mixture was stirred for 10 minutes and then vortex mixed for 2 minutes. The emulsion had an average particle size of less than 10 microns. It was stirred continuously to maintain homogeneity. No chemical degradation based on HPLC analysis or crystallization based on microscopic examination was detected in the oil after storage for 8 days or the emulsion after storage for 24 hr. 
 
     EXAMPLE 18  
      To 764 mg of olive oil and 223 mg of Cremophor® EL was added 13 mg of Compound A. The resulting mixture was stirred at ambient temperature for 20 minutes with scraping of container walls as needed. It was then probe sonicated for 3 minutes with occasional mixing to completely dissolve the drug. The solution was then stirred for 20 minutes at ambient temperature. The amounts (in mg) of each component in the oil solution per gram of solution are set forth in Table 18a.  
                           TABLE 18a                                   Ingredient   mg/g                                                    Compound A   13           Olive oil   764           Cremophor ® EL   223                      
 
 An emulsion was prepared by combining combining 1 volume of oil solution with an equal volume of de-ionized water. This mixture was stirred for 10 minutes and then vortex mixed for 2 minutes. The emulsion had an average particle size of less than 10 microns. It was stirred continuously to maintain homogeneity. No chemical degradation based on HPLC analysis or crystallization based on microscopic examination was detected in the oil after storage for 8 days or the emulsion after storage for 24 hr. 
 
     EXAMPLE 19  
      To 485 mg of Miglyol® 812, 199 mg of propylene carbonate and 183 mg of Cremophor® EL was added 133 mg of Compound D. The resulting mixture was stirred at ambient temperature for 20 minutes with scraping of container walls as needed. It was then probe sonicated for 3 minutes with occasional mixing to completely dissolve the drug. The solution was stirred for further stirred for 20 minutes at ambient temperature. The amounts (in mg) of each component in the oil solution per gram of solution are set forth in Table 19A.  
                           TABLE 19A                                   Ingredient   mg/g                          Cmpd D   133           Miglyol ® 812   485           Propylene carbonate   199           Cremophor ® EL   183                      
 
 An emulsion was prepared by combining combining 1 volume of oil solution with an equal volume of de-ionized water. This mixture was stirred for 10 minutes and then vortex mixed for 2 minutes. The emulsion had an average particle size of less than 10 microns. It was stirred continuously to maintain homogeneity. No chemical degradation based on HPLC analysis or crystallization based on microscopic examination was detected in the oil after storage for 8 days or the emulsion after storage for 24 hr. 
 
     EXAMPLE 20  
      Chemical and physical stability for the formulation of Example 8 was determined for 30 mgA Miglyol® (#11 oblong) softgels stored in white HPDE bottles (child-resistant closures). After storage at 40OC/75% RH for 6 months there was no change in potency and no degradation was detected (peak area &lt;0.05% relative to parent) as determined by HPLC analysis of the entire softgel. The appearance (color, shape, seal integrity) was unchanged, and disintegration occurred within 15 minutes in water (USP&lt;701&gt;). Softgels stored at 5° C. and 25° C./60% RH were stable for 18 months.  
     EXAMPLE 21  
      Either oils or preformed emulsions of Compound A were administered to Sprague Dawley rats by oral gavage and the results are shown in Table 21a. Emulsions were prepared as indicated in Examples 17-19. Emulsions prepared from olive oil/surfactant provided the best results. The solubility and thus the accessible dose could be increased by using cosolvents (e.g. caprylic acid and/or triacetin) or using a triglyceride with improved solubility (Miglyol® 812), but this did not provide any improvement in exposure over much lower doses in olive oil/Cremophor® EL. Administration of pre-formed emulsions gave superior results to the oil, especially at higher dose volumes where mixing of phases in vivo may be less efficient.  
      In contrast to the results in rats, emulsions in Miglyol® 812/Cremophor® EL yielded far superior results to olive oil/Cremophor® EL in cynomologous monkeys (Table 21 b), and much better results than for Miglyol® alone. Use of an emulsion prepared from crystalline (ethanolate) drug allowed comparible exposures to be achieved to those for more soluble amorphous drug in Miglyol® alone. Excellent dose proportionality was also obtained.  
      The need for the presence of a high concentration of the long chain triglyceride olive oil for efficient absorption in the rat, but not the monkey, suggests that the lymphatic pathway plays a more important role for absorption of this drug in rats. An important role for lymphatic absorption for Compound A is consistent with its very high lipophilicity.  
               TABLE 21a                          PK results in rat for Compound A                                                                 AUC                   Conc. in   Vol.       (0-Tlast)       Drug       Dose   oil   of oil   Cmax   (μg-       Form   Vehicle   (mg/kg)   (mg/mL)   (mg/kg)   (μg/mL)   hr/mL)                                                 Ethanol.   Olive oil/Cremophor ®/   100   20   5   6.2    33*           water 40/10/50       Ethanol.   Miglyol ®/Cremophor ®/   500   100   5   4.6    18*           water           40/10/50       Ethanol.   Olive oil/caprylic acid/   375   75   5   4.1    21*           Cremophor ®/water           10/30/10/50       Ethanol.   Olive oil/caprylic   625   125   5   4.8    26*           acid/triacetin/           Cremophor ®/water           10/15/15/10/50       Ethanol.   Olive oil/Cremophor ®   100   20   5   3.6   45           80/20       Ethanol.   Miglyol ®/Cremophor ®/   100   100   1   1.9   23           water 40/10/50       Ethanol.   Miglyol ®/Cremophor ®/   100   100   1   1.6   15           0.5% HPMCAS           40/10/50       Ethanol.   Miglyol ®   500   100   5   2.1   27       Amorph.   Olive oil   300   60   5   7.3   50                 *Tlast = 9 hr. Otherwise, Tlast = 24 hr.            Amorph. = amorphous anhydrous            Ethanol. = crystalline ethanolate            HPMCAS = Hydroxpyropyl methyl cellulose acetate succinate             
 
     
       
         
           
               
             
               
                 TABLE 21b 
               
             
            
               
                   
               
               
                   
               
               
                 PK results in monkeys for Compound A 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                   
                 Conc. 
                 Vol. 
                   
                   
               
               
                   
                   
                 Dose 
                 in oil 
                 of oil 
                 Cmax 
                 AUC 
               
               
                 Form* 
                 Vehicle 
                 (mg/kg) 
                 (mg/mL) 
                 (mg/kg) 
                 (μg/mL) 
                 (μg-hr/mL) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Ethanol. 
                 Miglyol ®/Cremophor ®/ 
                 100 
                 100 
                 1 
                 1.6-2.3 
                 24-29 
               
               
                   
                 water 40/10/50 
                 (BID) 
               
               
                 Ethanol. 
                 Miglyol ®/Cremophor ®/ 
                  50 
                 50 
                 1 
                 0.8-1.1 
                 13-15 
               
               
                   
                 water 
                 (BID) 
               
               
                   
                 40/10/50 
               
               
                 Ethanol. 
                 Miglyol ®/Cremophor ®/ 
                 100 
                 100 
                 1 
                 0.4-1.8 
               
               
                   
                 water 40/10/50 
               
               
                 Ethanol. 
                 Olive oil/Cremophor ®/ 
                  20 
                 20 
                 1 
                 0.1, 0.16 
                 N.D. 
               
               
                   
                 water 40/10/50 
               
               
                 Ethanol. 
                 Miglyol ® 
                 100 
                 100 
                 1 
                 ca. 0.17 
                 N.D. 
               
               
                 Amorph. 
                 Miglyol ® 
                 100 
                 100 
                 1 
                 ca. 1.6 
                 ca. 29 
               
               
                   
               
               
                   *Amorph. = amorphous anhydrous    
               
               
                   Ethanol. = crystalline ethanolate    
               
            
           
         
       
     
     EXAMPLE 22  
      A. 100 mgA/mL Fill  
      Capmul® MCM was heated to 55° C. and mixed. Then 48.5 gm of Miglyol® 812, 72.8 gm of triacetin, 48.5 gm of Polysorbate 80, and 72.8 gm of Capmul® MCM were combined. To this mixture was then added 25.0 gm Compound E and the resulting mixture stirred at ambient temperature for 10 minutes with scraping of walls as needed. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 22. The fill could be prepared on a larger scale for encapsulation into #10 oval softgels to provide a fill volume of 0.6 mL and a dose per softgel of 60 mgA.  
      B. 200 mgA/mL Fill  
      Capmul® MCM was heated to 55° C. and mixed. Then 650 mg of Miglyol® 812, 976 mg of triacetin, 650 mg of Polysorbate 80, and 976 mg of Capmul® MCM were combined and mixed for 10 min. To this mixture was then added 748 mg Compound E and the resulting mixture stirred at ambient temperature for 10 minutes with scraping of wall as needed. The amounts (in mg) of each component in the fill per gram of fill are set forth in Table 22. The fill could be prepared on a larger scale for encapsulation into #10 oval softgels to provide a fill volume of 0.6 mL and a dose per softgel of 120 mgA.  
                           TABLE 22                                      mg/g                                     Ingredient   100 mgA/mL   200 mgA/mL                                             Compound E   94   184           Miglyol ® 812   181   163           Triacetin   272   245           Polysorbate 80   181   163           Capmul ® MCM   272   245