MXPA05013424A

MXPA05013424A - Tetrahydrocarbazole derivatives and their pharmaceutical use

Info

Publication number: MXPA05013424A
Application number: MXPA/A/2005/013424A
Authority: MX
Inventors: Davis Boggs Sharon; Gudmundsson Kristjan
Original assignee: Davis Boggs Sharon; Gudmundsson Kristjan; Smithkline Beecham Corporation
Priority date: 2003-06-12
Filing date: 2005-12-09
Publication date: 2007-04-20

Abstract

The present invention relates to novel compounds of formula (I), that are useful in the treatment of human papillomaviruses, and also to the methods for the making and use of such compounds.

Description

DERIVATIVES OF TETRAHYDROCARBON A AND ITS PHARMACEUTICAL USE FIELD OF THE INVENTION The present invention relates to novel compounds that are useful in the treatment of human papillomavirus, and also to methods for the manufacture and use of such compounds.

BACKGROUND OF THE INVENTION Human Papilloma Virus (HPVs) are small, unwrapped DNA viruses, involved in many conditions and diseases. For example, HPVs cause a wide variety of benign and pre-malignant tumors. HPV spreads through direct contact. HPVs can be divided into two categories: cutaneous and mucosal. Cutaneous HPVs cause cysts on the hands and feet, such as common, plantar, filiform, or flat cysts. Mucosal HPV types infect the anogenital region and the oral cavity. Approximately 100 different types of HPV have been characterized to date. Approximately 40 types of HPV specifically infect the oral and genital mucosa. Mucosal HPVs are more frequently transmitted sexually, and with an incidence of approximately twice that of herpes simplex virus infection, HPVs are considered one of the most common sexually transmitted diseases (STDs) worldwide. Infection with the human papillomavirus (HPV) may not cause any symptoms and may not always produce visible genital cysts. When symptoms develop, they usually occur 2 to 3 months after infection with the virus. However, it is known that symptoms develop from 3 weeks to many years after the infection occurs. As such, HPV can spread without realizing it. More than 25 types of HPV that are implicated in anogenital diseases are broadly classified as either low risk or high risk. Low-risk HPVs, such as HPV-6 and HPV-1, are the etiologic cause of genital cysts (acuminata condyloma). High-risk HPVs, such as HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, usually do not produce visible genital cysts. Rather, high-risk viral types can be identified through DNA evaluation. High-risk HPVs such as HPV-16 and HPV-1 8 can be found in Pap smear evaluations and are related to precancerous cervical cell change, cervical dysplasia, and cervical cancer. In fact, high-risk types of HPV, such as 16, 18, 31, 33, and 35, are strongly associated with precancerous and cancerous changes of the cervix. Most cervical cancers (approximately 90%) contain one of these high-risk types. High-risk HPV infection creates a lifetime risk of invasive cancer in the range of 5-1 0% for the untreated infection. In addition to cervical cancer, high-risk HPVs are associated with a number of anal and perianal cancers. Current treatments for genital cysts and cervical dysplasia include physical removal such as cryotherapy, electrosurgery, and surgical removal. Currently, there are no effective antiviral treatments for HPV infection.

BRIEF DESCRIPTION OF THE INVENTION The present invention includes compounds of the formula (I): where n is 0, 1, or 2; t is 0 or 1; X is -NH-, -O-, -R10-, -OR10-, -R10O-, -R10OR1 0-, NR1 0-, -R10N-, -R10NR10-, R10S (O) m-, or -R10S ( O) mR1 0-; Y is -C (O) - or -S (0) m-; Each R is the same or different and is independently selected from the group consisting of halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R10cycloalkyl, Ay, -NHR10Ay, Het, -NHHet, -NHR 0Het, -OR2, -OAy, -OHet, -R10OR2, -NR2R3, -NR2Ay, -R10NR2R3, -R10NR2Ay, -R10C (O) R2, -C (0) R2, -C02R2, -R10CO2R2, -C (0) NR2R3, -C (0) Ay, -C (0) NR2Ay, -C (0) Het, -C (O) NH R1 0Het, -R10C (O) NR2R3, -C (S) NR2R3, -R10C (S) NR2R3, - R10NHC (NH) NR2R3, -C (NH) NR2R3, -R10C (NH) NR R3, -S (0) 2NR2R3, -S (0) 2NR2Ay, -R10SO2NHCOR2, -R 0SO2NR2R3, -R10SO2R2, -S (0) mR2, -S (0) mAy, cyano, nitro or azido; each R1 is the same or different and is independently selected from the group consisting of halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R1 0 cycloalkyl, Ay, -NHR 0Ay, Het, -NHHet, -NHR10Het, -OR2 , -OAy, -OHet, -R10OR2, -NR2R3, -NR2Ay, -R10N R2R3, -R10N R2 Ay, -R10C (O) R2, -C (0) R2, -C02R2, -R10CO2R2, -C (0) NR2R3, -C (0) Ay, -C (0) NR2Ay, -C (0) Het, -C (O) NHR10Het, -R10C (O) NR2R3, -C (S) NR2R3, -R 0C (S) NR2R3, R10NHC (NH) NR2R3, -C (NH) NR2R3, -R1 0C (NH) NR2R3, -S (0) 2NR2R3, -S (0) 2NR2Ay, -R10SO2NHCOR2, -R10SO2NR2R3, -R10SO2R2, -S (0 ) mR2, -S (0) mAy, cyano, nitro or azido; each m is independently 0, 1, or 2; each R10 is the same or different and is independently selected from alkylene, cycloalkylene, alkenylene, cycloalkenylene, and alkynylene; p and q each are independently chosen from 0, 1, 2, 3, 4 or 5; each of R 2 and R 3 are the same or different and are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R 10 cycloalkyl, -R 10 OH, -R 0 (OR 10) W, and -R 10 N R 4 R 5; w is from 1 -10; each of R4 and R5 are the same or different and are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl; Ay represents an aryl group; Het represents a 5- or 6-membered heterophenyl or heteroaryl group; the A chain is aryl or heteroaryl; provided that when the chain A is aryl, t is 0, and Y is S02, then p is not 0; and the salts, solvates and physiologically functional derivatives thereof. Preferably, in the description of the present invention in more detail, the alkyl is C ^ Ce alkyl, the alkoxy is Ci-Cd alkoxy, the haloalkyl is C -? - C6 haloalkyl, the alkylene is Ci-Ce alkylene, and the alkenylene it is C -? - C6 alkenylene. In a modality t is 0 and Y is -C (O) -. In another modality t is 0 and Y is -S (0) m-. In a modality t is 1, Y is -C (O) - and X is -NH-, -O-, R1 0-, or -OR1 0-. In another embodiment t is 1, Y is -S (0) m-, and X is -NH-, -O-, -R10-, or -OR10-. In a preferred embodiment, n is 1. Preferably p is 1 or more and when p is 1 or more, R is selected from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, cyano, nitro, or azido. More preferably, R is halogen, alkyl, haloalkyl. More preferably R is substituted for with respect to the N atom described. More preferably R is halogen. More preferably R is Br or Cl. Preferably q is one or more and when q is 1 or more, R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, Ay, Het, cyano, nitro, or azido. More preferably R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, or cyano. Preferably R2 and R3 each are C ^ Ce alkyl. More preferably R1 is chosen from halogen, alkyl, or -OR2. More preferably said halogen is fluoro or chloro, said alkyl is methyl, and said -OR2 is alkoxy. In one embodiment, preferably the A chain is aryl. Preferably the A chain is phenyl. More preferably q is 1 or more and R is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, Ay, Het, cyano, nitro, or azido. More preferably, R1 is selected from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, or cyano. In another embodiment, the A chain is heteroaryl. Preferably, the heteroaryl is pyridyl. Preferably, q is 0 or 1. Preferably when q is 1, then R1 is chosen from halogen, alkyl, haloalkyl, -OR2, NR2R3, -C (0) R2, -C02R2, A, H, cyano, nitro, or azido. More preferably when q is 1, then R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, or cyano. In another embodiment, p is 1, R is halogen, n is 1, Y is -C (0) -, t is 0, chain A is heteroaryl, and q is 0. Preferably R is chlorine or bromine and chain A is pyridyl. One embodiment includes a compound chosen from: One aspect of the present invention includes one or more of:? - (6-Bromo-2,3,4,9-tetrahydro-1 H-carbazol-1 -yl) -? / '- phenylurea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 H-carbazol-1 -yl) -? / '- (4-methoxyphenyl) urea; / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- (4-methoxy-2-methylphenyl) urea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -? / '- (3-chloro-3-methoxyphenyl) urea; N- (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) - '- [4- (dimethylamino) phenyl] urea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide; / V - [(1?) - 6-bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl] benzamide; ? / - [(1S) -6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-phenylacetamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1-carbazol-1-yl) -3-phenylpropanamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 t'-carbazoi-1-yl) -3-phenylprop-2-enamide; Benzyl 6-bromo-2,3,4,9-tetrahydro-1 H-carbazol-1-ylcarbamate; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-dichlorobenzamide; ? - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-nitrobenzamide; ? - (6-Bromo-2,3,4,9-tetrahydro-1f-carbazol-1-yl) -4-chlorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4- (trifluoromethyl) benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-fluorobenzamide; N- (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-f! Uorobenzamide; / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-nitrobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-chlorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-methylbenzamide; ? / - (2,3,4,9-Tetrahydro-1 / - / - carbazol-1-yl) benzamide; ? / - (6-Methyl-2,3,4,9-tetrahydro-1W-carbazoi-1-yl) benzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide; / V - [(1R) -6-chloro-2,3,4,9-tetrahydro-17-carbazol-1-yl] benzamide; ? / - [(1S) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1W-carbazol-1-y!) - 4-methylbenzenesulfonamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) pyridine-2-carboxamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) nicotinamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -6-chloronicotinamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -sonicotinamide; ? / - Phenyl -? / '- (2,3,4,9-tetrahydro-1H-carbazol-1-yl) urea; ? / - (6-Methyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl) - / V'-phenylurea; ? / - (6-Chloro-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -? / '- phenylurea; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-pyridinecarboxamide; / V - [(1R) -6-chloro-2,3,4,9-tetrahydro-1W-carbazol-1-yl] pyridine-2-carboxamide; ? / - [(1S) -6-chloro-2,3,4,9-tetrahydro-1AY-carbazol-1-yl] pyridine-2-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzamide; ? / - [(1fi) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fluorobenzamide; ? / - [(1S) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fíuorobenzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1-methyl-1H-imidazole-5-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1-methyl-1H-pyrazole-5-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1-methyl-1 - / - pyrazole-3-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro.-1 / - / - carbazol-1-yl) -1H-imidazole-4-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1H-pyrazole-3-carboxamide; ? / - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzenesulfonamide; and? / - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzenesulfonamide. Preferably, another aspect includes one or more of:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- [4- (dimethylamino) phenylurea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) benzamide; N - [(1R) -6-bromo-2,3,4,9-tetrahydro-17-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-phenylprop-2-enamide; Benzyl 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ylcarbamate; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -4-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -4-nitrobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-chlorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ii) -4-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -4- (trifluoromethyl) benzamide; V- (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-fluorobenzamide; N- (6-Bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -3-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-methylbenzamide; ? / - (6-Methyl-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) benza ida; ? / - (6-Chloro-2,3,4,9-tetrahydro-1W-carbazol-1-yl) benzamide; ? / - [1f?) - 6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methylbenzenesulfonamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) pyridine-2-carboxamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) nicotinamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -6-chloronicotinamide; - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) isonicotinamide; Α- (6-Chloro-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -2-pyridinecarboxamide; ? / - [1 / :?) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] pyridine-2-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzamide; ? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fluorobenzamide; ? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fluorobenzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1W-imidazole-4-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1H-pyrazole-3-carboxamide; ? / - (6-bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -2,6-difluorobenzamide; ? / - (6-bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -2-fluorobenzenesulfonamide; and? / - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzenesulfonamide. More preferably, one aspect includes one or more of: ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) benzamide; / V - [(1f?) - 6-bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl] benzamide; Benzyl 6-bromo-2,3,4,9-tetrahydro-1 H-carbazol-1-ylcarbamate; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-nitrobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazoI-1-yl) -4-chlorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methylbenzamide; ? - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -3-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / -carbazol-1-yl) -3-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1-carbazol-1-yl) -2-fluorobenzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide; ? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1W-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methyl benzenes ulfonam ida; / V- (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) pyridine-2-carboxamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -6-chloronicotinamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1f-carbazol-1-yl) -2-pyridinecarboxamide; / V - [(1R) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] pyridine-2-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzamide; ? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1W-carbazoI-1-y] -2-fluorobenzamide; ? / - (6-bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -2,6-difluorobenzamide; and? - (6-bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) -2-fluorobenzenesulfonamide.

Another embodiment of the present invention includes: including salts, solvates and pharmaceutically functional derivatives wherein R6 is H, alkyl, -OR2, -NR2R3, Ay, Het, -C (0) R2, -C02R2, -CONR2R3, -S (0) mR2, or oxo, in where the variables are as defined above; and R7 is H or alkyl; provided that R6 and R7 are not both H. An aspect of the present invention includes a pharmaceutical composition comprising a compound of the present invention and a pharmaceutically acceptable carrier. One aspect of the present invention includes a compound of the present invention for use as an active therapeutic substance. One aspect of the present invention includes a compound of the present invention for use in the treatment or prophylaxis of diseases and conditions caused by oncogenic viruses, including adenoviruses, retroviruses, and papovavirus family, including polyoma virus and papilloma virus. One aspect of the present invention includes a compound of the present invention for use in the treatment or prophylaxis of conditions or disorders due to HPV infection. Particularly the condition or disease is cysts, genital cysts, cervical dysplasia, recurrent respiratory papillomatosis, or cancers associated with papillomavirus infection. More particularly, cancer is anogenital cancers, head and neck cancers, and skin cancers. More particularly, anogenital cancers are cervical, anal, and perianal, vulval, vaginal, and penile cancer; cancers of the head and neck are cancers of the esophagus and the oral pharyngeal region; and skin cancers are basal cell carcinoma and squamous cell carcinoma. Another aspect of the present invention also includes the use of a compound of the present invention in the manufacture of a medicament for use in the treatment or prophylaxis of the oncogenic virus, including adenovirus, retrovirus, and papovavirus family, which includes polyoma virus and papilloma virus. One aspect of the present invention includes the use of a compound of the present invention in the manufacture of a medicament for use in the treatment or prophylaxis of conditions or disorders due to HPV infection. Particularly, the present invention includes utility with respect to cysts, genital cysts, cervical dysplasia, recurrent respiratory papillomatosis, or cancers associated with papillomavirus infection. One aspect of the present invention includes a method for the treatment or prophylaxis of oncogenic viruses, which includes adenovirus, retrovirus and papovavirus family, including polyoma virus and papilloma virus comprising the administration of a compound according to the present invention . An aspect of the present invention includes a method for the treatment or prophylaxis of conditions or disorders due to HPV infection comprising the administration of a compound according to the present invention. Particularly the condition or disorder is cysts, genital cysts, cervical dysplasia, recurrent respiratory papillomatosis, or cancers associated with papillomavirus infection. As noted herein, p and q are each independently defined as 0, 1, 2, 3, 4 or 5. Notably, as will be appreciated by those skilled in the art, the value (s) of p / oq they must not exceed the substitutable positions in the chains described.

DETAILED DESCRIPTION OF THE PREFERRED MODALI DAD The terms are used within the accepted meanings. The following definitions are intended to clarify, but not limit, the defined terms. As used herein, the term "alkyl" refers to a straight or branched chain hydrocarbon, preferably having from one to twelve carbon atoms, which optionally may be substituted, with multiple degrees of substitution included within the present invention. Examples of "alkyl" as used herein include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl, n-butyl, tert-butyl, isopentyl, n-pentyl, and substituted versions thereof. As used throughout the specification, the preferred number of atoms, such as carbon atoms, will be represented by, for example, the phrase "alkyl Cx-Cy", which refers to an alkyl group, as defined in the present, which contains the specified number of carbon atoms. It will apply similar terminology for other preferred terms and ranges as well. As used herein, the term "alkenyl" refers to a straight or branched chain aliphatic hydrocarbon that contains one or more optionally substituted carbon-to-carbon double bonds, with multiple degrees of substitution included within the present invention. Examples include, but are not limited to, vinyl, allyl, and the like and substituted versions thereof. As used herein, the term "alkynyl" refers to a straight or branched chain aliphatic hydrocarbon containing one or more carbon-to-carbon triple bonds that may be optionally substituted, with multiple degrees of substitution included within the scope of the invention. present invention. Examples include, but are not limited to, ethynyl, and the like and substituted versions thereof. As used herein "alkylene" refers to a branched or straight chain divalent hydrocarbon radical, preferably having from one to ten carbon atoms. Alkylene groups, as defined herein, may be optionally substituted, with multiple degrees of substitution included within the present invention. Examples of "alkylene" as used herein include, but are not limited to, methylene, ethylene, n-propyl, n-butylene, and substituted versions thereof. As used herein, the term "alkenylene" refers to a straight or branched chain divalent hydrocarbon radical, preferably having from one to ten carbon atoms, one containing more carbon-to-carbon double bonds that can be substituted optionally, with multiple degrees of substitution included within the present invention. Examples include, but are not limited to, vinylene, allylene or 2-propenylene, and the like and substituted versions thereof. As used herein, the term "alkynylene" refers to a branched or straight chain divalent hydrocarbon radical, preferably having from one to ten carbon atoms, containing one or more triple carbon-to-carbon bonds that are it may optionally be substituted, with multiple degrees of substitution included within the present invention. Examples include, but are not limited to, ethynylene and the like and substituted versions thereof. As used herein, the term "cycloalkyl" refers to an optionally substituted non-aromatic cyclic hydrocarbon chain, which optionally includes an alkylene linker through which cycloalkyl can be attached, with multiple degrees of substitution included within the present invention. Exemplary "cycloalkyl" groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and substituted versions thereof. As used herein, the term "cycloalkyl" includes an optionally substituted fused polycyclic hydrocarbon saturated chain, and aromatic chain system, namely polycyclic hydrocarbons with less than the maximum number of non-cumulative double bonds, for example wherein a saturated hydrocarbon chain (such as a cyclopentyl chain) is fused to an aromatic chain (in the present "aryl", such as a benzene chain) to form, for example, groups such as indane. As used herein, the term "cycloalkenyl" refers to an optionally substituted non-aromatic cyclic hydrocarbon chain containing one or more carbon-to-carbon double bonds which optionally includes an alkylene linker through which join the cycloalkenyl, with multiple degrees of substitution included within the present invention. Exemplary "cycloalkylene" groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and substituted versions thereof. As used herein, the term "cycloalkylene" refers to an optionally substituted, divalent, non-aromatic cyclic hydrocarbon chain with multiple degrees of substitution included within the present invention. Exemplary "cycloalkylene" groups include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, and substituted versions thereof. As used herein, the term "cycloalkenylene" refers to an optionally divalent substituted non-aromatic cyclic hydrocarbon chain containing one or more carbon-to-carbon double bonds with multiple degrees of substitution included within the present invention. Exemplary "cycloalkenylene" groups include, but are not limited to, cyclopropenylene, cyclobutenylene, cyclopentenylene, cyclohexenylene, cycloheptenylene, and substituted versions thereof. As used herein, the term "heterocycle" or "heterocyclyl" refers to an optionally substituted mono- or polycyclic chain system that contains one or more degrees of non-saturation and also contains one or more heteroatoms. Preferred heteroatoms include N, O, and / or S, including N-oxides, sulfur oxides, and dioxides. Preferably the chain is from three to twelve members and whether it is completely saturated or has one or more degrees of non-saturation. Multiple degrees of substitution are included within the present definition. Such chains can optionally be fused to one or more other "heterocyclic" chain (s) or cycloalkyl chain (s). Exemplary "heterocyclic" groups include, but are not limited to, tetrahydrofuran, pyran, 1,4-dioxane, 1,3-dioxane, piperidine, pyrrolidine, morpholine, tetrahydrothiopyran, and tetrahydrothiophene. As used herein, the term "aryl" refers to an optionally substituted fused benzene chain system or an optionally substituted benzene chain, for example anthracene, phenanthrene, or naphthalene chain systems. Multiple degrees of substitution are included within the present definition. Examples of "aryl" groups include, but are not limited to, phenyl, 2-naphthyl, 1 -naphthyl, and substituted derivatives thereof. As used herein, the term "heteroaryl" refers to an optionally substituted monocyclic five to seven aromatic chain, or to an optionally substituted fused bicyclic aromatic chain system comprising two such aromatic chains. These heteroaryl chains contain one or more nitrogen, sulfur, and / or oxygen atoms, wherein N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. Multiple degrees of substitution are included within the present definition. Examples of "heteroaryl" groups as used herein include, but are not limited to, furan, thiophene, pyrrole, imidazole, pyrazole, tricylla, tetrazole, thiazole, oxazole, isoxazole, oxadiazole, thiadiazole, siaiazole, pyridine, pyridazine, pyrazine, pyrimidine, quinoline, isoquinoline, benzofuran, benzothiophene, indole, indazole, benzimidizolyl, imidazopyridinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, and substituted versions thereof. As used herein, the term "halogen" refers to fluorine, chlorine, bromine, or iodine. As used herein, the term "haloalkyl" refers to an alkyl group, as defined herein, which is substituted with at least one halogen. Examples of branched chain or straight haloalkyl groups useful in the present invention include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, and t-butyl independently substituted with one or more halogens, for example , fluoro, chlorine, bromine, and iodine. The term "haloalkyl" should be construed to include such substituents as perfluoroalkyl groups and the like. As used herein, the term "alkoxy" refers to the group -ORa, wherein Ra is alkyl as defined above. As used herein, the term "alkoxycarbonyl" refers to groups such as: wherein Ra represents an alkyl group as defined herein. As used herein, the term "aryloxycarbonyl" refers to groups such as: wherein A y represents an aryl group as defined herein. As used herein, the term "heteroarylcarbonyl" refers to groups such as: in Het represents a heteroaryl group as defined herein. As used herein, the term "nitro" refers to the group -N02. As used herein, the term "cyano" refers to the -CN group. As used herein, the term "azido" refers to the group -N3. As used herein, the term "acyl" refers to the group RbC (0) -, wherein Rb is alkyl, aryl, heteroaryl, or heterocyclyl, as each one is defined in the present. As used herein, the term "oxo" refers to the group = 0. Also, as used herein throughout the present invention, the phrase "optionally substituted" or variations thereof denote an optional substitution, including multiple degrees of substitution, with one or more substituent groups. The phrase should not be interpreted as duplicative of the substitutions described and represented herein. Optional exemplary substituent groups include: acyl; I rent; alkenyl; alkynyl; alkylsulfonyl; alkoxy; alkoxycarbonyl; cyano, halogen; haloalkyl; hydroxy; nitro; aryl, which may further be substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; heteroaryl, which may be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; arylsulfonyl, which can be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; heteroarylsulfonyl, which can be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; aryloxy, which can be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; heteroaryloxy, which can be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; aryloxycarbonyl, which can be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; heteroaryloxycarbonyl, which can be further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro; or N (R *) 2; wherein for each occurrence R * is independently chosen from H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkylsulfonyl, arylsulfonyl, or heteroarylsulfonyl, wherein each presence of such aryl or heteroaryl can be substituted with one or more acyl, alkoxy, alkyl, alkenyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro, or the two R * may be combined to form a chain, optionally having additional heteroatoms, optionally having one or more grades of no saturation, and optionally being further substituted with acyl, alkoxy, alkyl, alkenyl, alkynyl, alkylsulfonyl, cyano, halogen, haloalkyl, hydroxy, or nitro The compounds of the formulas (I) can be crystallized in more than one way, a characteristic known as polymorphism, and such polymorphic forms ("polymorphs") are within the scope of formula (I). Polymorphisms can usually occur as a response to changes in temperature, pressure or both. The polymorphism can also result from variations in the crystallization process. The polymorphs can be distinguished through various physical characteristics known in the art, such as x-ray diffraction patterns, solubility, and melting point. Certain of the compounds described herein contain one or more chiral centers or otherwise may be capable of existing as multiple stereoisomers. The scope of the present invention includes mixtures of stereoisomers as well as purified enantiomers or mixtures enantiomerically / diastereomerically enriched. Also included within the scope of the invention are the individual isomers of the compounds represented by the formula (I), as well as any total or partially balanced mixture thereof. The present invention also includes the individual isomers of the compounds represented by the formulas above as mixtures with isomers thereof in which one or more chiral centers are inverted. Typically, but not absolutely, the salts of the present invention are pharmaceutically acceptable salts. Salts encompassed within the term "pharmaceutically acceptable salts" refer to non-toxic salts of the compounds of this invention. The salts of the compounds of the present invention may comprise acid addition salts. Representative salts include acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, calcium edetate, camsylate, carbonate, clavulanate, citrate, dihydrochloride, edisilate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycolylaminosanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate , lactate, lactobionate, laurate, malate, maleate, mandelato, mesylate, methylsulfate, monopotassium maleate, mucate, napsylate, nitrate, N-methylglucam ina, oxalate, pamoate (docking), palmitate, pentathione, phosphate / diphosphate, polygalacturonate, potassium , salicylate, sodium, stearate, subacetate, succinate, sulfate, tannate, tartrate, teoclate, tosylate, triethiodide, trimethylammonium, and valerate salts. Other salts, which are not pharmaceutically acceptable, may be useful in the preparation of the compounds of this invention and these should be considered to form a further aspect of the invention. As used herein, the term "solvate" refers to a complex of variable stoichiometry formed through a solute (in this invention, a compound of Formula I, or a salt or physiologically functional derivative thereof) and a solvent. Such solvents, for the purpose of the invention, should not interfere with the biological activity of the solute. Non-limiting examples of suitable solvents include, but are not limited to water, methanol, ethanol, and acetic acid. Preferably the solvent used is a pharmaceutically acceptable solvent. Non-limiting examples of suitable pharmaceutically acceptable solvents include water, ethanol, and acetic acid. More preferably, the solvent used is water. As used herein, the term "physiologically functional derivative" refers to any pharmaceutically acceptable derivative of a compound of the present invention which, based on administration to a mammal, is capable of providing (directly or indirectly) a compound of the present invention or an active metabolite thereof. Such derivatives, for example, esters and amides, will be clear to those skilled in the art, without undue experimentation. Reference may be made to the teaching of Burger's Medicinal Chemistry And Drug Discovery, 5th Edition, Vol. 1: Principles and Practice, which is incorporated herein by reference in the extent that it teaches physiologically functional derivatives. As used herein, the term "effective amount" means the amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal, or human that is observed, for example, by a researcher or clinical. The term "therapeutically effective amount" means any amount which, compared to a corresponding subject that has not received such an amount, results in improved treatment, cure, prevention, or improvement of a disease, disorder, or side effect, or a decrease in the speed of disease or disorder. The term also includes within its scope effective amounts to improve normal physiological function. For use in therapy, the therapeutically effective amounts of a compound of the formula (I), as well as salts, solvates, and physiological functional derivatives thereof, can be administered as the pure chemical. Additionally, the active ingredient may be presented as a pharmaceutical composition. Accordingly, the invention further provides pharmaceutical compositions which include effective amounts of compounds of the formula (I) and salts, solvates, and physiological functional derivatives thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients. The compounds of the formula (I) and salts, solvates, and physiologically functional derivatives thereof are as described herein. The carrier (s), diluent (s) or excipient (s) must be acceptable, in the sense of being compatible with the other ingredients of the formulation and not deleterious to the container of the pharmaceutical composition. According to another aspect of the invention there is also provided a process for the preparation of a pharmaceutical formulation which includes mixing a compound of the formula (I) or salts, solvents and physiological functional derivatives thereof, with one or more pharmaceutically acceptable carriers, diluents or excipients. A therapeutically effective amount of a compound of the present invention will depend on a number of factors. For example, the species, age, and weight of the recipient, the precise condition that requires treatment and its severity, the nature of the formulation and the route of administration are all factors to consider. The last therapeutically effective amount must be at the discretion of the attending physician or veterinarian. In spite of everything, an effective amount of a compound of the formula (I) for the treatment of humans suffering from weakness, generally, should be in the range of 0.1 to 100 mg / kg of the body weight of the recipient (mammal) by day. More usually the effective amount should be in the range of 1 to 10 mg / kg of body weight per day. Therefore, for an adult 70 kg mammal the current amount per day would usually be from 70 to 700 mg. This amount may be provided in a single dose per day or in a number (such as, two, three, four, five, or more) of sub-doses per day such that the total daily dose is the same. An effective amount of a salt, solvate, or physiologically functional derivative thereof can be determined as a proportion of the effective amount of the compound of the formula (I) per se. Similar dosages should be appropriate for the treatment of other conditions referred to herein. The pharmaceutical formulations can be presented in unit dosage forms containing a predetermined amount of active ingredient per unit dose. Such a unit may contain, as a non-limiting example, 0.5 mg to 1 g of a compound of the formula (I), depending on the condition being treated, the route of administration, and the age, weight, and condition of the patient. Preferred unit dosage formulations are those containing a daily dose or sub-dose, as set forth herein above, or an appropriate fraction thereof, of an active ingredient. Such pharmaceutical formulations can be prepared by any of the methods well known in the pharmacy art. The pharmaceutical formulations can be adapted for administration through any appropriate route, for example through an oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including subcutaneous) route. , intramuscular, intravenous or intradermal). Such formulations can be prepared by any method known in the pharmacy art, for example by compromising the association of the active ingredient with the carrier (s) or excipient (s). As an example, and does not mean limiting the invention, with respect to certain conditions and disorders for which the compounds of the present invention are believed to be useful, certain routes will be preferable to others. Based on the physical manifestations that are often associated with H PV infection, the rectal, topical or vaginal route of administration may be preferable. As an example, for the treatment or prophylaxis of cervical dysplasia the preferred route may be a vaginal route. Pharmaceutical formulations adapted for oral administration may be presented as discrete units such as capsules or tablets; powders or granules; solutions or suspensions, each with aqueous or non-aqueous liquids; foams or edible shakes; or liquid emulsions of oil in water or liquid emulsions of water in oil. For example, for oral administration in the form of a tablet or capsule, the active drug component can be combined with a non-toxic, oral pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Generally, the powders are prepared by comminuting the compound to a convenient fine size and mixing with an appropriate pharmaceutical carrier such as an edible carbohydrate, such as, for example, starch or mannitol. Flavors, preservatives, dispersing agents, and coloring agents may also be present. The capsules are made by preparing a powder, liquid or suspension mixture and encapsulating it with gelatin or some other suitable coating material. Glidants and lubricants such as colloidal silica, talc, magnesium stearate, calcium stearate, or solid polyethylene glycol can be added to the mixture before encapsulation. A disintegrating or solubilizing agent such as agar agar, calcium carbonate or sodium carbonate may also be added to improve the availability of the medicament when the capsule is ingested. In addition, when desired or necessary, suitable binders, lubricants, disintegrating agents, and coloring agents may also be incorporated into the mixture. Examples of suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural or synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. Useful lubricants in these dosage forms include, for example, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like. The tablets are formulated, for example, by preparing a powder mixture, granulating or dividing, adding a lubricant and desintegrator, and pressurizing the tablets. A powder mixture can be prepared by mixing the comminuted compound conveniently with a diluent or base as described above. Optional ingredients include binders such as carboxymethylcellulose, aliginates, gelatins, or polyvinyl pyrrolidone, solution retarders such as paraffin, resorption accelerators such as a quaternary salt, and / or absorption agents such as bentonite, kaolin, or dicalcium phosphate. The powder mixture can be granulated with moisture with a binder such as syrup, starch paste, acadia mucilage or solutions of cellulosic or polymeric materials, and forcing through a protection. As an alternative to the granulate, the powder mixture can be passed through the tablet machine and the result is pieces formed imperfectly broken into granules. The granules can be lubricated to prevent adhesion to the matrices forming the tablet by the addition of stearic acid, a stearate salt, talc or mineral oil. The lubricated mixture is then compressed into tablets. The compounds of the present invention can also be combined with an inert carrier which floats free and compresses into tablets directly without going through the stages of granulation or division. An opaque or transparent protective layer consisting of a sealing layer of shellac, a layer of sugar or polymeric material, and a wax sheen layer can be provided. Dyestuffs can be added to these layers to distinguish the different unit dosages. Oral fluids such as solutions, syrups and elixirs can be prepared in unit dosage form so that a given amount contains a predetermined amount of the compound. Syrups can be prepared, for example, by dissolving the compound in a conveniently flavored aqueous solution, while the elixirs are prepared through the use of a non-toxic alcoholic vehicle. Suspensions can be formulated generally by dispersing the compound in a non-toxic vehicle. Solubilizing agents and emulsifiers may also be added such as ethoxylated isostearyl alcohols and polyoxy ethylene sorbitol ethers, preservatives; flavor additives such as peppermint oil, or natural sweeteners, saccharin, or other artificial sweeteners; and the similar. When appropriate, dosage unit formulations for oral administration can be microencapsulated. The formulation can also be prepared to prolong or sustain the release as, for example, covering or stuffing the particulate material into polymers, wax or the like. The compounds of the formula (I) and the salts, solvates, and physiological functional derivatives thereof, can also be administered in the form of liposome distribution systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines. The compounds of the formula (I) and the salts, solvates, and physiologically functional derivatives thereof can also be distributed through the use of monoclonal antibodies as individual carriers to which the molecules of the compound are coupled. The compounds can also be coupled with soluble polymers as target drug carriers. Such polymers can include polyvinylpyrrolidone (PVP), pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethyl-aspartamidephenol, or polyethylene oxidepolylysine substituted with palmitoyl residues. In addition, the compounds can be coupled to a class of biodegradable polymers useful for achieving controlled release of a medicament; for example, polylactic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, p'olicianoacrylates, and degraded or amphipathic block copolymers of hydrogels. Pharmaceutical formulations adapted for transdermal administration may be presented as discrete patches designed to remain in intimate contact with the epidermis of the recipient for a prolonged period of time. For example, the active ingredient can be distributed from the patch through iontophoresis as generally described in Pharmaceutical Research, 3 (6), 318 (1986), which is incorporated herein by reference to the extent that it relates to such a distribution system. Pharmaceutical formulations adapted for topical administration can be formulated as ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols, or oils. For treatments of the eye or other external tissues, for example mouth and skin, the formulations can be applied as a topical cream or ointment. When formulated in an ointment, the active ingredient can be used with either a water miscible or a paraffinic ointment base. Alternatively, the active ingredient can be formulated in a cream with an oil-in-water cream base or a water-in-oil base. Pharmaceutical formulations adapted for topical administrations for the eye include eye drops wherein the active ingredient is dissolved or suspended in a convenient carrier, especially an aqueous solvent. Pharmaceutical formulations adapted for topical administration in the mouth include tablets, lozenges and rinses. Pharmaceutical formulations for nasal administration, wherein the carrier is a solid, include a coarse-grained powder having a particle size for example in the range of 20 to 500 microns. The powder is administered in the manner in which it is breathed, that is, through rapid inhalation through the nasal passage from a powder container that is held close to the nose. Suitable formulations wherein the carrier is a liquid, for administration as a nasal spray or as nasal drops, include aqueous or oil solutions of the active ingredient. Pharmaceutical formulations adapted for administration through inhalation include powders or bayos, which can be generated by means of various types of metered dose pressurized aerosols, sprays, or insufflators. Pharmaceutical formulations adapted for rectal administration can be presented as suppositories or as enemas. Pharmaceutical formulations adapted for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulations. Pharmaceutical formulations adapted for parenteral administration include non-aqueous and aqueous sterile injection solutions, which may contain antioxidants, regulators, bacteriostats, and solutes that produce the isotonic formulation with the blood of the projected receptor; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations can be presented in unit doses or multiple dose containers, for example ampoules and flasks, and can be stored in a frozen-dry (lyophilized) condition that requires only the addition of the sterile liquid carrier, for example water for injections, immediately before use. Extemporaneous injection solutions and suspensions can be prepared from powders, granules, and sterile tablets. In addition to the ingredients particularly mentioned above, the formulations may include other agents conventional in the art taking into account the type of formulation in question. For example, convenient formulations for oral administration may include flavoring or coloring agents.

The compounds of the present invention and their salts, solvates and physiologically functional derivatives thereof can be used alone or in combination with other therapeutic agents. The compound (s) of the formula (I) and the other pharmaceutically active agent (s) can be administered together or separately and, when administered separately, administration can occur Simually or sequentially, in any order. The amounts of the compound (s) of the formula (I) and the other pharmaceutically active agent (s) and the relative times of administration will be selected for the purpose of achieving the desired combined therapeutic effect. The administration in combination of a compound of the formula (I), salts, solvates or physiologically functional derivatives thereof with other treatment agents may be in combination for concomitant administration in: (1) a unitary pharmaceutical composition including both compounds; or (2) separate pharmaceutical compositions each including one of the compounds. Alternatively, the combination can be administered separately in a sequential manner wherein one treatment agent is administered first and the other second or vice versa. Such sequential administration can be close in time or remote in time. The compounds of the present invention can be used in the treatment of a variety of disorders and conditions and, as such, the compounds of the present invention can be used in combination with a variety of other suitable therapeutic agents useful in the treatment or prophylaxis of those disorders or conditions. The treatment will depend on the nature and type of HPV infection. As discussed briefly above, the treatment of cysts can be divided into ablative or medical approaches. The compounds of the present invention can be combined with either or both approaches. Ablative methods include destruction and classical surgical removal through electrodesiccation, laser, or liquid nitrogen. Therefore, the compounds of the present invention can be used in conjunction with such methods or based on the reappearance after such methods. The compounds of the present invention can be used in conjunction with ablative methods to reduce the frequency of reappearance. Alternatively, the present invention can be combined with other medical therapies including a variety of cytotoxic or antiviral agents. For example, and without intending to limit the invention, the compounds of the present invention can be combined with other therapeutic agents such as 5-fluorouracil, retinoic acid, podophyllin, podofilox, keratolytic agents such as salicylic acid and / or lactic acid. , haptens such as difenciprona (DPC), dibutyl ester of squaric acid (SADBE) or dinitrochlorobenzene (DNCB), formalin, topical trichloroacetic acid, topical tretinoin, cidofovira, resiquimod and / or cytokines such as interferon alfa-2b. One aspect of the present invention is the use of the compounds of the present invention for the treatment or prophylaxis of a variety of disorders including, but not limited to, diseases and conditions caused by oncogenic viruses, including adenovirus, retrovirus, and papovavirus family. , which includes polyoma virus and papilloma virus and more particularly viral papilloma infections. The present invention includes administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof. More specifically, the present invention includes the treatment or prophylaxis of conditions or diseases associated with viral papilloma infections. These conditions and diseases include cysts (e.g., plantar cysts), genital cysts, recurrent respiratory papillomatosis (e.g., laryngeal papillomas), and cancers associated with papillomavirus infection. Cancers that have been associated with papilloma virus infection include anogenital cancers (eg, cervical, anal and perianal cancers, vulval, vaginal, penile cancers), head and neck cancers (eg, oral pharynx, esophagus) , and skin cancers (e.g., basal cell carcinoma, squamous cell carcinoma). The present invention includes administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention or a salt, solvate or physiologically functional derivatives thereof. The compounds of this invention can be made through a variety of methods including the well-known standard synthetic methods. Illustrative general synthetic methods are discussed below and then the specific compounds of the invention are prepared in the Working Examples. In all the examples described below, protection groups are used for sensitive or reactive groups when necessary in accordance with the general principles of synthetic chemistry. Protection groups are manipulated according to standard methods of organic synthesis (T. W. Green and P. G. Wuts (991) Protecting Groups in Organic Shyntesis, John Wiley &; Sons, which is incorporated as a reference with respect to protection groups). These groups are removed at a convenient stage of compound synthesis using methods that are readily apparent to those skilled in the art. The selection of the processes as well as the reaction conditions and the order of their execution will be consistent with the preparation of the compounds of the formula (I). Those skilled in the art will recognize if there is a stereocenter in the compounds of the formula (I). Accordingly, the present invention includes all possible stereoisomers and includes not only racemic compounds but also individual enantiomers. When a compound is desired as a single enantiomer, such can be obtained through stereospecific synthesis, through the resolution of the final product or any convenient intermediate, or through chiral chromatography methods that are well known in the art. The resolution of the final product, an intermediary, or a raw material can be effected by any convenient method known in the art. See, for example, Stereochemestry of Organic Compounds by E. L. Eliel, S. H. Wilen, and L. N. Mander (Wiley-lnterscience, 1994), incorporated as a reference with respect to stereochemistry.

EXPERIMENTAL SECTION Abbreviations: As used herein, the symbols and conventions used in these processes, schemes and examples are consistent with those used in contemporary scientific literature, for example, the Journal of the American Chemical Society or the Journal of Biological Chemestry. Specifically, the following abbreviations can be used in the examples and throughout the specification: g (grams); mg (milligrams); L (liters); mL (milliliters); μL (microliters); psi (pounds per square inch); M (molar); mM (millimolar); Hz (Hertz); MHZ (megahertz); Mol (moles); mmol (millimoles); RT (room temperature); h (hours); min (minutes); TLC (thin layer chromatography); mp (melting point); RP (reverse phase); tr (retention time); TFA (trifluoroacetic acid); TEA (triethylamine); THF (tetrahydrofuran); TFAA (trifluoroacetic anhydride); CD30D (methanol deuterated); CDCl 3 (deuterated chloroform); DMSO (dimethylsulfoxide); Si02 (silica); atm (atmosphere); EtOAc (ethyl acetate); CHCl3 (chloroform); HCl (hydrochloric acid); Ac (acetyl); DMF (N, N-dimethylformamide); Me (methyl); Unless stated otherwise, all temperatures are expressed in ° C (degrees Celsius). All reactions were conducted at room temperature unless noted otherwise. The 1 H-NMR spectra were recorded on a Varian VXR-300, a Varian Unit-300, a Varian Unit-400 instrument, or a General Electric QE-300. Chemical changes are expressed in part per million (ppm, units d). The coupling constants are in units of hertz (Hz). The division patterns describe obvious multiplicities and are designated as s (single), d (duo), t (trio), q (quartet), m (multiple), or br (extended). The mass spectra were obtained in Micromass Platform or ZMD mass spectrometers from Micromass Ltd., Altricham, UK, using either Atmospheric Chemical Ionization (APCI) or Electrospray Ionization (ESI). Analytical thin layer chromatography was used to verify the purity of the intermediate (s) which might not be isolated or which were too unstable for complete characterization as well as to track the progress of the reaction (s). The absolute configuration of the compounds was assigned through Spectroscopy of Circular Dichroism of Start Vibration AN (VCD). The experimental VCD spectrum was acquired in CDCI3 using a QuiralI RTM Bomen VCD spectrometer operating between 2000 and 800 cnrf1. The Gaussian Suite 98 of the computer programs was used to calculate the model VCD spectra. The stereochemical assignments were made by comparing this experimental spectrum with respect to the VCD spectrum calculated for a model structure with (R) or (S) configuration. Incoroporated as reference with respect to such spectroscopy are: J. R. Chesseman, M.J. Frisch, F.J. Devlin and P.J. Stephens, Chem. Phys. Lett. 252 (1 996) 21 1; P.J. Stephens and F.J. Devlin, Chirality 1 2 (2000) 172; and Gaussian 98, Revision A.1 1 .4, M.J. Frisch et al. , Gaussian, I nc. , Pittsburg PA, 2002. The compounds of the formula (I) wherein the variables are as defined above and LV is an outlet group, namely halogen (F, Cl, Br, I), can be conveniently prepared at through the process outlined in Scheme 1 below: Scheme Generally, the process for preparing the compounds of the formula (I), wherein LV is an output group as defined above (all formulas and variables as defined above) comprises the steps of: a) reacting a compound of the formula (II) with ethyl format; b) reacting the compound of the formula (III) with diaza compound of the formula (IV); c) indolizing the compound of the formula (V) to prepare a compound of the formula (VI); d) reductive amination of the compound of the formula (VI) to form a compound of the formula (Vi l); and e) forming compounds of the formula (I) of the compound (Vi l) by reaction with the compound of the formula (VI I I); or alternatively f) forming compounds of the formula (I) wherein Y is CO and X is NH through the reaction of the compound of the formula (VII) with the compound of the formula (IX). More specifically, a compound of the formula (I) wherein all the variables are as defined above, can be prepared by reacting the compound of the formula (Vi l) with a compound of the formula (VI I I): The reaction can be carried out by adding the compound of the formula (VI I I) to a compound of the formula (VI) in a convenient solvent, optionally in the presence of base, and optionally with heating. Suitable solvents include tetrahydrofuran, dichloromethane, N, N-dimethylformamide, pyridine, dioxane, diethyl ether, acetonitrile, toluene, and the like. Suitable bases include triethylamine, diisopropylethylamine, pyridine, dimethylaminopyridine, and the like. As will be appreciated by those skilled in the art, the compounds of the formula (VI I I) are commercially available or can be prepared according to literature methods.

Additionally, as will be appreciated by those skilled in the art, a compound of the formula (!) Wherein Y is -C (O) -, can also be formed by coupling an amino of the formula (Vi l) and an acid of the formula (Xa). Any set of standard coupling conditions, which are known to those skilled in the art, can be used for this coupling.

Alternatively, a compound of the formula (I), wherein Y is -CO- and X is -NH-, can be formed through the treatment of a compound of the formula (Vi l) with an isocyanate compound of the formula ( IX) in a convenient solvent, optionally with heating. Suitable solvents include tetrahydrofuran and the like. The isocyanates of the formula (IX) are commercially available or can be prepared through literature methods that are appreciated by those skilled in the art.

An amino compound of the formula (VII) of a compound of the formula (VI) can be formed. Treatment of a compound of the formula (VI) in an inert solvent with an ammonium salt and a reducing agent, optionally with heating, yields an amino of the formula (Vi l). Suitable solvents include, but are not limited to, methanol, ethanol, dichloromethane, dichloroethane, and the like. Suitable reducing agents include, but are not limited to, sodium cyanoborohydride, sodium triacetoxyborohydride, sodium borohydride, and the like. Convenient ammonium salts include, but are not limited to, ammonium acetate, ammonium formate and the like. An amino of the formula (Vi l) can also be formed through the treatment of a compound of the formula (VI) with hydroxylamine, followed by reduction with suitable reducing agents, which include, but are not limited to, hydride lithium aluminum and the like. The compounds of the formula (VI) are prepared in a manner similar to that described in the literature (J. Med. Chem. 1973, 1 6, 425 and J. Org. Chem. 1 968, 32, 1265), which are incorporated herein as a reference in the extension of such teaching.

A compound of the formula (I) can be converted to another compound of the formula (I) by methods appreciated by those skilled in the art.

EXAMPLES Example 1: 6-Chloro-213.4,9-tetrahydro-1 / - / - carbazole-1 -one. a) Cyclohexane-1,2-dione (4-chlorophenyl) hydrazone. To a cold (0 ° C) solution of 4-chloroaniline (5.6 g, 44 mmol) in concentrated hydrochloric acid (5 mL) was added sodium nitrite (3.0 g, 44 mmol) dissolved in water (10 mL) as a portion for 20 minutes. The mixture was stirred at 0 ° C for 30 minutes. In a separate flask, a cold solution of 2- (hydromethylene) cyclohexanone (Syntheses Organ, Collective Vol 4, 1963, pg 536) (5.0 g.101 mmol) in methanol (30 mL) was treated with a solution of sodium acetate. sodium (8.3 g, 1 01 mmol) in water (25 mL). The mixture was stirred at 0 ° C for 20 minutes and the diazonium salt slurry was added. The combined mixture was stirred for 10-15 minutes, collected by filtration, triturated with ethanol, and collected by filtration to provide cyclohexane-1,2-dione (4-chlorophenyl) hydrazone (4.6 g, 49% yield) as a yellow solid. 1 H-NMR (DMSO-d 6): d 9.93 (s, 1 H), 7.29 (m, 4 H), 2.55 (m, 2 H), 2.40 (m, 2 H), 1.84-1.75 (m, 4 H). b) 6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-one. A solution of cyclohexane-1,2-dione (4-chlorophenyl) hydrazone (2.3 g, 9.7 mmol) in hydrochloric acid (2 mL) and acetic acid (8 mL) was heated at 120 ° C for 20 minutes. The mixture was cooled slightly and treated with ice water. The resulting precipitate was collected through filtration to give 6-chloro-2,3,4,9-tetrahydro-1/7-carbazol-1-one (1.9 g, 88% yield) as a brown solid. 1 H-NMR (DMSO-dβ): d 11.78 (s, 1H), 7.75 (m, 1H), 7.38 (d, 1H), 7.28 (dd, 1H), 2.92 (t, 2H), 2.55 (t, 2H) ), 2.13 (q, 2H); MS m / z 220 (M + 1).

Example 2: 6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino.

To a solution of 6-chloro-2,3,4,9-tetrahydro-1W-carbazol-1-one (500 mg, 2.3 mmol) and ammonium acetate (1.8 g, 23 mmol) in methanol (9 mL) were added. added sodium cyanoborohydride (720 mg, 11.5 mmol). After heating at 60 ° C for 15 hours, the mixture was cooled and treated with concentrated hydrochloric acid until pH = 1. The organics were removed under reduced pressure and the resulting precipitate was collected through filtration, dissolved in ethyl acetate, and dried. ethyl and methanol, and washed with saturated aqueous sodium carbonate.

The layers were separated and the organic phase was concentrated to yield 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-amino (260 mg, 52% yield) as a light brown solid. 1H-NMR (DMSO-cf6): d 10.90 (s, 1H), 7.34 (m, 1H), 7.27 (d, 1H), 6.97 (dd, 1H), 3.90 (t, 1H), 2.54 (m, 2H) ), 2.04-1.89 (m, 2H), 1.66 8m, 1H), 1.50 (m, 1H); MS m / z 221 (M + 1).

Example 3: 6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-one.

Bromoaniline and 2- (hydroxymethylene) cyclohexanone were prepared in a manner similar to that described in Example 1 to provide a brown solid. . 1 H-NMR (CDCl 3): d 8.79 (s, 1 H), 7.80 (s, 1 H), 7.44 (d, 1 H), 7.30 (d, 1 H), 2.97 (t, 2 H), 2.66 (t, 2 H), 2.27 (fifth, 2H); MS m / z 265 (M + 1).

Example 4: 6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-1-amino 6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-1-amino was prepared in a manner similar to that described in Example 2 to provide a solid. 1 H-NMR (CDCl 3): d 8.58 (s, 1 H), 7.55 (s, 1 H), 7.20 (m, 2 H), 4.12 (t, 1 H), 2.70 (t, 2 H), 2.24 (m, 1 H), 2.05 (m, 1H), 1.92 (m, 3H), 1.66 (m, 1H); MS m / z 266 (M + 1).

Example 5: 6-Methyl-2,3,4,9-tetrahydro-1 H-carbazol-1-one 6-Methyl-2,3,4,9-tetrahydro-1 / -carbazol-1-one of p-toluidino and 2- (hydroxymethylene) cyclohexanone was prepared in a manner similar to that described in Example 1 to provide a solid of brown color. 1 H-NMR (CDCl 3): d 8.65 (s, 1 H), 7.43 (s, 1 H), 7.30 (d, 1 H), 7.20 (d, 1 H), 2.98 (t, 2 H), 2.65 (t, 2 H), 2.45 (s, 3H), 2.26 (fifth, 2H); MS m / z 220 (M + 1).

Example 6: 6-Methyl-2,3,4,9-tetrahydro-1H-carbazole-1-amino 6-Methyl-2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino was prepared in a manner similar to that described herein to provide a solid. 1 H-NMR (DMSO-d 6): d 10.5 (s, 1 H), 7.15 (d, 1 H), 7.11 (s, 1 H), 6.81 (d, 1 H), 3.98 (t, 1 H), 3.30 (s, 2 H) ), 2.53 (t, 2H), 2.32 (s, 3H), 2.02 (m, 1H), 1.90 (m, 1H), 1.68 (m, 1H), 1.65 (m, 1H); MS m / z 201 (M + 1).

Example 7: 2,3,4,9-Tetrahydro-1-carbazol-1-one 2,3,4,9-Tetrahydro-1W-carbazol-1-one of aniline and 2- (hydroxymethylene) cyclohexanone was prepared in a manner similar to that described in Example 1 to provide a brown solid. 1 H-NMR (DMSO-d 6): d 11.6 (s, 1 H), 7.66 (d, 1 H), 7.38 (d, 1 H), 7.30 (t, 1 H), 7.07 (t, 1 H), 2.90 (t, 2 H) ), 2.56 (t, 2H), 2.15 (fifth, 2H); MS m / z 186 (M + 1).

Example 8: 2,3,4,9-tetrahydro-1H-carbazoyl-1-amino hydrochloride To a solution of 2,3,4,9-tetrahydro-1H-carbazol-1-one (1.5 g, 8.10 mmol) in ethanol (20 mL) was added a solution of hydroxylamino hydrochloride (1.13 g, 16.2 mmol) in water (10 mL) and a solution of sodium acetate (2.19 g, 26.7 mmol) in water (10 mL). The reaction mixture was heated to reflux for 2 h, cooled, and concentrated. The residue was diluted with water and extracted with ethyl acetate (2 x 1 00 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated to a brown solid. The maximum was dissolved in THF (80 mL) and lithium aluminum hydride (1.0 M in THF, 24.3 mL) was added drop wise. The reaction was heated to reflux for 7 h and cooled in an ice bath. The methanol was added dropwise until bubbling ceased. The mixture was diluted with aqueous Na / K tartrate, stirred vigorously for 1 5 min and extracted with ethyl acetate (2 x 1 00 mL). The extracts were combined, dried in sodium sulfate, filtered and concentrated. The crude amino was purified by flash chromatography on silica (2% to 5% methanol / methylene chloride gradient) to provide 2,3,4,9-tetrahydro-1V-carbazole-1-amino as a coffee oil The oil was diluted in diethyl ether and HCl (1.0 M in diethyl ether) was added. The resulting precipitate was collected through filtration to provide 2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino-hydrochloride (760 mg, 42%) as a light brown solid. 1 H-NMR (CD3OD): d 7.54 (d, 1 H), 7.42 (d, 1 H), 7.22 (t, 1 H), 7.09 (t, 1 H), 4.66 (t, 1 H), 2.95 -2.73 (m, 2H), 2.39-2.28 (m, 1 H), 2.1 8-2.03 (m, 3H); MS m / z (M + 1) 170.

Example 9:? / - (6-Bromo-2,3,4,9-tetrahydro-1 H-carbazol-1-yl) -? R-phenylurea To a solution of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole-1-amino (50 mg, 0.19 mmol) in dichloromethane (1 mL), phenyl isocyanate (23 μL, 0.21 mmol) was added. ). The mixture was stirred at room temperature for 15 hours and the resulting precipitate was collected through filtration to give a gray solid (62% yield). 1 H-NMR (DMSO-cf 6): d 11.01 (s, 1H), 7.60 (d, 1H), 7.45 (m, 2H), 7.33-7.23 (m, 4H), 7.17 (dd, 1H), 6.94 (m , 1H), 6.63 (d, 1H), 5.02 (m, 1H), 2.68 (m, 2H), 2.06 (m, 1H), 1.95-1.70 (m, 3H); MS m / z 384 (M-1).

Example 10: 7- (6-Bromo-2.3.4.9-tetrahydro-1H-carbazole-1-M) -? R- (4-methoxypheniPurea) It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -? / '- (4-methoxy-enyl) -urea of 6-bromo-2,3 , 4,9-tetrahydro-1H-carbazole-1-amino and 4-methoxyphenyl isocyanate in a manner similar to that described above to provide a gray solid (61% yield). 1H-NMR (DMSO- 6): d 10.99 (s, 1H), 8.16 (s, 1H), 7.60 (d, 1H), 7.38-7.27 (m, 3H), 7.17 (dd, 1H), 6.87 (d , 2H), 6.52 (d, 1H), 5.01 (m, 1H), 3.73 (s, 3H), 2.67 (m, 2H), 2.04 (m, 1H), 1.94-1.76 (m, 3H); MS m / z 414 (M-1).

Example 11:? / - (6-Bromo-2.3.4.9-tetrahydro-1H-carbazol-1-yl) -? / '- (4-methoxy-2-methylphenyl) urea Prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- (4-methoxy-2-methylf-enyl) urea of 6-bromo-2 3,4,9-tetrahydro-1H-carbazole-1-amino and 4-methoxy-2-methyl isocyanate in a manner similar to that described above to provide a dark brown solid (59% yield). 1H-NMR (DMSO-d6): d 11.00 (s, 1H), 7.71 (d, 1H), 7.60 (d, 1H), 7.47 (s, 1H), 7.32 (d, 1H), 7.17 (dd, 1H) ), 6.88 (d, 1H), 6.75 (m, 2H), 5.00 (m, 1H), 3.73 (s, 3H), 2.69 (m, 2H), 2.18 (s, 3H), 2.04 (m, 1H) , 1.94-1.77 (m, 3H); MS m / z 430 (M + 1).

Example 12:? / - (6-Bromo-2.3.4.9-tetrahydro-1H-carbazole-1 -n -? / '- (3-chloro-4-methoxyphen Purea It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-iI) -? / '- (3-chloro-4-methoxyphenyl) urea of 6-bromine -2,3,4,9-tetrahydro-1H-carbazole-1-amino and 3-chloro-4-methoxyphenyl isocyanate in a manner similar to that described above to provide a brown colored solid (42% yield) ). 1 H-NMR (DMSO-c 6): d 10.98 (s, 1 H), 8.33 (s, 1 H), 7.73 (d, 1 H), 7.60 (d, 1 H), 7.30 (d, 1 H), 7.25-7.14 (m , 2H), 7.08 (d, 1H), 6.63 (d, 1H), 5.01 (m, 1H), 3.82 (s, 3H), 2.65 (m, 2H), 2.04 (m, 1H), 1.94-1.76 ( m, 3H); MS m / z 448 (M-1).

Example 13:? / - (6-Bromo-2,3,4,9-tetrahydro-1 / V-carbazole-1-in-A / '- r4-dimethylamino) phenylurea There was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -? / '- [4-dimethylamino) phenylurea of 6-bromo-2,3, 4,9-tetrahydro-1 / - / - carbazole-1-amino-4-dimethylamino phenyl-socianate in a manner similar to that described above to provide a brown colored solid (40% yield). 1 H-NMR (DMSO-cy6): d 10.99 (s, 1H), 7.98 (s, 1H), 7.60 (d, 1H), 7.33-7.23 (m, 3H), 7.17 (dd, 1H), 6.71 (d , 2H), 6.44 (d, 1H), 5.00 (m, 1H), 2.84 (s, 6H), 2.67 (m, 2H), 2.04 (m, 1H), 1.94-1.74 (m, 3H); MS m / z 427 (M-1).

Example 14A:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -benzamide To a solution of 6-bromo-2,3,4,9-tetrahydro-1 -carbazol-1-amino (50 mg, 0.19 mmol) and benzoyl chloride (24 μL, 0.21 mmol) in dichloromethane (1 mL) at 0 ° C, diisopropylethylamine (66 μL, 0.38 mmol) was added. The mixture was stirred at room temperature for 15 hours, the solvent was removed, and the residue was purified by flash chromatography (0-30% ethyl acetate-hexanes) to provide 18 mg (26% yield) of a solid yellow. 1 H-NMR (CDCl 3: d 8.97 (s, 1 H), 7.78 (d, 2 H), 7.61 (m, 1 H), 7.52 (m, 1 H), 7.44 (t, 2 H), 7.23 (m, 1 H), 7.17 (d, 1H), 6.42 (d, 1H), 5.34 (m, 1H), 2.72 (m, 2H), 2.32 (m, 1H), 2.02-1.93 (m, 3H); MS m / z 369 (M -1).

Example 14B:? / - r (1ft) -6-bromo-2,3,4,9-tetrahydro-1rt-carbazole-1-illbenzamide Example 14C:? / - r (1S) -6-bromo-2,3,4,9-tetrahydro-1H-carbazole-1-illbenzamide? / - [(1S) -6-bromo-2,3,4,9- was separated tetrahydro-1H-carbazol-1-yl] benzamide in an analytical Berger SFC with an HP1100 diode-forming detector. The sample was monitored at 230 nm under the following conditions: 30% MeOH in C02 with a total flow rate of 2 mL / minute at 2250 psi, 50 ° C on a Diacel AD-H column (Chiral Technologies), 4.6 x 250 mm, 5 μm to give? / - [(1f?,) - 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl-benzamide (Example 14B; retention time = 12.37 minutes) and N - [(1 S) -6-bromo-2,3,4,9-tetrahydro-1 H-carbazol-1-yl] benzamide (Example 14C, retention time = 16.11 minutes ). Chirality assigned through VCD spectroscopy.

Example 15:? / - (6-Bromo-2,3,4,9'9-tetrahydro-1H-carbazol-1-yl) -2-phenylacetamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-phenylacetamide of 6-bromo-2,3,4,9- tetrahydro-1H-carbazole-1-amino and phenyl acetyl chloride in a manner similar to that described above to provide a white solid (86% yield). 1 H-NMR (CDCl 3): d 8.88 (s, 1 H), 7.57 (m, 1 H), 7.37-7.27 (m, 3 H), 7.27-7.20 (m, 3 H), 7.15 (d, 1 H), 5.74 (d , 1H), 5.08 (m, 1H), 3.61 (s, 2H), 2.62 (m, 2H), 2.13 (m, 1H), 1.81 (m, 2H), 1.67 (m, 1H); MS m / z 383 (M-1).

Example 16:? / - (6-Bromo-2.3.4.9-tetrahydro-1H-carbazol-1-n-3-phenylpropanamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -3-phenylpropanamide of 6-bromo-2,3,4,9-tetrahydro- 1H-carbazole-1-amino and hydrocinmoyl chloride in a manner similar to that described above to provide a white solid (53% yield). 1 H-NMR (CDCl 3): d 8.43 (s, 1 H), 7.58 (m, 1 H), 7.28-7.21 (m, 5 H), 7.20-7.15 (m, 2 H), 5.51 (d, 1 H), 505 (m , 1H), 3.00 (t, 2H), 2.62 (m, 2H), 2.58-2.43 (m, 2H), 2.12 (m, 1H), 1.80 (m, 2H), 1.67 (m, 1H); MS m / z 397 (M-1).

Example 17: / V- (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-n-3-phenylprop-2-enamide There was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -3-phenylprop-2-enamide of 6-bromo-2,3,4, 9-tetrahydro-1 - / - carbazole-1-amino and cinnamoyl chloride in a manner similar to that described above to provide a whitish solid (35% yield). 1 H-NMR (CDCl 3): d 8.98 (s, 1 H), 7.69 (d, 1 H), 7.60 (m, 1 H), 7.48 (m, 2 H), 7.36 (m, 3 H), 7.22 (dd, 1 H), 7.17 (d, 1H), 6.41 (d, 1H), 5.98 (d, 1H), 5.25 (m, 1H), 2.68 (m, 2H), 2.26 (m, 1H), 1.99-1.84 (m, 3H); MS m / z 395 (M-1).

Example 18: Benzyl 6-bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-ylcarbamate Benzyl 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ylcarbamate of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole-1-amino and benzyl chloroformate was prepared in a manner similar to that described above to provide a white solid (16% yield). 1 H-NMR (CDCl 3): d 8.69 (s, 1H), 7.60 (s, 1H), 7.43-7.31 (m, 5H), 7.27-7.21 (m, 1H), 7.17 (d, 1H), 5.16 (q , 2H), 5.08 (m, 1H), 4.92 (m, 1H), 2.66 (m, 2H), 2.20 (m, 1H), 1.89 (m, 2H), 1.80 (m, 1H); MS m / z 400 (M + 1).

Example 19:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-1 -0-2.6- dichlorobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2,6-dichlorobenzamide of 6-bromo-2,3,4,9- tetrahydro-1 / - / - carbazoI-1-amino and 2,6-dichlorobenzoyl chloride in a manner similar to that described above to provide a white solid (25% yield). 1 H-NMR (DMSO-d 6): d 10.80 (s, 1 H), 9.18 (d, 1 H), 7.61 (d, 1 H), 7.52 (d, 1 H), 7.49 (d, 1 H), 7.43 (dd, 1 H) ), 7.36 (d, 1H), 7.19 (dd, 1H), 5.27 (m, 1H), 2.69 (m, 2H), 2.08-1.82 (m, 4H); MS m / z 437 (M-1).

Example 20:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-fluorobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-fluorobenzamide of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole -1-amino and 4-fluorobenzoyl chloride in a manner similar to that described above to provide a white solid (15% yield). 1 H-NMR (DMSO- 6): d 11.03 (s, 1H), 8.90 (d, 1H), 8.05 (m, 2H), 7.61 (d, 1H), 7.34 (d, 2H), 7.30 (s, 1H) ), 7.17 (dd, 1H), 5.38 (m, 1H), 2.68 (m, 2H), 2.09 (m, 2H), 1.86 (m, 2H); MS m / z 387 (M-1).

Example 21:? / - (6-Bromo-2,3,4,9-tetrahydro-1rt-carbazol-1-yl) -4-methoxybenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methoxybenzamide of 6-bromo-2,3,4,9-tetrahydro-1 H -carbazole-1-amino and p-anisoyl chloride in a manner similar to that described above to provide a white solid (11% yield). 1 H-NMR (DMSO-d 6): d 10.99 (s, 1 H), 8.70 (d, 1 H), 7.96 (d, 2 H), 7.60 (d, 1 H), 7.29 (d, 1 H), 7.16 (dd, 1 H) ), 7.02 (d, 2H), 5.38 (m, 1H), 2.67 (m, 2H), 2.08 (m, 2H), 1.87 (m, 2H); MS m / z 399 (M-1).

Example 22:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-nitrobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-nitrobenzamide of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole -1-amino and 4-nitrobenzoyl chloride in a manner similar to that described above to provide an orange solid (32% yield). 1 H-NMR (DMSO-d 6): d 11.11 (s, 1 H), 9.24 (d, 1 H), 8.36 (d, 2 H), 8.19 (d, 2 H), 7.62 (m, 1 H), 7.29 (d, 1 H) ), 7.18 (dd, 1H), 5.41 (m, 1H), 2.69 (m, 2H), 2.10 (m, 2H), 1.89 (m, 2H); MS m / z 414 (M-1).

Example 23:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-in-4-chlorobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -4-chlorobenzamide of 6-bromo-2,3,4,9-tetrahydro- 1H-carbazole-1-amino and 4-chlorobenzoyl chloride in a manner similar to that described above to provide a brown solid (69% yield). 1 H-NMR (CDCl 3): d 8.89 (s, 1 H), 7.71 (d, 2 H), 7.60 (m, 1 H), 7.40 (d, 2 H), 7.23 (dd, 1 H), 7.17 (dd, 1 H), 6.36 (d, 1H), 5.30 (m, 1H), 2.69 (m, 2H), 2.29 (m, 1H), 1.96 (m, 3H); MS m / z 403 (M-1).

Example 24: / V- (6- Bromo-2,3,4,9-tetrahydro-1H-carbazole-1-in-4-methylbenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -4-methylbenzamide of 6-bromo-2,3,4,9-tetrahydro- 1 / - / - carbazole-1-amino and p-toluyl chloride in a manner similar to that described above to provide a yellow solid (62% yield). 1 H-NMR (CDC): d 8.97 (s, 1 H), 7.67 (d, 2 H), 7.61 (m, 1 H), 7.25-7.20 (m, 3 H), 7.17 (d, 1 H), 6.36 (d, 1 H) ), 5.30 (m, 1H), 2.71 (m, 2H), 2.39 (s, 3H), 2.30 (m, 1H), 1.97 (m, 3H); MS m / z 383 (M-1).

Example 25:? / - (6-Bromo-2.3.4.9-tetrahydro-1H-carbazole-1-M) -4- (trifluoromethyl) benzamide There was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4- (trifluoromethyl) benzamide of 6-bromo-2,3,4,9-tetrahydro- 1 / - / - carbazole-1-amino and 4-trifluoromethyl benzoyl chloride in a manner similar to that described above to provide a brown colored solid (63% yield). 1 H-NMR (CDCl 3): d 8.83 (s, 1 H), 7.89 (d, 2 H), 7.70 (d, 2 H), 7.61 (m, 1 H), 7.23 (d, 1 H), 7.18 (d, 1 H), 6.42 (d, 1H), 5.33 (m, 1H), 2.72 (m, 2H), 2.31 (m, 1H), 1.97 (m, 3H); MS m / z 437 (M-1).

Example 26:? / - (6-Bromo-2,3,4,9-tetrahydro-1 / tf-carbazol-1-yl) -3-fluorobenzamide There was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -3-fIuorobenzamide of 6-bromo-2,3,4,9-tetrahydro- 1 - / - carbazole-1-amino and 3-fluorobenzoyl chloride in a manner similar to that described above to provide a white solid (24% yield). 1 H-NMR (DMSO-d 6): d 11.04 (s, 1H), 8.97 (d, 1H), 7.85-7.81 (m, 1H), 7.81-7.74 (m, 1H), 7.62 (d, 1H), 7.59 -7.50 (m, 1H), 7.46-7.37 (m, 1H), 7.29 (d, 1H), 7.17 (dd, 1H), 5.38 (m, 1H), 2.68 (m, 2H), 2.08 (m, 2H) ), 1.87 (m, 2H); MS m / z 387 (M-1).

Example 27:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-iP-3-methoxybenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazoI-1-yl) -3-methoxybenzamide of 6-bromo-2,3,4,9-tetrahydro-1 / - / -carbazole-1-amino and m-anisoyl chloride in a manner similar to that described above to provide an orange solid (49% yield). 1 H-NMR (CDCl 3): d 8.92 (s, 1 H), 7.61 (m, 1 H), 7.38-7.30 (m, 2 H), 7.30-7.25 (m, 1 H), 7.23 (m, 1 H), 7.17 (d , 1H), 7.08-7.02 (m, 1H), 6.39 (d, 1H), 5.32 (m, 1H), 3.85 (s, 3H), 2.72 (m, 2H), 2.31 (m, 1H), 1.97 ( m, 3H); MS m / z 399 (M-1).

Example 28:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-p-3-methylbenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazoI-1-yl) -3-methylbenzamide of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole -1-amino and p-toluoyl chloride in a manner similar to that described above to provide a brown colored solid (51% yield). 1 H-NMR (CDCl 3): d 8.95 (s, 1 H), 7.63-7.59 (m, 2 H), 7.55 (m, 1 H), 7.33 (m, 2 H), 7.23 (m, 1 H), 7.17 (d, 1 H) ), 6.38 (d, 1H), 5.32 (m, 1H), 2.72 (m, 2H), 2.40 (s, 3H), 2.31 (m, 1H), 1.98 (m, 3H); MS m / z 383 (M-1).

Example 29:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-p-2-fluorobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2-fluorobenzamide of 6-bromo-2,3,4,9-tetrahydro- 1 - / - carbazole-1-amino and 2-fluorobenzoyl chloride in a manner similar to that described above to provide a yellow solid (57% yield). 1 H-NMR (CDCl 3): d 8.91 (s, 1 H), 8.15 (m, 1 H), 7.62 (m, 1 H), 7.50 (m, 1 H), 7.30 (m, 1 H), 7.23 (dd, 1 H), 7.18 (d, 1H), 7.12 (m, 2H), 5.35 (m, 1H), 2.72 (m, 2H), 2.31 (m, 1H), 1.98 (m, 3H); MS m / z 387 (M-1).

Example 30: A / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-in-2-methoxybenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2-methoxybenzamide of 6-bromo-2,3,4,9-tetrahydro- 1H-carbazole-1-amino and o-anisoyl chloride in a manner similar to that described above to provide a pale orange solid (67% yield). 1 H-NMR (CDCl 3): d 9.06 (s, 1H), 8.31 (d, 1H), 8.25 (dd, 1H), 7.60 (d, 1H), 7.46 (m, 1H), 7.20 (dd, 1H), 7.17 (dd, 1H), 7.10 (m, 1H), 6.96 (d, 1H), 5.31 (m, 1H), 3.91 (s, 3H), 2.72 (m, 2H), 2.31 (m, 1H), 1.98 (m, 3H); MS m / z 399 (M-1).

Example 31:? / - (6-Bromo-2,3,4,9-tetrahydro-1 H-carbazol-1-yl) -2-nitrobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2-nitrobenzamide of 6-bromo-2,3,4,9-tetrahydro- 1 / - / - carbazole-1-amino and 2-nitrobenzoyl chloride in a manner similar to that described above to provide an orange solid (39% yield). 1 H-NMR (CDCl 3): d 8.73 (s, 1 H), 8.08 (m, 1 H), 7.68 (m, 1 H), 7.60 (m, 2 H), 7.54 (m, 1 H), 7.29-7.21 (m, 2 H) ), 6.15 (d, 1H), 5.42 (m, 1H), 2.69 (m, 2H), 2.33 (m, 1H), 1.96 (m, 3H); MS m / z 414 (M-1).

Example 32:? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-in-2-chlorobenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2-chlorobenzamide of 6-bromo-2,3,4,9-tetrahydro- 1 / - / - carbazole-1-amino and 2-chlorobenzoyl chloride in a manner similar to that described above to provide a white solid (30% yield). 1H-NMR (DMSO-cf3): d 10.98 (s, 1H), 8.89 (d, 1H), 7.54 (dd, 2H), 7.48-7.44 (m, 1H), 7.42 (dd, 1H), 7.40-7.34 (m, 1H), 7.28 (d, 1H), 7.13 (dd, 1H), 5.26 (m, 1H), 2.60 (m, 2H), 2.08-1.91 (m, 2H), 1.90-1.73 (m, 2H) ); MS m / z 403 (M-1).

Example 33:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-methylbenzamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-methylbenzamide of 6-bromo-2,3,4,9-tetrahydro-1 - -carbazole-1-amino and o-toluoyl chloride in a manner similar to that described above to provide a gray solid (19% yield). 1 H-NMR (DMSO-d 6): d 11.01 (s, 1 H), 8.70 (d, 1 H), 7.59 (m, 1 H), 7.47 (d, 1 H), 7.33 (m, 2 H), 7.26 (m, 2 H) ), 7.17 (dd, 1H), 5.34 (m, 1H), 2.65 (, 2H), 2.42 (s, 3H), 2.07 (m, 2H), 1.87 (, 2H); MS m / z 383 (M-1).

Example 34:? / - (2,3,4,9-Tetrahydro-1H-carbazol-1-yl benzamide)? / - (2,3,4,9-Tetrahydro-1 / - / - carbazol-1-yl) was prepared Benzamide of 2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino-hydrochloride and benzoyl chloride in a manner similar to that described above to provide a pale yellow solid (73% yield) 1H-NMR (CDCl 3): d 8.79 (s, 1H), 7.81-7.75 (m, 2H), 7.54-7.48 (m, 2H), 7.47-7.40 (m, 2H), 7.32 (d, 1H) , 7.17 (m, 1H), 7.09 (d, 1H), 6.42 (d, 1H), 5.37 (m, 1H), 2.78 (m, 2H), 2.32 (m, 1H), 2.03-1.91 (m, 3H ); MS m / z 289 (M-1).

Example 35:? / - (6-Methyl-2,3,419-tetrahydro-1H-carbazol-1-yl) benzamide It was prepared? / - (6-Methyl-2,3,4,9-tetrahydro-1H-carbazol-1-l) benzamide of 6-methyl-2,3,4,9-tetrahydro-1H-carbazole-1 -amino and benzoyl chloride in a manner similar to that described above to provide a pale yellow solid (81%) of production). 1 H-NMR (CDCl 3): d 8.63 (s, 1 H), 7.81-7.75 (m, 2 H), 7.54-7.48 (m, 1 H), 7.47-7.40 (m, 2 H), 7.28 (m, 1 H), 7.20 (d, 1H), 6.99 (dd, 1H), 6.40 (d, 1H), 5.36 (m, 1H), 2.75 (m, 2H), 2.44 (s, 3H), 2.31 (m, 1H), 2.02- 1.91 (m, 3H); MS m / z 303 (M-1).

Example 36A:? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-t Dbenzamide It was prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) benzamide of 6-chloro-2,3,4,9-tetrahydro-1 / y -carbazole-1-amino and benzoyl chloride in a manner similar to that described above to provide a pale yellow solid (81% yield). 1 H-NMR (CDCl 3): d 9.02 (s, 1H), 7.79-7.73 (m, 2H), 7.54-7.48 (m, 1H), 7.46-7.39 (m, 3H), 7.21 (d, 1H), 7.10 (dd, 1H), 6.45 (d, 1H), 5.32 (m, 1H), 2.72 (m, 2H), 2.30 (m, 1H), 2.01-1.90 (m, 3H); MS m / z 323 (M-1).

Example 36B:? / - r (1f?) - 6-chloro-2.3.4.9-tetrahydro-1H-carbazole-1-illbenzamide Example 36C:? / - r (1S) -6-chloro-2.3.4.9-tetrahydro-1H-carbazole-1-illbenzamide ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide was separated in a Berger analytical SFC with an HP1100 diode-forming detector. The sample was monitored at 230 nm under the following conditions: 30% MeOH in C02, with a total flow rate of 2 mL / minute at 1500 psi, 40 ° C on a column of AS-H Diacel (Chiral Technologies), 4.6 x 250 mm, 5 μm to give R -? / - (6-cyoro-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) benzamide (retention time = 5.08 minutes) and S- ? / - (6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide (retention time = 7.45 minutes). Chirality assigned through VCD spectroscopy.

Example 37:? / - (6-Bromo-2.3.4.9-tetrahydro-1 / y-carbazol-1-yl) -4-methylbenzenesulfonamide Prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -4-methylbenzenesulfonamide of 6-bromo-2,3,4,9-tetrahydro-1H -carbazole-1-amino and p-toluene sulfonyl chloride in a manner similar to that described above to provide a brown solid (60% yield). 1 H-NMR (CDCl 3): d 8.63 (s, 1 H), 7.85 (d, 2 H), 7.57 (m, 1 H), 7.37 (d, 2 H), 7.25 (m, 1 H), 7.18 (d, 1 H), 4.74 (d, 1H), 4.46 (m, 1H), 2.61 (m, 2H), 2.48 (s, 3H), 2.00-1.82 (m, 2H), 1.80-1.60 (m, 2H); MS m / z 419 (M-1).

Example 38:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) pyridine-2-carboxamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) pyridine-2-carboxamide of 6-bromo-2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino and picolinoyl chloride in a manner similar to that described above to provide a whitish solid (64% yield). 1 H-NMR (CDCl 3): d 8.96 (s, 1 H), 8.52 (m, 1 H), 8.37 (d, 1 H), 8.21 (m, 1 H), 7.86 (m, 1 H), 7.61 (m, 1 H), 7.43 (m, 1H), 7.22 (dd, 1H), 7.17 (d, 1H), 5.31 (m, 1H), 2.72 (m, 2H), 2.31 (m, 1H), 1.98 (m, 3H); MS m / z 370 (M-1).

Example 39:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-1- Dnicotinamide There was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / -carbazol-1-yl) nicotinamide of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole- 1-amino and nicotinyl chloride in a manner similar to that described above to provide a white solid (54% yield). 1 H-NMR (DMSO-d 6): d 11.02 (s, 1H), 9.08-9.00 (m, 2H), 8.69 (dd, 1H), 8.25 (m, 1H), 7.57 (d, 1H), 7.53-7.43 (m, 1H), 7.24 (d, 1H), 7.13 (dd, 1H), 5.35 (m, 1H), 2.64 (m, 2H), 2.04 (m, 2H), 1.84 (m, 2H); MS m / z 370 (M-1).

Example 40:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -6-chloronicotinamide It was prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -6-cyoronicotinamide of 6-bromo-2,3,4,9-tetrahydro- 1H-carbazole-1-amino and 6-chloronicotinyl chloride in a manner similar to that described above to provide a white solid (48% yield). 1 H-NMR (DMSO-d 6): d 11.04 (s, 1H), 9.12 (d, 1H), 8.88 (dd, 1H), 8.30 (dd, 1H), 7.64 (dd, 1H), 7.57 (d, 1H) ), 7.24 (m, 1H), 7.13 (dd, 1H), 5.34 (m, 1H), 2.63 (m, 2H), 2.04 (m, 2H) 1.82 (, 2H); MS m / z 404 (M-1).

Example 41:? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-t-IOisonicotinamide Prepared? / - (6-Bromo-2,3,4,9-tetrahydro-1W-carbazol-1-yl) isonicotinamide of 6-bromo-2,3,4,9-tetrahydro-1H-carbazole-1 - amino and isonicotinyl chloride in a manner similar to that described above to provide a white solid (30% yield). 1 H-NMR (DMSO-c / e): d 11.04 (s, 1 H), 9.13 (d, 1 H), 8.71 (m, 2 H), 7.82 (m, 2 H), 7.57 (d, 1 H), 7.24 (d , 1H), 7.13 (dd, 1H), 5.35 (m, 1H), 2.64 (m, 2H), 1.84 (m, 2H); MS m / z 370 (M-1).

Example 42:? / - Phenyl -? / '- (2, 3,4, 9-tetrahydro-1H-carbazole-1-in urea) Prepared? / - Phenyl -? / '- (2,3,4,9-tetrahydro-1H-carbazol-1-yl) urea of 2,3,4,9-tetrahydro-1 / - / - carbazole-1 phenyl amino and p-isocyanate hydrochloride in a manner similar to that described above to provide a white solid (60% yield). 1 H-NMR (DMSO-d 6): d 10.72 (s, 1 H), 8.28 (s, 1 H), 7.43-7.33 (m, 3 H), 7.29-7.17 (m, 3 H), 7.00 (m, 1 H), 6.94 -6.83 (m, 2H), 6.52 (d, 1H), 4.95 (m, 1H), 2.62 (m, 2H), 1.99 (m, 1H), 1.88-1.70 (m, 3H); MS m / z 304 (M-1).

Example 43:? / - (6-Methyl-2,3,4,9-tetrahydro-1-yl-carbazol-1-yl) -? / '- phenylurea There was prepared? / - (6-Methyl-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -? / '- phenylurea of 6-methyl-2,3,4, 9-tetrahydro-1 / - / - carbazole-1-amino and phenyl isocyanate in a manner similar to that described above to provide a white solid (82% yield). 1 H-NMR (DMSO-d 6): d 10.57 (s, 1 H), 7.42-7.34 (m, 2 H), 7.20 (m, 2 H), 7.17-7.11 (m, 2 H), 6.87 (m, 1 H), 6.82 (m, 1H), 6.51 (d, 1H), 4.92 (m, 1H), 2.58 (m, 2H), 2.32 (s, 3H), 1.97 (m, 1H), 1.87-1.70 (m, 3H); MS m / z 318 (M-1).

Example 44:? / - (6-Chloro-2.3.4.9-tetrahydro-1H-carbazole-1-n -? / '- phenylurea It was prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- phenylurea of 6-chloro-2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino and phenyl isocyanate in a manner similar to that described above to provide a white solid (74% yield). 1H-NMR (DMSO-cf6): d 10.93 (s, 1H), 8.30 (s, 1H), 7.41-7.36 (m, 3H), 7.28 (d, 1H), 7.21 (m, 2H), 7.00 (dd) , 1H), 6.88 (m, 1H), 6.57 (d, 1H), 4.95 (m, 1H), 2.59 (m, 2H), 1.98 (m, 1H), 1.88-1.70 (m, 3H); MS m / z 338 (M-1).

Example 45A:? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-pyridinecarboxamide Prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-pyridinecarboxamide of 6-chloro-2,3,4,9-tetrahydro-1 / - / -carbazole-1-amino and picolinoyl chloride in a manner similar to that described in Example 14 to give an off-white solid (62% yield). 1H-NMR (DMSO-d6): d 10.93 (s, 1H), 8.78 (d, 1H), 8.61- (m, 1H), 8.12 (m, 1H), 8.02 (m, 1H), 7.61 (m, 1H), 7.43 (m, 1H), 7.26 (d, 1H), 7.01 (dd, 1H), 5.34 (m, 1H), 2.64 (m, 2H), 2.00 (m, 3H), 1.82 (m, 1H) ); MS m / z 348 (M + Na).

Example 45B:? / - r (1ft) -6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-n-pyridine-2-carboxamide Separated? / - (6-Chloro-2,3,4,9-tetrahydro-1 y-carbazol-1-yl] -2-pyridinecarboxamide in an analytical Berger SFC with an HP1100 diode-forming detector. monitored at 230 nm under the following conditions: 30% MeOH in C02, with a total flow rate of 2 mL / minute at 1500 psi, 40 ° C on a column of AS-H Diacel (Chiral Technologies), 4.6 x 250 mm , 5 μm to give? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1 - / - carbazole-1-ii] pyridine-2-carboxamide (retention time = 4.55 minutes) [a] D = +86, the R configuration was confirmed by X-ray crystallography and VCD, 1H-NMR and MS are identical to the racemic compound, 13C-NMR (DMSO-c / 6): d 164.1, 150.6 , 149.1, 138.4, 136.4, 135.3, 128.5, 127.2, 123.7, 122.7, 121.5, 117.8, 113.4, 111.2, 44.0, 30.8, 21.5, 21.0; HR MS m / z 348.0876 (M + Na); Analytical Calculated for C18H16CIN30 with % H20: C, 65.45; H, 5.04; N, 12.72, Found: C, 65.67; H, 4.91; N, 12.66, LC-UV purity check: Analytical LC-UV Waters consisting of a Waters 626 pumping system, a Waters 996 diode-array detector, and a Wilson 233XL auto-hob; column: Waters Symmetry RP1 8 Protective Layer, 3.9x1 50mm, 5m; 50-90% »acetonitrile-water (0.1% formic acid); total run time of 15 minutes; the flow rate remains constant at 1.5 m L / minute; Retention time = 7.41 minutes.

Example 45C:? / - r (1 S) -6-chloro-2, 3,4, 9-tetrahydro-1 H-carbazole-1 - pyridine-2-carboxamide Separated? / - (6-Chloro-2, 3,4, 9-tetrahydro-1 H-carbazol-1-yl] -2-pyridinecarboxamide in an analytical Berger SFC with a diode-forming detector HP1 1 00. The sample was monitored at 230 nm under the following conditions: 30% MeOH in C02, with a total flow rate of 2 mL / minute at 1 500 psi, 40 ° C on a column of AS-H Diacel (Chiral Technologies), 4.6 x 250 mm, 5 μm to give? 7 - [(1 S) -6-chloro-2,3,4, 9-tetrahydro-1 H-carbazole-1 -M] pyridine-2-carboxamide (retention time = 6.77 minutes; [a] D = -86); 1 H-NMR and MS are identical to the racemic compound.The stereochemistry was assigned through VCD.

Example 46A: A / - (6-Chloro-2,3,4,9-tetrahydro-1-carbazol-1-yl) -2-fluorobenzamide It was prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazoI-1-yl) -2-fluorobenzamide of 6-chloro-2,3,4,9-tetrahydro-1 / - / -carbazole-1-amino and 2-fluorobenzoyl chloride in a manner similar to that described in Example 14 to provide a white solid (63% yield). 1 H-NMR (CDCl 3): d 8.93 (s, 1 H), 8.14 (m, 1 H), 7.49 (m, 1 H), 7.45 (m, 1 H), 7.28 (m, 1 H), 7.22 (d, 1 H), 7.10 (m, 3H), 5.35 (m, 1H), 2.72 (m, 2H), 2.31 (m, 1H), 1.98 (m, 3H); MS m / z 343 (M + 1).

Example 46B:? / - r (1R) -6-chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-ill-2-fluorobenzamide Example 46C:? / - r (1S) -6-chloro-2.3.4.9-tetrahydro-1H-carbazol-1-p-2-fluorobenzamide Separated? / - (6-Chloro-2,3,4,9-tetrahydro-1 H-carbazol-1-yl] -2-fluorobenzamide in an analytical SFC 'Berger with an HP1100 diode-forming detector. was monitored at 254 nm under the following conditions: 30% MeOH in C02, with a total flow rate of 2 mL / minute at 1500 psi, 40 ° C on a OJ-H Diacel column (Chiral Technologies), 4.6 x 250 mm, 5 μm to give? / - [(1S) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fluorobenzamide (retention time = 6.29 minutes) and? / - [(1ft) -6-chloro-2, 3,4,9-tetrahydro-1 / - / - carbazol-1-yl] -2-fluorobenzamide (retention time = 9.32 minutes).

Example 47:? / - (6-Chloro-2,3,4,9-tetrahydro-1-carbazole-1-in-1-methyl-1H-imidazole-5-carboxamide To a solution of 1-methyl-1H-imidazole-5-carboxylic acid (45 mg, 3.36 mmol) in dichloromethane (3.6 mL) was added 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1. -amino (95 mg, 0.43 mmol), 1-ethyl-3- (3-dimethylaminopropMo) carbodiimide (83 mg, 0.43 mmol), and 1-hydroxybenzotriazole (54 mg, 0.4 mmol). After 5 minutes, triethylamine (100 μL, 0.72 mmol) was added and the reaction was stirred at room temperature for 15 hours. The reaction mixture was diluted with dichloromethane, washed with water, 1N hydrochloric acid, 1N sodium hydroxide, brine, dried with magnesium sulfate, filtered and concentrated. The residue was purified by preparative chromatography (10-90% acetonitrile-water) (0.1% trifluoroacetic acid)) and then diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, and dried with magnesium sulfate. to provide 43 mg (36% yield) of a white solid. 1 H-NMR (CDCl 3): d 9.21 (s, 1 H), 7.43 (m, 1 H), 7.32 (s, 1 H), 7.30 (s, 1 H), 7.20 (d, 1 H), 7.07 (dd, 1 H), 6.60 (d, 1H), 5.25 (m, 1H), 3.81 (s, 3H), 2.67 (m, 2H), 2.21 (m, 1H), 1.90 (m, 3H); MS m / z 327 (M-1).

Example 48:? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yn-1-methyl-1H-pyrazole-5-carboxamide Prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazoI-1-yl) -1-methyl-1 / - / - pyrazole-5-carboxamide from 2 - methyl-2H-pyrazole-3-carboxylic acid and 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-amino in a manner similar to that described above to provide a white solid (cf. % of production). 1 H-NMR (CDCl 3): d 8.69 (s, 1H), 7.45 (m, 2H), 7.22 (d, 1H), 7.10 (dd, 1H), 6.48 (d, 1H), 6.26 (d, 1H), 5.28 (m, 1H), 4.22 (s, 3H), 2.71 (m, 2H), 2.28 (m, 1H), 1.95 (m, 3H); MS m / z 327 (M-1).

Example 49:? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-n-1-methyl-1H-pyrazole-3-carboxamide Prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -1-methyl-1H-pyrazole-3-carboxamide of 1-methyl-2H- pyrazole-3-carboxylic acid and 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-amino in a manner similar to that described above to provide a whitish solid (20% yield) . 1 H-NMR (CDCl 3): d 8.95 (s, 1 H), 7.43 (m, 1 H), 7.37 (m, 1 H), 7.22 (d, 1 H), 7.07 (dd, 1 H), 6.80 (m, 1 H), 5.30 (m, 1H), 3.88 (s, 3H), 2.71 (m, 2H), 2.27 (m, 1H), 1.97 (m, 3H); MS m / z 327 (M-1).

Example 50:? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-n-1rt-imidazole-4-carboxamide It was prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1-imidazole-4-carboxamide of carboxylic acid 4-imidazole and 6-chloro-2,3 , 4,9-tetrahydro-1H-carbazole-1-amino in a manner similar to that described above to provide a white solid (4% yield). 1 H-NMR (CDCl 3): d 9.19 (s, 1 H), 7.62 (s, 1 H), 7.57 (s, 1 H), 7.41 (s, 1 H), 7.37 (d, 1 H), 7.17 (d, 1 H), 7.05 (dd, 1H), 6.60 (d, 1H), 5.25 (m, 1H), 2.62 (m, 2H), 2.21 (m, 1H), 1.91 (m, 3H); MS m / z 313 (M-1).

Example 51: A / - (6-Chloro-2.3.4.9-tetrahydro-1H-carbazol-1-yl) -1H-pyrazole-3-carboxamide Prepared? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -1W-pyrazo! -3-carboxamide of H-pyrazole-3-carboxylic acid and 6-chloro-2,3,4,9-tetrahydro-1 / - / - carbazole-1-amino in a manner similar to that described above to provide a white solid (16% yield). 1H-NMR (CD3OD-d4): d 7.70 (d, 1H), 7.37 (d, 1H), 7.22 (d, 1H), 6.99 (dd, 1H), 6.81 (d, 1H), 5.37 (m, 1H) ), 2.70 (m, 2H), 2.19 (m, 1H), 2.00 (m, 3H); MS m / z 313 (M-1).

Example 52:? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-iD-2,6-difluorobenzamide Prepared? / - (6-bromo-2,3,4,9-tetrahydro-1 / - / ~ carbazol-1-yl) -2,6-difluorobenzamide of 2,6-difluorobenzoylchloride and 6-bromo-2, 3,4,9-tetrahydro-1H-carbazole-1-amino in a manner similar to that described above to provide a white solid: 1 H-NMR (CDC): d 8.80 (s, 1H), 7.60 (m , 1H), 7.35 (m, 1H), 7.23 (overlapping dd and d, 2H), 6.94 (t, 2H), 6.37 (d, 1H), 5.35 (m, 1H), 2.7 (m, 2H), 2.26 ( m, 1H), 1.95 (m, 3H); MS m / z 404 (M-1).

Example 53: A / - (6-bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -2-fluorobenzenesulfonamide There was prepared? / - (6-bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2-fluorobenzenesulfonamide of 2-fluorobenzenesulfonylchloride and 6-bromo-2,3,4, 9-tetrahydro-1 / - / - carbazole-1-amino in a manner similar to that described above to provide a white solid: 1 H-NMR (CDCl 3): d 8.56 (s, 1H), 8.00 (m, 1H), 7.56 (m, 1H), 7.58 (m, 1H), 7.2-7.4 (m, 3H), 5.04 (d, 1H), 4.60 (m, 1H), 2.65 (m, 2H), 1.6-2.1 (m, 4H); MS m / z 421 (M-1).

Example 54:? / - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzenes ulfon a mida It was prepared? /, - (6-bromo-2,3,4, 9-tetrahydro-1 H-carbazol-1-yl) -2,6-difluorobenzenesulfonamide of 2,6-difluorobenzenesulfonylchloride and 6-bromo-2,3 , 4, 9-tetrahydro-1 H-carbazole-1-amino in a manner similar to that described above to provide a white solid: 1 H-NMR (CDCl 3): d 8.60 (s, 1 H), 7.48 -7.58 (m, 2H), 7.24 (dd, 1 H), 7.18 (d, 1 H), 7.04 (t, 1 H), 5.31 (m, 1 H), 4.73 (m, 1 H), 2.62 (m, 2H), 1.7-2.1 (m, 4H).

BIOLOGICAL ENTHAL DATA AND EXPERIMENTS The compounds of the present invention are believed to be useful in the treatment and / or prophylaxis of conditions and diseases associated with HPV infection. The activity mediated through HPV was determined using the following cellular test W-12.

Cell culture and medium The W 12 cell line used contains HPV DNA 16 and was derived from a tissue with low grade cervical dysplasia by Margaret Stanley and subsequently selected clonally by Paul Lambert (University of Wisconsin). One of these clones, W12-20850, contains 1,000 copies of episomal HPV 16 DNA and was used in the cell-based test. The W12- 20850 cells were routinely cultured with a feeder layer (6000 rads) irradiated with a range of 3T3 cells. However, tests were run in the absence of a 3T3 feeder layer. The W1 2-20850 and 3T3 cells were routinely divided when they were sub-confluent. The W12-20850 grew in the W12 Medium which consists of 25% DM EM (Gibco BRL, Cat # 12430-047, 75% Medium F12 (Gibco BTL, Ca # 1 1 765-021) and 2.5% FBS. include 24.0 mg / ml Adenine (Sigma, Cat # A-9795), 0.4 mg / ml Hydrocortisone (Calbiochem, Cat # 386698), 5.0 mg / ml Bovine Insulin (Sigma, Cat # 1-1 882), 8.4 ng / ml of cholera toxin (Fluka, Cat # 26694) and 1 0 ng / ml EGF (Invitrogen, Cat # 13247-051) The 3T3 cells grew in DMEM containing 10% FBS. incubated at 37 ° C, in the presence of C02 of 5%.

Cell-based test For the test, W12-20850 cells were seeded in a 96-well plate containing the compound. The plates were incubated at 37 ° C in the presence of C02 of 5% for four days. On the fourth day, the cells were used and the amount of episomal HPV-16 DNA was quantified using a non-radioactive hybrid capture technique with HPV-16 specific detection and capture scan. Then, percent inhibition relative to untreated control cells was determined.

Hybrid capture The hybrid capture test is run in a 96-hole plate format. The hybridization plates (Nunc Maxisorb Cat # 450320) were covered with a capture-solution mixture of ReactiBind for at least 4 hours and then washed with 0.2X SSC, 0.05% Tween20 (SSCT) before blocking with 1 50 μl / orifice of 0.2 N NaOH, 1% Igepal, 1 0 mG / ml of hsDNA for 6-8 hours. Hybridization was carried out by mixing 27 μl of used cells with 45 μl of denatured detection scan in 6M guanidine isothiocinate. To prevent evaporation, 50 μl of mineral oil was added to each hole. Then, the plate was heated to 90 ° C for 6.5 minutes and the hybridization continued at 42 ° C at night. The test plates were washed 6 times with SSC / T. Anti-digoxigenin HRP conjugate Ab (Boehringer Mannheim 1 207733), 1: 5000) was incubated in the orifices for 30 minutes at room temperature and washed with PBS / 0.05% Tween-20. The LBA SuperSignal substrate (Pierce Cat # 37070) was added and the chemiluminescence was measured using a Víctor Wallac 1420 plate reader. Example W-12 (nM) Example W-1 2 (nM) Example W-12 (nM) 9 548 21 22 39 130 10 24000 22 45 40 24 11 > 1000 23 17 41 180 12 > 10000 24 8 42 > 10000 13 237 25 58 43 > 10000 14a 32 26 14 44 1700 14B 10 27 28 45A 10 14C 5000 28 23 45B 5 15 580 29 9 45C 6000 16 1200 30 > 10000 46A 12 17 318 31 > 7300 46B 7 18 44 32 1400 46C > 3000 19 5800 33 497 47 810 20 20 34 > 10000 48 2240 35 184 49 1650 36A 60 50 440 36B 20 51 73 The evaluation compounds were used in free or salt form. All the research complied with the principles of laboratory animal care (NIH publication No. 85-23, revised in 1985) and GlaxoSmithKine policy on the use of animals. Although the specific embodiments of the present invention are illustrated and described in detail herein, the invention is not limited thereto. The detailed descriptions above are provided as exemplary of the present invention and should not be construed as constituting any limitation of the invention. Modifications will be obvious to those skilled in the art, and all modifications that do not depart from the spirit of the invention are intended to be included within the scope of the appended claims.

Claims

CLAIMS 1. A compound of the formula (I): where: n is 0, 1, or 2; t is 0 or 1; X is -NH-, -O-, -R10-, -OR10-, -R10O-, -R10OR10-, NR10-, -R10N-, -R10NR10-, R10S (O) m-, or -R10S (O) mR10-; Y is-C (O) - or -S (0) m-; Each R is the same or different and is independently selected from the group consisting of halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R10cycloaicyl, Ay, -NHR 0Ay, Het, -NHHet, -NHR10Het, -OR2, -OAy, -OHet, -R10OR2, -NR2R3, -NR2Ay, -R10NR2R3, -R10NR2Ay, -R10C (O) R2, -C (0) R2, -C02R2, -R10CO2R2, -C (0) NR2R3, -C (0) Ay, -C (0) NR2Ay, -C (0) Het, -C (O) NHR10Het, -R10C (O) NR2R3, -C (S) NR2R3, -R10C (S) NR2R3, -R10NHC ( NH) NR2R3, - C (NH) NR2R3, -R10C (NH) NR2R3, -S (0) 2NR2R3, -S (0) 2NR2Ay, R10SO2NHCOR2, -R10SO2NR2R3, -R10SO2R2, -S (0) mR2, -S (0) mAy, cyano, nitro or azido; each R1 is the same or different and is independently selected from the group consisting of halogen, haloalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R1 0 cycloalkyl, Ay, -NH R10Ay, Het, -NHHet, -NHR10Het, -OR2, -OAy, -OHet, -R1 0OR2, -NR2R3, -NR2Ay, -R1 0NR2R3, -R10N R2 Ay, -R 0C (O) R2, -C (0) R2 , -C02R2, -R10CO2R2, -C (0) NR2R3, -C (0) Ay, -C (0) NR Ay, -C (0) Het, -C (O) NHR10Het, -R1 0C (O) NR2R3 , -C (S) N R2R3, -R10C (S) NR2R3, R10NHC (NH) NR2R3, -C (NH) NR2R3, -R10C (NH) NR2R3, -S (0) 2NR2R3, -S (0) 2NR2Ay, -R10SO2NHCOR2, -R10SO2NR2R3, -R10SO2R2, -S (0) mR2, - S (0) mAy, cyano, nitro or azido; each m is independently 0, 1, or 2; each R10 is the same or different and is independently selected from alkylene, cycloalkylene, alkenylene, cycloalkenylene, and alkynylene; p and q each are independently chosen from 0, 1, 2, 3, 4 or 5; each of R2 and R3 are the same or different and are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, -R1 0 cycloalkyl, -R10OH, -R10 (OR10) W, and -R10NR4R5; w is 1 -1 0; each of R4 and R5 are the same or different and are independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl; Ay represents an aryl group; Het represents a 5- or 6-membered heterophenyl or heteroaryl group; the A chain is aryl or heteroaryl; provided that when the chain A is aryl, t is 0, and Y is S02, then p is not 0; and the salts, solvates and physiologically functional derivatives thereof.
2. The compound according to claim 1, characterized in that alkyl is alkyl, the alkoxy is C-) - C6 alkoxy, the haloalkyl is C -? - C6 haloalkyl, the alkylene is Ci-Ce alkylene, and the alkenylene is C? C6 3. The compound characterized in that, t is 0 and Y is -C (O) -. 4. The compound characterized in that, t is 0 and Y is - S (0) m-. 5. The compound according to claim 1, characterized in that t is 1, Y is -C (O) - and X is -NH-, -O-, R10-, or-OR10-. 6. The compound according to claim 1, characterized in that t is 1, Y is -S (0) m-, and X is -N H-, -O-, -R10-, u-OR10-. 7. The compound according to claim 1, characterized in that n is 1. The compound according to claim 1, characterized in that p is 1 or more and R is chosen from halogen, alkyl, haloalkyl, -OR2, -N R2R3, -C (0) R2, -C02R2, cyano, nitro, or azido . 9. The compound according to claim 8, characterized in that R is halogen, alkyl, haloalkyl. 10. The compound according to claim 9, characterized in that R is substituted for with respect to the N atom described. eleven . The compound according to claim 10, characterized in that R is halogen. 12. The compound according to claim 1, characterized in that R is Br or Cl. The compound according to claim 1, characterized in that q is one or more and R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -N R2R3, -C (0) R2, -C02R2, Ay, Het, cyano, nitro, or azido. The compound according to claim 13, characterized in that R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, or cyano. 1 5. The compound according to claim 14, characterized in that R2 and R3 are each CT -CS alkyl. The compound according to claim 14, characterized in that R1 is chosen from halogen, alkyl, or -OR2. The compound according to claim 16, characterized in that said halogen is fluoro or chloro, said alkyl is methyl, and said -OR2 is alkoxy. The compound according to claim 1, characterized in that the A chain is aryl. 9. The compound according to claim 18, characterized in that the A chain is phenyl. 20. The compound according to claim 1, characterized in that q is 1 or more and R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, Ay, Het, cyano, nitro, or azido. twenty-one . The compound according to claim 20, characterized in that q is one or more and R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NRR3, -C (0) R2, -C02R2, or cyano. 22. The compound according to claim 1, characterized in that the A chain is heteroaryl. 23. The compound according to claim 22, characterized in that the heteroaryl is pyridyl. 24. The compound according to claim 23, characterized in that q is 0 or 1. 25. The compound according to claim 24, characterized in that when q is 1, then R1 is chosen from halogen, alkyl, haloalkyl, -OR2, NR2R3, -C (0) R2, -C02R2, Ay, Het, cyano, nitro, or azido. 26. The compound according to claim 251, characterized in that when q is 1, then R1 is chosen from halogen, alkyl, haloalkyl, -OR2, -NR2R3, -C (0) R2, -C02R2, or cyano. The compound according to claim 1, characterized in that p is 1, R is halogen, n is 1, Y is -C (O) -, t is 0, the A chain is heteroaryl, and q is 0. 28. The compound according to claim 27, characterized in that R is chlorine or bromine and the chain A is pyridyl. 29. A compound chosen from: 30. The compound according to claim 1, chosen from ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- phenylurea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- (4-methoxyphenyl) urea; ? and- (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- (4-methoxy-2-methylphenyl) urea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -? / '- (3-chloro-3-methoxyphenyl) urea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? T- [4- (dimethylamino) phenyl] urea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide; ? / - [(1ft) -6-bromo-2,3,4,9-tetrahydro-1 / - / - carbazo-1-yl] benzamide; ? / - [(1S) -6-bromo-2,3,4,9-tetrahydro-1/7-carbazo-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl-2-phenylacetamide;? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazole-1 -3-phenylpropanamide; / V- (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazole-1 -3-phenylprop-2-enamide; Benzyl 6 -bromo-2,3,4,9-tetrahydro-1H-carbazo-1-ylcarbamate;? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-2,6-dichlorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-4-fluo robe nzam ida;? / - (6-Bromo-2,3,4,9-tetrahydro-1W- carbazole-l-? -4-methoxybenzamide;? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-4-nitrobenzamide;? / - (6-Bromo-2,3,4 , 9-tetrahydro-1H-carbazole-4-cl or robe nzam ida;? / - (6-Bromo-2,3,4,9-tetrahydro-H-carbazol-4-methylbenzamide;? / - (6 -Bromo-2,3,4,9-tetrahydro-1H-carbazole-4- (trifluoromethyl) benzamide;? / - (6-Bromo-2,3,4,9-tetrahydro-1W-carbazole- -3- fluorobenzamide;? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazole-3-methoxybenzamide;? / - (6-Bromo-2,3,4,9-tetrahydro- 1 / - / - carbazoI- -3-m ethyl be nzam ida;? / - (6-Bromo-2,3,4,9-tetrahydro-1 Y-carbazol-2-fluorobenzam Going; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 H-carbazole-2-methoxybenzamide;? / - (6-Bromo-2,3,4,9-tetrahydro-1W-carbazole- -2-nitrobenzamide; - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazole-2-chlorobenzamide;? / - (6-Bromo-2,3,4,9-tetrahydro-1H -carbazole-2-methylbenzamide; / V- (2,3,4,9-Tetrahydro-1 / - / - carbazol-1-yl) benzamide;? / - (6-Methyl-2,3,4, 9-tetrahydro-1H-carbazol-1-yl) benzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) benzamide; ? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? - [(1S) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methylbenzenesulfonamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / V-carbazol-1-yl) pyridine-2-carboxamide; / V- (6-Bromo-2,3,4,9-tetrahydro-1 / V-carbazol-1-yl) nicotinamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -6-chloronicotinamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -sonicotinamide; ? / - Phenyl -? / '- (2, 3,4, 9-tetrahydro-1W-carbazol-1-yl) urea; ? / - (6-Methyl-2,3,4,9-tetrahydro-1H-carbazol-1-i)) -? / '- phenylurea; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -? / '- phenylurea; ? / - (6-C lo ro-2, 3, 4, 9-tetrahydro-1H-carbazole-1-l) -2-pyridine carboxamide; ? / - [(1f?) - 6-chloro-2,3,4,9-tetrahydro-1W-carbazol-1-yl] pyridine-2-carboxamide; ? / - [(1S) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] pyridine-2-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -2-fluorobenzamide; ? / - [(1?) - 6-chloro-2,3,4,9-tetrahydro-1 / -carbazol-1-yl-2-fluorobenzamide; ? / - [(1S) -6-chloro-2,3,4,9-tetrahydro-1 tf-carbazol-1-yl] -2-fluorobenzamide; ? / - (6-Chloro-2, 3,4, 9-tetrahydro-1 / V-carbazol-1-yl) -1-methyl-1-imidazole-5-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1-methyl-1f-pyrazole-5-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1-methyl-1 / - / - pyrazole-3-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1 - / - carbazole-1-ii) -1 / - / - imidazole-4-carboxamide; / V- (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -1 / - / - pyrazole-3-carboxamide; ? / - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzenesulfonamide; and? - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzenesulphon amide. 31. The compound according to claim 1 chosen from N- (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-1) -? / '- [4- (dimethylamino) phenylurea; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide; ? / - [(1f?) - 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -3-phenylprop-2-enamide; Benzyl 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ylcarbamate; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -4-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetra idro-1 / - / - carbazol-1-yl) -4-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-H-carbazol-1-yl) -4-nitrobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-chlorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-W-carbazol-1-yl) -4- (trifluoromethyl) benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) -3-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / -carbazol-1-yl) -3-methoxybenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) -3-methylbenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-H-carbazol-1-yl) -2-fluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-methylbenzamide; ? / - (6-Methyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl) benzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) benzamide; ? / - [1R) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -4-methylbenzenesulfonamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) pyridine-2-carboxamide; N- (6-Brom o-2, 3, 4, 9-tetrahydro-1H ~ carbazol-1-yl) nicotine mida; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -6-chloronicotinamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1-yl) ison-tacinamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-pyridinecarboxamide; ? / - [(1f?) - 6-chloro-2,3,4,9-tetrahydro-1H-carbazoI-1-yl] pyridine-2-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzamide; ? / - [(1R) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fluorobenzamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1H-imidazole-4-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -1 / Y-prazole-3-carboxamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-H-carbazol-1-yl) -2,6-difluorobenzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzenesulfonamide; and? / - (6-bromo-2,3,4,9-tetrahydro-1 tf-carbazol-1-yl) -2,6-difluorobenzenesulfonamide. 32. The compound according to claim 1 chosen from? / - (6-Bromo-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) benzamide; ? / - [(1R) -6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl] benzamide; Benzyl 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ylcarbamate; N- ((6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-l) -4-fluorobenzamide; N- ((6-Bromo-2,3,4,9-tetrahydro-1 W-carbazol-1) -4-methoxybenzamide; N- ((6-Bromo-2,3,4,9-tetrahydro-H-carbazoyl) -4-nitrobenzamide; N- ((6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-l) -4-chlorobenzamide; N- ((6-Bromo-2,3,4,9-tetrahydro-1 / -carbazol-1) -4-methylbenzamide; N- ((6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1) -3-fluorobenzamide; ? / - ((6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1) -3-methoxybenzamide; N-. { (6-Bromo-2,3,4,9-tetrahydro-1 / - / - carbazol-1) -3-m ethyl be namm ida; N- ((6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-l) -2-fluorobenzamide; N- ((6-chloro-2,3,4,9-tetrahydro-1 - / - carbazol-1-yl) benzamide; N- [[(1f?) - 6-chloro-2,3,4,9 -tetrahydro-1H-carbazol-1-yl] benzamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl [4] -methylbenzenesulfonamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazoyl-1-yl) pyridine-2-carboxamide; ? / - (6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -6-chloronicotinamide; / V- (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-pyridinecarboxamide; ? / - [(1ft) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] pyridine-2-carboxamide; ? / - (6-Chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzamide; ? / - [(1ft) -6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl] -2-fluorobenzamide; ? / - (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2,6-difluorobenzamide; and / V- (6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl) -2-fluorobenzenesulfonamide. 33. The compound according to claim 1 further comprising: including salts, solvates and pharmaceutically functional derivatives wherein R6 is H, alkyl, -OR2, -NR2R3, Ay, Het, -C (0) R2, -C02R2, -CONR2R3, -S (0) mR2, or oxo, in where R2, R3, m, Ay, and Het are as defined; and R7 is H or alkyl; provided that R6 and R7 are not both H. 34. The compound according to claim 1 to 33 substantially as defined above with reference to any of one of the Examples. 35. A pharmaceutical composition comprising a compound according to claims 1 to 33, and a pharmaceutically acceptable carrier. 36. A compound according to claim 1 to 33 for use as an active therapeutic substance. 37. A compound according to claims 1 to 33 for use in the treatment or prophylaxis of diseases and conditions caused by oncogenic viruses, including adenoviruses, retroviruses, and papovavirus family, which includes polyoma virus and papilloma virus. 38. A compound according to claim 1 to 33 for use in the treatment or prophylaxis of conditions or disorders due to HPV infection. 39. The compound according to claim 38, characterized in that the condition or disease is cysts, genital cysts, cervical dlsplasia, recurrent respiratory papillomatosis, or cancers associated with papillomavirus infection. 40. The compound according to claim 39, characterized in that the cancer is anogenital cancers, cancers of the head and neck, and cancers of the skin. 41 The compound according to claim 40, characterized in that the anogenital cancers are cervical, anal and perianal, vulval, vaginal and penile cancers; cancers of the head and neck are cancers of the esophagus and the oral pharyngeal region; and skin cancers are basal cell carcinoma and squamous cell carcinoma. 42. The use of a compound according to any of claims 1 to 33 in the manufacture of a medicament for use in the treatment or prophylaxis of the oncogenic virus, including adenovirus, retrovirus, and papovavirus family, including polyoma virus and papilloma virus. 43. The use of a compound according to any of claims 1 to 33 in the manufacture of a medicament for use in the treatment or prophylaxis of conditions or disorders due to HPV infection. 44. The use of a compound according to claim 43, characterized in that the condition or disorder is cysts, genital cysts, cervical dysplasia, recurrent respiratory papillomatosis, or cancers associated with papillomavirus infection. 45. A method for the treatment or prophylaxis of oncogenic viruses, including adenovirus, retrovirus and papovavirus family, including polyoma virus and papillomavirus comprising the administration of a compound according to any of claims 1 to 33. 46 A method for the treatment or prophylaxis of conditions or disorders due to HPV infection comprising the administration of a compound according to any of claims 1 to 33. 47. The method according to claim 46 characterized in that the condition or disorder is cysts. , genital cysts, cervical dysplasia, recurrent respiratory papillomatosis, or cancers associated with papillomavirus infection.