WO2009132136A1 - Carboxamide compounds for the treatment of metabolic disorders - Google Patents

Carboxamide compounds for the treatment of metabolic disorders Download PDF

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Publication number
WO2009132136A1
WO2009132136A1 PCT/US2009/041448 US2009041448W WO2009132136A1 WO 2009132136 A1 WO2009132136 A1 WO 2009132136A1 US 2009041448 W US2009041448 W US 2009041448W WO 2009132136 A1 WO2009132136 A1 WO 2009132136A1
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WIPO (PCT)
Prior art keywords
alkyl
substituted
piperidin
haloalkyl
compound according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/US2009/041448
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English (en)
French (fr)
Inventor
Jiaxin Yu
Hui Hong
Ihab S. Darwish
Xiang Xu
Rajinder Singh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rigel Pharmaceuticals Inc
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Rigel Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Priority to JP2011506436A priority Critical patent/JP5658138B2/ja
Priority to CA2722139A priority patent/CA2722139C/en
Priority to EA201071231A priority patent/EA021119B1/ru
Priority to AU2009240643A priority patent/AU2009240643B2/en
Priority to CN200980123855.0A priority patent/CN102099357B/zh
Priority to ES09734272.9T priority patent/ES2552549T3/es
Priority to MX2010011288A priority patent/MX2010011288A/es
Priority to UAA201013901A priority patent/UA103767C2/ru
Priority to HK11107056.3A priority patent/HK1152939B/en
Application filed by Rigel Pharmaceuticals Inc filed Critical Rigel Pharmaceuticals Inc
Priority to KR1020107026058A priority patent/KR101662333B1/ko
Priority to BRPI0911681A priority patent/BRPI0911681B8/pt
Priority to EP09734272.9A priority patent/EP2276761B1/en
Priority to NZ588652A priority patent/NZ588652A/xx
Publication of WO2009132136A1 publication Critical patent/WO2009132136A1/en
Priority to IL208513A priority patent/IL208513A0/en
Priority to ZA2010/07127A priority patent/ZA201007127B/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P3/00—Drugs for disorders of the metabolism
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems

Definitions

  • This disclosure relates generally to compounds, pharmaceutical compositions and methods of use of the compounds and compositions containing them.
  • This disclosure relates more particularly to certain carboxamide compounds and pharmaceutical compositions thereof, and to methods of treating and preventing metabolic disorders such as type II diabetes, atherosclerosis and cardiovascular disease using certain carboxamide compounds.
  • Adiponectin is a protein hormone exclusively expressed in and secreted from adipose tissue and is the most abundant adipose-specific protein. Adiponectin has been implicated in the modulation of glucose and lipid metabolism in insulin-sensitive tissues. Decreased circulating adiponectin levels have been demonstrated in some insulin-resistant states, such as obesity and type 2 diabetes mellitus and also in patients with coronary artery disease, atherosclerosis and hypertension. Adiponectin levels are positively correlated with insulin sensitivity, HDL (high density lipoprotein) levels and insulin stimulated glucose disposal and inversely correlated with adiposity and glucose, insulin and triglyceride levels. Thiazolidinedione drugs, which enhance insulin sensitivity through activation of the peroxisome proliferator-activated receptor- ⁇ , increase endogenous adiponectin production in humans.
  • Adiponectin binds its receptors in liver and skeletal muscle and thereby activates the 5'-AMP-activated protein kinase (AMPK) pathway.
  • Adiponectin receptors 1 and 2 are membrane-bound proteins found in skeletal muscle and liver tissue. Being a multi-substrate enzyme, AMPK regulates a variety of metabolic processes, such as glucose transport, glycolysis and lipid metabolism. It acts as a sensor of cellular energy homeostasis and is activated in response to certain hormones and muscle contraction as well as to intracellular metabolic stress signals such as exercise, ischemia, hypoxia and nutrient deprivation.
  • AMPK switches on catabolic pathways (such as fatty acid oxidation and glycolysis) and switches off ATP-consuming pathways (such as lipogenesis).
  • Adiponectin improves insulin sensitivity by directly stimulating glucose uptake in adipocytes and muscle and by increasing fatty acid oxidation in liver and muscle, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents.
  • adiponectin decreases glycogen concentration by reducing the activity of glycogen synthase.
  • Adiponectin also plays a protective role against inflammation and atherosclerosis. It suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis.
  • compositions include those having at least one pharmaceutically acceptable carrier, diluent or excipient; and a compound, pharmaceutically acceptable salt, prodrug or N-oxide (or solvate or hydrate) as described herein.
  • Another aspect of the present disclosure includes methods for modulating metabolism in subjects. Accordingly, also disclosed are methods for treating metabolic disorders using the presently disclosed compounds and pharmaceutical compositions. DETAILED DESCRIPTION
  • Z is CH, CR 4 or ⁇ , provided that at least one of D and Z is ⁇ , and the bond between D and the carbon at the position denoted by "b" is a single bond or a double bond;
  • J is -O-, - ⁇ (R 38 )-C(O)-, -C(O)- or absent, provided that:
  • R 1 is H, -(Ci-C 4 alkyl), -C(O)-(Ci-C 4 alkyl) or -C(O)O-(Ci-C 4 alkyl), and
  • R 2 is -Hca, -Cak-N(R 9 )-G-R 22 or -(C 2 -C 8 alkyl)-N(R 9 )-R 24 in which one or two (e.g., non- adjacent) carbons of the (C 2 -Cg alkyl) are optionally replaced by -0-, -S- or -N(R 9 )-, and R 24 is -R 23 , -G-R 23 or -C(O)O-(Ci-C 6 alkyl), provided that two consecutive carbons of the (C 2 -Cs alkyl) are not replaced by -0-, or
  • each R 3 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl), -(Co-C 6 alkyl)-Ar, -(C 0 -C 6 alkyl)-Het, -(C 0 -C 6 alkyl)-Cak, -(C 0 -C 6 alkyl)-Hca, -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(0)o- 2 R 10 , -halogen, -NO 2 and -CN; w is O, 1, 2,
  • T is -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl) )--SS((OO)) 00 _. 22 RR 1 1 0 0 or
  • Q is -S(O) 2 -, L, or (C 0 -C 3 alkyl)-, in which each carbon of the -(C 0 -Cs alkyl)- is optionally and independently substituted with one or two R 16 ; the ring denoted by "A" is heteroaryl, aryl, cycloalkyl or heterocycloalkyl; each R 5 is independently selected from -(C 1 -Cg alkyl), -(C 1 -C 6 haloalkyl), -(Co-Ce alkyl)-Ar, -(C 0 -C 6 alkyl)-Het, -(C 0 -C 6 alkyl)-Cak, -(C 0 -C 6 alkyl)-Hca, -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C
  • R 38 is independently selected from -H, -(Ci-C 4 alkyl), -C(O)-(Ci-C 4 alkyl) and -C(O)O-(Ci-C 4 alkyl),
  • R 22 and R 23 are each independently Ar or Het, each Ar is an optionally substituted aryl, each Het is an optionally substituted heteroaryl, each Cak is an optionally substituted cycloalkyl, each Hca is an optionally substituted heterocycloalkyl, and each alkyl is optionally substituted.
  • J is -O- or -N(R 38 )-C(O)- and D is CH or C- substituted with one of the x R 4 groups.
  • J is -C(O)-.
  • D is N.
  • Z is N and D is C, CH or C- substituted with one of the x R 4 groups. In other embodiments, D is N and Z is CH or C- substituted with one of the x R 4 groups. In further embodiments, D is N and Z is N.
  • R 38 is -H. In other embodiments, R 38 is -(C 1 -C 4 alkyl), for example methyl, ethyl or propyl. In other embodiments, R 38 is -C(O)-(Ci-C 4 alkyl), for example acetyl. In other embodiments, R 38 is -C(O)-O-(Ci-C 4 alkyl)-, for example -C(O)-O-?-butyl. In certain embodiments, no alkyl of R 38 is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group .
  • ring system "B” is fused to ring system "C” at the position denoted by “b”; for example, the compounds can have structural formula (III):
  • J is -O-
  • Z is N
  • D is CH or C- substituted by one of the x
  • J is -O-
  • Z is N
  • D is CH or C- substituted by one of the x
  • J is -O-
  • Z is N
  • D is CH or C- substituted by one of the x R 4 .
  • Floating bonds indicate attachment on any carbon of the rmidazo[l,2- ⁇ ]pyridine ring system.
  • the J moiety is on the pyridine ring of the imidazo[l,2- ⁇ ]pyridine ring system
  • the carboxamide (i.e., -C(O)-NR 1 R 2 ) moiety is on the imidazo ring of the imidazo [l,2- ⁇ ]pyridine ring system
  • any R 3 groups can be on either ring of the imidazo [ 1 ,2- ⁇ ]pyridine ring system.
  • J is -O-
  • Z is N
  • D is CH or C- substituted by one of the x
  • ring system “B” is and is not fused to ring system "C”.
  • J is other than O.
  • J is -C(O)-
  • Z is N, CH or C- substituted by one of the x R 4 and D is N.
  • J is -N(R 38 )-C(O)-
  • Z is N and D is CH or C- substituted by one of the x R i 4.
  • the sum of p and q is 2 or 3.
  • the sum of p and q is 2 (e.g., p is 1 and q is 1).
  • ring system "B” is a phenyl and is fused to ring system "C" (i.e., J is absent), Z is N, D is C, q is 2 and p is 1, such that the compound has structural formula (IV):
  • T is
  • Q is -S(O) 2 -, L or -(C0-C3 alkyl)- in which each carbon of the (C0-C3 alkyl) is optionally and independently substituted with one or two R 16 , in which each R 16 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 5 haloalkyl), -(C 0 -C 6 alkyl)-Ar, -(C 0 -C 6 alkyl)-Het, -(C 0 -C 6 alkyl)-Cak, -(C 0 -C 6 alkyl)-Hca, -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -
  • each R 16 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl), and -(C 0 -C 6 alkyl)-S(O) 0 _ 2 -(C 0 -C 6 alkyl), and in which no alkyl or haloalkyl
  • each R 16 is -(Ci-C 3 alkyl), -(C r C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-NR 9 (C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-O-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-C(O)-(C 0 -C 2 alkyl) and -(C 0 -C 2 alkyl)-S(O) 0 .
  • Q has at most one R 16 or oxo substituted thereon.
  • Q can be, for example, an unsubstituted -(C 0 -C 3 alkyl)-.
  • Q is a (Ci-C 3 alkyl) having as its only substitution a single oxo group.
  • Q is -CH 2 -; a single bond; -S(O) 2 -; -C(O)-; or -CH(CH 3 )-.
  • Q is a single bond.
  • the number of substituents on the ring system denoted by "A", y, is 0, 1 , 2, 3 or 4.
  • y is 0, 1, 2 or 3, such as 1.
  • y is not zero and at least one R 5 is halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 or -C(O)-Hca wherein the Hca contains a ring nitrogen atom through which it is bound to the -C(O)-, and wherein no alkyl, haloalkyl or heterocycloalkyl is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.
  • each R 5 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) and -(C 0 -C 6 alkyl)-S(O) 0 - 2 -(C 0 -C 6 alkyl), and in which no alkyl or haloalkyl) (e.g., difluoromethyl, trifluoromethyl
  • each R 5 is -(C 1 -C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN, in which each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-NR
  • y is 0.
  • the ring system denoted by "A” is heteroaryl, aryl, cycloalkyl or heterocycloalkyl.
  • the ring system denoted by "A” is an aryl or a heteroaryl.
  • the ring system denoted by "A” can be, for example, a monocyclic aryl or heteroaryl.
  • Q is a -(C 0 -C 3 alkyl)- optionally substituted with oxo, and optionally substituted with one or more R 16 .
  • Q can be a -(Ci-C 3 alkyl)- having its only substitution a single oxo, or an unsubstituted -(C 0 -C 3 alkyl)-.
  • Q is -CH 2 -; a single bond; -S(O) 2 -; -C(O)-; or -CH(CH 3 )-.
  • the ring system denoted by "A” is a phenyl.
  • y is 1 and R 5 is attached to the phenyl in the para position relative to Q.
  • y is 1 and R 5 is selected from the group consisting of halo, cyano, -(C 1 -C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -O-(C r C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in which the Hca contains a ring nitrogen atom through which it is bound to the -C(O)-, and in which no (C 0 -C 4 alkyl) or (C 1 -C 4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.
  • R 5 can be, for example, -Cl, -F, cyano, -C(O)CH3, -C(O)OH, -C(O)NH 2 , trifluoromethyl, difluoromethyl, difluoromethoxy or trifluoromethoxy.
  • the moiety is a 3,4-dihalophenyl.
  • the ring system denoted by “A” is a heteroaryl.
  • the ring system denoted by “A” is a pyridyl, a thienyl, or a furanyl.
  • Q is a -(C 0 -C 3 alkyl)- optionally substituted with oxo, and optionally substituted with one or more R 16 .
  • Q can be a -(Ci-C 3 alkyl)- having its only substitution a single oxo, or an unsubstituted -(C 0 -C 3 alkyl)-.
  • Q is -CH 2 -; a single bond; -S(O) 2 -; -C(O)-; or -CH(CH 3 )-.
  • J is absent, Z is N, D is carbon, q is 2 and p is 1
  • T is not -C(O)O-(C O -C O alkyl).
  • V structural formula (V):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (VII):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (VIII):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (IX):
  • n 1, 2, 3 or 4, and all other variables are defined as described above with reference to structural formulae (I)-(IV). [0038] In one embodiment of the presently disclosed compounds, the compound has structural formula (X):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (XI):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (XII):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (XIV):
  • n 1, 2, 3 or 4
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • the compound has structural formula (XV):
  • the compound has structural formula (XVI): in which n is 1, 2, 3 or 4, w is 0 or 1, and all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • E 1 is N and E 2 is -CH- or -CR 3 -.
  • E 1 is -CH- or -CR 3 - and E 2 is N.
  • the compound has structural formula (XVI): in which n is 1, 2, 3 or 4, w is 0 or 1, and all other variables are defined as described above with reference to structural formulae (I)-(IV). When w is 0, the ring position shown occupied by R 3 bears a hydrogen atom.
  • the compound has structural formula (XVII):
  • n 1, 2, 3 or 4
  • w is 0 or 1
  • all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • w is 0, the ring position shown occupied by R bears a hydrogen atom.
  • n is 1 or 2.
  • n is 2.
  • n is 1.
  • the compound has structural formula (XVIII):
  • the compound has structural formula (XIX): in which all variables are defined as described above with reference to structural formulae (I)- (IV).
  • the compound has structural formula (XXIII): (XXIII), in which all variables are defined as described above with reference to structural formulae (I)-
  • E 1 is -CH- or -CR 3 - and E 2 is N. In another embodiment, E 1 is N and E 2 is -CH- or -CR 3 -.
  • the compound has structural formula (XXX): in which w is 0 or 1 and all other variables are defined as described above with reference to structural formulae (I)-(IV).
  • w is 0, the ring position shown occupied by R 3 bears a hydrogen atom.
  • the compound has structural formula (XXXI):
  • J is -C(O)-, Z is CH or C substituted with one of the x R 4 and D is N.
  • J is -C(O)-, Z is N and D is N.
  • J is -N(R 38 )-C(O)- (e.g., -NH-C(O)-), Z is N and D is CH or C substituted with one of the x R 4 .
  • J is -C(O)-, Z is CH or C substituted with one of the x R 4 and D is N.
  • J is -C(O)-, Z is N and D is N.
  • J is -N(R 38 )-C(O)- (e.g., -NH-C(O)-), Z is N and D is CH or C substituted with one of the x R 4 .
  • the compound has structural formula (XXXIII): (XXXIII), in which all variables are defined as described above with reference to structural formulae (I)- (IV).
  • J is -C(O)-, Z is CH or C substituted with one of the x R 4 and D is N.
  • J is -C(O)-, Z is N and D is N.
  • J is -N(R 38 )-C(O)- (e.g., -NH-C(O)-), Z is N and D is CH or C substituted with one of the x R 4 .
  • the sum of p and q is 2 or 3.
  • the sum of p and q is 2 (e.g., p is 1 and q is 1).
  • the sum of p and q is 3 (e.g., p is 1 and q is 2).
  • the compound has structural formula (XXXIV):
  • Z is N. In another such embodiment, Z is CH or C substituted with one of the x R 4 .
  • the compound has structural formula (XXXVII):
  • the compound has structural formula (XXXVIII):
  • the compound has structural formula (XL):
  • the compound has structural formula (XLI):
  • the compound has structural formula (XLII): in which all variables are defined as described above with reference to structural formulae (I)-
  • the compound has structural formula (XLIII):
  • R 1 is H, -(Ci-C 4 alkyl), -C(O)-(Ci-C 4 alkyl) or -C(O)O-(Ci-C 4 alkyl)
  • R 2 is -Hca, -Cak-N(R 9 )-G-R 22 or -(C 2 -C 8 alkyl)-N(R 9 )-R 24 in which one or two (for example, non-adjacent) carbons of the (C 2 -Cg alkyl) are optionally replaced by -O-, -S- or -N(R 9 )-
  • R 24 is -R 23 , -G-R 23 or -C(O)O-(Ci-C 6 alkyl), provided that two consecutive carbons of the (C 2 -Cs alkyl) are not replaced by -O-.
  • R 1 is H, -(Ci-C 4 alkyl), -C(O)-(Ci-C 4 alkyl) or -C(O)O-(Ci-C 4 alkyl), and R 2 is -Hca.
  • R 1 is -H.
  • R 1 is (Ci-C 4 alkyl), for example methyl, ethyl, n-propyl or isopropyl.
  • R 2 is -Hca. In certain embodiments, R 2 is an optionally-substituted monocyclic heterocycloalkyl.
  • R 2 is -(optionally-substituted azetidinyl), -(optionally-substituted pyrrolidinyl), -(optionally-substituted piperidinyl) or -(optionally-substituted azepanyl).
  • R 2 can be -(optionally substituted piperidinyl) or -(optionally substituted pyrrolidinyl).
  • R 2 is -(optionally substituted piperidinyl).
  • R 2 is -(optionally substituted pyrrolidinyl).
  • R 2 is -(optionally-substituted azetidin-3-yl), -(optionally substituted piperidin-4-yl), -(optionally substituted pyrrolidin-3-yl) or -(optionally-substituted azepan-4-yl).
  • R 2 is -(optionally substituted piperidin-4-yl).
  • R 2 is -(optionally substituted pyrrolidin-3-yl).
  • the azetidinyl, pyrrolidinyl, piperidinyl and azepanyl R 2 moieties described above are substituted at their 1 -positions.
  • R is substituted at its 1 -position with -(C0-C3 alkyl)-Ar or -(C0-C3 alkyl)-Het, for example -(unsubstituted C0-C3 alkyl)-Ar or -(unsubstituted C0-C3 alkyl)-Het.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1 -position with an optionally substituted benzyl or an optionally substituted phenyl.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R moiety is substituted at its 1 -position with a benzyl substituted with an electron withdrawing group; or with a pyridinylmethyl optionally substituted with an electron withdrawing group.
  • the benzyl or pyridinylmethyl can be substituted with an electron withdrawing group selected from the group consisting of halo, cyano, -(C 1 -C 4 fluoroalkyl), -O-(Ci-C 4 fluoroalkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), -S(O) 2 ⁇ -(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in which the Hca includes a nitrogen atom to which the -C(O)- is bound, in which no alkyl, fluoroalkyl or heterocycloalkyl is substituted with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1 -position with an unsubstituted benzyl or an unsubstituted phenyl.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1-position with an optionally substituted pyridinylmethyl, an optionally substituted furanylmethyl, an optionally substituted thienylmethyl, an optionally substituted oxazolylmethyl, or an optionally substituted imidazolylmethyl.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety can be substituted with an unsubstituted pyridinylmethyl, an unsubstituted furanylmethyl, an unsubstituted thienylmethyl, an unsubstituted oxazolylmethyl, or an unsubstituted imidazolylmethyl.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety can be substituted with an pyridinylmethyl, furanylmethyl, thienylmethyl, oxazolylmethyl or imidazolylmethyl substituted with an electron withdrawing group as described above.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1 -position with -L-Ar or -L-Het, in which Ar and Het can be, for example, as described above with reference to -(C 0 -C 3 alkyl)-Ar or -(C 0 -C 3 alkyl)-Het.
  • L is -C(O)-NR 9 -, such as -C(O)-NH-.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1-position with -C(O)-O(C 0 -C 6 alkyl), -C(O)-Het, -C(O)-Ar, -S(O) 2 -Het, -S(O) 2 -Ar or -S(O) 2 -O(Co-Ce alkyl), in which Ar and Het can be, for example, as described above with reference to -(C0-C3 alkyl)-Ar or -(C0-C3 alkyl)-Het.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1-position with -C(O)-Het or -C(O)-Ar; in another embodiment, it is substituted at its 1-position with -S(O) 2 -Het or -S(O) 2 -Ar.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R moiety is substituted at its 1-position with an optionally- substituted benzoyl (e.g., substituted with an electron withdrawing group as described above); or with an optionally-substituted nicotinyl, isonicotinyl or picolinyl (e.g., optionally substituted with an electron withdrawing group as described above).
  • an optionally- substituted benzoyl e.g., substituted with an electron withdrawing group as described above
  • an optionally-substituted nicotinyl, isonicotinyl or picolinyl e.g., optionally substituted with an electron withdrawing group as described above.
  • the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl R 2 moiety is substituted at its 1-position with an unsubstituted benzoyl; or an unsubstituted nicotinoyl, isonicotinoyl or picolinoyl.
  • R 2 is an optionally-substituted bridged azacycloalkyl or diazacycloalkyl, for example, a bridged azabicyclohexyl, a bridged azabicycloheptyl, a bridged azabicyclooctyl, a bridged diazabicyclohexyl, a bridged diazabicycloheptyl or a bridged diazabicyclooctyl.
  • R 2 moieties include optionally substituted azabicyclo[2.2.2]octyl, optionally substituted azabicyclo[3.2.1]octyl, and optionally substituted 2,5-diazabicyclo[2.2.1]heptyl.
  • R 2 is a bridged azacycloalkyl or diazacycloalkyl, it can be substituted as described above with reference to the azetidinyl, pyrrolidinyl, piperidinyl and azepanyl R 2 moieties.
  • a bridged azacycloalkyl or diazacycloalkyl R 2 moiety can be substituted (e.g., at a nitrogen) with -(C 0 -C 3 alkyl)-Ar, -(C 0 -C 3 alkyl)-Het, -L-Ar, -L-Het, -C(O)-O(C 0 -C 6 alkyl), -C(O)-Het, -C(O)-Ar, -S(0) 2 -Het, -S(O) 2 -Ar or -S(O) 2 -O(C 0 -C 6 alkyl), as described above.
  • R 2 is -Cak-N(R 9 )-G-R 22 , as described above.
  • R 2 is -Cak-N(R 9 )-G-R 22 , as described above.
  • R 2 has the structure , in which c is O, 1,
  • each R 21 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl), -(C 0 -C 6 alkyl)-Ar, -(C 0 -C 6 alkyl)-Het, -(C 0 -C 6 alkyl)-Cak, -(C 0 -C 6 alkyl)-Hca, -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(0)o_ 2 R 10 , -halogen, -NO 2 and -CN, and two R 21 on the same carbon optionally combine to form oxo.
  • each R 21 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN and two R 21 on the same carbon optionally combine to form oxo, in which each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl),
  • each R 21 is -(C 1 -C 3 alkyl), -(C 1 -C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN and two R 21 on the same carbon optionally combine to form oxo, in which each R 7 , R 8 and
  • c is 1 or 2. In other embodiments, c is O. In certain embodiments, R 9 is H. In certain embodiments, G is a single bond. In certain embodiments of the presently disclosed compounds, R 22 is not substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl- containing group. In certain embodiments of the presently disclosed compounds, R > 23 is not substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group. [0086] In one embodiment of compounds of any of structural formulae (I)-(XLIII), R 2
  • R 2 is -(C 2 -C 8 alkyl)-N(R 9 )-R 24 in which one or two carbons of the (C 2 -C 8 alkyl) are optionally replaced by -O- or -N(R 9 )- and R 24 is -R 23 , -GR 23 or -C(O)O-(Ci-C 6 alkyl).
  • the (C 2 -Cg alkyl) is unsubstituted and no carbon is replaced by -O- or -N(R 9 )-.
  • R 2 is -CH 2 -CH 2 -CH 2 -N(R 9 )-R 24 or -CH 2 -CH 2 -CH 2 -N(R 9 )-R 24 .
  • the (C 2 -C 8 alkyl) is substituted and/or one or two carbons are replaced by -O- or -N(R )-.
  • R 2 is -CH 2 -CH 2 -O-CH 2 -CH 2 -N(R 9 )-R 24 ; -CH 2 -CH(CH 3 )-N(R 9 )-R 24 ; or -CH 2 -CH 2 -O-CH 2 -C(O)-N(R 9 )-R 24 .
  • R 9 is H.
  • R 24 is Ar or Het.
  • R 24 is not substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group.
  • the (C 2 -C 8 alkyl) is a (C 2 -C 5 alkyl).
  • R 2 is not vicinally substituted (i.e., at the position next to the amide nitrogen) with -(Co-C 4 )-Het.
  • rings system "B” when rings system "B" is benzo-, pyrido-, pyrimido-, pyrazino- or pyridazino- fused azacycloalkyl.
  • R 2 is not 7-azabicyclo[2.2. l]hept-2-yl. In other embodiments, R 2 is not a quinuclidin-3-yl moiety.
  • R is not a 4,5- dihydroisoxazol-4-yl moiety or an optionally substituted optionally ring-fused azetidin-2-on- 3-yl moiety.
  • R 2 is not an oxo-substituted heterocycloalkyl.
  • R 1 , R 2 and the nitrogen can come together to form, for example, an optionally- substituted monocyclic azacycloalkyl or monocyclic diazacycloalkyl, such as a piperidine, a pyrrolidine, a piperazine or an imidazolidine.
  • an optionally- substituted monocyclic azacycloalkyl or monocyclic diazacycloalkyl such as a piperidine, a pyrrolidine, a piperazine or an imidazolidine.
  • R 1 and R 2 come together to form an optionally-substituted bridged azacycloalkyl or diazacycloalkyl, for example, a bridged azabicyclohexyl, a bridged azabicycloheptyl, a bridged azabicyclooctyl, a bridged diazabicyclohexyl, a bridged diazabicycloheptyl or a bridged diazabicyclooctyl.
  • Particular examples of such R 2 moieties include azabicyclo[2.2.2]octyl, azabicyclo[3.2.1]octyl, and 2,5-diazabicyclo[2.2.1]heptyl.
  • Hca can be substituted as described above with reference to the azetidinyl, pyrrolidinyl, piperidinyl and azepanyl R 2 moieties.
  • the heterocycloalkyl can be substituted with -(C0-C3 alkyl)-Ar, -(C 0 -C 3 alkyl)-Het, -L-Ar, -L-Het, -C(O)-O(C 0 -C 6 alkyl), -C(O)-Het, -C(O)-Ar, -S(O) 2 -Het, -S(O) 2 -Ar or -S(O) 2 -O(C 0 -C 6 alkyl), as described above.
  • R 1 and R 2 come together to form a diazacycloalkyl, it can be substituted at a nitrogen atom.
  • the -C(O)-NR 1 R 2 moiety is
  • R 1 , R 2 and the nitrogen come together to form a monocyclic azacycloalkyl or diazacycloalkyl. In other embodiments, when g is 1 or 2, R 1 , R 2 and the nitrogen come together to form a bridged bicyclic azacycloalkyl or diazacycloalkyl.
  • the c R 21 moieties can be disposed anywhere on the azacycloalkyl or diazacycloalkyl ring system.
  • Each R 21 is independently selected from -(C 1 -C 6 alkyl), -(C 1 -C 6 haloalkyl), -(C 0 -C 6 alkyl)-Ar, -(C 0 -C 6 alkyl)-Het, -(C 0 -C 6 alkyl)-Cak, -(C 0 -C 6 alkyl)-Hca, -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN, and two R 21 on the same carbon optionally combine to form oxo.
  • each R 21 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN and two R 21 on the same carbon optionally combine to form oxo, in which each R 7 , R 8 and R 10 is independently selected from H, -(C x -C 6 alkyl), -(C x -C 6 haloal
  • each R 21 is -(C 1 -C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN and two R 21 on the same carbon optionally combine to form oxo, in which each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl
  • c is 1 or 2. In other embodiments, c is 0. In certain embedments, G is a single bond, CH 2 , or C(O). In certain embodiments of the presently disclosed compounds, R 28 is not substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group.
  • R 28 is monocyclic aryl or heteroaryl substituted with 0-3 substitutuents selected from halo, cyano, -(C 1 -C 4 haloalkyl), -O-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), - C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl) and NO 2 , in which each alkyl is not further substituted.
  • the -G-R 28 moiety, when present, can in some embodiments be as described below for -G-R 17 .
  • the -C(O)-NR R moiety is
  • the number of substituents on ring system "B", w is 0, 1, 2 or 3.
  • w is 0, 1 or 2.
  • w is 0.
  • w is at least 1, and at least one R 3 is selected from the group consisting of halo, cyano, -(Ci-C 4 fluoroalkyl), -0-(Ci-C 4 fluoroalkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), -S(O) 2 O-(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in which the Hca includes a nitrogen atom to which the -C(O)- is bound, in which no alkyl, fluoroalkyl or heterocycloalkyl is substituted with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.
  • At least one R is halo (e.g., chloro) or -(Ci-C 4 alkyl) (e.g., methyl, ethyl or propyl).
  • an R is substituted on the "B" ring system at a 6- membered aromatic ring position in the meta position relative to the J moiety.
  • each R 3 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(C x -C 6 alkyl), -(C x -C 6 haloalkyl), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl), and -(C 0 -C 6 alkyl)-S(O) 0 _ 2 -(C 0 -C 6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-,
  • each R 3 is -(C 1 -C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(C x -C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-NR 9 (C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-O-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-C(O)-(C 0 -C 2 alkyl) and -(C 0 -C 2 alkyl)-S(O) 0 .
  • each R 3 is halo (e.g., chloro) or -(C 1 -C 4 alkyl) (e.g., methyl, ethyl or propyl).
  • w is at least one, and at least one R 3 is -NR 8 R 9 .
  • w is 1.
  • R 3 is substituted on the "B" ring system at a 6-membered aromatic ring position in the meta position relative to the J moiety.
  • w is at least one, and at least one R 3 is -(C 0 -C 3 alkyl)-Y 1 -(C 1 -C 3 alkyl)- Y 2 -(C 0 -C 3 alkyl), in which each of Y 1 and Y 2 is independently L, -O-, -S- or -NR 9 -.
  • w is 1.
  • R is substituted on the "B" ring system at a 6-membered aromatic ring position in the meta position relative to the J moiety.
  • R 3 is -CH 2 -N(CHs)-CH 2 -C(O)-OCH 3 .
  • the imidazo portion of the central imidazo [l,2- ⁇ ]pyridine ring system has no substitutions other than the carboxamide substitution.
  • no R 3 at the 2-position of the imidazo [l,2- ⁇ ]pyridine core is -(Ci alkyl)-N(R 8 )-(5,6,7,8-tetrahydroquinolin-8-yl); -(Ci alkyl)-N(R 8 )-(6,7-dihydro-5H-cyclopenta[/?]pyridin-7-yl); -(Ci alkyl)-N(R 8 )-(6,7,8,9- tetrahydro-5H-cyclohepta[ ⁇ ]pyridin-9-yl); -(Ci alkyl)-N(R 8 )-(2,3-dihydrofuro[3,2-&]pyridin- 3-yl); -
  • the compound does not have two R 3 moieties that include Ar or Het in the moieties' structure.
  • an R 3 is -NR 9 -(C 0 -C 5 alkyl)-Ar, -NR 9 -(C 0 -C 6 alkyl)-Het, -NR 9 -Hca, -0-(Co-C6 alkyl)-Ar or -0-(Co-C6 alkyl)-Het
  • it is not substituted on the pyrazine core at a position ortho to (i.e., on the carbon adjacent to) the amide.
  • an R 3 is -Ar or -Het, it is substituted on the pyrazine core at a position para to (i.e., directly across the ring from) the amide.
  • ring system "B" is C 4 alkyl)-O-(C 0 -C 4 alkyl)-(optionally-substituted phenyl); (C 0 -C 4 alkyl)-S(O) 0 - 2 -(C 0 -C 4 alkyl)-(optionally-substituted phenyl) or (Co-C 4 alkyl)- S(0)o_ 2 -(Co-C 4 alkyl)-O-(optionally- substituted phenyl), it is not at the 2 position of the thiazole core (i.e., not on the carbon between the N and the S of the thiazole). In one embodiment, the compound does not have two R 3 moieties that include Ar or Het in the moieties' structure.
  • the number of substituents on ring system "C", x is 0 or an integer less than or equal to the sum of p and q. when D or Z is CR 4 , the R 4 of D or Z is one of the x R 4 groups on ring system "C". In one embodiment, x is 0, 1, 2 or 3. For example, x can be 0, or can be 1 or 2. [0103] In certain embodiments of the presently disclosed compounds of any of structural formula (I)-(XLIII), two R 4 groups combine to form an oxo. The oxo can be bound, for example, at the position alpha to a nitrogen of ring system "C". In other embodiments, no two R 4 groups combine to form an oxo.
  • each R 4 is independently selected from -(C 1 -CO alkyl), -(C 1 -Ce haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 _ 2 R 10 , -halogen,
  • each R 4 is -(Ci-C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-NR 9 (C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-O-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-C(O)-(C 0 -C 2 alkyl) and -(C 0 -C 2 alkyl)-S(0)o- 2 -(C 0 -C 2 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or
  • each R 15 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl), -(C 0 -C 6 alkyl)-Ar, -(C 0 -C 6 alkyl)-Het, -(C 0 -C 6 alkyl)-Cak, -(C 0 -C 6 alkyl)-Hca, -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl),
  • Q is a single bond.
  • Q is -CH 2 -.
  • Q is -C(O)- or -S(O) 2 -.
  • G is -CH 2 -.
  • G is -C(O)- or -S(O) 2 -.
  • G is -CH(CHs)-.
  • G is -C(O)-NH-.
  • Q is a single bond and G is -CH 2 - or -C(O)-.
  • the ring system denoted by "A” is aryl or heteroaryl.
  • the ring system denoted by "A” is substituted with one or more electron-withdrawing groups as described above.
  • R 17 is substituted with one or more electron-withdrawing groups as described above.
  • the ring system denoted by "A", R 17 or both are not substituted with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.
  • the azacycloalkyl to which -G-R 17 is bound is a piperidinyl; in other embodiments, it is a pyrrolidinyl.
  • v is 0, 1, 2, 3 or 4. In one embodiment, v is 0, 1, 2 or 3. For example, v can be 0, or can be 1 or 2.
  • two R 15 groups combine to form an oxo.
  • the oxo can be bound, for example, at the position alpha relative to the nitrogen of the azacycloalkyl ring. In other embodiments, no two R 15 groups combine to form an oxo.
  • each R 15 is independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 6 alkyl), -(C x -C 6 haloalkyl), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) and -(C 0 -C 6 alkyl)-S(O) 0 _ 2 -(C 0 -C 6 alkyl), and in which no alkyl or haloalkyl
  • each R 15 is -(Ci-C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-NR 9 (C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-O-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-C(O)-(C 0 -C 2 alkyl) and -(C 0 -C 2 alkyl)-S(O) 0 _ 2 -(C 0 -C 2 alkyl), and in which no alkyl or haloalkyl is substitute
  • one R 15 is -C(O)NR 9 R 7 , which can be bound, for example, at a position alpha relative to the piperidine nitrogen, or at the position linked to the -N(R 1 )-.
  • R 17 is an unsubstituted aryl or heteroaryl.
  • the R 17 Ar or Het is substituted with 1, 2 or 3 substituents independently selected from -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-R 7 , -(C 0 -C 6 alkyl)-NR 8 R 9 , -(C 0 -C 6 alkyl)-OR 10 , -(C 0 -C 6 alkyl)-C(O)R 10 , -(C 0 -C 6 alkyl)- S(O) 0 _ 2 R 10 , -halogen, -NO 2 and -CN, in which each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 6 alkyl), -(C x -C 6 haloalkyl), -(C 0 -
  • the R 17 Ar or Het is substituted with 1, 2 or 3 substituents independently selected from -(Ci-C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R ⁇ -(C 0 -C 3 alkyl)-NR 8 R y , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 .
  • each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-NR 9 (C 0 -C 2 alkyl), -(C 0 -C 2 alkyl)-0-(Co-C 2 alkyl), -(C 0 -C 2 alkyl)-C(O)-(C 0 -C 2 alkyl) and -(C 0 -C 2 alkyl)-S(O) 0 .
  • R 17 is substituted with 1, 2 or 3 substituents selected from halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C 1 -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca.
  • R 17 can be substituted with, for example, one such substituent, or two such substituents.
  • the presently disclosed compounds have the structural formula (XLV):
  • R , 27 is selected from H, -(C I -CO alkyl), -(C 1 -Ce haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)- S(0)o-2-(C 0 -C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cyclo
  • the presently disclosed compounds have the structural formula (XLVIII):
  • R 27 is selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)- S(0)o_ 2 -(C 0 -C 6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl) (e.g
  • R 27 and R 29 are both H.
  • the presently disclosed compounds have the structural formula (XLIX):
  • R 27 is selected from H, -(C 1 -C O alkyl), -(C 1 -C O haloalkyl) (e.g., difluoromethyl, trifiuoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)- S(O) 0 2 -(C 0 -C 6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalky
  • the presently disclosed compounds have the structural formula (L):
  • R > 27 . is selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifiuoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)-S(0)o_ 2 -(C 0 -C 6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl
  • the presently disclosed compounds have the structural formula (LI):
  • the presently disclosed compounds have the structural formula (LII):
  • R , 25 is selected from halo, cyano, -(C 1 -C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(0)-Hca in which the Hca contains a ring nitrogen atom through which it is bound to the -C(O)-, in which no alkyl or haloalkyl is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group; and all other variables are as described above with reference to any of structural formulae (I)-(XLVI).
  • R 25 can be, for example, -Cl, -F, cyano, -C(O)CH 3 , -C(O)OH, -C(O)NH 2 , trifiuoromethyl, difiuoromethyl, difluoromethoxy or trifluoromethoxy.
  • the presently disclosed compounds have the structural formula (LIII):
  • the presently disclosed compounds have the structural formula (LIV):
  • R > 27 . is selected from H, -(C 1 -Ce alkyl), -(C 1 -Ce haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)- S(0)o_ 2 -(C 0 -C 6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl
  • R 27 and R 29 are both H.
  • the compounds of structural formula (LIV) are present as racemic mixtures or scalemic mixtures. In other embodiments, the compounds of structural formula (LIV) are present in an enantiomerically-enriched form, for example as a substantially pure stereoisomer.
  • the presently disclosed compounds have the structural formula (LV): in which R > 27 i ⁇ s selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)- S(0)o- 2 -(Co-C 6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl), in which no heterocycloal
  • R 27 and R 29 are both H.
  • the compounds of structural formula (LV) are present as racemic mixtures or scalemic mixtures. In other embodiments, the compounds of structural formula (LV) are present in an enantiomerically-enriched form, for example as a substantially pure stereoisomer.
  • the presently disclosed compounds have the structural formula (LVI):
  • the presently disclosed compounds have the structural formula (LVII): in which G, v, R 15 and R 17 are defined as described above with reference to structural formula
  • the presently disclosed compounds have the structural formula (LVIII):
  • the presently disclosed compounds have the structural formula (LIX):
  • the presently disclosed compounds have the structural formula (LXI):
  • the presently disclosed compounds have the structural formula (LXII):
  • the presently disclosed compounds have the structural formula (LXIII):
  • the presently disclosed compounds have the structural formula (LXIV):
  • the presently disclosed compounds have the structural formula (LXV): in which G, v, R 15 and R 17 are defined as described above with reference to structural formula
  • the presently disclosed compounds have the structural formula (LXVI):
  • G, v, R 15 and R 17 are defined as described above with reference to structural formula (XLIV), and all other variables are defined as described above with reference to structural formulae (I)-(IV) and (XXVIII).
  • R 5 , y, v, R 15 , R 17 , Q, G and the ring denoted by "A” can be defined, for example, as described with reference to any of structural formulae (XLVII)- (LV).
  • E 1 is carbon and E 2 is N. In another embodiment, E 1 is N and E 2 is carbon.
  • the presently disclosed compounds have the structural formula (LXVII):
  • G, v, R 15 and R 17 are defined as described above with reference to structural formula (XLIV), and all other variables are defined as described above with reference to structural formulae (I)-(IV) and (XXXIV).
  • R 5 , y, v, R 15 , R 17 , Q, G and the ring denoted by "A” can be defined, for example, as described with reference to any of structural formulae (XLVII)- (LV).
  • Z is N. In other embodiments, Z is CH or C substituted with one of the x R 4 .
  • the presently disclosed compounds have the structural formula (LXX): in which G, v, R 15 and R 17 are defined as described above with reference to structural formula
  • the presently disclosed compounds have the structural formula (LXXI):
  • G, v, R 15 and R 17 are defined as described above with reference to structural formula (XLIV), and all other variables are defined as described above with reference to structural formulae (I)-(IV) and (XXXVI).
  • R 5 , y, v, R 15 , R 17 , Q, G and the ring denoted by "A” can be defined, for example, as described with reference to any of structural formulae (XLVII)- (LV).
  • Z is N. In other embodiments, Z is CH or C substituted with one of the x R 4 .
  • the presently disclosed compounds have the structural formula (LXXII):
  • the presently disclosed compounds have the structural formula (LXXIII):
  • the presently disclosed compounds have the structural formula (LXXIV):
  • G, v, R 15 and R 17 are defined as described above with reference to structural formula (XLIV), and all other variables are defined as described above with reference to structural formulae (I)-(IV) and (XL).
  • R 5 , y, v, R 15 , R 17 , Q, G and the ring denoted by "A” can be defined, for example, as described with reference to any of structural formulae (XLVII)- (LV).
  • the presently disclosed compounds have the structural formula (LXXVI):
  • the presently disclosed compounds have the structural formula (LXXVII):
  • the presently disclosed compounds have the structural formula (LXXVIII):
  • G is -CH 2 -, -CH(CH 3 )-, -C(O)-, -S(O) 2 - or -C(O)-NH-.
  • G is -CH 2 -.
  • G is -C(O)- or -S(O) 2 -.
  • G is -C(O)-NH-.
  • G is -CH 2 -, -C(O)-, -S(O) 2 - or -
  • R , 2 2 7' is selected from H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) -(C 0 -C 6 alkyl)- S(0)o- 2 -(Co-C 6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl (e.
  • the compounds can be present as racemic mixtures or scalemic mixtures, or in an enantiomerically-enriched form, for example as a substantially pure stereoisomer.
  • the R 17 moiety has the structure , in which R 27 is selected from H, -(C r C 6 alkyl), -(C r C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-
  • w is 1, and R 3 is -NR 8 R 9 .
  • R 3 is substituted at a 6- membered aromatic ring position in the meta position relative to the J moiety.
  • w is 1, and R 3 is -(C 0 -C 3 alkyl)-Y 1 -(Ci-C 3 alkyl)-Y 2 -(C 0 -C 3 alkyl), in which each of Y 1 and Y 2 is independently L, -O-, -S- or -NR 9 -.
  • R 3 is substituted at a 6-membered aromatic ring position in the meta position relative to the J moiety.
  • each R 27 is selected from -(Ci-C 3 alkyl), -(Ci-C 3 haloalkyl), -(C 0 -C 3 alkyl)-L-R 7 , -(C 0 -C 3 alkyl)-NR 8 R 9 , -(C 0 -C 3 alkyl)-OR 10 , -(C 0 -C 3 alkyl)-C(O)R 10 , -(C 0 -C 3 alkyl)-S(O) 0 - 2 R 10 , -halogen, -NO 2 and -CN and two R 21 on the same carbon optionally combine to form oxo, in which each R 7 , R 8 and R 10 is independently selected from H, -(Ci-C 2 alkyl), -(Ci-C 2 haloalkyl), -(C 0 -C 2 alkyl)-L-(C 0 -
  • At least one R 5 moiety is a haloalkyl group, and in exemplary
  • the moiety is /?-(trifluoromethyl)phenyl.
  • the presently disclosed compounds of any of structural formulae (I)-(XLIII) have a T moiety having the structural formula
  • R 1 1 l 8 ⁇ is H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (Co-C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) and -(C 0 -C 6 alkyl)-S(O) 0 2 -(C 0 -C 6 alkyl), in which no alky
  • R 18 is H, -(C x -C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) and -(C 0 -C 6 alkyl)-S(O) 0 .
  • R 18 and R 19 are both H.
  • R 2 moiety having the structural formula , in which Q and
  • R 5 are defined as described above with reference to any of structural formulae (I)-(LXXVIII), R 18 is H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalkyl) (e.g., difluoromethyl, trifluoromethyl and the like), -(C 0 -C 6 alkyl)-L-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-NR 9 (C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-O-(C 0 -C 6 alkyl), -(C 0 -C 6 alkyl)-C(O)-(C 0 -C 6 alkyl) and -(C 0 -C 6 alkyl)-S(O) 0 .
  • R 18 is H, -(Ci-C 6 alkyl), -(Ci-C 6 haloalky
  • R 18 and R 19 are both H.
  • the presently disclosed compounds have the structural formula (LXXIX):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LVI); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl),
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]oxazole.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7 is substituted on the benzo moiety of the central benzo [djoxazole.
  • the presently disclosed compounds have the structural formula (LXXX):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LVII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]oxazole.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the benzo moiety of the central benzo [djoxazole.
  • the presently disclosed compounds have the structural formula (LXXXI):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LVI); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]oxazole.
  • one R 3 (e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7) is substituted on the benzo moiety of the central benzo [djoxazole.
  • the presently disclosed compounds have the structural formula (LXXXII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LVI); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H. In another embodiment, R 1 is methyl, ethyl, propyl or butyl. In one embodiment, no R 3 is substituted on the benzo moiety of the central benzo[d]oxazole.
  • one R 3 (e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the benzo moiety of the central benzo [d]oxazole.
  • the presently disclosed compounds have the structural formula (LXXXIII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LVIII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]thiazole.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the benzo moiety of the central benzo[d]thiazole.
  • the presently disclosed compounds have the structural formula (LXXXIV): (LXXXIV), in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LIX); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Cj-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(
  • R . 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]thiazole.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the benzo moiety of the central benzo[d]thiazole.
  • the presently disclosed compounds have the structural formula (LXXXV):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LVIII); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C r C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]thiazole.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7 is substituted on the benzo moiety of the central benzo [djthiazo Ie.
  • the presently disclosed compounds have the structural formula (LXXXVI):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LIX); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the benzo moiety of the central benzo[d]thiazole.
  • one R e.g., -Cl, -F, -CH3, -C 2 H 5 , -C3H7 is substituted on the benzo moiety of the central benzo [d]thiazo Ie.
  • the presently disclosed compounds have the structural formula (LXXXVII): (LXXXVII), in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LX); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(C 1 -C 4 haloalkyl), -(C r C 4 alkyl), -0-(C 1 -C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)O-(C 0
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 Hs, -C 3 H 7 ) is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (LXXXVIII):
  • R 11 , R 1Z and R u are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -0-(C 1 -C 4 haloalkyl), -(C 1 -C 4 alkyl), -0-(C 1 -C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in which the Hca contains a ring nitrogen atom through which it is bound to the -C(O)-, in which no alkyl, haloalkyl or heterocycloalkyl is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7 is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (LXXXIX):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl),
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (XC): in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXIII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(C 1 -C 4 alkyl), -0-(C 1 -C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (XCI):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LX); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in which
  • R , 1 1 2 and R 13 is not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 (e.g., -Cl, -F, -CH 3 , -C 2 H5, -C3H7) is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (XCII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXI); and R 12 and R 13 are independently selected from H, halo, cyano, -(C1-C4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 Hs, -C3H7 is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (XCIII): (XCIII), in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXII); and R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(C r C 4 alkyl), -O-(C r C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (XCIV):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXIII); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in
  • R , 1 1 2 and R 13 is not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central imidazo[l,2-a]pyridine.
  • one R 3 (e.g., -Cl, -F, -CH 3 , -C 2 H5, -C3H7) is substituted on the central imidazo[l,2-a]pyridine.
  • the presently disclosed compounds have the structural formula (XCV):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXIV); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central pyrazine.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7 is substituted on the central pyrazine.
  • the presently disclosed compounds have the structural formula (XCVI): in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXV); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -CVI): in which Q is
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central pyrazine.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 Hs, -C3H7 is substituted on the central pyrazine.
  • the presently disclosed compounds have the structural formula (XCVII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I) and (LXIV); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-H
  • R 12 and R 1 13 is not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central pyrazine.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central pyrazine.
  • the presently disclosed compounds have the structural formula (XCVIII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXV); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central pyrazine.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H5, -C3H7 is substituted on the central pyrazine.
  • the presently disclosed compounds have the structural formula (XCIX): in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; E 1 , E 2 , R 1 and R 3 are as described above with reference to any of structural formulae (I)-(IV) and (LXVI); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)- (C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)O-(C 0 -
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central thiazole.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • E 1 is carbon and E 2 is N. In another embodiment, E 1 is N and E 2 is carbon.
  • the presently disclosed compounds have the structural formula (C):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXVII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central thiazole (i.e., the ring position shown occupied by R bears a hydrogen atom).
  • one R e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central thiazole.
  • the presently disclosed compounds have the structural formula (CI):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXVIII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central thiazole (i.e., the ring position shown occupied by R 3 bears a hydrogen atom).
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central thiazole.
  • the presently disclosed compounds have the structural formula (CII): in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; E 1 , E 2 , R 1 and R 3 are as described above with reference to any of structural formulae (I)-(IV) and (LXVI); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)- (C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H. In another embodiment, R 1 is methyl, ethyl, propyl or butyl. In one embodiment, no R 3 is substituted on the central thiazole. In another embodiment, one R 3 (e.g., -Cl, -F, -CH3, - C 2 H 5 , -C 3 H 7 ) is substituted on the central thiazole.
  • E 1 is carbon and E 2 is N. In another embodiment, E 1 is N and E 2 is carbon.
  • the presently disclosed compounds have the structural formula (CIII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXVII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central thiazole (i.e., the ring position shown occupied by R 3 bears a hydrogen atom).
  • one R 3 (e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7) is substituted on the central thiazole.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXVIII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central thiazole (i.e., the ring position shown occupied by R 3 bears a hydrogen atom).
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central thiazole.
  • the presently disclosed compounds have the structural formula (CV): in which Q is -CH 2 -, -C(O)- or a single bond; G is a single bond, -CH 2 -, -C(O)-, -S(O) 2 - or -C(O)-NH-; Z, R 1 and R 3 are as described above with reference to any of structural formulae (I)-(IV) and (LXIX); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(C 1 -C 4 alkyl), -0-(C 1 -C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • Z is N. In another embodiment, Z is CH.
  • R 1 , R 3 and R 38 are as described above with reference to any of structural formulae (I)-(IV) and (LXX); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 H5, -C3H7
  • R 38 is H.
  • R 38 is methyl, ethyl, propyl or butyl.
  • R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(C r C 4 alkyl), -O-(C r C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • Z is N. In another embodiment, Z is CH.
  • R 1 , R 3 and R 38 are as described above with reference to any of structural formulae (I)-(IV) and (LXXII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), - C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • R 38 is H.
  • R 38 is methyl, ethyl, propyl or butyl.
  • the presently disclosed compounds have the structural formula (CIX):
  • R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • Z is N. In another embodiment, Z is CH.
  • R 1 , R 3 and R 38 are as described above with reference to any of structural formulae (I)-(IV) and (LXXIV); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • R 38 is H.
  • R 38 is methyl, ethyl, propyl or butyl.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)-(IV) and (LXIX); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • Z is N.
  • Z is CH.
  • R 1 , R 3 and R 38 are as described above with reference to any of structural formulae (I)-(IV) and (LXX); and R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -0-(C 1 -C 4 haloalkyl), -(C r C 4 alkyl), -O-(C r C 4 alkyl), - C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • R 38 is H.
  • R 38 is methyl, ethyl, propyl or butyl.
  • R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • Z is N.
  • Z is CH.
  • R 1 , R 3 and R 38 are as described above with reference to any of structural formulae (I)-(IV) and (LXXII); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • R 38 is H.
  • R 38 is methyl, ethyl, propyl or butyl.
  • the presently disclosed compounds have the structural formula (CXV):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)-(IV) and (LXXIII); and R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(C r C 4 alkyl), -O-(C r C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • Z is N.
  • Z is CH.
  • R 1 , R 3 and R 38 are as described above with reference to any of structural formulae (I)-(IV) and (LXXIV); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)- (C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central phenyl ring.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • R 38 is H.
  • R 38 is methyl, ethyl, propyl or butyl.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXV); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl),
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH3, -C 2 Hs, -C3H7 is substituted on the central benzo moiety.
  • the presently disclosed compounds have the structural formula (CXVIII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXVI); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -O-(C r C 4 haloalkyl), -(C r C 4 alkyl), -0-(C 1 -C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central benzo moiety.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXVII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central benzo moiety.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXVIII); and R 11 , R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -
  • R 11 , R 12 and R 13 is not H.
  • R 11 is attached in the para position relative to the G moiety; in another embodiment, R 11 is attached in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central benzo moiety.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXV); and R 12 and R 13 are independently selected from H, halo, cyano, -(C 1 -C 4 haloalkyl), -0-(Cj-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -C(O)-H
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central benzo moiety.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXVI); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7
  • the presently disclosed compounds have the structural formula (CXXIII):
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXVII); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(C x -C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central benzo moiety.
  • R 1 and R 3 are as described above with reference to any of structural formulae (I)- (IV) and (LXXVIII); and R 12 and R 13 are independently selected from H, halo, cyano, -(Ci-C 4 haloalkyl), -0-(Ci-C 4 haloalkyl), -(Ci-C 4 alkyl), -0-(Ci-C 4 alkyl), -C(O)-(C 0 -C 4 alkyl), - C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), NO 2 and -
  • R 12 and R 13 are not H.
  • the pyridine nitrogen is positioned in the para position relative to the G moiety; in another embodiment, the pyridine nitrogen is positioned in the meta position relative to the G moiety.
  • R 1 is H.
  • R 1 is methyl, ethyl, propyl or butyl.
  • no R 3 is substituted on the central benzo moiety.
  • one R 3 e.g., -Cl, -F, -CH 3 , -C 2 H 5 , -C 3 H 7 ) is substituted on the central benzo moiety.
  • the compound has the structural formula (XLIV), in which the "A" ring system is an aryl or heteroaryl; and in which the compound has a computed low energy three-dimensional conformer in which the oxygen of the carboxamide -C(O)- group is positioned at (O A, O A, O A); the centerpoint of an aromatic ring of the aryl or heteroaryl of the "B" ring system is positioned within 3.5 A of (-3.1 A, 0.4 A, 1.2 A); the nitrogen of the right-hand azacycloalkyl (i.e., the ring to which -G-R 17 is bound) is positioned within 3.5 A of (0.8 A, 1.6 A, -5.3 A); the centerpoint of the left-hand azacycloalkyl (i.e., the ring to which -Q-(A ring)-(R 5 ) y is bound) is positioned within 3.5 A of (-6.2 A, 0.1 A
  • the oxygen of the carboxamide -C(O)- group is positioned at (0 A, 0 A, 0 A); the centerpoint of an aromatic ring of the aryl or heteroaryl of the "B" ring system is positioned within 2.5 A of (-3.1 A, 0.4 A, 1.2 A); the nitrogen of the right-hand azacycloalkyl is positioned within 1.8 A of (0.8 A, 1.6 A,
  • the centerpoint of the left-hand azacycloalkyl is positioned within 2.5 A of (-6.2 A, 0.1 A,
  • the centerpoint of an aromatic ring of the aryl or heteroaryl of the "A" ring system is positioned within 2.5 A of (-7.4 A, -1.9 A, 10.7 A).
  • the "A" ring system is an aryl or heteroaryl substituted with a hydrophobic moiety; R 17 is substituted with an electron acceptor; and the compound has a computed low energy three-dimensional conformer in which the oxygen of the carboxamide -C(O)- group is positioned at (0 A, 0 A, 0 A); the centerpoint of an aromatic ring of the aryl or heteroaryl of the "B” ring system is positioned within 3.5 A of (-3.1 A, 0.4 A, 1.2 A); the nitrogen of the right-hand azacycloalkyl is positioned within 3.5 A of (0.8 A, 1.6 A,
  • the centerpoint of the left-hand azacycloalkyl is positioned within 3.5 A of (-6.2 A, 0.1 A,
  • hydrophobic moiety can be, for example, any of the following, as defined in SMARTS query format:
  • the electron acceptor can be, for example, any of the following, as defined in SMARTS query format:
  • the "A" ring system is an aryl or heteroaryl substituted with a hydrophobic moiety; R 17 is substituted with an electron acceptor; and the compound has a computed low energy three-dimensional conformer in which the oxygen of the carboxamide -C(O)- group is positioned at (0 A, 0 A, 0 A); the centerpoint of an aromatic ring of the aryl or heteroaryl of the "B" ring system is positioned within 2.5 A of (-3.1 A, 0.4 A, 1.2 A); the nitrogen of the right-hand azacycloalkyl is positioned within 1.8 A of (0.8 A, 1.6 A,
  • the centerpoint of the left-hand azacycloalkyl is positioned within 2.5 A of (-6.2 A, 0.1 A,
  • the computed low energy three-dimensional conformer has a root mean square deviation from the given points of no greater than 3 A, and a vector score greater than 0.2.
  • the computed low energy three-dimensional conformer has a root mean square deviation from the given points of no greater than 1.5 A, and a vector score greater than 0.4.
  • the computed lowenergy three-dimensional conformer has a root mean square deviation from the given points of no greater than 1.2 A, and a vector score greater than 0.5.
  • a centerpoint of a carbocyclic or heterocyclic ring is the average position of the constituent atoms of the ring (i.e., excluding any substituents) as positioned in the low energy three-dimensional conformer.
  • the centerpoint of the left-hand azacycloalkyl is the average position of its ring carbon and nitrogen atom(s).
  • the centerpoint of a phenyl ring is the average position of its six ring carbons. Centerpoints are calculated only on single rings; multi-ring systems have multiple centerpoints, one for each ring.
  • Low energy three-dimensional conformers can be calculated using the Phase software package version 3.0, available from Schr ⁇ dinger LLC. Low energy three-dimensional conformers can be generated by a torsion search procedure under OPLS_2005 force field with a distance dependent dielectric constant.
  • the low energy conformer should be translated and rotated so that the the oxygen of the E -C(O)- group is positioned at (0 A, 0 A, 0 A), or one of the oxygens of the E -S(O) 2 - group is positioned at (0 A, 0 A, 0 A), and so that the root mean square deviation of the rest of the listed features with respect to the given points is minimized.
  • Q is -CH 2 -, as described above
  • G is -CH 2 -, as described above.
  • the ring system denoted by “A” is a phenyl not fused to the azacycloalkyl
  • the ring system denoted by “B” is a phenyl
  • J is -N(R 38 )-
  • D is a carbon
  • Z is N.
  • Examples of compounds according to structural formula (I) include those listed below in Table 1. These compounds can be made according to the general schemes described below, for example using procedures analogous to those described below in the Examples.
  • paragraph [0020] discloses certain embodiments of ring system "B” and paragraph [0023] discloses certain embodiments of T; also contemplated are embodiments in which ring system "B” is as described as in paragraph [0020], and T is as described in paragraph [0023].
  • This disclosure contemplates all such combinations, to the extent the definitions of the various structural features do not conflict with one another.
  • chemical moieties are defined and referred to throughout primarily as univalent chemical moieties (e.g., alkyl, aryl, etc.). Nevertheless, such terms are also used to convey corresponding multivalent moieties under the appropriate structural circumstances clear to those skilled in the art.
  • an "alkyl” moiety can refer to a monovalent radical (e.g. CH3-CH 2 -)
  • a bivalent linking moiety can be "alkyl,” in which case those skilled in the art will understand the alkyl to be a divalent radical (e.g., -CH 2 -CH 2 -), which is equivalent to the term "alkylene.”
  • alkyl a divalent radical
  • aryl a divalent moiety
  • Nitrogens in the presently disclosed compounds can be hypervalent, e.g., an N-oxide or tetrasubstituted ammonium salt.
  • a moiety may be defined, for example, as (A) a - B-, wherein a is 0 or 1. In such instances, when a is 0 the moiety is B- and when a is 1 the moiety is A-B-.
  • alkyl includes alkyl, alkenyl and alkynyl groups of a designed number of carbon atoms, desirably from 1 to about 12 carbons (i.e., inclusive of 1 and 12).
  • C 1n -C n alkyl means an alkyl group having from m to n carbon atoms (i.e., inclusive of m and n).
  • C m -C n alkyl means an alkyl group having from m to n carbon atoms.
  • C 1 -C O alkyl is an alkyl group having from one to six carbon atoms.
  • Alkyl and alkyl groups may be straight or branched and depending on context, may be a monovalent radical or a divalent radical (i.e., an alkylene group).
  • a divalent radical i.e., an alkylene group.
  • the group is simply a single covalent bond if it is a divalent radical or is a hydrogen atom if it is a monovalent radical.
  • the moiety "-(Co-C 6 alkyl)-Ar" signifies connection of an optionally substituted aryl through a single bond or an alkylene bridge having from 1 to 6 carbons.
  • alkyl examples include, for example, methyl, ethyl, propyl, isopropyl, butyl, iso-, sec- and tert-butyl, pentyl, hexyl, heptyl, 3-ethylbutyl, 3-hexenyl and propargyl. If the number of carbon atoms is not specified, the subject "alkyl” or “alkyl” moiety has from 1 to 12 carbons.
  • haloalkyl is an alkyl group substituted with one or more halogen atoms, e.g. F, Cl, Br and I.
  • fluoroalkyl is an alkyl group substituted with one or more fluorine atoms.
  • fluoroalkyl include fluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, hexafluoroisopropyl and the like.
  • each haloalkyl is a fluoroalkyl.
  • aryl represents an aromatic ring system having a single ring (e.g., phenyl) which is optionally fused to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings.
  • Aryl includes ring systems having multiple condensed rings and in which at least one is carbocyclic and aromatic, (e.g., 1,2,3,4-tetrahydronaphthyl, naphthyl).
  • aryl groups include phenyl, 1 -naphthyl, 2-naphthyl, indanyl, indenyl, dihydronaphthyl, fluorenyl, tetralinyl, and 6,7,8, 9-tetrahydro-5H-benzo[a]cycloheptenyl.
  • aryl groups include those having a first carbocyclic, aromatic ring fused to an aromatic or aliphatic heterocycle, for example, 2,3-dihydrobenzofuranyl..
  • the aryl groups herein are unsubstituted or, when specified as "optionally substituted", can unless stated otherwise be substituted in one or more substitutable positions with various groups, as described below.
  • heteroaryl refers to an aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen and sulfur in an aromatic ring.
  • the heteroaryl may be fused to one or more cycloalkyl or heterocycloalkyl rings.
  • heteroaryl groups include, for example, pyridyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pyridazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, benzo[l,4]oxazinyl, triazolyl, tetrazolyl, isothiazolyl, naphthyridinyl, isochromanyl, chromanyl,
  • Preferred heteroaryl groups include pyridyl, pyrimidyl, quinolinyl, indolyl, pyrrolyl, furanyl, thienyl and imidazolyl, pyrazolyl, indazolyl, thiazolyl and benzothiazolyl.
  • each heteroaryl is selected from pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, isothiazolyl, pyridinyl-N-oxide, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N- oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide
  • Preferred heteroaryl groups include pyridyl, pyrimidyl, quinolinyl, indolyl, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, indazolyl, thiazolyl and benzothiazolyl.
  • the heteroaryl groups herein are unsubstituted or, when specified as “optionally substituted", can unless stated otherwise be substituted in one or more substitutable positions with various groups, as described below.
  • heterocycloalkyl refers to a non-aromatic ring or ring system containing at least one heteroatom that is preferably selected from nitrogen, oxygen and sulfur, wherein said heteroatom is in a non-aromatic ring.
  • the heterocycloalkyl may be saturated (i.e., a heterocycloalkyl) or partially unsaturated (i.e., a heterocycloalkenyl).
  • Heterocycloalkyl includes monocyclic groups as well as bicyclic and polycyclic ring systems, including bridged and fused systems.
  • the heterocycloalkyl ring is optionally fused to other heterocycloalkyl rings and/or non-aromatic hydrocarbon rings and/or phenyl rings.
  • the heterocycloalkyl groups have from 3 to 7 members in a single ring. In other embodiments , heterocycloalkyl groups have 5 or 6 members in a single ring.
  • heterocycloalkyl groups include, for example, azabicyclo[2.2.2]octyl (in each case also "quinuclidinyl” or a quinuclidine derivative), azabicyclo[3.2.1]octyl, 2,5- diazabicyclo[2.2.1]heptyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S,S-dioxide, 2-oxazolidonyl, piperazinyl, homopiperazinyl, piperazinonyl, pyrrolidinyl, azepanyl, azetidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl,
  • heterocycloalkyl groups include morpholinyl, 3,4-dihydroisoquinolin- 2(lH)-yl, tetrahydropyranyl, piperidinyl, aza-bicyclo[2.2.2]octyl, ⁇ -butyrolactonyl (i.e., an oxo-substituted tetrahydrofuranyl), ⁇ -butryolactamyl (i.e., an oxo-substituted pyrrolidine), pyrrolidinyl, piperazinyl, azepanyl, azetidinyl, thiomorpholinyl, thiomorpholinyl S,S-dioxide, 2-oxazolidonyl, imidazolidonyl, isoindolindionyl, piperazinonyl.
  • the heterocycloalkyl groups herein are unsubstituted or, when specified as "optionally
  • cycloalkyl refers to a non-aromatic carbocyclic ring or ring system, which may be saturated (i.e., a cycloalkyl) or partially unsaturated (i.e., a cycloalkenyl).
  • the cycloalkyl ring optionally fused to or otherwise attached (e.g., bridged systems) to other cycloalkyl rings.
  • Certain examples of cycloalkyl groups present in the disclosed compounds have from 3 to 7 members in a single ring, such as having 5 or 6 members in a single ring.
  • cycloalkyl groups include, for example, cyclohexyl, cyclopentyl, cyclobutyl, cyclopropyl, tetrahydronaphthyl and bicyclo[2.2.1]heptane.
  • the cycloalkyl groups herein are unsubstituted or, when specified as “optionally substituted", may be substituted in one or more substitutable positions with various groups.
  • ring system encompasses monocycles, as well as fused and/or bridged poly cycles.
  • oxa means a divalent oxygen radical in a chain, sometimes designated as -O-.
  • electron withdrawing group means a group that withdraws electron density from the structure to which it is attached than would a similarly-attached hydrogen atom.
  • electron withdrawing groups can be selected from the group consisting of halo, cyano, -(Ci-C 4 fluoroalkyl), -0-(C 1 -C 4 fluoroalkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)O-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), -S(O) 2 O-(C 0 -C 4 alkyl), NO 2 and -C(O)-Hca in which the Hca includes a nitrogen atom to which the -C(O)- is bound, in which no alkyl, fluoroalkyl or heterocycloalkyl is substituted with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group .
  • substituted when used to modify a specified group or radical, means that one or more hydrogen atoms of the specified group or radical are each, independently of one another, replaced with the same or different substituent groups as defined below.
  • Each R 72 is independently hydrogen, (Ci-C ⁇ alkyl) or (Ci-C ⁇ fluoroalkyl); each R 82 is independently R 72 or alternatively, two R 82 S, taken together with the nitrogen atom to which they are bonded, form a 5-, 6- or 7-membered heterocycloalkyl which may optionally include 1, 2, 3 or 4 of the same or different additional heteroatoms selected from the group consisting of O, N and S, of which N may have -H or Ci-C 3 alkyl substitution.
  • Each M + may independently be, for example, an alkali ion, such as K + , Na + , Li + ; an ammonium ion, such as + N(R 60 ) 4 ; or an alkaline earth ion, such as [Ca 2+ ] 0 .s, [Mg 2+ J 0 S , or [Ba 2+ ] 0 . 5 ("subscript 0.5 means e.g.
  • -NR 80 R 80 is meant to include -NH 2 , -NH-alkyl, N-pyrrolidinyl, N-piperazinyl, 4-methyl-piperazin-l-yl and N-morpholinyl.
  • Substituent groups for hydrogens on unsaturated carbon atoms in "substituted" alkene, alkyne, aryl and heteroaryl groups are, unless otherwise specified, -R 60 , halo, -0 " M + , -OR 70 , -SR 70 , -STvI + , -NR 80 R 80 , trihalomethyl, -CF 3 , -CN, -OCN, -SCN, -NO, -NO 2 , -N 3 , -SO 2 R 70 , -SO 3 M + , -SO 3 R 70 , -OSO 2 R 70 , -OSO 3 M + , -OSO 3 R 70 , -PO 3 ⁇ 2 (M + ) 2 , -P(O)(OR 70 )O M + , -P(O)(OR 70 ) 2 , -C(O)R 70 , -C(S)R 70 , -
  • Substituent groups for hydrogens on nitrogen atoms in "substituted" heteroalkyl and heterocycloalkyl groups are, unless otherwise specified, -R 60 , -O M + , -OR 70 , -SR 70 , -S ⁇ M + , -NR 80 R 80 , trihalomethyl, -CF 3 , -CN, -NO, -NO 2 , -S(O) 2 R 70 , -S(O) 2 O M + , -S(O) 2 OR 70 , -OS(O) 2 R 70 , -OS(O) 2 O M + , -OS(O) 2 OR 70 , -P(O)(O " ) 2 (M + ) 2 , -P(O)(OR 70 )O " M + , -P(O)(OR 70 XOR 70 ), -C(O)R 70 , -C(S)R 70 , -C
  • a group that is substituted has 1, 2, 3, or 4 substituents, 1, 2, or 3 substituents, 1 or 2 substituents, or 1 substituent.
  • substituent groups on "substituted" alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups are -halo, -OH, -0-(Ci-C 4 alkyl), -0-(Ci-C 4 haloalkyl), -N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), -SH, -S(O) 0-2 -(Ci-C 4 alkyl), -(Ci-C 4 alkyl), -(Ci-C 4 haloalkyl), -C(O)-(C 0 -C 4 alkyl), -C(O)N(C 0 -C 4 alkyl)(C 0 -C 4 alkyl), -N(C 0 -C 4 alkyl)C(O 0 -C 4 alkyl)(C 0 -C 4 alkyl)(C 0 -C 4 al
  • compositions disclosed herein can also be provided as pharmaceutically acceptable salts.
  • pharmaceutically acceptable salts or “a pharmaceutically acceptable salt thereof refer to salts prepared from pharmaceutically acceptable non-toxic acids or bases including inorganic acids and bases and organic acids and bases. If the compound is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids.
  • Such salts may be, for example, acid addition salts of at least one of the following acids: benzenesulfonic acid, citric acid, ⁇ -glucoheptonic acid, D-gluconic acid, glycolic acid, lactic acid, malic acid, malonic acid, mandelic acid, phosphoric acid, propanoic acid, succinic acid, sulfuric acid, tartaric acid (d, 1, or dl), tosic acid (toluenesulfonic acid), valeric acid, palmitic acid, pamoic acid, sebacic acid, stearic acid, lauric acid, acetic acid, adipic acid, carbonic acid, 4-chlorobenzenesulfonic acid, ethanedisulfonic acid, ethylsuccinic acid, fumaric acid, galactaric acid (mucic acid), D-glucuronic acid, 2-oxo-glutaric acid, glycerophosphoric acid, hippuric acid, isethi
  • prodrug refers to a derivative of an active compound (drug) that undergoes a transformation under the conditions of use, such as within the body, to release the active drug.
  • Prodrugs are frequently, but not necessarily, pharmacologically inactive until converted into the active drug.
  • Prodrugs are typically obtained by masking a functional group in the drug believed to be in part required for activity with a progroup (defined below) to form a promoiety which undergoes a transformation, such as cleavage, under the specified conditions of use to release the functional group, and hence the active drug.
  • the cleavage of the promoiety can proceed spontaneously, such as by way of a hydrolysis reaction, or it can be catalyzed or induced by another agent, such as by an enzyme, by light, by acid, or by a change of or exposure to a physical or environmental parameter, such as a change of temperature.
  • the agent can be endogenous to the conditions of use, such as an enzyme present in the cells to which the prodrug is administered or the acidic conditions of the stomach, or it can be supplied exogenously.
  • progroups, as well as the resultant promoieties, suitable for masking functional groups in the active drugs to yield prodrugs are well-known in the art.
  • a hydroxyl functional group can be masked as a sulfonate, ester or carbonate promoiety, which can be hydrolyzed in vivo to provide the hydroxyl group.
  • An amino functional group can be masked as an amide, carbamate, imine, urea, phosphenyl, phosphoryl or sulfenyl promoiety, which can be hydrolyzed in vivo to provide the amino group.
  • a carboxyl group can be masked as an ester (including silyl esters and thioesters), amide or hydrazide promoiety, which can be hydrolyzed in vivo to provide the carboxyl group.
  • the compounds disclosed herein can also be provided as N-oxides.
  • the presently disclosed compounds, salts, prodrugs and N-oxides can be provided, for example, in solvate or hydrate form.
  • isotopes includes those atoms having the same atomic number but different mass numbers.
  • certain atoms can be enriched an isotope of that atom.
  • compounds having a fluorine atom may be synthesized in a form enriched in the radioactive fluorine isotope 18 F.
  • compounds may be enriched in the heavy isotopes of hydrogen, deuterium and tritium, and can be enriched in a radioactive isotope of carbon, such as 13 C.
  • Such compounds can be useful, for example, in studying the AMPK pathway and its role in metabolism.
  • Compounds can be assayed for binding to a membrane-bound adiponectin receptor by performing a competitive binding assay with adiponectin.
  • HEK 293 cellular membrane is coated onto a COSTAR 384 plate, which is then blocked with 1% casein.
  • Polyhistidine-tagged globular adiponectin and a candidate compound is incubated with the membrane in HEPES buffer. Unbound ligands are washed away and the degree of binding of the adiponectin is determined using horseradish peroxidase-conjugated anti- polyhistidine.
  • Compounds that compete with adiponectin binding to the membrane ⁇ i.e., give a reduced signal compared to a control performed without a candidate compound) can be chosen as hits and further screened using the below-described functional assays to identify adiponectin receptor agonists.
  • An in-cell western assay can be performed to demonstrate the activation of AMPK in human liver cells by globular adiponectin using glutathione S-transferase (GST).
  • GST glutathione S-transferase
  • AMPK activity can be measured by the relative concentration of phosphorylated acetyl Co-A carboxylase, which is one of the products of AMPK.
  • An increase in pACC correlates with an increase in the rate of fatty acid oxidation.
  • the compounds of structural formulae (I)-(CXXIV) can be administered, for example, orally, topically, parenterally, by inhalation or spray or rectally in dosage unit formulations containing one or more pharmaceutically acceptable carriers, diluents or excipients.
  • parenteral as used herein includes percutaneous, subcutaneous, intravascular (e.g., intravenous), intramuscular, or intrathecal injection or infusion techniques and the like.
  • Pharmaceutical compositions can be made using the presently disclosed compounds.
  • a pharmaceutical composition includes a pharmaceutically acceptable carrier, diluent or excipient, and compound as described above with reference to structural formulae (I)-(CXXIV).
  • one or more compounds of structural formulae (I)-(CXXIV) may be present in association with one or more pharmaceutically acceptable carriers, diluents or excipients, and, if desired, other active ingredients.
  • the pharmaceutical compositions containing compounds of structural formulae (I)-(CXXIV) may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or elixirs.
  • compositions intended for oral use can be prepared according to any suitable method for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preservative agents in order to provide pharmaceutically elegant and palatable preparations.
  • Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets.
  • excipients can be for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc.
  • the tablets can be uncoated or they can be coated by known techniques. In some cases such coatings can be prepared by suitable techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period.
  • a time delay material such as glyceryl monostearate or glyceryl distearate can be employed.
  • Formulations for oral use can also be presented as hard gelatin capsules, wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.
  • Formulations for oral use can also be presented as lozenges.
  • Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions.
  • excipients can be suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydropropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents such as a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate.
  • dispersing or wetting agents such as a naturally-occurring phosphatide, for example, lecithin, or
  • the aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin.
  • Oily suspensions can be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin.
  • the oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents and flavoring agents may be added to provide palatable oral preparations. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid.
  • Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives.
  • a dispersing or wetting agent for example sweetening, flavoring and coloring agents, can also be present.
  • compositions can also be in the form of oil-in- water emulsions.
  • the oily phase can be a vegetable oil or a mineral oil or mixtures of these.
  • Suitable emulsifying agents can be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate.
  • the emulsions can also contain sweetening and flavoring agents.
  • Syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol, glucose or sucrose. Such formulations can also contain a demulcent, a preservative, flavoring, and coloring agents.
  • the pharmaceutical compositions can be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above.
  • the sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol.
  • Suitable vehicles and solvents that can be employed are water, Ringer's solution and isotonic sodium chloride solution.
  • sterile, fixed oils can be employed as a solvent or suspending medium.
  • any bland fixed oil can be employed including synthetic mono- or diglycerides.
  • fatty acids such as oleic acid find use in the preparation of injectables.
  • Compounds of structural formulae (I)-(CXXIV) can also be administered in the form of suppositories, e.g., for rectal administration of the drug. These compositions can be prepared by mixing the compound with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols.
  • a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
  • Such materials include cocoa butter and polyethylene glycols.
  • Compounds of structural formula (I)-(CXXIV) can also be administered parenterally in a sterile medium. The drug, depending on the vehicle and concentration used, can either be suspended or dissolved in the vehicle.
  • adjuvants such as local anesthetics, preservatives and buffering agents can be dissolved in the vehicle.
  • the compounds disclosed herein can be made using procedures familiar to the person of ordinary skill in the art and as described herein.
  • compounds of structural formulae (V)-(VI) can be prepared according to Scheme 1 , below, or analogous synthetic schemes:
  • a 4-aminoresorcinol i for example, is reacted with methyl trimethoxyacetate to form a methyl hydroxybenzo[ ⁇ f]oxazolecarboxylate ii, which in turn is saponified then condensed with a heterocycloalkylamine (e.g., a protected 4-aminopiperidine) to form an N-heterocycloalkyl hydroxybenzo[ ⁇ i]oxazolecarboxamide iv.
  • a heterocycloalkylamine e.g., a protected 4-aminopiperidine
  • Hydroxybenzo[ ⁇ fjoxazolecarboxamide iv is coupled with, for example, a 1 -substituted piperidin-4-ol (e.g., l-(4-(trifluoromethyl)phenyl)piperidin-4-ol) to form an N-substituted- heterocycloalkyloxybenzofffloxazolecarboxamide v.
  • a 1 -substituted piperidin-4-ol e.g., l-(4-(trifluoromethyl)phenyl)piperidin-4-ol
  • the heterocycloalkyl moiety of the carboxamide can then be further substituted.
  • thiazole carboxamide v is coupled with, for example, a 1 -substituted piperidin-4-ol (e.g., l-(4-trifluoromethylphenyl)piperidin-4-ol) then deprotected to form an N-substituted-heterocycloalkyloxybenzofdjthiazolecarboxamide vi.
  • the heterocycloalkyl moiety of the carboxamide can then be further substituted.
  • the N-substituent of the amide is a 1 -protected piperidin-4-yl
  • the protecting group can be removed and the piperidine nitrogen can be coupled with an arylmethyl halide (or e.g. an aroyl halide) to form compound viii.
  • an arylmethyl halide or e.g. an aroyl halide
  • a 2-amino-4-methoxypyridine is reacted with ethyl 3- bromo-2-oxopropanoate to form an ethyl 7-methoxyimidazo[l,2- ⁇ ]pyridine-2-carboxylate ii, which is hydrolyzed, for example, with hydrobromic acid to provide 7-hydroxyimidazo[l,2- ⁇ ]pyridine-2-carboxylic acid as its hydrobromide salt iii.
  • the 7-hydroxyimidazo[l,2- ⁇ ]pyridine-2-carboxylic acid iii is then condensed with a heterocycloalkylamine (e.g., a protected 4-aminopiperidine) to form an N-heterocycloalkyl 7-hydroxyimidazo[l,2- ⁇ ]pyridine-2-carboxamide iv.
  • a heterocycloalkylamine e.g., a protected 4-aminopiperidine
  • 7-Hydroxyimidazo[l,2- ⁇ ]pyridine-2-carboxamide iv is coupled with, for example, a 1 -substituted piperidin-4-ol (e.g., l-(4- trifluoromethylphenyl)piperidin-4-ol) to form an N-substituted- heterocycloalkyloxyimidazo[l,2- ⁇ ]pyridinecarboxamide v.
  • the heterocycloalkyl moiety of the carboxamide can then be further substituted.
  • the N-substituent of the amide is a 1 -protected piperidin-4-yl
  • the protecting group can be removed and the piperidine nitrogen can be coupled with an arylmethyl halide (or alternatively an aroyl halide) to form compound vii.
  • an arylmethyl halide or alternatively an aroyl halide
  • a methyl chloropyrazine-2-carboxylate i for example, is reacted with a 1-substituted piperidin-4-ol (e.g., l-(4-trifluoromethylphenyl)piperidin-4-ol) to form a methyl (piperidin-4-yloxy)pyrazine-2-carboxylate ii, which in turn is saponified and then acidified to form the corresponding carboxylic acid iii.
  • piperidin-4-ol e.g., l-(4-trifluoromethylphenyl)piperidin-4-ol
  • the (piperidin-4- yloxy)pyrazine-2-carboxylic acid iii is condensed with a heterocycloalkylamine (e.g., a protected 4-aminopiperidine) to form an N-substituted- heterocycloalkyloxypyrazinecarboxamide iv.
  • a heterocycloalkylamine e.g., a protected 4-aminopiperidine
  • the heterocycloalkyl moiety of the carboxamide can then be further substituted.
  • the N-substituent of the amide is a 1 -protected piperidin-4-yl
  • the protecting group can be removed and the piperidine nitrogen can be coupled with an arylmethyl halide (or alternatively an aroyl halide) to form compound vi.
  • an arylmethyl halide or alternatively an aroyl halide
  • a bromothiazolecarboxylic acid i can be condensed with an appropriately substituted heterocycloalkylamine (e.g., 4-((4-aminopiperidin- 1 - yl)methyl)benzonitrile in the example of Scheme 1) to form the TV-heterocycloalkyl bromothiazolecarboxamide ii.
  • an appropriately substituted heterocycloalkylamine e.g., 4-((4-aminopiperidin- 1 - yl)methyl
  • Bromothiazolecarboxamide ii can then be coupled with, for example, a 1 -substituted piperidin-4-ol (e.g., 1 -(4-trifluoromethylphenyl)piperidin-4-ol) to form an N-substituted heterocycloalkyloxybromothiazolecarboxamide iii.
  • a 1 -substituted piperidin-4-ol e.g., 1 -(4-trifluoromethylphenyl)piperidin-4-ol
  • a 1 -substituted piperidin-4-ol e.g., 1 -(4-trifluoromethylphenyl)piperidin-4-ol
  • carboxylic acid ester i can be condensed with an appropriately substituted heterocycloalkylamine (e.g., 4-((4-aminopiperidin- 1 - yl)methyl)benzonitrile in the example of Scheme 6) to form the methyl (heterocycloalkylcarbamoy ⁇ benzoate ii.
  • an appropriately substituted heterocycloalkylamine e.g., 4-((4-aminopiperidin- 1 - yl)methyl
  • Benzoate ii can then be saponified to form the corresponding benzoic acid iii, which is then coupled with an appropriate amine (e.g., a substituted piperidine as shown in Scheme 6, or alternatively a substituted piperazine, or a substituted piperidinylamine) to form an N-substituted terephthalamide ii.
  • an appropriate amine e.g., a substituted piperidine as shown in Scheme 6, or alternatively a substituted piperazine, or a substituted piperidinylamine
  • an appropriate amine e.g., a substituted piperidine as shown in Scheme 6, or alternatively a substituted piperazine, or a substituted piperidinylamine
  • a cyano-1, 2,3, 4-tetrahydroisoquino line i can be converted to the corresponding methyl ester ii, then reductively coupled with an aryl aldehyde to form a methyl 2-benzyl-l,2,3,4-tetrahydroisoquinoline carboxylate iii.
  • Saponification of iii to its corresponding carboxylic acid iv followed by condensation with a heterocycloalkylamine in this case, a 1 -benzylpiperidin-4-ylamine
  • a heterocycloalkylamine in this case, a 1 -benzylpiperidin-4-ylamine
  • the person of skill in the art can modify this scheme to provide the desired substitution and regiochemistry of the final compound.
  • one of ordinary skill in the art will use different reagents to affect one or more of the individual steps or to use protected versions of certain of the substituents. Specific synthetic examples are provided below in Example 7.
  • Compounds suitable for use in the presently disclosed pharmaceutical compositions include compounds of Table 1, above. These compounds can be made according to the general schemes described above, for example using a procedure similar to that described below in the Examples.
  • compounds of structural formulae (I)-(CXXIV) are mimics of adiponectin which act as adiponectin receptor agonists, thereby activating the AMPK pathway.
  • Activation of the AMPK pathway has the effect of increasing glucose uptake, decreasing glycogen synthesis and increasing fatty acid oxidation, thereby reducing glycogen, intracellular triglyceride and fatty acid concentration and causing an increase in insulin sensitivity.
  • compounds of structural formulae (I)-(CXXIV) should also inhibit the inflammatory processes which occur during the early phases of atherosclerosis. Accordingly, compounds of structural formulae (I)-(CXXIV) can be useful in the treatment of type II diabetes and in the treatment and prevention of atherosclerosis, cardiovascular disease, obesity and non-alcoholic fatty liver disease.
  • a method for activating the AMPK pathway in a cell includes contacting the cell with an effective amount of a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • a method of increasing fatty acid oxidation in a cell includes contacting the cell with an effective amount of a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • Acetyl Co-A carboxylase (ACC) catalyzes the formation of malonyl Co-A, a potent inhibitor of fatty acid oxidation; phosphorylation of ACC greatly reduces its catalytic activity, thereby reducing the concentration of malonyl Co-A and increasing the rate of fatty acid oxidation. Because the presently disclosed compounds can increase the rate of phosphorylation of ACC, they can reduce the inhibition of fatty acid oxidation and therefore increase its overall rate.
  • a method of decreasing glycogen concentration in a cell includes contacting the cell with an effective amount of a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • a method of increasing glucose uptake in a cell includes contacting the cell with an effective amount of a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • a method of reducing triglyceride levels in a subject includes administering to the subject an effective amount of a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • a method of increasing insulin sensitivity of a subject includes administering to the subject an effective amount of a compound, pharmaceutically acceptable salt prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • a method of treating type II diabetes in a subject in need of such treatment includes administering to the subject an effective amount of a compound, pharmaceutically acceptable salt, prodrug, solvate, hydrate, N-oxide or composition described above.
  • a method of treating or preventing atherosclerosis or cardiovascular disease in a subject includes administering to the subject an effective amount of a compound, pharmaceutically acceptable salt, prodrug prodrug, N-oxide (or solvate or hydrate thereof) or composition described above.
  • the compounds disclosed herein can act as activators of the AMPK pathway.
  • a method comprises modulating the AMPK pathway (either in vitro or in vivo) by contacting a cell with a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above, or administering a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition described above to a mammal (e.g., a human) in an amount sufficient to modulate the AMPK activity and study the effects thereby induced.
  • a mammal e.g., a human
  • Such methods are useful for studying the AMPK pathway and its role in biological mechanisms and disease states both in vitro and in vivo.
  • Another embodiment is the use of a compound, pharmaceutically acceptable salt, prodrug, N-oxide (or solvate or hydrate thereof) or composition as described above in the manufacture of a medicament for any of the therapeutic purposes described above.
  • the medicament can be for the reduction of triglyceride levels in a subject, the treatment of type II diabetes in a subject, or the treatment or prevention of atherosclerosis or cardiovasclular disease in a subject.
  • the compounds disclosed herein can be linked to labeling agents, for example for use in variety of experiments exploring their receptor binding, efficacy and metabolism.
  • another embodiment is a labeled conjugate comprising a compound as disclosed herein covalently linked to a labeling agent, optionally through a linker.
  • the labeling agent can be, for example, an affinity label such as biotin or strepavidin, a hapten such as digoxigenin, an enzyme such as a peroxidase, or a fluorophoric or chromophoric tag.
  • Any suitable linker can be used.
  • an ethylene glycol, oligo(ethylene glycol) or poly(ethylene glycol) linker is used.
  • Other examples of linkers include amino acids, which can be used alone or in combination with other linker groups, such as ethylene glycol, oligoethylene glycol or polyethylene glycol.
  • Suitable linkers include, without limitation, single amino acids, as well as di- and tripeptides.
  • the linker includes a glycine residue.
  • an alkylene chain is the linker.
  • the linker has the structure -[(C0-C3 alkyl)-Y m -] m -, in which each Y m is -O-, -N(R 9 )-, or L, and m is in the range of 1-40.
  • a labeled conjugate has structural formula (CXXV):
  • the "LINK” moiety is a linker and is optional, and the "LABEL” moiety is a labeling agent, and all other variables are as described above, for example with reference to structural formula (I).
  • Any of the compounds disclosed with reference to structural formulae (I)-(CXXIV) can be used in the labeled conjugate of structural formula (CXXV).
  • the -(LINK) 0 . 1 -(LABEL) moiety is attached the "B" ring system at a benzo, pyrido, pyrazino or thieno ring position in the meta position relative to the J moiety.
  • a labeled conjugate has structural formula (CXXVI):
  • a labeled conjugate has structural formula (CXXVII):
  • Compounds 14-16 were assayed for their ability to activate AMPK using an enzyme-linked immunosorbent assay.
  • the EC50 values for AMPK activation for compounds 14-16 are presented in Table 3 below, in which "A” is less than 0.1 ⁇ M; “B” is 0.1-1 ⁇ M; “C” is 1-10 ⁇ M; and “D” is 10-100 ⁇ M:
  • N-(l-(4-Cyanobenzyl)piperidin-4-yl)-2-(4-fluorobenzyl)-l,2,3,4- tetrahydroisoquinoline-7-carboxamide (compound 40) was prepared from methyl 2-(4- fluorobenzyl)-l,2,3,4-tetrahydroisoquinoline-7-carboxylate as described in step 4 of Example 7(a) above to yield the compound as a tan crystalline solid (70 mg, 83%).

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PCT/US2009/041448 2008-04-23 2009-04-22 Carboxamide compounds for the treatment of metabolic disorders Ceased WO2009132136A1 (en)

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HK11107056.3A HK1152939B (en) 2008-04-23 2009-04-22 Carboxamide compounds for the treatment of metabolic disorders
EA201071231A EA021119B1 (ru) 2008-04-23 2009-04-22 Карбоксамидные соединения для лечения метаболических расстройств
KR1020107026058A KR101662333B1 (ko) 2008-04-23 2009-04-22 대사성 장애의 치료를 위한 카르복스아미드 화합물
CN200980123855.0A CN102099357B (zh) 2008-04-23 2009-04-22 用于治疗代谢障碍的甲酰胺化合物
ES09734272.9T ES2552549T3 (es) 2008-04-23 2009-04-22 Compuestos de carboxamida para el tratamiento de trastornos metabólicos
MX2010011288A MX2010011288A (es) 2008-04-23 2009-04-22 Compuestos de carboxamida para el tratamiento de trastornos metabolicos.
UAA201013901A UA103767C2 (ru) 2008-04-23 2009-04-22 Карбоксамидные соединения для лечения метаболических расстройств
JP2011506436A JP5658138B2 (ja) 2008-04-23 2009-04-22 代謝障害の処置のためのカルボキサミド化合物
AU2009240643A AU2009240643B2 (en) 2008-04-23 2009-04-22 Carboxamide compounds for the treatment of metabolic disorders
CA2722139A CA2722139C (en) 2008-04-23 2009-04-22 Carboxamide compounds for the treatment of metabolic disorders
BRPI0911681A BRPI0911681B8 (pt) 2008-04-23 2009-04-22 composto, composição farmacêutica, e, método para ativar a via de proteína quinase ativada por 5'-amp em uma célula in vitro
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NZ588652A (en) 2012-09-28
JP2015028046A (ja) 2015-02-12
CN106928211B (zh) 2020-09-08
US8314107B2 (en) 2012-11-20
CN104016980B (zh) 2016-12-07
JP5964906B2 (ja) 2016-08-03
JP2011527665A (ja) 2011-11-04
HK1152939A1 (en) 2012-03-16
JP5658138B2 (ja) 2015-01-21
MX2010011288A (es) 2010-11-09
CN102099357B (zh) 2014-07-02
CN104016980A (zh) 2014-09-03
US20140148467A1 (en) 2014-05-29
BRPI0911681B8 (pt) 2021-05-25
US20160122321A1 (en) 2016-05-05
KR101662333B1 (ko) 2016-10-04
US20150011582A1 (en) 2015-01-08
ZA201007127B (en) 2011-12-28
BRPI0911681A2 (pt) 2017-05-02
EA021119B1 (ru) 2015-04-30
US20090275609A1 (en) 2009-11-05
KR20110002484A (ko) 2011-01-07
US9255085B2 (en) 2016-02-09
IL208513A0 (en) 2010-12-30
EP2276761A1 (en) 2011-01-26
US9353111B2 (en) 2016-05-31
CA2722139C (en) 2017-04-11
AU2009240643A1 (en) 2009-10-29
US20130023660A1 (en) 2013-01-24
BRPI0911681B1 (pt) 2020-11-10
US8785449B2 (en) 2014-07-22
CN102099357A (zh) 2011-06-15
AU2009240643B2 (en) 2014-03-06
EP2276761B1 (en) 2015-07-29
US20150232451A1 (en) 2015-08-20
CA2722139A1 (en) 2009-10-29
US9062052B2 (en) 2015-06-23
CN106928211A (zh) 2017-07-07

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