Androgen Receptor Modulator Compounds and Methods

• US 20090030027A1
• Filed: 06/12/2006
• Published: 01/29/2009
• Est. Priority Date: 06/17/2005
• Status: Active Grant

• Current Assignee: Ligand Pharmaceuticals, Inc.
• Original Assignee: Ligand Pharmaceuticals, Inc.
• Inventors: Shen, Yixing, Zhao, Shuo, Pedram, Bijan, Zhi, Lin, Van Oeveren, Cornelis Arjan
• Granted Patent: US 8,193,357 B2
• Time in Patent Office: Days
• US Class Current: 514/285
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/06 : Anabolic agents androgens A61P5/26
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/26 : Androgens
• CPC Class Codes: A61P 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

Claims

1. A compound of Formula I or Formula II:

wherein;

R¹ and R³ each independently is selected from among hydrogen, optionally substituted C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl;

or

R¹ and R³ taken together form a C₃-C₈ carbocyclic ring;

R² and R⁴ are each hydrogen;

or

R² and R⁴ taken together form a bond;

R⁵ is selected from among hydrogen, C₁-C₈ alkyl, C₁-C₈ haloalkyl, C₁-C₈ heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈ heteroarylalkyl;

R⁶ is hydrogen or F;

R⁷ is selected from among hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl;

R⁸ and R⁹ each independently is selected from among hydrogen, F, and hydroxyl; and

R¹⁰ is selected from among hydroxyl, Cl, Br, C₁-C₃ fluoroalkyl, C₁-C₃ heteroalkyl, C₂-C₄ alkenyl, and C₂-C₄ alkynyl;

and pharmaceutically acceptable salts and prodrugs thereof.

2. The compound of claim 1, wherein R¹ and R³ each independently is selected from among fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄ heteroalkyl, fully saturated C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl.

3. The compound of claim 1, wherein:

R¹ is selected from among hydrogen, fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄ heteroalkyl, fully saturated C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl; and

R³ is selected from among C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl, heteroaryl, and optionally substituted aryl.

4. The compound of claim 1, wherein:

R¹ is selected from among hydrogen, C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl; and

R³ is selected from among hydrogen, fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄ heteroalkyl, fully saturated C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl.

9. The compound of claim 1, wherein the compound is a selective androgen receptor modulator.

10. The selective androgen modulator of claim 9, wherein the selective androgen receptor modulator is a selective androgen receptor agonist.

11. The selective androgen modulator of claim 9, wherein the selective androgen receptor modulator is a selective androgen receptor antagonist.

12. The selective androgen modulator of claim 9, wherein the selective androgen receptor modulator is a selective androgen receptor partial agonist.

13. The selective androgen receptor modulator of claim 9, wherein the compound is a tissue-specific modulator.

14. The compound of claim 1, wherein the compound is a selective androgen receptor binding compound.

15. A method for modulating an activity of an androgen receptor, comprising contacting an androgen receptor with a compound of claim 1.

16. The method of claim 15, wherein the androgen receptor is in a cell.

17. A method for identifying a compound that modulates an activity of an androgen receptor, comprising:

contacting a cell expressing an androgen receptor with a compound of claim 1; and

monitoring an effect of the compound upon the cell.

18. A method for treating a patient having a condition susceptible to treatment with an androgen receptor modulator, comprising administering to the patient a pharmaceutical agent comprising a compound of claim 1.

19. The method of claim 18, wherein the condition is selected from among maintenance of muscle strength and function;

reversal or prevention of frailty or age-related functional decline in the elderly;

treatment of catabolic side effects of glucocorticoids;

treatment of reduced bone mass, density or growth;

treatment of chronic fatigue syndrome;

chronic myalgia;

treatment of acute fatigue syndrome and muscle loss;

accelerating of wound healing;

accelerating bone fracture repair;

accelerating healing of complicated fractures;

in joint replacement;

prevention of post-surgical adhesion formation;

acceleration of tooth repair or growth;

maintenance of sensory function;

treatment of periodontal disease;

treatment of wasting secondary to fractures and treatment of wasting in connection with chronic obstructive pulmonary disease, treatment of wasting in connection with chronic liver disease, treatment of wasting in connection with AIDS, cancer cachexia, burn and trauma recovery, chronic catabolic state, eating disorders and chemotherapy;

treatment of cardiomyopathy;

treatment of thrombocytopenia;

treatment of growth retardation in connection with Crohn'"'"'s disease;

treatment of short bowel syndrome;

treatment of irritable bowel syndrome;

treatment of inflammatory bowel disease;

treatment of Crohn'"'"'s disease and ulcerative colitis;

treatment of complications associated with transplantation;

treatment of physiological short stature including growth hormone deficient children and short stature associated with chronic illness;

treatment of obesity and growth retardation associated with obesity;

treatment of anorexia;

treatment of hypercortisolism and Cushing'"'"'s syndrome;

Paget'"'"'s disease;

treatment of osteoarthritis;

induction of pulsatile growth hormone release;

treatment of osteochondrodysplasias;

treatment of depression, nervousness, irritability and stress;

treatment of reduced mental energy and low self-esteem;

improvement of cognitive function;

treatment of catabolism in connection with pulmonary dysfunction and ventilator dependency;

treatment of cardiac dysfunction;

lowering blood pressure;

protection against ventricular dysfunction or prevention of reperfusion events;

treatment of adults in chronic dialysis;

reversal or slowing of the catabolic state of aging;

attenuation or reversal of protein catabolic responses following trauma;

reducing cachexia and protein loss due to chronic illness;

treatment of hyperinsulinemia;

treatment of immunosuppressed patients;

treatment of wasting in connection with multiple sclerosis or other neurodegenerative disorders;

promotion of myelin repair;

maintenance of skin thickness;

treatment of metabolic homeostasis and renal homeostasis;

stimulation of osteoblasts, bone remodeling and cartilage growth;

regulation of food intake;

treatment of insulin resistance;

treatment of insulin resistance in the heart;

treatment of hypothermia;

treatment of congestive heart failure;

treatment of lipodystrophy;

treatment of muscular atrophy;

treatment of musculoskeletal impairment;

improvement of the overall pulmonary function;

treatment of sleep disorders; and

the treatment of the catabolic state of prolonged critical illness;

treatment of hirsutism, acne, seborrhea, androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy, adenomas and neoplasies of the prostate and malignant tumor cells including the androgen receptor;

osteosarcoma;

hypercalcemia of malignancy;

metastatic bone disease;

treatment of spermatogenesis, endometriosis and polycystic ovary syndrome;

counteracting preeclampsia, eclampsia of pregnancy and preterm labor;

treatment of premenstrual syndrome;

treatment of vaginal dryness;

age related decreased testosterone levels in men, male menopause, hypogonadism, male hormone replacement, male and female sexual dysfunction, male and female contraception, hair loss, Reaven'"'"'s Syndrome and the enhancement of bone and muscle strength.

20. The method of claim 18, wherein the patient has a condition selected from among acne, male-pattern baldness, wasting diseases, hirsutism, hypogonadism, osteoporosis, infertility, impotence and cancer.

21. A method for stimulating hematopoiesis in a patient, comprising administering to the patient a pharmaceutical agent comprising a compound of claim 1.

22. A method of contraception, comprising administering to patient a pharmaceutical agent comprising a compound of claim 1.

23. A method of improving athletic performance in an athlete, comprising administering to the athlete a pharmaceutical agent comprising a compound of claim 1.

24. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

28. An article of manufacture, comprising:

packaging material;

a compound of claim 1, a composition comprising a compound of claim 1, or a pharmaceutically acceptable derivative of a compound of claim 1, wherein the compound, composition or pharmaceutically acceptable derivative is effective for modulating the activity of androgen receptor, or for treatment, prevention or amelioration of one or more symptoms of androgen receptor mediated diseases or disorders, or diseases or disorders in which androgen receptor activity is implicated, within the packaging material; and

a label that indicates that the compound, composition, or pharmaceutically acceptable derivative, is used for modulating the activity of androgen receptor or for treatment, prevention or amelioration of one or more symptoms of androgen receptor mediated diseases or disorders, or diseases or disorders in which androgen receptor activity is implicated.

5. A compound of Formula II:

R² and R⁴ are each hydrogen;

or

R² and R⁴ taken together form a bond;

R⁷ is selected from among hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, and optionally substituted aryl;

R⁸ and R⁹ each independently is selected from among hydrogen, F, and hydroxyl; and

R¹⁰ is selected from among hydroxyl, Cl, Br, C₁-C₃ fluoroalkyl, optionally substituted C₁-C₅ heteroalkyl, C₂-C₄ alkenyl and C₂-C₄ alkynyl, wherein if R¹⁰ is a C₂-C₄ alkynyl, then R⁸ and R⁹ do not exist;

and pharmaceutically acceptable salts and prodrugs thereof.

6. A compound of Formula III:

wherein;

R¹¹ is C₁-C₄ alkyl;

R¹² is selected from among hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, hydroxymethyl, optionally substituted heteroaryl, and optionally substituted aryl;

or

R¹¹ and R¹² taken together form a C₃-C₈ carbocyclic ring, wherein if R¹¹ and R¹² taken together form a C₃-C₈ carbocyclic ring, then R¹⁶ is not Cl or F;

R¹⁴ is selected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl;

R¹⁵ is selected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl;

R¹³ is hydrogen;

or

R¹³ and R¹⁶ taken together form a bond, wherein if R¹³ and R¹⁶ taken together form a bond, then R¹⁴ and R¹⁵ are each C₁-C₄ alkyl;

R¹⁶ is selected from among hydroxyl, Cl, F, Br, C₁-C₃ fluoroalkyl, C₁-C₃ heteroalkyl, C₂-C₄ alkenyl, and C₂-C₄ alkynyl;

wherein if R¹³ is F, then R¹² is hydroxymethyl or C₁-C₄ haloalkyl;

n is 0 or 1, wherein if n is 0, then R¹⁶ is C₂-C₄ alkenyl or C₂-C₄ alkynyl;

and pharmaceutically acceptable salts and prodrugs thereof.

7. A compound selected from among:

9-Chloro-1,2-dimethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     105);

9-Chloro-2-ethyl-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     106);

9-Chloro-1,2-trimethylene-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     107);

9-Chloro-1-methyl-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     108);

9-Chloro-2-methyl-1-ethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     109);

9-Chloro-1-methyl-2-phenyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     110);

9-Chloro-1-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-2-carboxylic acid ethyl ester (Compound III);

9-Chloro-2-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     112);

9-Chloro-1,2-tetramethylene-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     113);

9-Chloro-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     114);

9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     115);

9-Chloro-2-(4-fluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     116);

9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     117);

9-Chloro-2-(4-chlorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     118);

9-Chloro-2-(2-fluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     119);

9-Chloro-1 methyl-2-thien-2-yl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     120);

2-Acetyl-9-chloro-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     121);

(9-Chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinolin-1-yl)-acetic acid (Compound

     122);

9-Chloro-1-ethyl-2-thien-2-yl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     123);

9-Chloro-2-methyl-1-propyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     124);

9-Chloro-1-ethyl-2-phenyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     125);

(±

)-9-Chloro-3-(2,2,2-trifluoroethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     126);

(±

)-9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     127);

(±

)-9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     128);

(±

)-9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     129)

(±

)-9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     130);

(±

)-9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     131);

(±

)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]-quinolin-7-one (Compound

     132);

(±

)-9-Chloro-1,2-tetramethylene-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     133);

(±

)-9-Chloro-3-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     134);

(±

)-9-Chloro-1,2-dimethyl-3-ethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     135);

(±

)-9-Chloro-1,2,3-trimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     136);

(±

)-9-Chloro-1,2-dimethyl-3-propyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     137);

(±

)-9-Chloro-3-(2-chloro-2,2-difluoro-ethyl)-1,2-dimethyl-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     138);

(±

)-9-Chloro-1,2-dimethyl-3-(2-hydroxyethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     139);

(±

)-9-Chloro-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     140);

(±

)-9-Chloro-1,2-dimethyl-3-(2,2-dimethylpropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     141);

(±

)-9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     142);

(±

)-9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     143);

(±

)-9-Chloro-1,2-dimethyl-3-phenylmethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     144);

(±

)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     145);

(±

)-9-Chloro-2-(3-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     146);

(±

)-9-Chloro-1-methyl-2-(4-trifluoromethyl-phenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     147);

(±

)-9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     148);

(±

)-9-Chloro-2-(4-fluoro-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     149);

(±

)-9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     150);

(±

)-9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     151);

(±

)-9-Chloro-2-(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     152);

(±

)-2-(3-Bromophenyl)-9-chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     153);

(±

)-9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     154);

(±

)-9-Chloro-2-(4-hydroxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     155);

(±

)-9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     156);

(±

)-9-Chloro-2-(3,4-dichlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     157);

(±

)-9-Chloro-2-(3,5-bis(trifluoromethyl)phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     158);

(±

)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-2-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     159);

(±

)-9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     160);

(±

)-9-Chloro-1-methyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     161);

(+)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     162);

(−

)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     163);

(±

)-9-Chloro-1-ethyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]quinolin-7-one (Compound

     164);

(±

)-9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     165);

(±

)-9-Chloro-2,3-diethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     166);

(±

)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]quinolin-7-one (Compound

     167);

(±

)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     168);

(±

)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     169);

(±

)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     170);

(±

)-9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     171);

(±

)-9-Chloro-1-methyl-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     172);

(±

)-1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     173);

(±

)-1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     174);

(±

)-3-(2-Chloro-2,2-difluoroethyl)-1,2-dimethyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     175);

(±

)-9-Chloro-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     176);

(±

)-9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     177);

(±

)-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     178);

(±

)-2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     179);

(±

)-2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     180);

(±

)-2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     181);

(±

)-1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     182);

9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     183);

9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     184);

9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     185);

9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     186);

9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     187);

3-Benzyl-9-chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehyde (Compound

     188);

9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     189);

9-Chloro-3-(2-hydroxy-ethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     190);

9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     191);

9-Chloro-3-(2-hydroxy-ethyl)-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]-quinoline-1-carbaldehyde (Compound

     192);

9-Chloro-3-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     193);

9-Chloro-2-(4-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     194);

9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     195);

9-Chloro-1,2-dimethyl-3-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     196);

9-Chloro-2-(4-methoxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     197);

2-(3-Bromophenyl)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     198);

9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     199);

9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     200);

9-Chloro-1-methyl-2-(3-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     201);

9-Chloro-1-methyl-2-(4-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     202);

9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     203);

9-Chloro-1-methyl-2-(4-methylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     204);

9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     205);

9-Chloro-2(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     206);

9-Chloro-1-methyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     207);

9-Chloro-1,2,3-trimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     208);

9-Chloro-1-ethyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     209);

9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     210);

9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     211);

9-Chloro-3-(2-chloro-2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     212);

9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     213);

9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     214);

9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     215);

9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     216);

9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     217);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     218);

1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     219);

1,2-Dimethyl-3-(2-chloro-2,2-difluoroethyl)-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     220);

1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     221);

9-Chloro-3-(2-chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     222);

9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     223);

3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     224);

2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     225);

2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     226);

1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     227);

2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     228);

9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     229);

9-Chloro-2-hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     230);

(±

)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     231);

(±

)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     232);

(±

)-9-Chloro-1-methyl-3-(3,3,3-trifluoro-2-hydroxypropyl)-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     233);

1-Methyl-3-(2,2,2-trifluoro-ethyl)-2,9-bis-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     234);

2-Hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     235);

3-Allyl-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     236);

1,2-Dimethyl-3-(2-methyl-allyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     237);

1,2-Dimethyl-3-(2-methylprop-1-enyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     238);

3-(3-Hydroxy-3-methyl-butyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     239);

1,2-Dimethyl-3-(2-hydroxyethyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     240);

3-(2-Acetoxyethyl)-1,2-Dimethyl-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     241);

1,2-Dimethyl-3-(prop-2-ynyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound

     242);

(±

)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     243);

(±

)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     244);

(−

)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-j]quinolin-7-one (Compound

     245);

(±

)-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     246);

(±

)-2-Ethyl-1-methyl-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     247);

1,2-Dimethyl-3-(3-fluoropropyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     248);

1,2-Dimethyl-3-(3-hydroxypropyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     249);

3-(3-Acetoxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     250);

and a pharmaceutically acceptable salt or a prodrug of any of these compounds.

8. A compound selected from among:

9-Chloro-2-(3-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     251);

9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     252);

9-Chloro-1-methyl-2-(3-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     253);

9-Chloro-1-methyl-2-(4-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     254);

9-Chloro-1-methyl-2-(pentafluoroethyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     255);

9-Chloro-1-methyl-2-(5-methyl-2-furyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     256);

9-Chloro-1-methyl-2-(2-oxazolyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     257);

9-Chloro-1-methyl-2-(5-methyl-2-thiophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     258);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-thiophen-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     259);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(trifluoromethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     260);

9-Chloro-1-methyl-2-(2-furyl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one (Compound

     261);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(1,3-thiazol-2-yl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     262);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(4-pyridyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     263);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(3-pyridyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     264);

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(2-pyridyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one (Compound

     265);

9-Chloro-1-methyl-2-(oxazol-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     266);

9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     267);

9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     268);

9-Chloro-1-(3-chloropropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     269);

9-Chloro-1-(3-iodopropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     270);

(S)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     271);

(S)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     272);

(S)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     273);

(S)-9-Chloro-1-methyl-2-(3-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     274);

(S)-9-Chloro-1-methyl-2-(2-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     275);

(S)-9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     276);

(S)-9-Chloro-2-(2-furyl)-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     277);

(R)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     278);

rac-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one (Compound

     279);

9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     280);

(R)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     281);

(R)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     282);

(R)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     283);

(R)-9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     284);

(R)-9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     285);

2-Ethyl-3-(3-hydroxypropyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     286);

9-Chloro-1,2-dimethyl-3-(3-hydroxypropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     287);

3-(3-Bromopropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     288);

1,2-Dimethyl-3-[3-(2-hydroxy-ethylamino)-propyl]-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     289);

9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     290);

(S)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     291);

(R)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     292);

3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     293);

3-(3-chloro-2-hydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     294);

(S)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     295);

(R)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     296);

9-Chloro-3-(2,3-dihydroxypropyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one (Compound

     297);

3-{2-[2-(2-Hydroxy-ethoxy)-ethoxy]-ethyl}-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound

     298); and

a pharmaceutically acceptable salt or a prodrug of any of these compounds.

25-27. -27. (canceled)