Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

FLUORINATED INTEGRIN ANTAGONISTS

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof. 2. The method of claim 1 , wherein R and R′ are each H.4. The method of claim 3 , wherein X is N and Y is CH.5. The method of claim 3 , wherein X and Y are each CH.6. The method of claim 3 , wherein X and Y are each N.7. The method of claim 3 , wherein Ris straight chain C-Cor branched C-Calkyl claim 3 , and is substituted with 1 claim 3 , 2 claim 3 , 3 claim 3 , 4 claim 3 , 5 claim 3 , 6 claim 3 , 7 claim 3 , 8 claim 3 , or 9 fluorine atoms.8. The method of claim 3 , wherein Ris methyl substituted with 1 claim 3 , 2 claim 3 , or 3 fluorine atoms.9. The method of claim 3 , wherein Ris straight chain C-Cor branched C-Calkoxy claim 3 , and is substituted with 0 claim 3 , 1 claim 3 , 2 claim 3 , 3 claim 3 , 4 claim 3 , 5 claim 3 , 6 claim 3 , or 7 fluorine atoms.10. The method of claim 9 , wherein Ris methoxy substituted with 0 claim 9 , 1 claim 9 , 2 claim 9 , or 3 fluorine atoms.12. The method of claim 11 , wherein X is N and Y is CH; and Ris OCHF.13. The method of claim 11 , wherein X and Y are each N; and Ris CF.17. The method of claim 1 , wherein the αv integrin is an αvβ33 or αvβ5 integrin.18. The method of claim 1 , wherein the disease or condition is selected from the group consisting of macular degeneration claim 1 , diabetic retinopathy (DR) claim 1 , macular edema claim 1 , diabetic macular edema (DME) claim 1 , and macular edema following retinal vein occlusion (RVO).19. The method of claim 1 , further comprising administering a second therapy.20. The method of ...

Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.

DIARYL ETHER DERIVATIVES AS NOTCH SPARING GAMMA SECRETASE INHIBITORS

The invention encompasses a novel class of diaryl ether derivatives which inhibit the processing of APP by the putative γ-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included. 2. The compound according to wherein Ris bonded to one of the nitrogen atoms of the pyrazole ring and represents a hydrocarbon group of 1-5 carbon atoms which is optionally substituted with up to 3 halogen atoms or hydroxy.3. The compound according to wherein Ar represent phenyl claim 2 , which bears 0-3 substituents independently selected from R.4. The compound according to wherein Ar represents 4-CF-phenyl.5. The compound according to wherein Ris bonded to one of the nitrogen atoms of the pyrazole ring and represents ethyl.6. The compound according to wherein A represents —C(R)(R)— and B represent H.7. The compound according to wherein Rand Rare methyl.8. The compound according to wherein Rand Rare joined together with the atom to which they are attached to form cyclopropyl claim 6 , cyclobutyl or oxetanyl.10. The compound according to wherein X represents a bond.11. The compound according to wherein Rrepresent CF—CH—.12. The compound according to wherein X represents NR.13. The compound according to wherein Y and Z each represent CH.14. The compound according to wherein:Y and Z each represent CH;{'sup': '8', 'Ar represent phenyl, which bears 0-3 substituents independently selected from R;'}{'sup': '3', 'Rrepresents H;'}{'sup': '6', 'Ris bonded to one of the nitrogen atoms of the pyrazole ring and represents ethyl;'}{'sup': '7', 'Rrepresents H;'}{'sup': 4', '5, 'A represents —C(R)(R)— and B represent H;'}{'sup': 4', '5', '4', '5, 'Rand Rare methyl or Rand Rare joined together with the atom to which they are attached to form cyclopropyl, cyclobutyl or oxetanyl; and'}{'sup': '2', 'X ...

SPIROCYCLIC COMPOUNDS

The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo. 6. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to any one of to , and a pharmaceutically acceptable carrier.7. The use of the compound according to any one of to for the preparation of a medicament useful in the treatment or prevention of cancer in a mammal. This application is a divisional application of U.S. application Ser. No. 12/085,396, which is a §371 application of PCT/US06/044754 that was filed on Nov. 17, 2006, which claims priority from the U.S. Provisional Application No. 60/739,324, filed on Nov. 23, 2005, now expired.The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present ...

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

FLUORINATED 3-(2-OXO-3-(3-ARYLPROPYL)IMIDAZOLIDIN-1-YL)-3-ARYLPROPANOIC ACID DERIVATIVES

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described. 6. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.7. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 2 , diluent claim 2 , or excipient.8. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 3 , diluent claim 3 , or excipient.9. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 4 , diluent claim 4 , or excipient.10. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 5 , diluent claim 5 , or excipient.11. A method of treating and/or preventing a condition claim 1 , eliciting an integrin receptor antagonizing effect claim 1 , inhibiting bone resorption claim 1 , or treating tumor growth in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of .12. A method of treating and/or preventing a condition claim 2 , eliciting an integrin receptor antagonizing effect claim 2 , inhibiting bone resorption claim 2 , or treating tumor growth in a subject in need thereof claim 2 , comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in ...

Fluorinated 3-(2-Oxo-3-(3-Arylpropyl)Imidazolidin-1-yl)-3-Arylpropanoic Acid Derivatives

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3 -arylpropyl)imidazolidin-1-yl)-3 -arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described. 6. The method of claim 1 , wherein said compound is administered orally claim 1 , intravenously claim 1 , intraperitoneally claim 1 , topically claim 1 , subcutaneously claim 1 , intramuscularly claim 1 , or transdermally.7. The method of claim 6 , wherein the compound is administered topically.8. The method of claim 1 , further comprising administering a second therapy.10. The method of claim 9 , wherein the second therapy comprises administering an inhibitor of VEGF.13. The method of claim 1 , wherein said condition is selected from the group consisting of bone resorption claim 1 , osteoporosis claim 1 , restenosis claim 1 , diabetic retinopathy claim 1 , macular degeneration claim 1 , angiogenesis claim 1 , atherosclerosis claim 1 , inflammation claim 1 , viral disease claim 1 , cancer claim 1 , tumor growth claim 1 , and metastasis.14. The method of claim 1 , wherein said condition is selected from the group consisting of cancer and osteoporosis.15. The method of claim 1 , wherein said condition is osteoporosis.16. The method of claim 1 , wherein said integrin receptor antagonizing effect is selected from the group consisting of an αvβ3 integrin antagonizing effect claim 1 , an αvβ5 integrin antagonizing effect claim 1 , an αvβ6 integrin antagonizing effect claim 1 , and combinations thereof.17. The method of claim 16 , wherein said integrin receptor antagonizing effect is an αvβ3 integrin antagonizing effect and said antagonizing effect is selected from the group consisting of inhibition of bone resorption claim 16 , restenosis claim 16 , angiogenesis claim 16 , diabetic retinopathy claim 16 , macular degeneration claim 16 , inflammation claim 16 , viral disease claim 16 , tumor growth ...

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.

FLUORINATED 3-(2-OXO-3-(3-ARYLPROPYL)IMIDAZOLIDIN-1-YL)-3-ARYLPROPANOIC ACID DERIVATIVES

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described. 8. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.9. The pharmaceutical composition of claim 8 , further comprising an additional active ingredient selected from the group consisting ofa) an organic bisphosphonate or a pharmaceutically acceptable salt or ester thereof,b) an estrogen receptor modulator,c) a cytotoxic/antiproliferative agent,d) a matrix metalloproteinase inhibitor,e) an inhibitor of epidermal-derived, fibroblast-derived, or platelet-derived growth factors,f) an inhibitor of VEGF,g) an inhibitor of Flk-1/KDR, Flt-1, Tck/Tie-2, or Tic-1,h) a cathepsin K inhibitor, andi) a prenylation inhibitor,and a mixture thereof.10. The pharmaceutical composition of claim 9 , wherein the additional active ingredient is selected from the group consisting of a) an organic bisphosphonate or a pharmaceutically acceptable salt or ester thereof claim 9 , b) an estrogen receptor modulator claim 9 , and c) a cathepsin K inhibitor claim 9 , and a mixture thereof.11. The pharmaceutical composition of claim 10 , wherein the additional active ingredient is an organic bisphosphonate or pharmaceutically acceptable salt or ester.12. The pharmaceutical composition of claim 11 , wherein the additional active ingredient is alendronate monosodium trihydrate.13. The pharmaceutical composition of claim 9 , wherein the additional active ingredient is selected from the group consisting of a) a cytotoxic/antiproliferative agent claim 9 , b) a matrix metalloproteinase inhibitor claim 9 , c) an inhibitor of epidermal-derived claim 9 , fibroblast-derived claim 9 , or platelet-derived growth ...

FLUORINATED INTEGRIN ANTAGONISTS

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof. This application is a continuation of U.S. Ser. No. 16/717,403, filed on Dec. 17, 2019, which is a continuation of U.S. Ser. No. 16/409,960, filed on May 13, 2019 (now abandoned), which is a continuation of U.S. Ser. No. 16/133,094, filed on Sep. 17, 2018 (now abandoned), which is a continuation of U.S. Ser. No. 15/633,946, filed on Jun. 27, 2017 (now U.S. Pat. No. 10,106,537), which is a continuation of U.S. Ser. No. 15/343,823, filed on Nov. 4, 2016 (now U.S. Pat. No. 9,717,729), which is a continuation of U.S. Ser. No. 14/766,322, filed on Aug. 6, 2015 (now U.S. Pat. No. 9,518,053), which is a U.S. National Phase application of International Application No. PCT/US2014/015372, filed on Feb. 7, 2014, which claims priority to and the benefit of U.S. Ser. No. 61/762,087, filed on Feb. 7, 2013, and U.S. Ser. No. 61/900,706, filed on Nov. 6, 2013, the contents of each of which are incorporated herein by reference in their entireties.Age-related macular degeneration (AMD) is the leading cause of blindness in people over the age of 55; and diabetic retinopathy (DR) is the leading cause in people under 55 (Klein, 1994; Williams, 2004). Both diseases are characterized by new blood vessel growth—choriodal neovascularization in AMD and retinal neovascularization in DR (Freund, 1993; Speicher, 2003; Zarbin, 2004). Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye (a yellow central area of the retina) and cause it to thicken and swell ( ...

Fluorinated 3-(2-Oxo-3-(3-Arylpropyl)Imidazolidin-1-yl)-3-Arylpropanoic Acid Derivatives

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described. 6. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.7. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 2 , diluent claim 2 , or excipient.8. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 3 , diluent claim 3 , or excipient.9. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 4 , diluent claim 4 , or excipient.10. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 5 , diluent claim 5 , or excipient.11. A method of treating and/or preventing a condition claim 1 , eliciting an integrin receptor antagonizing effect claim 1 , inhibiting bone resorption claim 1 , or treating tumor growth in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of .12. A method of treating and/or preventing a condition claim 2 , eliciting an integrin receptor antagonizing effect claim 2 , inhibiting bone resorption claim 2 , or treating tumor growth in a subject in need thereof claim 2 , comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in ...

FLUORINATED 3-(2-OXO-3-(3-ARYLPROPYL)IMIDAZOLIDIN-1-YL)-3-ARYLPROPANOIC ACID DERIVATIVES

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described. 6. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.7. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 2 , diluent claim 2 , or excipient.8. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 3 , diluent claim 3 , or excipient.9. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 4 , diluent claim 4 , or excipient.10. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of and a pharmaceutical carrier claim 5 , diluent claim 5 , or excipient.11. A method of treating and/or preventing a condition claim 1 , eliciting an integrin receptor antagonizing effect claim 1 , inhibiting bone resorption claim 1 , or treating tumor growth in a subject in need thereof claim 1 , comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of .12. A method of treating and/or preventing a condition claim 2 , eliciting an integrin receptor antagonizing effect claim 2 , inhibiting bone resorption claim 2 , or treating tumor growth in a subject in need thereof claim 2 , comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in ...

FLUORINATED INTEGRIN ANTAGONISTS

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof. 2. The compound of claim 1 , wherein R and R′ are each H.5. The compound of claim 1 , wherein Ris F.6. The compound of claim 1 , wherein Ris F and Ris H.7. The compound of claim 1 , wherein Ris CHF claim 1 , CHF claim 1 , or CF.8. The compound of claim 1 , wherein Ris F.9. The compound of claim 1 , wherein Ris F and Ris H.10. The compound of claim 1 , wherein Ris CHF claim 1 , CHF claim 1 , or CF.11. The compound of claim 1 , wherein Rand Rare each F.15. The method of claim 14 , wherein X is N and Y is CH.16. The method of claim 14 , wherein X and Y are each CH.17. The method of claim 14 , wherein X and Y are each N.19. The method of claim 13 , wherein the disease or condition is a disease or condition in which angiogenesis is involved.20. The method of claim 13 , wherein the disease is bone resorption claim 13 , osteoporosis claim 13 , vascular restenosis claim 13 , diabetic retinopathy claim 13 , macular degeneration claim 13 , atherosclerosis claim 13 , inflammation claim 13 , viral disease claim 13 , tumor growth claim 13 , or metastasis. This application is a continuation of U.S. Ser. No. 15/343,823 (now allowed), filed on Nov. 4, 2016, which is a continuation of U.S. Ser. No. 14/766,322, filed on Aug. 6, 2015 (now U.S. Pat. No. 9,518,053), which is a U.S. National Phase application of International Application No. PCT/US2014/015372, filed on Feb. 7, 2014, which claims priority to and the benefit of U.S. Ser. No. 61/762,087, filed on Feb. 7, 2013, and U.S. Ser. No. ...

Histone deacetylase inhibitors with aryl-pyrazolyl-motifs

The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

Silicon derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of Silicon derivatives. The Silicon compounds can be used to treat cancer. The Silicon compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the Silicon derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the Silicon derivatives in vivo.

Hydroxyalkylarylamide derivatives

The present invention relates to a novel class of hydroxyalkylarylamide derivatives. The instant compounds can be used to treat cancer. The fluorinated arylamide derivatives can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

Pyridyl derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of pyridyl and pyrimidinyl derivatives. The pyridyl and pyrimidinyl compounds can be used to treat cancer. The pyridyl and pyrimidinyl compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the pyridyl and pyrimidinyl derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the pyridyl and pyrimidinyl derivatives in vivo.

Hydroxyalkylarylamide derivatives

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

Pyridyl and pyrimidinyl derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of pyridyl and pyrimidinyl derivatives. The pyridyl and pyrimidinyl compounds can be used to treat cancer. The pyridyl and pyrimidinyl compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the pyridyl and pyrimidinyl derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the pyridyl and pyrimidinyl derivatives in vivo.

Spirocyclic compounds

The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR 1 2 , NR 1a , C(O) and O; E is selected from a bond, CR 1 2 , NR 1a , C(O) and O; wherein at least one of A, B, D or E is CR 1 2 ; and provided that when A is O, then E is not O; G is CR 1 2 ; R is selected from NH 2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

Spirocyclic compounds as hdac inhibitors

The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR1 2, NRla, C(O) and O; E is selected from a bond, CR1 2. NR1 a, C(O) and O; wherein at least one of A, B, D or E is CR1 2; and provided that when A is O, then E is not O; G is CRl 2; R is selected from NH2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

Sulfated glycosaminoglycan biomaterials as proteoglycan mimics

Polymer conjugates are provided that are capable of mimicking functions of natural proteoglycans found in the extracellular matrix of connective tissues. The polymer conjugates of the invention have utility in treating a subject suffering soft tissue degenerative conditions. Also provided are simple and scalable chemical processes for the preparation of the polymer conjugates of the invention.

Pyridyl and pyrimidinyl derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of pyridyl and pyrimidinyl derivatives. The pyridyl and pyrimidinyl compounds can be used to treat cancer. The pyridyl and pyrimidinyl compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the pyridyl and pyrimidinyl derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the pyridyl and pyrimidinyl derivatives in vivo.

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Phosphorus derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the phosphorus derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the phosphorus derivatives in vivo.

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Hydrazinyl lipidoids and uses thereof

The present disclosure is directed to hydrazinyl lipidoids, formulations thereof further comprising at least one active agent, as well as methods of delivering the at least one active agent to a target organism. The present disclosure also relates generally to methods of preparing such hydrazinyl lipidoids, their formulation with one or more active agents, and the delivery of such formulations to target organisms.

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Spirocyclic compounds as hdac inhibitors

The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR1 2, NRla, C(O) and O; E is selected from a bond, CR1 2. NR1 a, C(O) and O; wherein at least one of A, B, D or E is CR1 2; and provided that when A is O, then E is not O; G is CRl 2; R is selected from NH2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

Diaryl ether derivatives as notch sparing gamma secretase inhibitors

The invention encompasses a novel class of diaryl ether derivatives which inhibit the processing of APP by the putative ϒ-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included.

Hydrazinyl lipidoids and uses thereof

The present disclosure is directed to hydrazinyl lipidoids, formulations thereof further comprising at least one active agent, as well as methods of delivering the at least one active agent to a target organism. The present disclosure also relates generally to methods of preparing such hydrazinyl lipidoids, their formulation with one or more active agents, and the delivery of such formulations to target organisms.

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

Spirocyclic compounds as hdac inhibitors

The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR12, NRla, C(O) and O; E is selected from a bond, CR12. NR1 a, C(O) and O; wherein at least one of A, B, D or E is CR12; and provided that when A is O, then E is not O; G is CRl2; R is selected from NH2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.

Fluorinated .alpha..nu.integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Phosphorus derivatives as histone deacetylase inhibitors

The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the phosphorus derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the phosphorus derivatives in vivo.

Diaryl ether derivatives as notch sparing gamma secretase inhibitors

The invention encompasses a novel class of diaryl ether derivatives which inhibit the processing of APP by the putative γ-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included.

Fluorescent compounds that bind to histone deacetylase

The present invention relates to a novel class of fluorescent compounds that bind to histone deacetylases. The fluorescent compounds can be used to determine binding association and dissociation rates of histone deacetylase inhibitors via fluorescence polarization.

Sulfated glycosaminoglycan biomaterials as proteoglycan mimics

Sulfated glycosaminoglycan biomaterials as proteoglycan mimics

Polymer conjugates are provided that are capable of mimicking functions of natural proteoglycans found in the extracellular matrix of connective tissues. The polymer conjugates of the invention have utility in treating a subject suffering soft tissue degenerative conditions. Also provided are simple and scalable chemical processes for the preparation of the polymer conjugates of the invention.

Fluorinated integrin antagonists

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Macrolactam compounds and methods for the treatment of malaria

The present invention relates to a macrolactam compound, and methods for treating a subject with malaria using the macrolactam compound, represented by the following structural formula (l), wherein the values and preferred values of the variables are defined herein.

Cyclobutyl sulfones as notch sparing gamma secretase inhibitors

The invention encompasses a novel class of cyclobutyl sulfone derivatives which inhibit the processing of APP by the putative γ-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included.

Macrolactam compounds and methods for the treatment of malaria

The present invention relates to a macrolactam compound, and methods for treating a subject with malaria using the macrolactam compound, represented by structural formula (l), wherein the values and preferred values of the variables are defined herein.

Macrolactam compounds and methods for the treatment of malaria

The present invention relates to a macrolactam compound, and methods for treating a subject with malaria using the macrolactam compound, represented by structural formula (l), wherein the values and preferred values of the variables are defined herein.

Cyclobutyl sulfones as notch sparing gamma secretase inhibitors

Cyclobutyl sulfones as notch sparing gamma secretase inhibitors

The invention encompasses a novel class of cyclobutyl sulfone derivatives which inhibit the processing of APP by the putative γ-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included.

Sulfated Glycosaminoglycan Biomaterials as Proteoglycan Mimics

Polymer conjugates are provided that are capable of mimicking functions of natural proteoglycans found in the extracellular matrix of connective tissues. The polymer conjugates of the invention have utility in treating a subject suffering soft tissue degenerative conditions. Also provided are simple and scalable chemical processes for the preparation of the polymer conjugates of the invention.