Raymond J Horvath

US Patent:

6355651, Mar 12, 2002

Filed:

Sep 6, 2000

Appl. No.:

09/657634

Inventors:

Raymond F. Horvath - North Branford CT
Alan Hutchison - Madison CT

Assignee:

Neurogen Corporation - Branford CT

International Classification:

A61K 31437

US Classification:

514292, 514183, 51421205, 514293, 544328, 544331, 544333, 540479, 540583, 546 82, 546 87, 546113

Abstract:

Disclosed are compounds of the formula: wherein Ar is optionally substituted aryl or heteroaryl R is hydrogen or alkyl; R is hydrogen or alkyl; R is hydrogen, halogen, alkyl or alkoxy; or R taken together with the ring to which they are attached form a 5-9 membered saturated or aromatic ring optionally having a hetero atom selected from oxygen, sulfur or nitrogen; R and R are independently hydrogen, alkyl, cycloalkyl, aryl or heteroaryl groups; or R and R together with the nitrogen atom to which they are attached form a 5-8 membered ring; and R is hydrogen, halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy or thioalkoxy having 1-6 carbon atoms, which compounds are highly selective partial agonists or antagonists at human Corticotropin-Releasing Factor 1 (CRF1) receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post trumatic stress disorder (PTSD) as well as depression, headache and anxiety.

US Patent:

6362186, Mar 26, 2002

Filed:

Nov 6, 2000

Appl. No.:

09/707387

Inventors:

Raymond F. Horvath - North Branford CT
James W. Darrow - Wallingford CT
George D. Maynard - Clinton CT

Assignee:

Neurogen Corporation - Branford CT

International Classification:

C07D23970

US Classification:

5142521, 514267, 544250, 544106, 544336, 544361, 540476, 540597, 546 87

Abstract:

Disclosed are compounds of the formula: wherein Ar, R , W and X are substituents as defined herein, which compounds are (1) antagonists at CRF receptors and are, therefore, useful in the diagnosis and treatment of stress related disorders such as post traumatic stress disorder (PTSD) as well as depression, headache and anxiety; and (2) are neuropeptide Y , receptor antagonists, and are therefore useful in the treatment of a variety of clinical conditions which are characterized by the presence of an excess of neuropeptide Y.

US Patent:

6436932, Aug 20, 2002

Filed:

Sep 4, 2001

Appl. No.:

09/947045

Inventors:

Ping Ge - Branford CT
Raymond F. Horvath - North Branford CT
Stephane De Lombaert - Madison CT

Assignee:

Neurogen Corporation - Branford CT

International Classification:

A61K 31519

US Classification:

5142345, 514258, 544117, 544280

Abstract:

Disclosed are compounds of the formula: wherein Ar, Q , Q , R , W and X are substituents as defined herein, which compounds are water-soluble CRF receptor antagonists, and are therefore useful for the treatment of psychiatric disorders and neurological diseases, including major depression, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders, as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

US Patent:

6472402, Oct 29, 2002

Filed:

Sep 30, 1999

Appl. No.:

09/408613

Inventors:

Raymond F. Horvath - North Branford CT
James W. Darrow - Wallingford CT
George D. Maynard - Clinton CT

Assignee:

Neurogen Corporation - Branford CT

International Classification:

C07D47104

US Classification:

514292, 546 87, 540476, 540597, 544106, 544250, 544336, 544361

Abstract:

Disclosed are compounds of the formula: wherein Ar, R , W, X and m are substituents as defined herein. These compounds are modulators of CRF receptors and are therefore useful for treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimers disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of Formula I.

US Patent:

6506762, Jan 14, 2003

Filed:

Sep 29, 2000

Appl. No.:

09/676941

Inventors:

Raymond F. Horvath - Guilford CT
Jennifer Tran - Guilford CT
Kevin J. Hodgetts - Killingworth CT
Philip A. Carpino - Groton CT
David A. Griffith - Old Saybrook CT

Assignee:

Neurogen Corporation - Branford CT
Pfizer Inc. - New York NY

International Classification:

C07D48704

US Classification:

5142594, 544 80, 544278, 544262, 544276, 544277, 544254, 544281, 544282, 544236, 544256, 544257, 544279, 51425941, 5142632, 51426321, 51426322, 51426323, 5142634, 51426411, 5142651

Abstract:

The present invention also provides a general method to whereby mono-, bi-, or tricyclic heterocycles may be modified to obtain potent antagonists at the NPY receptor. The present invention provides novel, potent, non-peptidic antagonists of NPY receptors, particularly, the NPY receptors, designed from a selection of mono-, bi-, or tri-cyclic heterocyclic cores. This invention relates to novel compounds, compositions, and methods for the treatment of physiological disorders associated with an excess of neuropeptide Y. The novel compounds encompassed by the present invention are those of the formula I-XV. wherein X is N or CR ; W is S, O, or NR ; Y is N or CR ; E, F, and G are each, independently, CR or N; I and J are each, independently, C O, S, O, CR R or NR when single bonded to both adjacent ring atoms, or N, or CR when double bonded to an adjacent ring atom; K is N or CR when double bonded to L or J, or O, S, C O, CR R , or NR when single bonded to both adjacent ring atoms, or N or CR when double bonded to an adjacent ring atom; L is N or CR when single bonded to all atoms to which it is attached, or C (carbon) when double bonded to K; the 6- or 7-membered ring that contains I, J, K, and L may contain from 1 to 3 double bonds, from 0 to 2 heteroatoms, and from 0 to 2 C O groups, wherein the carbon atom of such groups are part of the ring and the oxygen atom is a substituent on the ring; Q is O or NR. Such compounds inhibit the activity of neuropeptide Y at those receptors are useful in treating physiological disorders associated with an excess of neuropeptide Y, including eating disorders, such as, for example, obesity and bulimia, and certain cardiovascular diseases, for example, hypertension.

US Patent:

6583169, Jun 24, 2003

Filed:

Aug 13, 2001

Appl. No.:

09/928722

Inventors:

Raymond F. Horvath - Guilford CT
Ping Ge - Durham CT
Taeyoung Yoon - Guilford CT
Alan Hutchison - Madison CT

Assignee:

Neurogen Corporation - Branfod CT

International Classification:

A61K 31404

US Classification:

514419, 548495, 5483097, 514394

Abstract:

Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein; A is N or CH; R and R represents hydrogen or lower alkyl; G, R , R , R , R , R and R are variables defined herein. These compounds are modulators of CRF receptors and are therefore useful for treating affective disorders, anxiety, depression, eating disorders, and stress disorders in humans and other animals. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.

US Patent:

6670371, Dec 30, 2003

Filed:

Mar 12, 2002

Appl. No.:

10/096239

Inventors:

Raymond F. Horvath - Guilford CT
Alan Hutchison - Madison CT

Assignee:

Neurogen Corporation - Branford CT

International Classification:

A61K 31437

US Classification:

514292, 514183, 514256, 514275, 51421205, 514293, 540479, 540583, 544328, 544331, 544333, 544322, 546 82, 546 87, 546113

Abstract:

Disclosed are compounds of the formula: wherein Ar is optionally substituted aryl or heteroaryl R is hydrogen or alkyl; R is hydrogen or alkyl; R is hydrogen, halogen, alkyl or alkoxy; or R and R taken together with the ring to which they are attached form a 5-9 membered saturated or aromatic ring optionally having a hetero atom selected from oxygen, sulfur or nitrogen; R and R are independently hydrogen, alkyl, cycloalkyl, aryl or heteroaryl groups; or R and R together with the nitrogen atom to which they are attached form a 5-8 membered ring; and R is hydrogen, halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy or thioalkoxy having 1-6 carbon atoms, which compounds are highly selective partial agonists or antagonists at human Corticotropin-Releasing Factor 1 (CRF1) receptors and are useful in the diagnosis and treatment of treating stress related disorders such as post trumatic stress disorder (PTSD) as well as depression, headache and anxiety.

US Patent:

6696445, Feb 24, 2004

Filed:

Nov 8, 2002

Appl. No.:

10/291446

Inventors:

Raymond F. Horvath - Guilford CT
Jennifer N Tran - Guilford CT
Kevin J. Hodgetts - Killingworth CT
Philip A. Carpino - Groton CT
David A. Griffith - Old Saybrook CT

Assignee:

Neurogen Corporation - Branford CT
Pfizer Inc. - New York NY

International Classification:

C07D40112

US Classification:

514245, 544196, 544197, 544198, 544199, 544208, 544209, 544210

Abstract:

The present invention also provides a general method to whereby mono-, bi-, or tricyclic heterocycles may be modified to obtain potent antagonists at the NPY receptor. The present invention provides novel, potent, non-peptidic antagonists of NPY receptors, particularly, the NPY receptors, designed from a selection of mono-, bi-, or tri-cyclic heterocyclic cores. This invention relates to novel compounds, compositions, and methods for the treatment of physiological disorders associated with an excess of neuropeptide Y. The novel compounds encompassed by the present invention are those of the formula I-XV. wherein X is N or CR ; W is S, O, or NR ; Y is N or CR ; E, F, and G are each, independently, CR or N; I and J are each, independently, C O, S, O, CR R or NR when single bonded to both adjacent ring atoms, or N, or CR when double bonded to an adjacent ring atom; K is N or CR when double bonded to L or J, or O, S, C O, CR R , or NR when single bonded to both adjacent ring atoms, or N or CR when double bonded to an adjacent ring atom; L is N or CR when single bonded to all atoms to which it is attached, or C (carbon) when double bonded to K; The 6- or 7-membered ring that contains I, J, K, and L may contain from 1 to 3 double bonds, from 0 to 2 heteroatoms, and from 0 to 2 C O groups, wherein the carbon atom of such groups are part of the ring and the oxygen atom is a substituent on the ring; Q is O or NR. Such compounds inhibit the activity of neuropeptide Y at those receptors are useful in treating physiological disorders associated with an excess of neuropeptide Y, including eating disorders, such as, for example, obesity and bulimia, and certain cardiovascular diseases, for example, hypertension.