Indoline derivatives

This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: wherein R¹ and R² may be single substituents or fused to form spirocyclic rings.

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

Contraceptive methods using benzimidazolones

This invention relates to cyclic combination therapies and regimens utilizing indoline compounds which are antagonists of the progesterone receptor and having the general structure:A is O, S, or NR<4>; B is a bond or CR<5>R<6>;R<4>, to R<6 >are H, C1 to C6 alkyl, C2 to C6 alkenyl, C2 to C6 alkynyl, C3 to C8 cycloalkyl, aryl, or heterocyclic, or R<4 >and R<5 >are fused to form a ring; R<1 >is H, OH, NH2, C1 to C6 alkyl, C3 to C6 alkenyl, alkynyl, or COR; Ris as defined; R<2 >is H, halogen, CN, NO2, C1 to C6 alkyl, C1 to C6 alkoxy, or C1 to C6 aminoalkyl; R<3 >is a substituted benzene ring, or heteroaromatic ring, in combination with a progestational agent and/or an estrogen to treat or prevent secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, carcinomas and adenocarcinomas, and contraception, among others.

Glucocortiocoid-selective antinflammatory agents

Compounds having Formula Iare useful for partially or fully antagonizing, repressing, agonizing, or modulating the glucocorticoid receptor and treating immune, autoimmune and inflammatory diseases in a mammal. Also disclosed are pharmaceutical compositions comprising compounds of Formula I and methods of inhibiting immune or autoimmune diseases in a mammal.

Benzoimidazol-2-yl pyridines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyridines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H₄ receptor activity, including allergy, asthma, autoimmune diseases, and pruritis.

BENZOFURO-AND BENZOTHIENOPYRYIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

Benzofuro-and benzothienopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis. © KIPO & WIPO 2009 ...

Substituted pyrazoles and methods of treatment with substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases or allergic conditions, including atopic allergic conditions, mediated by cathepsin S are described.

Heterocyclic Compounds

Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H₄ receptor, including allergic rhinitis.

Thieno- and furo-pyrimidine modulators of the histamine H4 receptor

Thieno- and furo-pyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as inflammation.

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4receptor

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, including allergy, asthma, autoimmune diseases, and pruritis.

Heterocyclic compounds

Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H 4 receptor, including allergic rhinitis.

GLUCOCORTICOID-SELECTIVE ANTI-INFLAMMATORY AGENTS

Compounds having Formula (I), are useful for partially or fully antagonizing, repressing, agonizing, or modulating the glucocorticoid receptor and treating immune, autoimmune and inflammatory diseases in a mammal. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I) and methods of inhibiting immune or autoimmune diseases in a mammal. © KIPO & WIPO 2007 ...

PHENYL AND PYRIDYL LTA4H MODULATORS

Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and inflammatory conditions. © KIPO & WIPO 2008 ...

Cyclothiocarbamate derivatives as progesterone receptor modulators

Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R₁ and R₂ are selected from the group of H, optionally substituted C₁ to C₆ alkyl, alkenyl, alkynyl, or alkynyl groups C₃ to C₈ cycloalkyl, aryl, substituted aryl, or heterocyclic groups, or COR^A or NR^BCOR^A; or R¹ and R² are fused to form an optionally substituted ring structure as defined herein; R^A and R^B are as defined herein; R³ is H, OH, NH₂, COR^C, or optionally substituted C₁ to C₆ alkyl, C₃ to C₆ alkenyl, or alkynyl groups; R^C is as defined herein; Q¹ is S, NR ...

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

SECONDARY ALCOHOL QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 6. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.7. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.8. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.9. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .10. The method of claim 9 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 9 , rheumatoid arthritis claim 9 , psoriasis claim 9 , chronic obstructive pulmonary disorder claim 9 , psoriatic arthritis claim 9 , ankylosing spondylitis claim 9 , neutrophilic asthma claim 9 , steroid resistant asthma claim 9 , multiple sclerosis claim 9 , and systemic lupus erythematosus.11. The method of claim 9 , wherein the disease is psoriasis.12. The method of claim 9 , wherein the disease is rheumatoid arthritis.13. The method of claim 10 , wherein the inflammatory bowel disease is ulcerative colitis.14. The method of claim 10 , wherein the inflammatory bowel disease is Crohn's disease.15. The method of claim 9 , wherein the disease is multiple sclerosis.16. The method of claim 9 , wherein the disease is neutrophilic asthma.17. The method of claim 9 , wherein the disease is steroid resistant asthma.18. The method of claim 9 , wherein the disease is psoriatic arthritis.19. The method of claim 9 , wherein the disease is ankylosing spondylitis.20. The method of claim 9 , wherein the disease is systemic lupus erythematosus.21. The method of claim 9 , wherein the disease is chronic obstructive pulmonary disorder.22. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

Benzoimidazole compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

CYCLOTHIOCARBAMATE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS

Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R1, R2, R3, R4, R5, and Q1 are defined herein.

BENZIMIDAZOLE, BENZTHIAZOLE AND BENZOXAZOLE DERIVATIVES AND THEIR USE AS LTA4H MODULATORS

Leukotriene A4 hydrolase (LTA4H) inhibitors of Formula (I), compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation. Wherein X is selected from the group consisting of NRO, and S, with R being on of H and CHY is selected from the group consisting; W is selected from the group consisting Of CH and CHR-CHwith R being one H and OH, wherein R-attached carbon member in said CHR-CH is not directly attached; R is selected from the group consisting of H, OCH, CI, F Br, OH, NH, CN, CF and CH; R is H or F; and R and R are each independently selected from various groups.5, 5111146233; 22,23233 © KIPO & WIPO 2007 ...

Combination regimens using progesterone receptor modulators

This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure:wherein R1 and R2 may be single substituents or fused to form spirocyclic or hetero-spirocyclic rings; R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 allyl C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, or substituted alknyl, CORC; RC is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; R4 is H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl alkynyl, or substituted alkynyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, amino, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; and R5 is selected from a trisubstituted benzene ring of a five or six membered ring with 1, 2, or 3 heteroatoms from the group including O, S, SO, SO2 or NR6 ...

Benzofuro- and benzothienopyrimidine modulators of the histamine H4 receptor

Benzofuro- and benzothienopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Aryl-substituted bridged or fused diamines as modulators of leukotriene A4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

QUINOXALINE COMPOUNDS

Quinoxaline compounds, compositions, methods of making them, and methods of using them in leukocyte recruitment inhibition, in modulating an H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions. Formula (I): wherein B is, independently from other member and substituent assignments, N or CR 7; Y is independently from other member and substituent assignments, O, S or NH; n is, independently from member and substituent assignments, 1 or 2. © KIPO & WIPO 2007 ...

Methylene linked quinolinyl modulators of RORt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Method for treating allergies using substituted pyrazoles

A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Tricyclic quinolinone and tricyclic quinoline androgen receptor modulator compounds and methods

Novel non-steroidal tricyclic quinolinone and tricyclic quinoline compounds and compositions that are agonists, partial agonists and/or antagonists for androgen receptors (AR), their preparation and their uses are described.

2-aminopyrimidine modulators of the histamine H4 receptor

... 2-Aminopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

用取代的吡唑治疗变态反应的方法

... 一种使用取代的吡唑类化合物治疗变应性病症，包括特应性变应性病症的方法。 ...

Thio-oxindole derivatives

This invention relates to compounds which are agonists of the progesterone receptor which have the general structure:wherein:R1, R2, R3, R4, R5 and Q1 are as defined herein, or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.

CYCLOCARBAMATE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS

This invention provides compounds of Formula (I) wherein R 1 and R 2 may be single substituents or fused to form spirocyclic or heterospirocyclic rings; R 3 is H, OH, NH 2, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 3 to C 6 alkenyl, substituted C 1 to C 6 alkenyl, alkynyl, or substituted alkynyl, COR C ; R C is H, C 1 to C 3 alkyl, substituted C 1 to C 3 alkyl, aryl, substituted aryl, C 1 to C 3 alkoxy, substituted C 1 to C 3 alkoxy, C 1 to C 3 aminoalkyl, or substituted C 1 to C 3 aminoalkyl; R 4 is H, halogen, CN, NO 2, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, alkynyl, or substituted alkynyl, C 1 to C 6 alkoxy, substituted C 1 to C 6 alkoxy, substituted C 1 to C 6 alkoxy, amino, C 1 to C 6 aminoalkyl, or substituted C 1 to C 6 aminoalkyl; and R 5 is selected from a trisubstituted benzene ring of a five or six membered ring with 1, 2, or 3 heteroatoms from the group including O, S, SO, SO 2 or NR 6 and containing one or two independent substituents from the group including ...

Cyclothiocarbamate derivatives as progesterone receptor modulators

The present invention provides compounds which are agonists of the progesterone receptor and have the structures:wherein R1 and R2 are independent substituents selected from the group of H, optionally substituted C1 to C6 alkyl, alkenyl, alkynyl, or alkynyl groups C3 to C8 cycloalkyl, aryl, substituted aryl, or heterocyclic groups, or CORA or NRBCORA; or R1 and R2 are fused to form an optionally substituted 3 to 8 membered Spiro cyclic alkyl or alkenyl ring or a Spiro cyclic ring containing one to three heteroatoms selected from O, S and N; RA is selected from H, amino, or optionally substituted C1 to C3 alkyl, aryl, C1 to C3 alkoxy, or C1 to C3 aminoalkyl groups; RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2, CORC, or optionally substituted C1 to C6 alkyl, C3 to C6 alkenyl, or alkynyl groups; RC is selected from H or optionally substituted C1 to C3 alkyl, aryl, C1 to C3 alkoxy, or C1 to C3 aminoalkyl groups; Q1 is S, NR7, or CR8R9; R5 is an optionally trisubstituted ...

Cyclocarbamate derivatives as progesterone receptor modulators

This invention provides compounds of Formula (I):wherein R<1 >and R<2 >are independent substituents or are fused to form spirocyclic rings; R<3>, R, and R<4 >are as defined herein; and R<5 >is a substituted benzene ring or a substituted five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms including O, S, SO, SO2 or NR<6>; or pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions and methods using the compounds as antagonists of the progesterone receptor.

Thio-oxindole derivatives

This invention relates to methods of co-administering compounds of formula 1 which are agonists of the progesterone receptor which have the general structure: wherein: R₁, R₂, R₃, R₄, R₅ and Q¹ are as defined herein, or a pharmaceutically acceptable salt thereof, with estrogen, an estrone, or an estrogen receptor agonist for contraception, hormone replacement therapy, or treating progesterone-related carcinomas and adenocarcinomas.

Aryl-substituted bridged or fused diamines as modulators of leukotriene A4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

THIO-OXINDOLE DERIVATIVES

This invention relates to compounds which are agonists of the progesterone receptor which have general structures (1) or (2) wherein the substituents are as defined; or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas. © KIPO & WIPO 2007 ...

Benzoimidazole compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

GLUCOCORTICOID-SELECTIVE ANTIINFLAMMATORY AGENTS

Compounds having Formula (I) are useful for partially of fully antagonizing, repressing, agonizing, or modulating the glucocorticoid receptor in a mammal and treating immune, autoimmune and inflammatory diseases in a mammal. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I) and methods of inhibiting immune or autoimmune diseases in a mammal. © KIPO & WIPO 2007 ...

Cyanopyrroles

This invention provides a progesterone receptor antagonist of formula 1 having the structure wherein T is O, S, or absent; R₁, and R₂ are each, independently, hydrogen, alkyl, substituted alkyl; or R₁ and R₂ are taken together form a ring and together contain -CH₂(CH₂)_nCH₂-, -CH₂CH₂CMe₂CH₂CH₂-, -O(CH₂)_pCH₂-, -O(CH₂)_qO-, -CH₂CH₂OCH₂CH₂-, or -CH₂CH₂NR₇CH₂CH₂-; n=1-5; p=1-4; q=1-4; R₃ is hydrogen, OH, NH₂, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR^A; R^A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R₄ is hydrogen, halogen, CN, NH_{2< ...}

3,3-substituted indoline derivatives

This invention provides compounds of the formula I:wherein:R1 and R2 are independently H, OH, OAc, alkylaryl, alkylheteroaryl, 1-propynyl, 3-propynyl, and substituted alkyl, O(alkyl), aryl, or heteroaryl;or R1 and R2 are joined to form a ring comprising -CH2(CH2)nCH2- where n=0-5; -CH2CH2C(CH3)2CH2CH2-; -O(CH2)mCH2- where m=1-4; O(CH2)pO- where p=1-4; -CH2CH2OCH2CH2-; -CH2CH2N(H or alkyl)CH2CH2-;or R1 and R2 together comprise a double bond to C(CH3)2, C(cycloalkyl), O, or C(cycloether);R3 is H, OH, NH2, COR, or optionally substituted alkenyl or alkynyl groups;R=H or optionally substituted alkyl, alkoxy, or aminoalkyl groups;R4=H, halo, CN, NH2, or optionally substituted alkyl, alkoxy, or aminoalkyl;R5 is optionally substituted benzene ring; five or six membered heterocyclic ring; 4 or 7-substituted indole or a substituted benzothiophene;or pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions and methods of using the compounds as progesterone receptor antagonists ...

Cyclothiocarbamate derivatives as progesterone receptor modulators

Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R1, R2, R3, R4, R5, and Q1 are defined herein.

Benzoimidazole compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

2-AMINOPYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

... 2-Aminopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis. COPYRIGHT KIPO & WIPO 2010 ...

Heteroaryl linked quinolinyl modulators of RORgammat

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S

Carbon-linked tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.

BENZIMIDAZOLE, BENZTHIAZOLE AND BENZOXAZOLE DERIVATIVES AND THEIR USE AS LTA4H MODULATORS

Leukotriene A4 hydrolase (LTA4H) inhibitors of formula I, compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation, wherein X is selected from the group consisting of NR5, O, and S, with R5 being one of the H and CH3; Y is selected from the group consisting of CH2 and O; R4 is selected from the group consisting of H, OCH3, Cl, F, Br, I, OH, NH2, CN, CF3. © KIPO & WIPO 2007 ...

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, including allergy, asthma, autoimmune diseases, and pruritis. 132-. (canceled)33. A chemical entity selected from:[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(6-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Difluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-methyl-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-isopropyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclobutyl-5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(6-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-trifluoromethyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Bis-trifluoromethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4-Chloro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-ethyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclopropyl-5-(6-fluoro-4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclopropyl-5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4-Chloro-6-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;and pharmaceutically acceptable salts thereof.3445-. (canceled) This application claims the benefit of U.S. provisional patent application Ser. No. 60/788,190, filed on Mar. 31, 2006, which is incorporated herein by ...

Cyclic regimens utilizing indoline derivatives

This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure:wherein R1 and R2 may be single substituents or fused to form spirocyclic rings, in combination with progestins, estrogens, or both. These methods of treatment may be used for contraception, for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, or prostate, minimization of side effects, cyclic menstrual bleeding, or stimulation of food intake.

Thio-oxindole derivatives

This invention relates to compounds which are agonists of the progesterone receptor which have the general structures:wherein:R1 and R2 are H, alkyl, substituted alkyl; OH; O(alkyl); O(substituted alkyl); OAc; aryl; substituted aryl; heteroaryl; substituted heteroaryl; alkylaryl; alkylheteroaryl; 1-propynyl; or 3-propynyl; or R1 and R2 are joined to form an alkyl, alkenyl or heterocyclic ring; or R1 and R2 together comprise a double bond to CMe2; C(cycloalkyl), O, or C(cycloether); R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, alkynyl, substituted alkynyl, or CORA; RA is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl; R4 is H, halogen, CN, NH2, NO2, C1 to C6 alkyl, or substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; R5 is optionally substituted and selected from a benzene ...

(1H-BENZOIMIDAZOL-2-YL)-(PIPERAZINYL)-METHANONE DERIVATIVES AND RELATED COMPOUNDS AS HISTAMINE H4-RECEPTOR ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS

... (1H-Benzoimidazol-2-YL)-(Piperazinyl)- Methanone derivatives of formula (I) and related compounds as histamine H4-receptor antagonists for the treatment of inflammatory and allergic disorders (I) wherein B and B are C or up to one of B and B maybe N; Y is O, Sor NR, where R is H or Calkyl; Zis O or S; R is H and R is (a), where RIs H or Calkyl, or R and R are taken together with their N of attachment to form (b); n is 1 or 2; m is 1 or 2; n + m is 2 or 3; other substituents as defined in claim 1.1 1228 910 891-41-4 © KIPO & WIPO 2007 ...

Benzoimidazole compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

CYCLOTHIOCARBAMATE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS

The present invention provides compounds which are agonists of the progesterone receptor and have structures (I) or (II) wherein R 1 and R 2 are independent substituents selected from the group of H, optionally substituted C 1 to C 6 alkyl, alkenyl, alkynyl, or alkynyl groups C 3 to C 8 cycloalkyl, aryl, substituted aryl, or heterocyclic groups, or COR A or NR B COR A ; or R 1 and R 2 are fused to form an optionally substituted 3 to 8 membered Spiro cyclic alkyl or alkenyl ring or a Spiro cyclic ring containing one to three heteroatoms selected from O, S and N; R A is selected from H, amino, or optionally substituted C 1 to C 3 alkyl, aryl, C 1 to C 3 alkoxy, or C 1 to C 3 aminoalkyl groups; R B is H, C1 to C 3 alkyl, or substituted C 1 to C 3 alkyl; R 3 is H, OH, NH 2 COR C, or optionally substituted C 1 to C 6 alkyl, C 3 to C 6 alkenyl, or alkynyl groups; R C is selected from H or optionally substituted C 1 to C 3 alkyl, aryl, C 1 to C 3 alkoxy, or C 1 to C 3 aminoalkyl groups; Q 1 is ...

Indoles and benzoimidazoles as histamine H4 receptor modulators

Benzoimidazole and indole compounds are described, which are useful as H₄ receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H₄ receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Thieno- and furo-pyrimidine modulators of the histamine H4 receptor

Thieno- and furo-pyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as inflammation.

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for H4 receptor activity modulation and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, including allergy, asthma, autoimmune diseases, and pruritis.

Indoline derivatives

This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure:wherein R1 and R2 may be single substituents or fused to form spirocyclic rings.

Cyanopyrroles

This invention provides a progesterone receptor antagonist of formula 1 having the structure wherein, T is O, S, or absent; R1, and R2 are each, independently, hydrogen, alkyl, substituted alkyl; or R1 and R2 are taken together form a ring and together contain CH2(CH2)nCH2, CH2CH2CMe2CH2CH2, O(CH2)pCH2, O(CH2)qO, CH2CH2OCH2CH2, or CH2CH2NR7CH2CH2; n=1-5; p=1-4; q=1-4; R3 is hydrogen, OH, NH2, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or CORA; RA is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R4 is hydrogen, halogen, CN, NH2, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R5 is hydrogen, alkyl, or substituted alkyl; R6 is hydrogen, alkyl, substituted alkyl, or CORB; RB is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R7 is hydrogen or alkyl; or a pharmaceutically acceptable salt thereof ...

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H₄ receptor expression, and in treating conditions such as inflammation, H₄ receptor-mediated conditions, and related conditions.

2,1-benzisothiazoline 2,2-dioxides

This invention provides a progesterone receptor antagonist of formula 1 having the structurewherein R1, and R2 are each, independently, hydrogen, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, heteroarylalkyl, and alkynyl. R1 and R2 may be taken together to form a ring and together contain -CH2(CH2)nCH2-, -CH2CH2CMe2CH2CH2-, -O(CH2)PCH2-, O(CH2)qO-, -CH2CH2OCH2CH2-, -CH2CH2NR7CH2CH2-. R1 and R2 may be taken together to form a double bond, the double bond having two methyl groups bonded to the terminal end, having a cycloalkyl group bonded to the terminal end, having an oxygen bonded to the terminal end, or having a cycloether bonded to the terminal end; or a double bond. R3 is hydrogen, hydroxyl, NH2, alkyl, substituted alkyl, alkenyl, alkynyl, substituted or, CORA. R4 is hydrogen, halogen, -CN, -NH2, alkyl, substituted alkyl, alkoxy, alkoxy, aminoalkyl, or substituted aminoalkyl; R5 is a trisubstituted ...

Cyclic regimens using cyclocarbamate and cyclic amide derivatives

This invention relates to cyclic combination therapies and regimens utilizing, in combination with progestins, substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure:where A and B are independent substituents selected from S, CH or N; provided that when A is S, B is CH or N; and when B is S, A is CH or N; and A and B cannot both be CH; and when A and B both equal N, one N may be optionally substituted with an C1 to C6 alkyl group; R1 and R2 are independent substituents selected from the group of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C2 to C6 alkenyl, substituted C2 to C6 alkenyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, or NRBCORA; or R1 and R2 are fused to form optionally substituted 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic ring, the heterocyclic ring containing one ...

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

Thio-oxindole derivatives

This invention relates to compounds which are agonists of the progesterone receptor which have the general structure:wherein:R1, R2, R3, R4, R5 and Q<1 >are as defined herein, or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

Benzoimidazole compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H 4 receptor, and in treating conditions such as inflammation, H 4 receptor-mediated conditions, and related conditions.

Benzoimidazole compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

A METHOD FOR TREATING ALLERGIES USING SUBSTITUTED PYRAZOLES

A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles of formula (I). © KIPO & WIPO 2007 ...

8-substituted-6-triflouromethyl-9-pyrido [3,2-G] quinoline compounds as androgen receptor modulators

Non-steroidal compounds and compositions which are agonists, partial agonists, and antagonists for androgen receptors and methods of preparation for the non-steroidal compounds and compositions.

Glucocorticoid-selective anti-inflammatory agents

Compounds having Formula I are useful for partially or fully antagonizing, repressing, agonizing, or modulating the glucocorticoid receptor and treating immune, autoimmune and inflammatory diseases in a mammal. Also disclosed are pharmaceutical compositions comprising compounds of Formula I and methods of inhibiting immune or autoimmune diseases in a mammal.

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

Aryl-substituted bridged or fused diamines as modulators of leukotriene A4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S.

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H₄ receptor expression, and in treating conditions such as inflammation, H₄ receptor-mediated conditions, and related conditions.

Cyclocarbamate derivatives as progesterone receptor modulators

This invention provides compounds of Formula (I):wherein R1 and R2 may be single substituents or fused to form spirocyclic or hetero-spirocyclic rings; R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, or substituted alkynyl, CORC; RC is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;R4 is H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, alkynyl, or substituted alkynyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, amino, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl; and R5 is selected from a trisubstituted benzene ring of a five or six membered ring with 1, 2, or 3 heteroatoms from the group including O, S, SO, SO2 or NR6 and containing one or two independent substituents from the group including H, halogen, CN, NO2, amino, and C1 to C3 alky, C1 to C3 alkoxy, C1 to C3 ...

Thio-oxindole derivatives

This invention relates to compounds which are agonists of the progesterone receptor which have the general structure:wherein:R1, R2, R3, R4, R5 and Q1 are as defined herein, or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.

Method for treating allergies using substituted pyrazoles

A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

Thieno-and furo-pyrimidine modulators of the histamine h4 receptor

Thieno- and furo-pyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as inflammation.

Cyclocarbamate derivatives as progesterone receptor modulators

This invention provides compounds of Formula (I): wherein R1 and R2 are independent substituents or are fused to form spirocyclic rings; R3, RC, and R4 are as defined herein; and R5 is a substituted benzene ring or a substituted five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms including O, S, SO, SO2 or NR6; or pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions and methods using the compounds as antagonists of the progesterone receptor.

2-aminopyrimidine modulators of the histamine H4 receptor

... 2-Aminopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

USE OF INDOLYL DERIVATIVES FOR THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT ALLERGIC RHINITIS

A method to treat allergic rhinitis is disclosed in which patients are administered certain indolyl compounds. © KIPO & WIPO 2007 ...

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

Cyanopyrroles

This invention provides a progesterone receptor antagonist of formula 1 having the structure wherein, T is O, S, or absent; R₁, and R₂ are each, independently, hydrogen, alkyl, substituted alkyl; or R₁ and R₂ are taken together form a ring and together contain -CH₂(CH₂)_nCH₂-, -CH₂CH₂CMe₂CH₂CH₂-, -O(CH₂)_pCH₂-, -O(CH₂)_qO-, -CH₂CH₂OCH₂CH₂-, or -CH₂CH₂NR₇CH₂CH₂-; n=1-5; p=1-4; q=1-4; R₃ is hydrogen, OH, NH₂, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR^A; R^A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R₄ is hydrogen, halogen, CN, NH_{2 ...}

SUBSTITUTED PYRAZOLES

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described. © KIPO & WIPO 2007 ...

Thieno- and furo-pyrimidine modulators of the histamine H4 receptor

Thieno- and furo-pyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as inflammation.

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H₄ receptor expression, and in treating conditions such as inflammation, H₄ receptor-mediated conditions, and related conditions.

Method for treating allergies using substituted pyrazoles

A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles.

BENZOIMIDAZOL-2-YL PYRIMIDINES AND PYRAZINES AS MODULATORS OF THE HISTAMINE H4 RECEPTOR

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H receptor activity, including allergy, asthma, autoimmune diseases, and pruritis.4 © KIPO & WIPO 2009 ...

Substituted pyrazoles

Substituted pyrazoles of general formula methods of manufacturing them, compositions containing them, and methods of using them to, for example, treat autoimmune diseases mediated by cathepsin S, and inhibit cathepsin S activity, are described.

Benzoimidazole Compounds

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

INDOLINE DERIVATIVES AS PROGESTERONE ANTAGONISTS

This invention comprises compounds of formula (I), which are antagonists of the progesterone receptor, their preparation and utility. © KIPO & WIPO 2007 ...

Indoline derivatives

This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: wherein R1 and R2 may be single substituents or fused to form spirocyclic rings.

使用取代的吡唑治疗变应性疾病的方法

... 应用取代的吡唑治疗变应性疾病，包括特应性变应性疾病。 ...

BENZOIMIDAZOLE COMPOUNDS

Benzoimidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating Hreceptor, and in treating conditions such as inflammation, H receptor- medidated conditions, and related conditions.4 4 © KIPO & WIPO 2007 ...

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H₄ receptor expression, and in treating conditions such as inflammation, H₄ receptor-mediated conditions, and related conditions.

Heteroaryl linked quinolinyl modulators of RORt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H₄ receptor expression, and in treating conditions such as inflammation, H₄ receptor-mediated conditions, and related conditions.

Indoline derivatives

This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: wherein R¹ and R² may be single substituents or fused to form spirocyclic rings.

Benzimidazolones and analogues

The present invention provides compounds and pharmaceutical formulations useful as progesterone receptor agonists and antagonists and having the general formula: wherein: A is O, S, or NR 4 ; B is a bond between A and C═Q, or the moiety CR 5 R 6 ; R 4 , R 5 , R 5 are independently selected from H or optionally substituted C 1 to C 6 alkyl, C 2 to C 6 alkenyl, C 2 to C 6 alknyl, C 3 to C 8 cycloalkyl, substituted C 3 to C 8 cycloalkyl, aryl, or heterocyclic groups, or cyclic alkyl constructed by fusing R 4 and R 5 to from a 5 to 7 membered ring; R 1 is selected from H, OH, NH 2 , C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 3 to C 6 alkenyl, substituted C 1 to C 6 alkenyl, alkynyl, substituted alknyl, —COH, or optionally substituted —CO(C 1 to C 3 alkyl), —CO(aryl), —CO(C 1 to C 3 alkoxy), or —CO(C 1 to C 3 aminoalkyl) groups; R 2 is selected from H, halogen, CN, NO 2 , or optionally substituted C 1 to C 6 alkyl, C 1 to C 6 alkoxy, or C 1 to C 6 aminoalkyl groups; R 3 is selected from a trisubstituted benzene ring; or a 5- or 6-membered heteroaromatic ring containing 1 or 2 substituents; Q is O, S, NR 8 , or CR 9 R 10 ; or a pharmaceutically acceptable salt thereof. The invention also includes methods of contraception and methods of treating or preventing maladies associated with the progesterone receptor.

METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 4. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.5. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.6. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .8. The method of claim 7 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 7 , rheumatoid arthritis claim 7 , psoriasis claim 7 , chronic obstructive pulmonary disorder claim 7 , psoriatic arthritis claim 7 , ankylosing spondylitis claim 7 , neutrophilic asthma claim 7 , steroid resistant asthma claim 7 , multiple sclerosis claim 7 , and systemic lupus erythematosus9. The method of claim 7 , wherein the disease is psoriasis.10. The method of claim 7 , wherein the disease is rheumatoid arthritis.11. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.12. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.13. The method of claim 7 , wherein the disease is multiple sclerosis.14. The method of claim 7 , wherein the disease is neutrophilic asthma.15. The method of claim 7 , wherein the disease is steroid resistant asthma.16. The method of claim 7 , wherein the disease is psoriatic arthritis.17. The method of claim 7 , wherein the disease is ankylosing spondylitis.18. The method of claim 7 , wherein the disease is systemic lupus erythematosus.19. The method of claim 7 , wherein the disease is chronic obstructive pulmonary disorder.20. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising administering to ...

Thieno- and furo-pyrimidine modulators of the histamine h4 receptor

Thieno- and furo-pyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine H 4 receptor activity and for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as inflammation.

THIENO- ADN FURO-PYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

Thieno- and furo-pyrimidine compounds are described, which are useful as Hreceptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine Hreceptor activity and for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, such as inflammation. 2. A chemical entity as in claim 1 , wherein Rand Rtaken together form —(CH)— optionally substituted with one or two substituents selected from the group of Calkyl claim 1 , Calkoxy claim 1 , CF claim 1 , and fluoro.8. A chemical entity as in claim 1 , wherein Ris NH.9. An chemical entity selected from the group consisting of:4-(4-Methyl-piperazin-1-yl)-thieno[3,2-d]pyrimidin-2-ylamine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidin-2-ylamine;4-piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidin-2-ylamine;4-[(3aR,6aR)-Hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]-6,7,8,9-tetrahydro[1]benzothieno[3,2-d]pyrimidin-2-amine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidin-2-ylamine;4-piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidin-2-ylamine;4-[(3aR,6aR)-Hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]-6,7,8,9-tetrahydro[1]benzofuro[3,2-d]pyrimidin-2-amine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidine;4-piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidine;4-piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidine;7-Methyl-4-[(3R)-3-(methylamino)pyrrolidin-1-yl]thieno[3,2-d]pyrimidin-2-amine;7-Methyl-4-(4-methylpiperazin-1-yl)thieno[3,2-d]pyrimidin-2-amine;7-Bromo-4-[(3R)-3-(methylamino)pyrrolidin-1-yl]thieno[3,2-d]pyrimidin-2-amine;6-tert-Butyl-4-(4-methylpiperazin-1-yl)thieno[3,2-d]pyrimidin-2-amine;6-tert-Butyl-4-[(3R)-3-(methylamino)pyrrolidin-1-yl]thieno[3,2-d]pyrimidin-2-amine;6-tert-Butyl-4-piperazin-1-ylthieno[3,2-d] ...

THIENO- AND FURO-PYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

Thieno- and furo-pyrimidine compounds are described, which are useful as Hreceptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the modulation of histamine Hreceptor activity and for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, such as inflammation. 2. A chemical entity as in claim 1 , wherein X is O.3. A chemical entity as in claim 1 , wherein Ris H.4. A chemical entity as in claim 1 , wherein Ris H or tert-butyl.5. A chemical entity as in claim 1 , wherein Rand Rtaken together form —(CH)— optionally substituted with one or two substituents selected from the group of Calkyl claim 1 , Calkoxy claim 1 , CF claim 1 , and fluoro.8. A chemical entity as in claim 1 , wherein Ris NH.9. An chemical entity selected from the group consisting of:4-(4-Methyl-piperazin-1-yl)thieno[3,2-d]pyrimidin-2-ylamine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidin-2-ylamine;4-Piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidin-2-ylamine;4-[(3aR,6aR)-Hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]-6,7,8,9-tetrahydro[1]benzothieno[3,2-d]pyrimidin-2-amine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidin-2-ylamine;4-Piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidin-2-ylamine;4-[(3aR,6aR)-Hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]-6,7,8,9-tetrahydro[1]benzofuro[3,2-d]pyrimidin-2-amine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidine;4-Piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]furo[3,2-d]pyrimidine;4-(4-Methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidine;4-Piperazin-1-yl-6,7,8,9-tetrahydro-benzo[4,5]thieno[3,2-d]pyrimidine;7-Methyl-4-[(3R)-3-(methylamino)pyrrolidin-1-yl]thieno[3,2-d]pyrimidin-2-amine;7-Methyl-4-(4-methylpiperazin-1-yl)thieno[3,2-d]pyrimidin-2-amine;7-Bromo-4-[(3R)-3-(methylamino)pyrrolidin-1-yl]thieno[3,2-d]pyrimidin-2-amine;6-tert-Butyl-4-(4-methylpiperazin- ...

Cyclothiocarbamate Derivatives as Progesterone Receptor Modulators

Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: 1. A method of contraception , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a female of child bearing age.2. A method for providing hormone replacement therapy , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a mammalian subject3. A method of treating fibroids , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a female patient.4. A method of treating endometriosis , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a female patient.5. A method of treating dysfunctional bleeding , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a female patient.6. A method of treating uterine leiomyomata , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a female patient.7. A method of treating polycystic ovary syndrome , said method comprising delivering 5-(4 ,4-Dimethyl-2-thioxo-1 ,4-dihydro-2H-3 ,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile or a pharmaceutically acceptable salt thereof to a female patient.8. ...

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for Hreceptor activity modulation and for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, including allergy, asthma, autoimmune diseases, and pruritis. 1. A hydrated hemitartrate salt of a compound selected from:[5-(5-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(6-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-methyl-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Difluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclobutyl-5-(4,5-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclobutyl-5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Methyl-5-(4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-ethyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclopropyl-5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4-Chloro-6-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Ethyl-5-(5-fluoro-4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4-Chloro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(1H-Benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine; and[5-(4,5-dimethyl-1H-benzoimidazol-2-yl)-4-propyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine. ...

2-AMINOPYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

2-Aminopyrimidine compounds are described, which are useful as Hreceptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, such as allergy, asthma, autoimmune diseases, and pruritis. 2. A chemical entity as in claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , benzyl claim 1 , tetrahydrofuran-3-yl claim 1 , or tetrahydropyran-4-yl.3. A chemical entity as in claim 1 , wherein Ris cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl.4. A chemical entity as in claim 1 , wherein Ris H.11. A chemical entity as in claim 1 , wherein Ris H.12. A chemical entity as in claim 1 , wherein Rand Rare each independently H or methyl.13. An chemical entity selected from:4-Cyclopentyl-6-piperazin-1-yl-pyrimidin-2-ylamine;4-Cyclopentyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;(R)-4-(3-Amino-piperidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;(R)-4-Cyclopentyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;trans-1-(2-Amino-6-cyclopentyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;4-Cyclopentyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;4-Cyclopentyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;4-Isopropyl-6-piperazin-1-yl-pyrimidin-2-ylamine;(R)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;(S)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;(R)-4-Isopropyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;(R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;trans-1-(2-Amino-6-isopropyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;(S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;(R,R)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;4-(cis-Hexahydro-pyrrolo[3,4-b] ...

2-AMINOPYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

2-Aminopyrimidine compounds are described, which are useful as Hreceptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, such as allergy, asthma, autoimmune diseases, and pruritis. 2. A chemical entity as in claim 1 , wherein Rand Rtaken together form —(CH)—.9. A chemical entity as in claim 1 , wherein Ris H.10. A chemical entity as in claim 1 , wherein Rand Rare each independently H or methyl.11. An chemical entity selected from:4-(4-Methyl-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;4-(4-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;(R)-4-(3-Amino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;(R)-4-(3-Methylamino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;(R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;(R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;(S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine;4-(4-Methyl-piperazin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine;(R)-4-(3-Methylamino-pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine;and pharmaceutically acceptable salts thereof.12. An chemical entity as in claim 1 , wherein said chemical entity is a compound of Formula (I) or a pharmaceutically acceptable salt of said compound of Formula (I). This application is a divisional application of U.S. application Ser. No. 13/043,420 filed on Mar. 8, 2011, which is a divisional application of U.S. application Ser. No. 12/070,051, filed on Feb. 14, 2008, now U.S. Pat. No. 7,923,451, which claims the benefit of U.S. provisional patent application Ser. No. 60/889,798, filed on Feb. 14, 2007. The present application is also a divisional application of U.S. application Ser. No. 13/043,391 ...

Cyclothiocarbamate Derivatives as Progesterone Receptor Modulators

Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and Q 1 are defined herein.

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, including allergy, asthma, autoimmune diseases, and pruritis. 132-. (canceled)33. A chemical entity selected from:[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,5-Difluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,5-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Methyl-5-(4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(5-Fluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(5-Chloro-6-fluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(5-Chloro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(5,6-Dichloro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(6-Chloro-5-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;and pharmaceutically acceptable salts thereof.3445-. (canceled)46. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an effective amount of a compound selected from:[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,5-Difluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,5-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Methyl-5-(4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(5-Fluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-( ...

METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 10. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.11. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.12. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.13. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .14. The method of claim 13 , wherein the disease is selected from the group consisting of: rheumatoid arthritis claim 13 , psoriasis claim 13 , chronic obstructive pulmonary disorder claim 13 , psoriatic arthritis claim 13 , ankylosing spondylitis claim 13 , Crohn's disease claim 13 , neutrophilic asthma claim 13 , steroid resistant asthma claim 13 , multiple sclerosis claim 13 , systemic lupus erythematosus claim 13 , and ulcerative colitis.15. The method of claim 13 , wherein the disease is psoriasis.16. The method of claim 13 , wherein the disease is rheumatoid arthritis.17. The method of claim 13 , wherein the disease is ulcerative colitis.18. The method of claim 13 , wherein the disease is Crohn's disease.19. The method of claim 13 , wherein the disease is multiple sclerosis.20. The method of claim 13 , wherein the disease is neutrophilic asthma.21. The method of claim 13 , wherein the disease is steroid resistant asthma.22. The method of claim 13 , wherein the disease is psoriatic arthritis.23. The method of claim 13 , wherein the disease is ankylosing spondylitis.24. The method of claim 13 , wherein the disease is systemic lupus erythematosus.25. The method of claim 13 , wherein the disease is chronic obstructive pulmonary disorder.26. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 7. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.8. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.9. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.10. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .11. The method of claim 10 , wherein the disease is selected from the group consisting of: rheumatoid arthritis claim 10 , psoriasis claim 10 , chronic obstructive pulmonary disorder claim 10 , psoriatic arthritis claim 10 , ankylosing spondylitis claim 10 , Crohn's disease claim 10 , neutrophilic asthma claim 10 , steroid resistant asthma claim 10 , multiple sclerosis claim 10 , systemic lupus erythematosus claim 10 , and ulcerative colitis.12. The method of claim 10 , wherein the disease is psoriasis.13. The method of claim 10 , wherein the disease is rheumatoid arthritis.14. The method of claim 10 , wherein the disease is ulcerative colitis.15. The method of claim 10 , wherein the disease is Crohn's disease.16. The method of claim 10 , wherein the disease is multiple sclerosis.17. The method of claim 10 , wherein the disease is neutrophilic asthma.18. The method of claim 10 , wherein the disease is steroid resistant asthma.19. The method of claim 10 , wherein the disease is psoriatic arthritis.20. The method of claim 10 , wherein the disease is ankylosing spondylitis.21. The method of claim 10 , wherein the disease is systemic lupus erythematosus.22. The method of claim 10 , wherein the disease is chronic obstructive pulmonary disorder.23. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

1,2,6-SUBSTITUTED BENZIMIDAZOLES AS FLAP MODULATORS

The present invention relates to compounds of Formula (I), 9. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and at least one pharmaceutically acceptable carrier.10. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and at least one pharmaceutically acceptable carrier.11. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and at least one pharmaceutically acceptable carrier.12. A method of treating a subject suffering from or diagnosed with a disease and/or disorder mediated by FLAP activity claim 1 , comprising administering to the subject a therapeutically effective amount of at least one compound of .13. The method according to claim 12 , wherein the disease and/or disorder is selected from the group consisting of respiratory claim 12 , cardiac and cardiovascular claim 12 , autoimmune and allergic claim 12 , carcinogenesis disease and/or disorder claim 12 , and associated symptoms or complications thereof.14. The method according to claim 13 , wherein the respiratory disease and/or disorder is selected from the group consisting of exacerbations claim 13 , non-allergic asthma claim 13 , fibrotic lung diseases claim 13 , acute respiratory distress syndrome and chronic obstructive pulmonary disease claim 13 , or associated symptoms or complications thereof.15. The method according to claim 13 , wherein the cardiac and cardiovascular disease and/or disorder is selected from the group consisting of myocardial infarction claim 13 , atherosclerosis claim 13 , atherosclerosis and stroke aortic aneurisms claim 13 , or associated symptoms or complications thereof.16. The method according to claim 13 , wherein the autoimmune and allergic disease and/or disorder is selected from the group consisting of rheumatoid arthritis claim 13 , inflammatory bowel disease claim 13 , nephritis claim 13 , spondyloarthritis claim ...

1,2,5-SUBSTITUTED BENZIMIDAZOLES AS FLAP MODULATORS

The present invention relates to compounds of Formula (I), 2. The compound of claim 1 , wherein{'sup': '2', 'sub': 2', '3', '3', '3', '2', '3', '3', '3', '2', '3', '2', '3', '2', '2', '2', '2', '3', '3, 'Ris H, Br, Cl, F, —CN, —CHCN, OCF, CF, CH, pyrrole-2-yl, pyrid-3-yl, pyrid-2-yl, pyrimid-2-yl, pyrimid-5-yl, 2-methoxy pyrimid-5-yl, 2-dimethylamino-pyrimid-5-yl, 2-methoxy-pyrid-5-yl, 2-methoxy-3-trifluoromethyl-pyrid-5-yl, 2-ethoxy pyrid-5-yl, 2-trifluoromethyl-pyrid-5-yl, 2-dimethylamino-pyrid-5-yl, pyrazol-1-yl, 1-methyl-pyrazol-4-yl, 1-methyl pyrazol-5-yl, 1-H-pyrazol-4-yl, thiazolyl, isoxazol-4yl, 1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl, furan-3-yl, 3,5-dimethylisoxazol-4-yl, 5-methyl-1,2,4-oxadiazol-3-yl, —CH-(3,3-difluoropiperidin-1-yl), azetidin-1-yl, 3,3-difluoroazetidin-1-yl, pyrrolidin-2-yl, 3,3-difluoropyrrolidin-1-yl, piperidin-1-yl, 4-trifluoromethylpiperidin-1-yl, 3,3-difluoropiperidin-1-yl, 4,4-difluoropiperidin-1-yl, morpholin-1-yl, 1,2-difluoro-phen-4-yl or phenyl, wherein said phenyl is optionally substituted with one substituent selected from the group consisting of F, CH, CF, CH(CH), —CN, CHSO—, CHSONH—, NHSO—, NHC(O)—, CHC(O)NH, and CHO—;'}{'sup': '3', 'sub': 2', '3', '3', '3', '3', '2', '2', '3', '2', '3', '2, 'Ris H, Br, Cl, —CN, —CHCN, OCF, CF, CH, pyrrol-2-yl, thiazol-5-yl, thiazol-4-yl, 2-methoxy pyrid-5-yl, 2-trifluoromethyl-pyrid-5-yl, pyrimid-2-yl, 2-methoxy pyrimid-5-yl, 1-methyl-pyrazolyl, 1-H-pyrazol-5-yl, furan-3-yl, 3,5-dimethylisoxazol-4-yl, pyrrolidin-2-yl, 1,2-difluoro-phen-4-yl, or phenyl; wherein said phenyl is optionally substituted with one substituent selected from the group consisting of F, CF, NHSO—, CHSONH—, and CHSO—;'}and solvates, hydrates, and pharmaceutically acceptable salts thereof.5. The compound of claim 1 , selected from the group consisting ofracemic cis-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid,(1R*,2S*)-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H- ...

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORgammat

The present invention comprises compounds of Formula I. 4. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.5. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.6. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .8. The method of claim 7 , wherein the disease is selected from the group consisting of:inflammatory bowel diseases, rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disorder, psoriatic arthritis, ankylosing spondylitis, neutrophilic asthma, steroid resistant asthma, multiple sclerosis, and systemic lupus erythematosus.9. The method of claim 7 , wherein the disease is psoriasis.10. The method of claim 7 , wherein the disease is rheumatoid arthritis.11. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.12. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.13. The method of claim 7 , wherein the disease is multiple sclerosis.14. The method of claim 7 , wherein the disease is neutrophilic asthma.15. The method of claim 7 , wherein the disease is steroid resistant asthma.16. The method of claim 7 , wherein the disease is psoriatic arthritis.17. The method of claim 7 , wherein the disease is ankylosing spondylitis.18. The method of claim 7 , wherein the disease is systemic lupus erythematosus.19. The method of claim 7 , wherein the disease is chronic obstructive pulmonary disorder.20. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising administering to the subject an effective amount of a compound of or composition or medicament ...

ALKYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 5. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.6. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.7. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.8. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .9. The method of claim 12 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 12 , rheumatoid arthritis claim 12 , psoriasis claim 12 , chronic obstructive pulmonary disorder claim 12 , psoriatic arthritis claim 12 , ankylosing spondylitis claim 12 , neutrophilic asthma claim 12 , steroid resistant asthma claim 12 , multiple sclerosis claim 12 , and systemic lupus erythematosus.10. The method of claim 8 , wherein the disease is psoriasis.11. The method of claim 8 , wherein the disease is rheumatoid arthritis.12. The method of claim 9 , wherein the inflammatory bowel disease is ulcerative colitis.13. The method of claim 9 , wherein the inflammatory bowel disease is Crohn's disease.14. The method of claim 8 , wherein the disease is multiple sclerosis.15. The method of claim 8 , wherein the disease is neutrophilic asthma.16. The method of claim 8 , wherein the disease is steroid resistant asthma.17. The method of claim 8 , wherein the disease is psoriatic arthritis.18. The method of claim 8 , wherein the disease is ankylosing spondylitis.19. The method of claim 8 , wherein the disease is systemic lupus erythematosus.20. The method of claim 8 , wherein the disease is chronic obstructive pulmonary disorder.21. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising ...

PHENYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 4. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.5. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.6. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.7. A method for treating or ameliorating a RORγt mediated inflammatory syndrome claim 1 , disorder or disease comprising administering to a subject in need thereof an effective amount of a compound of .8. The method of claim 8 , wherein the disease is selected from the group consisting of: inflammatory bowel diseases claim 8 , rheumatoid arthritis claim 8 , psoriasis claim 8 , chronic obstructive pulmonary disorder claim 8 , psoriatic arthritis claim 8 , ankylosing spondylitis claim 8 , neutrophilic asthma claim 8 , steroid resistant asthma claim 8 , multiple sclerosis claim 8 , and systemic lupus erythematosus.9. The method of claim 7 , wherein the disease is psoriasis.10. The method of claim 7 , wherein the disease is rheumatoid arthritis.11. The method of claim 8 , wherein the inflammatory bowel disease is ulcerative colitis.12. The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease.13. The method of claim 7 , wherein the disease is multiple sclerosis.14. The method of claim 7 , wherein the disease is neutrophilic asthma.15. The method of claim 7 , wherein the disease is steroid resistant asthma.16. The method of claim 7 , wherein the disease is psoriatic arthritis.17. The method of claim 7 , wherein the disease is ankylosing spondylitis.18. The method of claim 7 , wherein the disease is systemic lupus erythematosus.19. The method of claim 7 , wherein the disease is chronic obstructive pulmonary disorder.20. A method of treating or ameliorating a syndrome claim 1 , disorder or disease claim 1 , in a subject in need thereof comprising administering ...

INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE

The present disclosure is directed to compounds of Formula (I) and methods of their use and preparation, as well as compositions comprising compounds of Formula (I). 153-. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/265,836, filed on Dec. 10, 2015, which is incorporated herein by reference in its entirety.The present disclosure is directed to small molecule tyrosine kinase inhibitors.Rheumatoid arthritis (“RA”) is a chronic, autoimmune, inflammatory disorder that affects the lining of the joints, causing painful swelling that can result in bone erosion and joint deformation. RA presents a significant societal impact—it has a relatively high prevalence (about 1% of the United States population suffers from RA), produces irreversible joint damage, and has a widespread occurrence of co-morbities. While many patients benefit from currently marketed biologic and small molecule medicines, most patients still suffered from the chronic pain and inflammation of the disease.Cancer, in particular mantle cell lymphoma, chronic lymphocytic leukemia, macroglobulinemia, and multiple myeloma, continues to afflict patients. Alternative, effective treatments of cancer are still needed.Human Bruton's tyrosine kinase (“Btk”) is a ˜76 kDa protein belonging to the Tec family of non-receptor tyrosine kinases. Tec kinases form the second largest family of cytoplasmic tyrosine kinases in mammalian cells, which consists of four other members in addition to BTK: the eponymous kinase TEC, ITK, TXK/RLK and BMX. Tec kinases are evolutionarily conserved throughout vertebrates. They are related to, but structurally distinct from, the larger Src and Syk kinase families. Tec family proteins are abundantly expressed in hematopoietic tissues and play important roles in the growth and differentiation of blood and endothelial cells in mammals.Based upon Btk expression from IHC studies described in the art, Btk inhibition has the potential to modulate biology ...

1,2,5-SUBSTITUTED BENZIMIDAZOLES AS FLAP MODULATORS

The present invention relates to compounds of Formula (I), 116-. (canceled)17. A compound selected from the group consisting of:racemic cis-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid;(1R*,2S*)-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid;(1S*,2R*)-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid;racemic cis-2-[1-(3-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid as the TFA salt;racemic cis-2-[1-(4-Bromo-2-fluorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid;racemic trans-2-[1-(4-Bromo-2-fluorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid;racemic trans-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid as the TFA salt;2-{[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}-2-ethylbutanoic acid as the TFA salt;1-{[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]methyl}cyclopentanecarboxylic acid as the TFA salt;racemic cis-2-{5-(Quinolin-2-ylmethoxy)-1-[4-(trifluoromethyl)benzyl]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid as the hydrochloride salt;racemic cis-2-{1-(4-Bromobenzyl)-5-[(6-fluoroquinolin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid as the formic acid salt;racemic trans-2-{1-(4-Bromobenzyl)-5-[(8-fluoroquinolin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid;racemic cis-2-{1-(4-Bromobenzyl)-5-[(8-fluoroquinolin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid as the formic acid salt;racemic cis-2-{1-(4-Bromobenzyl)-5-[(7-chloroquinolin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid as the formic acid salt;racemic cis-2-{1-(4-Bromobenzyl)-5-[(6-chloroquinolin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid;1-({5-(Quinolin-2-ylmethoxy)-1-[4-(trifluoromethyl ...

QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I.

1,2,6-SUBSTITUTED BENZIMIDAZOLES AS FLAP MODULATORS

The present invention relates to compounds of Formula (I), 19.-. (canceled)11. A method according to claim 10 , wherein the disease and/or disorder is selected from the group consisting of respiratory claim 10 , cardiac and cardiovascular claim 10 , autoimmune and allergic claim 10 , carcinogenesis disease and/or disorder claim 10 , and associated symptoms or complications thereof.12. A method according to claim 11 , wherein the respiratory disease and/or disorder is selected from the group consisting of exacerbations claim 11 , non-allergic asthma claim 11 , fibrotic lung diseases claim 11 , acute respiratory distress syndrome and chronic obstructive pulmonary disease claim 11 , or associated symptoms or complications thereof.13. A method according to claim 11 , wherein the cardiac and cardiovascular disease and/or disorder is selected from the group consisting of myocardial infarction claim 11 , atherosclerosis claim 11 , atherosclerosis and stroke aortic aneurisms claim 11 , or associated symptoms or complications thereof.14. A method according to claim 11 , wherein the autoimmune and allergic disease and/or disorder is selected from the group consisting of rheumatoid arthritis claim 11 , inflammatory bowel disease claim 11 , nephritis claim 11 , spondyloarthritis claim 11 , polymyositis claim 11 , dermatomyositis claim 11 , gouty effusions claim 11 , systemic lupus erythematosus claim 11 , systemic sclerosis claim 11 , Alzheimer's disease claim 11 , multiple sclerosis claim 11 , allergic rhinitis claim 11 , allergic dermatitis and asthma claim 11 , or associated symptoms or complications thereof.15. A method according to claim 11 , wherein the carcinogenesis disease and/or disorder is selected from the group consisting of tumor cell proliferation claim 11 , differentiation claim 11 , apoptosis claim 11 , tumor-associated angiogenesis claim 11 , and the migration or invasion of carcinoma cells.16. The method of claim 10 , wherein the therapeutically effective ...

QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. 6. A method of claim 4 , wherein in the compound claim 4 , Ris H.7. The method of claim 1 , wherein the disease is psoriasis.8. The method of claim 1 , wherein the disease is rheumatoid arthritis.9. The method of claim 1 , wherein the inflammatory bowel disease is ulcerative colitis.10. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease.11. The method of claim 1 , wherein the disease is multiple sclerosis.12. The method of claim 1 , wherein the disease is neutrophilic asthma.13. The method of claim 1 , wherein the disease is steroid resistant asthma.14. The method of claim 1 , wherein the disease is psoriatic arthritis.15. The method of claim 1 , wherein the disease is ankylosing spondylitis.16. The method of claim 1 , wherein the disease is systemic lupus erythematosus.17. The method of claim 1 , wherein the disease is chronic obstructive pulmonary disorder. This application is a divisional of U.S. application Ser. No. 14/513,426, filed on Oct. 14, 2014, which claims priority from provisional U.S. Application No. 61/890,889, filed on Oct. 15, 2013, which are all incorporated herein by reference.The invention is directed to substituted quinoline compounds, which are modulators of the nuclear receptor RORγt, pharmaceutical compositions, and methods for use thereof. More particularly, the RORγt modulators are useful for preventing, treating or ameliorating an RORγt mediated inflammatory syndrome, disorder or disease.Retinoic acid-related nuclear receptor gamma t (RORγt) is a nuclear receptor, exclusively expressed in cells of the immune system, and a key transcription factor driving Th17 cell differentiation. Th17 cells are a subset of CD4 T cells, expressing CCR6 on their surface to mediate their migration to sites of inflammation, and dependent on IL-23 stimulation, through the IL-23 receptor, for their maintenance and expansion. Th17 cells produce several proinflammatory ...

1,2,5-SUBSTITUTED BENZIMIDAZOLES AS FLAP MODULATORS

The present invention relates to compounds of Formula (I), 2. The compound of claim 1 , wherein{'sup': '2', 'sub': 2', '3', '3', '3', '2', '3', '3', '3', '2', '3', '2', '3', '2', '2', '2', '2', '3', '3, 'Ris H, Br, Cl, F, —CN, —CHCN, OCF, CF, CH, pyrrole-2-yl, pyrid-3-yl, pyrid-2-yl, pyrimid-2-yl, pyrimid-5-yl, 2-methoxy pyrimid-5-yl, 2-dimethylamino-pyrimid-5-yl, 2-methoxy-pyrid-5-yl, 2-methoxy-3-trifluoromethyl-pyrid-5-yl, 2-ethoxy pyrid-5-yl, 2-trifluoromethyl-pyrid-5-yl, 2-dimethylamino-pyrid-5-yl, pyrazol-1-yl, 1-methyl-pyrazol-4-yl, 1-methyl pyrazol-5-yl, 1-H-pyrazol-4-yl, thiazolyl, isoxazol-4yl, 1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl, furan-3-yl, 3,5-dimethylisoxazol-4-yl, 5-methyl-1,2,4-oxadiazol-3-yl, —CH-(3,3-difluoropiperidin-1-yl), azetidin-1-yl, 3,3-difluoroazetidin-1-yl, pyrrolidin-2-yl, 3,3-difluoropyrrolidin-1-yl, piperidin-1-yl, 4-trifluoromethylpiperidin-1-yl, 3,3-difluoropiperidin-1-yl, 4,4-difluoropiperidin-1-yl, morpholin-1-yl, 1,2-difluoro-phen-4-yl or phenyl, wherein said phenyl is optionally substituted with one substituent selected from the group consisting of F, CH, CF, CH(CH), —CN, CHSO—, CHSONH—, NHSO—, NHC(O)—, CHC(O)NH, and CHO—;'}{'sup': '3', 'sub': 3', '3', '3', '3', '2', '2', '3', '2', '3', '2, 'Ris H, Br, Cl, —CN, OCF, CF, CH, pyrrol-2-yl, thiazol-5-yl, thiazol-4-yl, 2-methoxy pyrid-5-yl, 2-trifluoromethyl-pyrid-5-yl, pyrimid-2-yl, 2-methoxy pyrimid-5-yl, 1-methyl-pyrazolyl, 1-H-pyrazol-5-yl, furan-3-yl, 3,5-dimethylisoxazol-4-yl, pyrrolidin-2-yl, 1,2-difluoro-phen-4-yl, or phenyl; wherein said phenyl is optionally substituted with one substituent selected from the group consisting of F, CF, NHSO—, CHSONH—, and CHSO—;'}and solvates, hydrates, and pharmaceutically acceptable salts thereof.5. The compound of claim 1 , selected from the group consisting ofracemic cis-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl]cyclohexanecarboxylic acid,(1R*,2S*)-2-[1-(4-Bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl ...

1,2,6-SUBSTITUTED BENZIMIDAZOLES AS FLAP MODULATORS

The present invention relates to compounds of Formula (I), 8. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and at least one pharmaceutically acceptable carrier.9. The pharmaceutical composition of comprising at least one compound of .10. A method of treating a subject suffering from or diagnosed with a disease and/or disorder mediated by FLAP activity claim 1 , comprising administering to the subject a therapeutically effective amount of at least one compound of .11. A method according to claim 10 , wherein the disease and/or disorder is selected from the group consisting of respiratory claim 10 , cardiac and cardiovascular claim 10 , autoimmune and allergic claim 10 , carcinogenesis disease and/or disorder claim 10 , and associated symptoms or complications thereof.12. A method according to claim 11 , wherein the respiratory disease and/or disorder is selected from the group consisting of exacerbations claim 11 , non-allergic asthma claim 11 , fibrotic lung diseases claim 11 , acute respiratory distress syndrome and chronic obstructive pulmonary disease claim 11 , or associated symptoms or complications thereof.13. A method according to claim 11 , wherein the cardiac and cardiovascular disease and/or disorder is selected from the group consisting of myocardial infarction claim 11 , atherosclerosis claim 11 , atherosclerosis and stroke aortic aneurisms claim 11 , or associated symptoms or complications thereof.14. A method according to claim 11 , wherein the autoimmune and allergic disease and/or disorder is selected from the group consisting of rheumatoid arthritis claim 11 , inflammatory bowel disease claim 11 , nephritis claim 11 , spondyloarthritis claim 11 , polymyositis claim 11 , dermatomyositis claim 11 , gouty effusions claim 11 , systemic lupus erythematosus claim 11 , systemic sclerosis claim 11 , Alzheimer's disease claim 11 , multiple sclerosis claim 11 , allergic rhinitis claim 11 , allergic ...

1,2,5-substituted benzimidazoles as flap modulators

The present invention relates to compounds of Formula (I), and solvates, hydrates, and pharmaceutically acceptable salts thereof, wherein ring A, R 1 , R 5 and R 6 are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

CYCLIC DINUCLEOTIDES AS STING AGONISTS

Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I), wherein R, R′, X, B, R, R′, B, X, R, Z-M-Y, and Y-M-Zare as defined herein. 2. The compound of claim 1 , wherein Ror Ris Calkoxy optionally substituted with one to seven halogen claim 1 , methoxy claim 1 , or optionally substituted Caryl.3. The compound of claim 2 , wherein the Caryl is optionally substituted with one to two fluoro claim 2 , chloro claim 2 , bromo claim 2 , iodo claim 2 , Calkoxy claim 2 , Calkyl claim 2 , hydroxy claim 2 , nitro or cyano.4. The compound of claim 1 , wherein Ror Ris Calkyl substituted with one to three fluoro claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , or hydroxy.5. The compound of claim 1 , wherein Ris F.6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris OH.8. The compound of claim 1 , wherein R is H.9. The compound of claim 1 , wherein R′ is F.10. The compound of claim 1 , wherein Ris F.11. The compound of claim 1 , wherein Ris H.12. The compound of claim 1 , wherein Ris OH.13. The compound of claim 1 , wherein R′ is H.14. The compound of claim 1 , wherein Ris H.15. The compound of claim 1 , wherein L is CH.16. The compound of claim 1 , wherein Lis CH.17. The compound of claim 1 , wherein M is P(O)(OH).18. The compound of claim 1 , wherein M is P(O)(SH).19. The compound of claim 1 , wherein M is S(O).20. The compound of claim 1 , wherein Mis S(O).21. The compound of claim 1 , wherein Mis P(O)(OH).22. The compound of claim 1 , wherein Mis P(O)(SH).23. The compound of claim 1 , wherein X is O.24. The compound of claim 1 , wherein X is CH.25. The compound of claim 1 , wherein Xis O.26. The compound of claim 1 , wherein Xis CH.27. The compound of claim 1 , wherein Y is O28. The compound of claim 1 , wherein Y is NH.29. The compound of claim 1 , wherein Yis NH.30. The compound of claim 1 , wherein ...

ALKYL LINKED QUINOLINYL MODULATORS OF RORγt

The present invention comprises compounds of Formula I. 12-. (canceled)3. The method of claim 17 , wherein the disease is psoriasis.41. The method of claim claim 17 , wherein the disease is rheumatoid arthritis.52. The method of claim claim 17 , wherein the inflammatory bowel disease is ulcerative colitis.62. The method of claim claim 17 , wherein the inflammatory bowel disease is Crohn's disease.71. The method of claim claim 17 , wherein the disease is multiple sclerosis.81. The method of claim claim 17 , wherein the disease is neutrophilic asthma.91. The method of claim claim 17 , wherein the disease is steroid resistant asthma.101. The method of claim claim 17 , wherein the disease is psoriatic arthritis.111. The method of claim claim 17 , wherein the disease is ankylosing spondylitis.121. The method of claim claim 17 , wherein the disease is systemic lupus erythematosus.131. The method of claim claim 17 , wherein the disease is chronic obstructive pulmonary disorder.14. A method of treating or ameliorating a syndrome claim 17 , disorder or disease claim 17 , in a subject in need thereof comprising administering to the subject an effective amount of a compound of or composition or medicament thereof in a combination therapy with one or more anti-inflammatory agents claim 17 , or immunosuppressive agents claim 17 , wherein said syndrome claim 17 , disorder or disease is selected from the group consisting of: rheumatoid arthritis claim 17 , and psoriasis.15. (canceled)20. A method of wherein the disease is selected from the group consisting of: rheumatoid arthritis and psoriasis. This application is a divisional of U.S. application Ser. No. 14/513,455, filed on Oct. 14, 2014, which claims priority from U.S. Application No. 61/890,890, filed on Oct. 15, 2013, each of which is incorporated herein by reference.The invention is directed to substituted quinoline compounds, which are modulators of the nuclear receptor RORγt, pharmaceutical compositions, and methods for ...

PHENYL LINKED QUINOLINYL MODULATORS OF RORgammat

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHOD OF THEIR USE

The present disclosure is directed to compounds of Formula (I) and methods of their use and preparation, as well as compositions comprising compounds of Formula (I). 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein Ris cyclopentyl.47-. (canceled)8. The compound of claim 1 , wherein Ris substituted with NR—C(O)—C(R)═CR(R).9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris H.1113-. (canceled)14. The compound of claim 1 , wherein Ris H and Ris H.1516-. (canceled)17. The compound of claim 1 , wherein A is phenyl.18. The compound of claim 1 , wherein A is pyridyl.1921-. (canceled)22. The compound of claim 1 , wherein A is substituted with Calkyl.23. The compound of claim 1 , wherein E is O.24. The compound of claim 1 , wherein E is a bond.2528-. (canceled)29. The compound of claim 1 , wherein G is phenyl.30. The compound of claim 1 , wherein G is pyridyl.3133-. (canceled)34. The compound of claim 1 , wherein G is substituted with Calkyl.36. The compound of claim 1 , wherein Ris H; Ris cyclopentyl substituted with 1 or 2 substituents wherein one of the substituents is NR—C(O)—C(R)═CR(R) claim 1 , wherein R claim 1 , R claim 1 , and Rare each H; A is phenyl or pyridyl claim 1 , wherein the phenyl or pyridyl is substituted with CH; E is O or a bond; and G is phenyl or Calkyl.3738-. (canceled)39. The compound of claim 1 , wherein the compound is selected from the group consisting of:N-((1S,4S)-4-Acrylamidocyclohexyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,3S)-3-Acrylamidocyclohexyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1S,4S)-4-Acrylamidocyclohexyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2R)-2-Hydroxycyclopentyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2- ...

INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHOD OF THEIR USE

The present disclosure is directed to compounds of formula I′ and methods of their use and preparation, as well as compositions comprising compounds of formula I′. 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein Ris piperidinyl claim 1 , CHCH-piperidinyl claim 1 , pyrrolidinyl claim 1 , CH-pyrrolidinyl claim 1 , or CHCH-pyrrolidinyl.413.-. (canceled)14. The compound of claim 1 , wherein Ris substituted with (C═O)—C(R)═CR(R).15. The compound of claim 14 , wherein Ris H.1619.-. (canceled)20. The compound of claim 1 , wherein Ris H and Ris H.2126.-. (canceled)27. The compound of claim 1 , wherein A is pyridyl.2830.-. (canceled)31. The compound of claim 1 , wherein A is substituted with CH.32. The compound of claim 1 , wherein E is O.3338.-. (canceled)39. The compound of claim 1 , wherein G is phenyl.40. The compound claim 1 , wherein G is pyridyl.4151.-. (canceled)52. The compound of claim 1 , wherein Ris H; Ris piperidinyl substituted with 1 or 2 substituents wherein one of the substituents is (C═O)—C(R)═CR(R) claim 1 , wherein R claim 1 , R claim 1 , and Rare each H; A is phenyl or pyridyl substituted with CH; E is O; and G is phenyl.53. (canceled)54. The compound of claim 1 , wherein the compound is selected from the group consisting of:N-((3R,5R)-1-Acryloyl-5-fluoropiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-hydroxypiperidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-fluoropiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpiperidin-3-yl)-5-(3-fluoro-2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2- ...

INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHOD OF THEIR USE

The present disclosure is directed to compounds of Formula (I) and methods of their use and preparation, as well as compositions comprising compounds of Formula (I). 138-. (canceled)39. A compound selected from the group consisting of:N-((1S,4S)-4-Acrylamidocyclohexyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,3S)-3-Acrylamidocyclohexyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1S,4S)-4-Acrylamidocyclohexyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2R)-2-Hydroxycyclopentyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-Aminocyclohexyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-Hydroxycyclopentyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-(Dimethylamino)cyclohexyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-Hydroxycyclopentyl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2R)-2-Hydroxycyclopentyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-Aminocyclohexyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2R)-2-Acetamidocyclopentyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-Aminocyclopentyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,4R)-4-Acrylamidocyclohexyl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((1R,2S)-2-(Dimethylamino) ...

2,4-DIAMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 MODULATORS

The present invention relates to 2,4-diaminopyrimidines and pharmaceutically acceptable salts thereof, purification methods for the same, pharmaceutical compositions containing them, methods of obtaining and using them for the treatment of disease states, disorders, and conditions mediated by the histamine Hreceptor activity. 2. A compound as claimed in claim 1 , wherein Ris S(O)Ror SF.3. A compound as claimed in claim 1 , wherein Ris S(O)R claim 1 , Ris C-Calkyl claim 1 , and n is 2.46-. (canceled)7. A compound as claimed in claim 1 , wherein Ris selected from the group consisting of SOCH claim 1 , SOCF claim 1 , SF claim 1 , F claim 1 , and OCF.813-. (canceled)14. A compound as claimed in claim 1 , wherein Ris halo.1545-. (canceled)46. A compound as claimed in claim 1 , wherein Ris SOCH claim 1 , Ris cyclobutyl claim 1 , and Ris ethyl.49. A compound as claimed in claim 1 , wherein Ris F claim 1 , Ris OCHCH claim 1 , and Ris isopropyl.50. A compound or a pharmaceutically acceptable salt thereof claim 1 , wherein said compound is selected from the group consisting of{'sup': '4', '(2-Ethoxy-4-fluorophenyl)-N-isopropylpyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-((1H-Pyrazol-5-yl)methyl)-N-(4-fluoro-2-methylphenyl)pyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-(2-Ethoxy-4-fluorophenyl)-N-(isoxazol-4-ylmethyl)pyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-Benzyl-N-(2-ethoxy-4-fluorophenyl)pyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-(Oxazol-4-ylmethyl)-N-(2-propyl-4-(trifluoromethoxy)phenyl)pyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-(2-Cyclobutyl-4-(trifluoromethoxy)phenyl)-N-(oxazol-4-ylmethyl)pyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-(2-Methyl-4-(trifluoromethoxy)phenyl)-N-(oxazol-4-ylmethyl)pyrimidine-2,4-diamine;'}{'sup': 4', '4, 'N-(2-Isobutyl-4-(trifluoromethoxy)phenyl)-N-(oxazol-4-ylmethyl)pyrimidine-2,4-diamine;'}2-(4-((2-Aminopyrimidin-4-yl)(oxazol-4-ylmethyl)amino)-3-ethylphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol;{'sup': 4', '4, 'N-(2-Ethoxy-4-fluorophenyl)-N-( ...

INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHOD OF THEIR USE

The present disclosure is directed to compounds of formula I′ and methods of their use and preparation, as well as compositions comprising compounds of formula I′. 153-. (canceled)54. A compound selected from the group consisting of:N-((3R,5R)-1-Acryloyl-5-fluoropiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-hydroxypiperidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-fluoropiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpiperidin-3-yl)-5-(3-fluoro-2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5R)-1-Acryloyl-5-hydroxypiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(3-fluoro-2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5R)-1-Acryloyl-5-methoxypiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpiperidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpiperidin-3-yl)-5-(2-fluoro-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(2-chloro-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-hydroxypiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5- ...

INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHOD OF THEIR USE

The present disclosure is directed to compounds of formula I′ and methods of their use and preparation, as well as compositions comprising compounds of formula I′. 158-. (canceled)6063-. (canceled)64. The method of claim 59 , wherein the disease claim 59 , disorder claim 59 , or medical condition mediated by Bruton's tyrosine kinase is rheumatoid arthritis.6573-. (canceled)74. A method of treating a subject suffering from or diagnosed with a disease claim 59 , disorder claim 59 , or medical condition mediated by Bruton's tyrosine kinase activity claim 59 , comprising administering to a subject in need of such treatment an effective amount of at least one compound selected from the group consisting ofN-((3R,5R)-1-Acryloyl-5-fluoropiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-hydroxypiperidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5S)-1-Acryloyl-5-fluoropiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpiperidin-3-yl)-5-(3-fluoro-2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5R)-1-Acryloyl-5-hydroxypiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpyrrolidin-3-yl)-5-(3-fluoro-2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;N-((3R,5R)-1-Acryloyl-5-methoxypiperidin-3-yl)-5-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1-Acryloylpiperidin-3-yl)-5-(*S)-(2-methyl-4-phenoxyphenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide;(R)—N-(1- ...

BENZOIMIDAZOLE-2-YL PYRIDINES AND PYRAZINES AS HISTAMINE H4 RECEPTOR MODULATORS

BENZOIMIDAZOL-2-IL PYRIMIDINS AS MODULATORS OF THE HISTAMINE RECEIVER H4.

Una entidad química que es un compuesto de Fórmula (I) o Fórmula (II): en las que cada uno de R 1-4 es independientemente H, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, fenilo, -CF3, -OCF3, -CN, halo, -NO2, -Oalquilo C1-4, - Salquilo C1-4, -S(O)alquilo C1-4, -SO2alquilo C1-4, -C(O)alquilo C1-4, - C(O)fenilo, -C(O)NR a R b ,-CO2alquilo C1-4, -CO2H, -C(O)NR a R b o -NR a R b ; en los que cada uno de R a y R b es independientemente H, alquilo C1-4 o cicloalquilo C3-7; n es 1 ó 2; Z es N, CH o C(alquilo C1-4); al menos uno de R 5 y R 5 ' es H y el otro es H, metilo, hidroximetilo, dimetilaminometilo, etilo, propilo, isopropilo, -CF3, ciclopropilo o ciclobutilo; R 6 es H, alquilo C1-6 o cicloalquilo monocíclico; cada uno de R 7 es H; o ambos grupos R 7 tomados juntos forman un carbonilo; R 8 es H o alquilo C1-4; cada uno de R 9 y R 10 es independientemente H o alquilo C1-4; y R 11 es H o alquilo C1-4, con la condición de que donde ambos grupos R 7 tomados juntos forman un carbonilo, R 11 no sea H; 25 una sal farmacéuticamente aceptable del compuesto de Fórmula (I) o Fórmula (II). A chemical entity that is a compound of Formula (I) or Formula (II): in which each of R 1-4 is independently H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, - CF3, -OCF3, -CN, halo, -NO2, -C1-4alkyl, -C1-4alkyl, -S (O) C1-4alkyl, -SO2C1-4alkyl, -C (O) C1-4alkyl , - C (O) phenyl, -C (O) NR to R b, -CO2C 1-4 alkyl, -CO2H, -C (O) NR to R bo -NR to R b; wherein each of R a and R b is independently H, C1-4 alkyl or C3-7 cycloalkyl; n is 1 or 2; Z is N, CH or C (C1-4 alkyl); at least one of R 5 and R 5 'is H and the other is H, methyl, hydroxymethyl, dimethylaminomethyl, ethyl, propyl, isopropyl, -CF3, cyclopropyl or cyclobutyl; R 6 is H, C 1-6 alkyl or monocyclic cycloalkyl; each of R 7 is H; or both R 7 groups taken together form a carbonyl; R 8 is H or C 1-4 alkyl; each of R 9 and R 10 is independently H or C1-4 alkyl; and R 11 is H or C1-4 alkyl, with the proviso that where both R 7 ...

Phenyl and pyridyl lta4h modulators

Leukotrfene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and inflammatory conditions.

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

SECONDARY ALCOHOL QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. Formula I wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Secondary alcohol quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Methylene linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Alkyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Alkyl linked quinolinyl modulators of RORγt

The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Quinolinyl modulators of ror(gamma)t

Secondary alcohol quinolinyl modulators of ror gamma t

The present invention comprises compounds of FormulaI.wherein:R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are defined in the specification.The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl linked quinolinyl modulators of RORγt

The present invention comprises compounds of Formula I. wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Quinolinyl modulators of RORγt

The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Phenyl-linked quinolinyl modulators of ROR-GAMA-T

Los compuestos de Fórmula 1: **Fórmula** en donde: R1 es pirrolilo, pirazolilo, imidazolilo, triazolilo, tiazolilo, piridilo, piridilo N-óxido, pirazinilo, pirimidinilo, piridazilo, piperidinailo, quinazolinilo, cinolinilo, benzotiazolilo, indazolilo, tetrahidropiranilo, tetrahidrofuranilo, furanilo, fenilo, oxazolilo, isoxazolilo, tiofenilo, benzoxazolilo, bencimidazolilo, indolilo, tiadiazolilo, oxadiazolilo o quinolinilo; en el que dicho piridilo, piridilo N-óxido, pirazinilo, pirimidinilo, piridazilo, piperidinailo, quinazolinilo, cinolinilo, benzotiazolilo, indazolilo, imidazolilo, fenilo, tiofenilo, benzoxazolilo, bencimidazolilo, indolilo, quinolinilo, y pirazolilo están opcionalmente sustituidos con C(O)C(1-4)alquilo, C(O)NH2, C(O)NHC(1-2)alquilo, C(O)N(C(1-2)alquilo)2, NHC(O)C(1-4)alilo, NHSO2C(1-4)alquilo, C(1-4)alquilo, CF3, CH2CF3, Cl, F, -CN, OC(1-4)alquilo, N(C(1-4)alquilo)2, (CH2)3OCH3, SC(1-4)alquilo, OH, CO2H, CO2C(1-4)alquilo, C(O)CF3, SO2CF3, OCF3, OCHF2, SO2CH3, SO2NH2, SO2NHC(1-2)alquilo, SO2N(C(1-2)alquilo)2, C(O)NHSO2CH3, o OCH2OCH3; y opcionalmente sustituidos con hasta dos sustituyentes adicionales seleccionados independientemente del grupo que consiste en Cl, C(1-2)alquilo, SCH3, OC(1-2)alquilo, CF3, -CN, y F; y en los que dichos triazolilo, oxazolilo, isoxazolilo, pirrolilo, y tiazolilo están opcionalmente sustituidos con hasta dos sustituyentes seleccionados independientemente del grupo que consiste en SO2CH3, SO2NH2, alquilo C(O)NH2, -CN, OC(1-2), (CH2)(2-3)OCH3, SCH3, CF3, F, Cl, y C(1-2)alquilo; y dicho tiadiazolilo y oxadiazolilo están opcionalmente sustituidos con C(1-2)alquilo; y dichos piridilo, piridiloóxido, pirimidinilo, piridazilo, y pirazinilo están opcionalmente sustituidos con hasta tres sustituyentes adicionales seleccionados independientemente del grupo que consiste en C(O)NHC(1-2)alquilo, C(O)N(C(1-2)alquilo)2, NHC(O)C(1-4)alquilo, NHSO2C(1-4)alquilo, C(O)CF3, SO2CF3, SO2NHC(1-2)alquilo, SO2N(C(1-2)alquilo)2, C(O)NHSO2CH3 ...

Methylene linked quinolinyl modulators of ror-gamma-t

The present invention comprises compounds of Formula (I), wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR?t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. Wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Alkyl linked quinolinyl modulators of RORyt

The present invention comprises compounds of Formula I. wherein: R

METHYLENE-CONNECTED QUINOLINYL MODULATORS OF ROR-GAMMA-T

Use of substituted pyrazoles for the manufacture of a drug for the treatment of allergies

Glucocorticoid-selective anti-inflammatory agents

Tetracyclic progesterone receptor modulator compounds and methods

Nonsteroidal compounds that are high affinity, high selectivity modulators for progesterone receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring progesterone receptor agonist, partial agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the progesterone receptor modulator compounds.

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H receptor activity, including allergy, asthma, autoimmune diseases, and pruritis.

Method for treating allergies using substituted pyrazoles

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as lta4h modulators

Leukotriene A4 hydrolase (LTA4H) inhibitors of Formula (I), compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation. Wherein X is selected from the group consisting of NR5' 0, and S, with R5 being on of H and CH3; Y is selected from the group consisting; W is selected from the group consisting of CH2 and CHR, -CH2, with R' being one H and OH, wherein R1-attached carbon member in said CHR'- CH2 is not directly attached; R4 is selected from the group consisting of H, OCH3, Cl, F Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently selected from various groups.

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as lta4h modulators

Leukotriene A4 hydrolase (LTA4H) inhibitors of Formula (I), compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation. Wherein X is selected from the group consisting of NR5, O, and S, with R5 being on of H and CH3; Y is selected from the group consisting; W is selected from the group consisting Of CH2 and CHR1-CH2,with R1 being one H and OH, wherein R1-attached carbon member in said CHR1-CH2 is not directly attached; R4 is selected from the group consisting of H, OCH3, CI, F Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently selected from various groups.

Benzimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as lta4h modulators

A method for treating allergies using substituted pyrazoles

A method for the treatment of an allergic condition, including an atopic allergic condition, using substituted pyrazoles of formula (I).

Cyclocarbamate derivatives as progesterone receptor modulators

This invention provides compounds of Formula (I): wherein R 1 and R 2 are independent substituents or are fused to form spirocyclic rings; R 3 , R C , and R 4 are as defined herein; and R 5 is a substituted benzene ring or a substituted five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms including O, S, SO, SO 2 or NR 6 ; or pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions and methods using the compounds as antagonists of the progesterone receptor.

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyridines as modulators of the histamine H4 receptor

Benzoimidazol-2-yl pyridines, pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, including allergy, asthma, autoimmune diseases, and pruritis.

Contraceptive compositions containing cyclic carbamates and amide derivatives

This invention relates to cyclic combination therapies and regimens utilizin g, in combination with progestins, estrogens, or both, substituted indoline derivative compounds which are antagonists of the progesterone receptor havi ng general structure (I) wherein A and B are independent substituents selected from S, CH or N; provided that when A is S, B is CH or N; and when B is S, A is CH or N; and A and B cannot both be CH; and when A and B both equal N, on e N may be optionally substituted with a C1 to C6 alkyl group; R1 and R2 are independent substituents selected from the group of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C2 to C6 alkenyl, substituted C2 to C6 alkenyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C3 to C8 cycloalkyl, substitute d C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, or NRBCORA; or R1 and R2 are fused to form optionally substituted 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic ring, the heterocyclic ring containing one to three heteroatoms selected from the group of O, S and N; or pharmaceutically useful salts thereof. These methods of treatment may be used for contraception or for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses o f the invention include stimulation of food intake.

Cyclocarbamate and cyclic amide derivatives

This invention provides compounds of the formula: wherein A and B are independent substituents selected from S, CH or N; provided that when A is S, B is CH or N; and when B is S, A is CH or N; and A and B cannot both be CH; and when A and B both equal N, one N may be optionally substituted with an C 1 to C 6 alkyl group; R 1 and R 2 are independent substituents selected from the group of H, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 2 to C 6 alkenyl, substituted C 2 to C 6 alkenyl, C 2 to C 6 alkynyl, substituted C 2 to C 6 alkynyl, C 3 to C 8 cycloalkyl, substituted C 3 to C 8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, COR A , or NR B COR A ; or R 1 and R 2 are fused to form optionally substituted 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic ring, the heterocyclic ring containing one to three heteroatoms selected from the group of O, S and N; or pharmaceutically useful salts thereof. The compounds of this invention are useful as agonists and antagonists of the progesterone receptor and in methods of inducing contraception and in the treatment or prevention of benign or malignant neoplastic diseases.

Androgen receptor modulator compounds and methods

Non-steroidal compounds which are high affinity, high selectivity modulators for androgen receptors are disclosed, having the formula: (see formula I, III, IV, V) (see formula VI) Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring androgen receptor agonist, partial agonist or antagonist therapy, intermediates usefully in the preparation of the compounds and processes for the preparation of the androgen receptor modulator compounds.

Aryl-substituted bridged or fused diamines as modulators of leukotriene a4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

Thio-oxindole derivatives

This invention relates to compounds which are agonists of the progesterone receptor which have the general structure: wherein: R 1 , R 2 , R 3 , R 4 , R 5 and Q 1 are as defined herein, or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.

Phenyl linked quinolinyl modulators of ror.gamma.t

The present invention comprises compounds of Formula (I). wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR.gamma.t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Aryl-substituted bridged or fused diamines as modulators of leukotriene a4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

Indoles and benzoimidazoles as histamine H4 receptor modulators

Benzoimidazole and indole compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Contraceptive compositions containing quinazolinone and benzoxazine derivatives

This invention relates to cyclic combination therapies utilizing, in combination with progestins, estrogens, or both, compounds which are progesterone receptor antagonists of general structure: (I) wherein: R?1~ an d R?2~ are H, COR?A~, or NR?B~COR?A~, alkyl, alkenyl, alkynyl, cycloalkyl, ary l, or heterocyclic; or R?1~ and R?2~ fuse to form 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; R?A~ is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; R?B~ is H or alkyl; R?3~ is H, OH , NH~2?, COR?C~ or alkyl, alkenyl, or alkynyl; R?C~ is H, alkyl, aryl, alkoxy, or aminoalkyl; R?4~ is H, halogen, CN, NO~2?, alkyl, alkynyl, alkoxy, amino or aminoalkyl; R?5~ is benzen or 5- or 6-membered heterocyclic ring; R?6~ is H or alkyl; G~1? is O, NR~7?, or CR~7?R~8?; G~2? is CO or CR~7?R~8?; provided tha t when G~1? is O, G~2? is CR~7?R~8?, and G~1? and G~2? cannot both be CR~7?R~8 ?; R~7? and R~8? are H or an optionally substituted alkyl, aryl, or heterocycli c moiety; or pharmaceutically acceptable salt thereof. These methods may be us ed for contraception or treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleedin g. Additional uses of the invention include stimulation of food intake.

Printing device

Process for reinforcing foam rubber and product made thereby

Benzofuro- and benzothienopyrimidine modulators of the histamine H4 receptor

Benzofuro- and benzothienopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Substituted pyrazoles

Substituted pyrazoles of general formula methods of manufacturing them, compositions containing them, and methods of using them to, for example, treat autoimmune diseases mediated by cathepsin S, and inhibit cathepsin S activity, are described.

Heterocyclic compounds

A compound of formula (I) wherein: wherein X4 is NR1 or S; _ X1 is CR3; X2 is NRe or O, provided that X2 is NRe where X1 is N; X3 is N; to treat or prevent disorders ans conditions mediated by the histamine H4 receptor.

Contraceptive compositions containing antiprogestinic and progestinic

Secondary alcohol quinolinyl modulators of roryt

The present invention comprises compounds of Formula I. Formula I wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating ROR?t activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

Imidazole compounds

Imidazole compounds, compositions, and methods of using them in leukocyte recruitment inhibition, in modulating H4 receptor expression, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.

Methylene linked quinolinyl modulators of ror-gamma-t

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

Cyclothiocarbamate derivatives as progesterone receptor modulators

The present invention provides compounds which are agonists of the progesterone receptor and have structures (I) or (II) wherein R1 and R2 are independent substituents selected from the group of H, optionally substituted Cl to C6 alkyl, alkenyl, alkynyl, or alkynyl groups C3 to C8 cycloalkyl, aryl, substituted aryl, or heterocyclic groups, or CORA or NR B COR A; or RI and R2 are fused to form an optionally substituted 3 to 8 membered Spiro cyclic alkyl or alkenyl ring or a Spiro cyclic ring containing one to three heteroatoms selected from O, S and N; R A is selected from H, amino, or optionally substituted C1 to C3 alkyl, aryl, Cl to C3 alkoxy, or Cl to C3 aminoalkyl groups; R B is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2 COR C, or optionally substituted C1 to C6 alkyl, C3 to C6 alkenyl, or alkynyl groups; R C is selected from H or optionally substituted Cl to C3 alkyl, aryl, Cl to C3 alkoxy, or Ci to C3 aminoalkyl groups; Q1 is S, NR7; or CR8R9, R5 is an optionally trisubstituted benzene ring or an optionally substituted five or six membered heterocyclic ring with 1, 2, or 3 ring heteroatoms selected from the group of O, S, SO, SO2 or NR6; or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds for contraception and the treatment of progesterone-related maladies.

Cyclothiocarbamate derivatives as progesterone receptor modulators

Contraceptive compositions contaning indolone derivatives and progestational agents

This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having general structure (1), wherein R?1 and R2¿ may be single substituents or fused to form spirocyclic rings, in combination with progestins, estrogens, or both. These methods of treatment may be used for contraception or for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake.