KR20120115481A - Novel thiourea or urea derivative, process for preparing the same and pharmaceutical composition for preventing or treating aids comprising the same - Google Patents

Abstract

PURPOSE: A thiourea ore urea derivative is provided to have excellent degrading activity of HIV by restraining expression of HIV virus, thereby capable of being useful for preventing or treating AIDS. CONSTITUTION: A preparing method of a thiourea or urea derivative comprises: a step of preparing a compound indicated in chemical formula 3 by reacting a carboxylic acid compound indicated in chemical formula 2 and oxalyl chloride under the presence of an organic solvent; a step of preparing a compound indicated in chemical formula 4 by reacting the compound indicated in chemical formula 3 with potassium thiocyanate under the presence of organic solvent; and a step of reacting the compound in chemical formula 4 with a compound indicated in chemical formula 5.

Description

Novel thiourea or urea derivative, process for preparing the same and pharmaceutical composition for preventing or treating AIDS comprising the same}

The present invention relates to a novel thiourea or urea derivative, a preparation method thereof and a pharmaceutical composition for preventing or treating AIDS containing the same as an active ingredient.

Human Immunodeficiency Virus (HIV) has been identified as an important cause of AIDS by separating HIV, the AIDS virus, from AIDS patients in 1984 after the first AIDS patient was reported.

HIV belongs to the taxonomic retrovirus, among which it is subdivided into the lentivirus group. HIV particles are about 10 microns in diameter, the outer part is wrapped in phospholipids like normal cell membranes, and inside, two viral genomes of RNA are protected in a capsid (core protein). The HIV genome is made up of 10 genes, which contain many genes compared to the size of the genome.

HIV infection is caused by conjugation of an envelope protein (gp120) on the surface of a virus to a receptor on the surface of a target cell. This receptor is a cell surface protein molecule called CD4 antigen. CD4 cells (macrophage T cells) or macrophages, which contain many of these CD4 antigens on the cell surface, are the main causes of HIV. The virus's conjugation causes the virus's phospholipid shell to fuse to the cell surface, and the virus's genome and nuclear proteins enter the cell. At this time, the viral genome is changed from RNA to DNA by reverse transcriptase in the virus particles, then transported into the cell nucleus and inserted into the genome of the host cell. This process is one of the characteristics that only retroviruses have. HIV hides in this safest place in the host cell and receives all the mechanisms and resources needed for growth. In addition, depending on the situation and conditions, while suppressing or promoting proliferation, and protects itself from the immune system and survives.

The AIDS virus is largely divided into two types, HIV-1 and HIV-2. Since HIV-1 is found in patients in many countries, including Korea, it is synonymous with the AIDS virus. HIV-2 is mainly found in patients in West Africa, whose genome sequence is only 55% identical to HIV-1, and is more similar to Simian Immunodeficiency Virus (SIV), a monkey AIDS virus. The toxicity of HIV-2 is known to be generally weaker than HIV-1. HIV is very diverse, both genetically and biologically. The HIV sequences isolated from different AIDS patients are different, as well as from the same patient, depending on the disease progression. Even when a virus is separated from the same patient at a certain time, a virus having a different sequence is detected depending on the tissue region. These various sequences are of great interest in determining the various biological properties of the virus. Viruses with different sequences have different infection preferences for specific cells, proliferation rate, virus production level, toxicity to cells, multinucleated giant cell formation rate, incubation and activation, and sensitivity to neutralizing antibodies. To date, studies on the association between these various biological properties and the development of AIDS show that viruses isolated from early patients usually do not form multinuclear giant cells (NSI; Nonsyncytia-Inducing) and prefer macrophages to infect them. However, as it progresses to the end of AIDS, Syncytia-Inducing capacity (SI) increases and it becomes a virus that infects and prefers helper T cells instead of macrophages. This suggests that the biological characteristics of HIV and disease development are not related.

One week after infection with HIV, the virus proliferates so that the virus can be easily detected in the patient's blood. This stage is called viremia. The virus diminishes rapidly, making it difficult to isolate within a week or two. This incubation period is maintained for a considerable period of time, then progresses to AIDS, the virus proliferates again and becomes viremia. As a result of recent studies using polymerase chain polymerization, there have been reports that the virus continues to be produced even during the incubation period. CD4 cells suddenly decrease in numbers during the initial viremia, then recover to a constant level as the virus proliferates (healthy people: 500-1000 CD4 cells / ㎣). Over the next few years, CD4 cells gradually decrease, dropping below 200 per kilogram of blood, leading to ARC (AIDS-related complex) or AIDS. In patients with AIDS, the likelihood of opportunistic infections increases, leading to death from pneumonia (Pneumocysitis carinii) pneumonia. It is known that the time when HIV was rapidly decreased and the time when CD8 cells were increased was increased. CD8 T cells are known to play a role in inhibiting cell growth or selecting and killing virus-infected cells. Thus, CD8 cells have been shown to exhibit significant immune effects against early infected viruses. Antibodies are produced after the virus has decreased in time. CD8 cells and antibodies continue to exist from the beginning of infection until the onset of AIDS, but have already lost or altered their function, and even promote viral infection. How the immune system, which had had a clear antiviral effect in the early stages of infection, loses its function is still a challenge to be solved. Because of the uniqueness of AIDS, which only affects humans, understanding the causes of HIV is a very rudimentary step. Although all scholars agree that the reduction of CD4 cells is a direct cause of immunodeficiency, there are many differences between how HIV reduces CD4 cells. Many of the theories include the formation of multinucleated giant cells, accumulation of uninserted viral DNA, effects on host cell membrane structure, abandon programmed cell death, secretion of toxic substances from infected cells, and cell destruction by autoimmunity. Presented. However, nothing has yet been proven to be true in vivo. Much research has been done on the pathogenesis of HIV using monkeys and the monkey AIDS virus SIV, but there are no significant new findings.

Currently, the most widely used AIDS therapy is AZT (Zidovudine), which inhibits the function of HIV reverse transcriptase, and its effects are most studied. However, when AZT was used early in the infection, the clinical condition was improved to some extent, but it did not affect the life of the patient. In other words, there are side effects such as toxicity to the bone marrow, the emergence of a virus resistant to long-term use, such as the limitation of the AIDS treatment revealed. FDA-approved DDI, DDC, and d4T as AZT-like drugs also developed resistant viruses, but the toxicity was less than that of AZT.

In addition, many methods have been developed to inhibit the growth of the virus is being validated. For example, how to inhibit virus conjugation to cells, select and kill only virus-infected cells, drugs that inhibit enzyme function important for virus growth (eg, proteases, integrases, tat inhibitors, rev inhibitors) ), Cytokine therapy, CD8 cell injection, gene therapy. Much progress has also been made in the development of vaccines for HIV. Method of using dead virus or attenuated virus which is live but lacking the ability to develop disease, using genetic engineering method to express specific protein of virus (subunit vaccine), anti-idiotype antibody, DNA gene There are many different developments, including direct injection. However, the fundamental problem of vaccine development is that the virus is too diverse. For example, when challenged with the original virus used for vaccine development after vaccination, the growth of the virus is inhibited by the antibody, but not when challenged with newly infected cells or viruses collected from the patient. Overcoming this variety of viruses remains a challenge.

Therefore, there is an urgent need to develop an AIDS therapeutic agent that can replace and overcome problems such as the side effects of the AIDS therapeutic agent and the emergence of resistant viruses.

The inventors of the present invention, while studying the AIDS therapeutic agent with less emergence of side effects and resistant virus, produced a novel thiourea or urea derivative, and confirmed that the thiourea or urea derivative prepared above had excellent HIV inhibitory activity and the present invention. Completed.

The present invention is to provide a novel thiourea or urea derivative, a preparation method thereof and a pharmaceutical composition for preventing or treating AIDS containing the same as an active ingredient.

Thiourea or urea derivatives according to the present invention can be usefully used for preventing or treating AIDS due to excellent HIV inhibitory activity by inhibiting HIV virus expression.

The present invention provides a thiourea or urea derivative represented by the following formula (1), or a pharmaceutically acceptable salt thereof.

[Formula 1]

In Formula 1,

A is -CH ₂ or -C (= O),

B is -C (= O) or -C (= S),

이며,R 1 is H, a halogen atom, C ₁ -C ₄ straight or branched alkyl, C ₁ -C ₄ straight or branched alkyl substituted or unsubstituted, C ₁ -C ₄ straight or branched alkoxy, C _6- Aryloxy of C ₂₀ , or

Is,

,

, 5,6,7,8-테트라히드로나프탈렌-1-일, (나프텔렌-2-일)-메틸,

, (피리딘-3-일)-메틸, 2-클로로-피리딘-4-일, 피라진-2-일, 퀴놀린-5-일, 퀴놀린-8-일, 4-히드록시-바이페닐-3-일, 또는 R2 및 R3가 서로 연결되어 고리가 형성된

또는

이고,R2 and R3 are each independently the same or different and are H, C ₁ -C ₄ straight or branched alkyl, C ₃ -C ₈ cycloalkyl,-(C ₂ -C ₆ straight or branched alkyl) -N- ( C ₁ -C ₂ alkyl) ₂ ,-(C ₁ -C ₄ straight or branched alkyl) -NH- (C ₁ -C ₄ straight or branched alkyl),

,

, 5,6,7,8-tetrahydronaphthalen-1-yl, (naphthylene-2-yl) -methyl,

, (Pyridin-3-yl) -methyl, 2-chloro-pyridin-4-yl, pyrazin-2-yl, quinolin-5-yl, quinolin-8-yl, 4-hydroxy-biphenyl-3-yl Or R2 and R3 are linked to each other to form a ring

or

ego,

n is 0 or an integer of 1 to 4,

m is an integer of 0, 1 or 2,

X is H, C ₁ -C ₄ straight or branched alkyl, C ₆ -C ₂₀ aryl, hydroxy or halogen atom,

Y is H or hydroxy,

인 경우를 제외하며,Provided that when A is -C (= O), B is -C (= S), and R1 is H, then R2 is H, and R3 is -CH ₂ -C (CH ₃ ) ₂ -CH ₂ -N- ( Except for CH ₃ ) ₂ ,-(CH ₂ ) ₃ -N- (CH ₃ ) ₂ , phenyl, 4-methyl-benzyl, 4-chloro-benzyl, or (pyridin-2-yl) -ethyl, In addition, R2 is not H, but is linked to R3 to form a ring.

Except when

When A is -C (= 0), B is -C (= S), and R1 is tert-butyl, except when R2 is H and R3 is phenyl or (pyridin-2-yl) -methyl,

If A is -C (= O), B is -C (= S), and R1 is methyl, then R2 is H and R3 is phenyl or pyridin-2-yl,

When A is -C (= 0), B is -C (= S), and R1 is Cl, except when R2 is H and R3 is cyclohexyl and naphthalene,

If A is -C (= 0), B is -C (= 0), and R1 is H, then R2 is H and R3 is benzyl.

Preferably, in Chemical Formula 1,

이며,R 1 is H, Cl, methyl, tert-butyl, phenyl, (tert-butyl) -phenyl, isopropoxy, phenoxy, or

Is,

, 나프탈렌-1-일, 5-히드록시-나프탈렌-1-일, 7-히드록시-나프탈렌-1-일, 5,6,7,8-테트라히드로나프탈렌-1-일, 피리딘-2-일, (피리딘-2-일)-메틸, (피리딘-2-일)-에틸, (피리딘-3-일)-메틸, 2-클로로-피리딘-4-일, 피라진-2-일, 퀴놀린-5-일, 퀴놀린-8-일, 4-히드록시-바이페닐-3-일, 또는 R2 및 R3가 서로 연결되어 고리가 형성된

또는

이고,R2 and R3 are each independently the same or different, H, methyl, cyclohexyl, -CH ₂ CH ₂ -N- (CH ₃ ) ₂ , -CH ₂ CH ₂ CH ₂ -N- (CH ₃ ) ₂ , -CH ₂ -C (CH ₃ ) ₂ -CH ₂ -N- (CH ₃ ) ₂ , -CH ₂ CH ₂ -N- (CH ₂ CH ₃ ) ₂ , -CH (CH ₃ ) CH ₂ CH ₂ CH ₂ -N -(CH ₂ CH ₃ ) ₂ ,-(CH ₂ ) ₃ -NH- (CH ₂ CH ₂ CH ₃ ),

, Naphthalen-1-yl, 5-hydroxy-naphthalen-1-yl, 7-hydroxy-naphthalen-1-yl, 5,6,7,8-tetrahydronaphthalen-1-yl, pyridin-2-yl , (Pyridin-2-yl) -methyl, (pyridin-2-yl) -ethyl, (pyridin-3-yl) -methyl, 2-chloro-pyridin-4-yl, pyrazin-2-yl, quinoline-5 -Yl, quinolin-8-yl, 4-hydroxy-biphenyl-3-yl, or R2 and R3 are linked together to form a ring

or

ego,

n is 0 or an integer of 1 to 4,

X is H, methyl, tert-butyl, phenyl, hydroxy, F, Cl or Br.

Preferred examples of the compound of formula 1 according to the present invention include the following compounds:

1- (4-tert-butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-dimethylamino-propyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-dimethylamino-propyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),

4-tert-butyl-N- (4-ethyl-piperazine-1-carbothioyl) -benzoamide

(4-tert-Butyl-N- (4-ethyl-piperazine-1-carbothioyl) -benzamide),

3- (4-tert-butyl-benzoyl) -1- (2-diethylamino-ethyl) -1-methyl-thiourea

(3- (4-tert-Butyl-benzoyl) -1- (2-diethylamino-ethyl) -1-methyl-thiourea),

3- (4-tert-butyl-benzoyl) -1- (2-dimethylamino-ethyl) -1-methyl-thiourea

(3- (4-tert-Butyl-benzoyl) -1- (2-dimethylamino-ethyl) -1-methyl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (4-diethylamino-1-methyl-butyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-diethylamino-1-methyl-butyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (4-methyl-benzyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-methyl-benzyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (2-methyl-benzyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (2-methyl-benzyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-propylamino-propyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-propylamino-propyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3-phenethyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-phenethyl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (4-chloro-benzyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-chloro-benzyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-chloro-benzyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-chloro-benzyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3-naphthalen-2-ylmethyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-naphthalen-2-ylmethyl-thiourea),

4-tert-butyl-N- [4- (4-fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide

(4-tert-Butyl-N- [4- (4-fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide),

1- (4-tert-butyl-benzoyl) -3-cyclohexyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-cyclohexyl-thiourea),

1-benzoyl-3-naphthalen-2-ylmethyl-thiourea

(1-Benzoyl-3-naphthalen-2-ylmethyl-thiourea),

1-benzoyl-3- (4-diethylamino-1-methyl-butyl) -thiourea

(1-Benzoyl-3- (4-diethylamino-1-methyl-butyl) -thiourea),

3-benzoyl-1- (2-diethylamino-ethyl) -1-methyl-thiourea

(3-Benzoyl-1- (2-diethylamino-ethyl) -1-methyl-thiourea),

N- (4-Ethyl-piperazine-1-carbosanyl) -4-methyl-benzamide

(N- (4-Ethyl-piperazine-1-carbothioyl) -4-methyl-benzamide),

1-cyclohexyl-3- (4-methyl-benzoyl) -thiourea

(1-Cyclohexyl-3- (4-methyl-benzoyl) -thiourea),

1- (4-Chloro-benzyl) -3- (4-methyl-benzoyl) -thiourea

(1- (4-Chloro-benzyl) -3- (4-methyl-benzoyl) -thiourea),

1- (3-dimethylamino-propyl) -3- (4-methyl-benzoyl) -thiourea

(1- (3-Dimethylamino-propyl) -3- (4-methyl-benzoyl) -thiourea),

1- (4-Methyl-benzoyl) -3- (3-methyl-benzyl) -thiourea

(1- (4-Methyl-benzoyl) -3- (3-methyl-benzyl) -thiourea),

1- (4-Methyl-benzoyl) -3- (4-methyl-phenyl-butyl) -thiourea

(1- (4-Methyl-benzoyl) -3- (4-phenyl-butyl) -thiourea),

1- (4-Methyl-benzoyl) -3- (3-phenyl-propyl) -thiourea

(1- (4-Methyl-benzoyl) -3- (3-phenyl-propyl) -thiourea),

1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -thiourea

(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -thiourea),

1-benzoyl-3- [2- (4-fluoro-phenyl) -ethyl] -thiourea

(1-Benzoyl-3- [2- (4-fluoro-phenyl) -ethyl] -thiourea),

1- (4-Methyl-benzoyl) -3-pyridin-3-ylmethyl-thiourea

(1- (4-Methyl-benzoyl) -3-pyridin-3-ylmethyl-thiourea),

1- (4-Methyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea

(1- (4-Methyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea),

1- [2- (3-Bromo-phenyl) -ethyl] -3- (4-methyl-benzoyl) -thiourea

(1- [2- (3-Bromo-phenyl) -ethyl] -3- (4-methyl-benzoyl) -thiourea),

1- (4-Methyl-benzoyl) -3- (2-pyridin-2-yl-ethyl) -thiourea

(1- (4-Methyl-benzoyl) -3- (2-pyridin-2-yl-ethyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3-pyridin-2-yl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-pyridin-2-yl-thiourea)

1- (4-Chloro-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea

(1- (4-Chloro-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),

1- (4-Chloro-benzoyl) -3-naphthalen-2-ylmethyl-thiourea

(1- (4-Chloro-benzoyl) -3-naphthalen-2-ylmethyl-thiourea),

1- (4-Chloro-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea

(1- (4-Chloro-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea),

1- (4-phenoxy-benzoyl) -3-pyridin-2-yl-thiourea

(1- (4-Phenoxy-benzoyl) -3-pyridin-2-yl-thiourea),

1- (biphenyl-4-carbonyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea

(1- (Biphenyl-4-carbonyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),

1- (4'-tert-butyl-biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea

(1- (4'-tert-Butyl-biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea),

1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (naphthalene-2-carbonyl) -thiourea

(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (naphthalene-2-carbonyl) -thiourea),

1- (biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea

(1- (Biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (5,6,7,8-tetrahydro-naphthalen-1-yl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (5,6,7,8-tetrahydro-naphthalen-1-yl) -thiourea),

1- (4-tert-butyl-benzoyl) -3-quinolin-5-yl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-quinolin-5-yl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (4-tert-butyl-phenyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-tert-butyl-phenyl) -thiourea),

1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-isopropoxy-benzoyl) -thiourea

(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-isopropoxy-benzoyl) -thiourea),

1- (4-isopropoxy-benzoyl) -3-naphthalen-1-yl-thiourea

(1- (4-Isopropoxy-benzoyl) -3-naphthalen-1-yl-thiourea),

1- (5-hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea

(1- (5-Hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea),

1- (4-isopropoxy-benzoyl) -3-pyridin-2-yl-thiourea

(1- (4-Isopropoxy-benzoyl) -3-pyridin-2-yl-thiourea),

1- (4-isopropoxy-benzoyl) -3-m-tolyl-thiourea

(1- (4-Isopropoxy-benzoyl) -3-m-tolyl-thiourea),

1- (4-tert-butyl-benzoyl) -3 (-4-phenyl-butyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-phenyl-butyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-phenyl-propyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-phenyl-propyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- [2- (2-chloro-phenyl) -ethyl] -thiourea

(1- (4-tert-Butyl-benzoyl) -3- [2- (2-chloro-phenyl) -ethyl] -thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-methyl-benzyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-methyl-benzyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3-quinolin-8-yl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-quinolin-8-yl-thiourea),

1- (4-tert-butyl-benzoyl) -3-pyrazin-2-yl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-pyrazin-2-yl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-hydroxy-phenyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-hydroxy-phenyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (7-hydroxy-naphthalen-1-yl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (7-hydroxy-naphthalen-1-yl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (2-chloro-pyridin-4-yl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (2-chloro-pyridin-4-yl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (4-hydroxy-biphenyl-3-yl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-hydroxy-biphenyl-3-yl) -thiourea),

1-biphenyl-3-yl-3- (4-tert-butyl-benzoyl) -thiourea

(1-Biphenyl-3-yl-3- (4-tert-butyl-benzoyl) -thiourea),

1- (2-Fluoro-phenyl) -3- (4-isopropoxy-benzoyl) -thiourea

(1- (2-Fluoro-phenyl) -3- (4-isopropoxy-benzoyl) -thiourea),

1- (4-tert-butylphenyl) -3- (4-isopropoxy-benzoyl) -thiourea

(1- (4-tert-Butyl-phenyl) -3- (4-isopropoxy-benzoyl) -thiourea),

1- (biphenyl-3-yl-3- (4-isopropoxy-benzoyl) -thiourea

(1-Biphenyl-3-yl-3- (4-isopropoxy-benzoyl) -thiourea),

1- (7-hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea

(1- (7-Hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea),

1- (4-tert-butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea

(1- (4-tert-Butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea),

1- (4-tert-butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -urea

(1- (4-tert-Butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -urea),

1- (4-tert-butyl-benzyl) -3-cyclohexyl-urea

(1- (4-tert-Butyl-benzyl) -3-cyclohexyl-urea),

1- (4-tert-butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -urea

(1- (4-tert-Butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -urea),

1- (4-tert-butyl-benzoyl) -3-pyridin-2-yl-urea

(1- (4-tert-Butyl-benzoyl) -3-pyridin-2-yl-urea),

1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -urea

(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -urea),

1-cyclohexyl-3- (4-methyl-benzoyl) -urea

(1-Cyclohexyl-3- (4-methyl-benzoyl) -urea),

1- (4-Methyl-benzoyl) -3-naphthalen-2-ylmethyl-urea

(1- (4-Methyl-benzoyl) -3-naphthalen-2-ylmethyl-urea),

1-benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -urea

(1-Benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -urea),

3-benzoyl-1- (2-dimethylamino-ethyl) -1-methyl-urea

(3-Benzoyl-1- (2-dimethylamino-ethyl) -1-methyl-urea),

1-benzoyl-3-phenyl-thiourea

(1-Benzoyl-3-phenyl-thiourea),

1- (4-tert-butyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea),

1- (4-tert-butyl-benzoyl) -3-pyridin-4-ylmethyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-pyridin-4-ylmethyl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (4-hydroxy-phenyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (4-hydroxy-phenyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3- (5-hydroxy-naphthalen-2-yl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (5-hydroxy-naphthalen-2-yl) -thiourea).

Thiourea or urea derivatives of Formula 1 of the present invention may be prepared with pharmaceutically acceptable salts and solvates according to methods conventional in the art.

As the pharmaceutically acceptable salt, acid addition salts formed by free acid are useful. Acid addition salts are prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and acid or alcohol (eg, glycol monomethylether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.

Organic acids and inorganic acids may be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. may be used as the inorganic acid, and methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid, etc. , Citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, Galacturonic acid, glutamic acid, glutaric acid (glutaric acid), glucuronic acid (glucuronic acid), aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid and the like can be used.

Bases may also be used to prepare pharmaceutically acceptable metal salts. An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable to prepare sodium, potassium or calcium salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

Pharmaceutically acceptable salts of the thiourea or urea derivatives of the invention include salts of acidic or basic groups which may be present in the thiourea or urea derivative, unless otherwise specified. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate, dihydrogen Phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p -toluenesulfonate (tosylate) salts. It can be prepared through.

In addition, the present invention provides a method for preparing a thiourea or urea derivative of the formula (1), represented by Schemes 1-5.

When A is -C (= O) and B is -C (= S) in the compound of Formula 1, the method for preparing a thiourea or urea derivative of Formula 1 of the present invention,

1) preparing a compound of formula 3 by reacting a carboxylic acid compound of formula 2 with oxalyl chloride in an organic solvent,

2) preparing a compound of formula 4 by reacting the compound of formula 3 prepared in step 1) with potassium thiocyanate (KSCN) in an organic solvent, and

3) reacting the compound of Formula 4 prepared in step 2) with an amine compound of Formula 5 under an organic solvent to prepare a compound of Formula 1-1, and is represented by the following Scheme 1.

Scheme 1

In Scheme 1, R1, R2 and R3 are as defined in Formula 1.

In addition, when A is -CH ₂ and B is -C (= S) in the compound of Formula 1,

In the method for preparing a thiourea or urea derivative of formula (I) of the present invention, the amine compound of formula (5) is stirred with sodium hydrogen carbonate in an organic solvent, and then reacted with thiophosphene and the amine compound of formula (6) to To prepare a compound, it is represented by the following scheme 2.

Scheme 2

In Scheme 2, R1, R2 and R3 are as defined in the formula (1).

In addition, when A is -CH ₂ and B is -C (= O) in the compound of Formula 1, the method for preparing a thiourea or urea derivative of Formula 1 according to the present invention is an organic solvent After stirring with sodium hydrogen carbonate under the following reaction, it is reacted with phosgene and an amine compound of formula 6 to prepare a compound of formula 1-3, and is represented by the following scheme 3.

Scheme 3

In Scheme 3, R1, R2 and R3 are as defined in Formula 1.

In addition, when A is -C (= O) and B is -C (= O) in the compound of Formula 1, the method for preparing a thiourea or urea derivative of Formula 1 of the present invention,

1) preparing a compound of Chemical Formula 7 by reacting a carboxylic acid compound of Chemical Formula 2 with 1,1′-carbonyldiimidazole under an organic solvent, and

2) stirring the amine compound of formula 5 with sodium hydrogen carbonate in an organic solvent, and then reacting with phosgene and the compound of formula 7 prepared in step 1) to prepare a compound of formula 1-4. It is represented by Scheme 4 below.

Scheme 4

In Scheme 4, R1, R2 and R3 are as defined in the formula (1).

In addition, when A is -C (= O) and B is -C (= O) in the compound of Formula 1, another method for preparing a thiourea or urea derivative of Formula 1 of the present invention is

1) preparing a compound of formula 3 by reacting a carboxylic acid compound of formula 2 with oxalyl chloride in an organic solvent, and

2) preparing a compound of formula 1-4 by reacting the compound of formula 3 prepared in step 1) with tin chloride (SnCl ₄ ), sodium cyanate (NaOCN) and an amine compound of formula 5 in an organic solvent It consists of, and is represented by the following Scheme 5.

Scheme 5

In Scheme 5, R1, R2 and R3 are as defined in Formula 1.

The organic solvent used in Schemes 1 to 5 includes one or more selected from the group consisting of methylene chloride, acetonitrile, tetrahydrofuran and toluene, but is not limited thereto.

In another aspect, the present invention provides a pharmaceutical composition for preventing or treating AIDS comprising the following compounds in the compound of Formula 1:

N- [4- (4-Fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide

(N- [4- (4-Fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide),

1- (4-tert-butyl-benzoyl) -3-naphthalen-1-yl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-naphthalen-1-yl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (3-chloro-phenyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (3-chloro-phenyl) -thiourea),

1- (4-Methyl-benzoyl) -3-naphthalen-1-yl-thiourea

(1- (4-Methyl-benzoyl) -3-naphthalen-1-yl-thiourea),

1- (4-tert-butyl-benzoyl) -3-naphthalen-1-yl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-naphthalen-1-yl-thiourea),

1- (4-tert-butyl-benzoyl) -3-m-tolyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-m-tolyl-thiourea),

1- (4-tert-butyl-benzoyl) -3- (2-fluoro-phenyl) -thiourea

(1- (4-tert-Butyl-benzoyl) -3- (2-fluoro-phenyl) -thiourea),

4-tert-butyl-N- (4-methyl-piperazine-1-carbothioyl) -benzamide

(4-tert-Butyl-N- (4-methyl-piperazine-1-carbothioyl) -benzamide),

1-benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea

(1-Benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),

1-benzoyl-3- (4-methyl-benzyl) -thiourea

(1-Benzoyl-3- (4-methyl-benzyl) -thiourea),

1-benzoyl-3- (3-dimethylamino-propyl) -thiourea

(1-Benzoyl-3- (3-dimethylamino-propyl) -thiourea),

N- (4-Ethyl-piperazine-1-carbosanyl) -benzamide

(N- (4-Ethyl-piperazine-1-carbothioyl) -benzamide),

1-benzoyl-3- (4-chloro-benzyl) -thiourea

(1-Benzoyl-3- (4-chloro-benzyl) -thiourea),

1-benzoyl-3- (2-pyridin-2-yl-ethyl) -thiourea

(1-Benzoyl-3- (2-pyridin-2-yl-ethyl) -thiourea),

1- (4-tert-butyl-benzoyl) -3-phenyl-thiourea

(1- (4-tert-Butyl-benzoyl) -3-phenyl-thiourea),

1- (4-Methyl-benzoyl) -3-pyridin-2-yl-thiourea

(1- (4-Methyl-benzoyl) -3-pyridin-2-yl-thiourea),

1- (4-Methyl-benzoyl) -3-phenyl-thiourea

(1- (4-Methyl-benzoyl) -3-phenyl-thiourea),

1- (4-Chloro-benzoyl) -3-cyclohexyl-thiourea

(1- (4-Chloro-benzoyl) -3-cyclohexyl-thiourea),

1- (4-Chloro-benzoyl) -3-naphthalen-1-yl-thiourea

(1- (4-Chloro-benzoyl) -3-naphthalen-1-yl-thiourea),

1-benzoyl-3-benzyl-urea

(1-Benzoyl-3-benzyl-urea).

Thiourea or urea derivatives according to the present invention have excellent HIV inhibitory activity by inhibiting HIV virus expression. Therefore, thiourea or urea derivatives according to the present invention can be usefully used for preventing or treating AIDS.

The composition of the present invention may contain one or more known active ingredients having HIV inhibitory activity together with thiourea or urea derivatives.

The composition of the present invention may further comprise at least one pharmaceutically acceptable carrier in addition to the above-described effective ingredients for administration. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, as an antioxidant, buffer And other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.

The composition of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and the dosage is based on the weight, age, sex and health of the patient. The range varies depending on the diet, the time of administration, the method of administration, the rate of excretion and the severity of the disease. The daily dosage of the thiourea or urea derivative is about 0.1 to 50 mg / kg, preferably about 2 to 10 mg / kg, and more preferably administered once to several times a day.

The composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug treatment and biological response modifiers for the prevention and treatment of AIDS.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

Example  One  : 1- (4- according to Scheme 1 tert Butyl Benzoyl ) -3- (5-hydroxy-naphthalen-1-yl)- Thiourea  Produce

1. 4- ( tert -Butyl)- Benzoyl  Preparation of Chloride

Methylene chloride (28 mL, 0.1 M) and 2M oxalyl chloride (4.2 mL, 8.4 mmol) were added to 4- (tert-butyl) -benzoic acid (0.5 g, 2.80 mmol) at room temperature, and dimethylformamide was added in 2 to 3 After dropping, the mixture was stirred at 70 ° C for 6 hours. The reaction mixture was concentrated under reduced pressure to give the title compound.

2. 4- ( tert -Butyl)- Benzoyl  Preparation of Isothiocyanate

Acetonitrile (24 mL, 0.2 M) and potassium thiocyanate (1.08 g, 11.2 mmol) were added to 4- (tert-butyl) -benzoyl chloride prepared in 1 above at room temperature, followed by stirring at 70 ° C. for 12 hours. The reaction mixture was cooled to room temperature, filtered to remove salts, and then concentrated under reduced pressure to obtain the title compound.

3. 1- (4- tert Butyl Benzoyl ) -3- (5-hydroxy-naphthalen-1-yl)- Thiourea  Produce

At room temperature, acetonitrile (24 mL, 0.2 M) and 5-amino-naphthalen-1-ol (0.89 g, 5.60 mmol) were added and refluxed to 4- (tert-butyl) -benzoyl isothiocyanate prepared in 2 above. I was. The reaction mixture was filtered to remove salts and then concentrated under reduced pressure. Methylene chloride was added thereto, the resulting salt was once more removed, and then concentrated under reduced pressure. The product thus obtained was purified by silica gel column chromatography to obtain 0.37 g (yield: 36.43%) of the title compound.

¹ H NMR (500 MHz, CDCl ₃ ): 12.78 (s, 1 H), 9.27 (s, 1 H), 8.23 (d, J = 8.5 Hz, 1 H), 8.08 (d, J = 8.0 Hz, 1H), 7.91 ( d, J = 8.5 Hz, 2H), 7.63-7.55 (m, J = 4H), 7.40 (t, J = 8.5 Hz, 1H), 6.88 (d, J = 7.0 Hz, 1H), 1.39 (s, 9H )

LC-MS (M ⁺ H): 379

Example  2 ~ 73  :

In the same manner as described in Example 1, the compounds of Examples 2 to 73 were prepared. Structural formulas, MS data and ¹ H NMR data of the compounds of Examples 2 to 73 prepared above are shown in Tables 1 to 9.

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 2

322

3

350

4

334

5

350

6

322

7

378

8

341

9

341

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 10

336

11

341

12

361

13

361

14

377 15

400

16

319 17

345

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 18

321

19

319

20

322

21

344

22

294 23

292

24

277

25

319

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 26

280

27

299

28

327

29

313

30

308

31

303

32

286

33

286

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 34

377

35

3 00

36

363

37

314 38

347

39

321

40

328 41

355

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 42

357 43

350

44

370

45

423

46

344

47

367

48

363

49

367

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 50

364

51

369

52

352

53

365

54

381

55

316

56

329

57

369

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 58

355 59

375 60

341

61

364 62

327

63

315

64

329

65

379

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 66

348

67

415 68

389 69

331

70

333

71

371

72

391

73

391

Example  74  : 1- (4- according to Scheme 2 tert -Butyl-benzyl) -3- (5-hydroxy-naphthalene-1-

Methylene chloride (31.4 mL, 0.1 M) and sodium bicarbonate (2.64 g, 31.4 mmol) were added to 5-amino-naphthalen-1-ol (0.5 g, 3.14 mmol) at room temperature and stirred at 0 ° C. for 15 minutes. Thiophosgene (1.20 mL, 15.71 mmol) was added to the reaction mixture and stirred for 2 hours. 4-tert-butyl-benzylamine (0.60 ml, 3.45 mmol) was then added to the reaction mixture, which was stirred for 6 hours at room temperature. The product was concentrated under reduced pressure and purified by silica gel column chromatography to give 65 mg (yield: 5.73%) of the title compound.

¹ H NMR (500 MHz, CDCl ₃ ): 12.92 (s, 1H), 10.59 (s, 1H), 7.65 (d, J = 8.5 Hz, 1H), 7.48-7.45 (m, 2H), 7.36-7.32 (m , 2H), 7.23 (s, 1H), 7.17 (d, J = 8.0Hz, 1H), 6.89 (s, 1H), 6.84 (d, J = 8.0Hz, 1H), 6.69 (s, 1H), 4.63 (s, 1H), 4.56 (s, 2H), 1.33 (s, 9H)

LC-MS (M ⁺ H): 365

Example  75  : 1- (4- according to Scheme 3 tert -Butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl)- Urea  Produce

Methylene chloride (31.4 mL, 0.1 M) and sodium bicarbonate (2.64 g, 31.4 mmol) were added to 5-amino-naphthalen-1-ol (0.5 g, 3.14 mmol) at room temperature and stirred at 0 ° C. for 15 minutes. Phosgene (8.26 mL, 15.71 mmol) was added to the reaction mixture and stirred for 2 hours. 4-tert-butyl-benzylamine (0.60 ml, 3.45 mmol) was then added to the reaction mixture, which was stirred for 6 hours at room temperature. The product was concentrated under reduced pressure and purified by silica gel column chromatography to give 157 mg (yield: 14.33%) of the title compound.

¹ H NMR (500 MHz, CDCl ₃ ): 8.17 (d, J = 9.0 Hz, 1H), 7.53 (s, 2H), 7.48 (s, 1H), 7.37-7.32 (m, 2H), 7.17 (d, J = 7.5 Hz, 2H), 6.88 (d, J = 7.0 Hz, 1H), 4.43 (s, 2H), 4.14 (d, J = 7.5 Hz, 2H), 1.37-1.26 (m, 9H)

LC-MS (M ⁺ H): 349

Examples 76-77  :

In the same manner as described in Example 75, the compound of Examples 76 to 77 was prepared. Structural formulas, MS data, and ¹ H NMR data of the compounds prepared in Examples 76 to 77 are shown in Table 10.

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 76

317 77

289

Example  78  : 1- (4- according to Scheme 4 tert Butyl Benzoyl ) -3- (5-hydroxy-naphthalen-1-yl)- Urea  Produce

4- tert Butyl Benzoamide  Produce

Tetrahydrofuran (224.4 mL, 0.05 M) and 1,1'-carbonyldiimidazole (2 g, 12.34 mmol) were added to 4-tert-butyl-benzoic acid (2 g, 11.22 mmol) at room temperature, followed by stirring for 12 hours. 28% ammonia water (56.1 mL, 0.2 M) was added to the reaction mixture, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was separated from the water layer and the organic layer to obtain an organic layer. The organic layer was dried over magnesium sulfate and distilled under reduced pressure. The obtained product was purified by silica gel column chromatography to obtain the title compound.

2. 1- (4- tert Butyl Benzoyl ) -3- (5-hydroxy-naphthalen-1-yl)- Urea  Produce

Methylene chloride (10.46 mL, 0.3 M) and sodium hydrogen carbonate (0.97 g, 31.4 mmol) were added to 5-amino-naphthalen-1-ol (0.5 g, 3.14 mmol) at room temperature and stirred at 0 ° C. for 15 minutes. Phosgene (8.26 mL, 15.71 mmol) was added to the reaction mixture and stirred for 2 hours. Then, 4-tert-butyl-benzoamide (0.61 g, 3.45 mmol) prepared in 1 was added to the reaction mixture, followed by stirring at room temperature for 6 hours. The product was concentrated under reduced pressure, and then purified by silica gel column chromatography to obtain 120 mg (yield: 10.51%) of the title compound.

¹ H NMR (500 MHz, DMSO): 11.54 (s, 1H), 11.14 (s, 1H), 10.28 (s, 1H), 8.17-7.87 (m, 3H), 7.59-7.47 (m, 5H), 6.96 ( s, 1H), 4.14 (t, J = 6.8 Hz, 1H), 1.33 (s, 9H)

Example  79  : 1- (4- according to Scheme 5 tert Butyl Benzoyl ) -3-pyridin-2-yl- Urea  Produce

1. 4- ( tert -Butyl)- Benzoyl  Preparation of Chloride

Methylene chloride (112.2 mL, 0.1 M) and 2M oxalyl chloride (16.8 mL, 33.6 mmol) were added to 4- (tert-butyl) -benzoic acid (2 g, 11.22 mmol) at room temperature, and 2-3 drops of dimethylformamide were added. After dropping, the mixture was stirred at 70 ° C for 6 hours. The reaction mixture was concentrated under reduced pressure to give the title compound.

2. 1- (4- tert Butyl Benzoyl ) -3- (pyridin-2-yl)- Urea  Produce

Acetonitrile (22.44 mL, 0.5 M) and toluene (22.44 mL, 0.5 M) were added to 4- (tert-butyl) -benzoyl chloride prepared in 1, followed by mixing, 1 M tin chloride (SnCl ₄ ) (0.56 mL). , 0.56 mmol) and sodium cyanate (NaOCN) (0.88 g, 13.46 mmol) were added and refluxed for 8 hours. After distilling the reaction mixture under reduced pressure, 2-aminopyridine (1.06 g, 11.22 mmol) was added thereto and stirred at room temperature for 2 hours. The reaction mixture was separated from the water layer and the organic layer to obtain an organic layer. The organic layer was dried over magnesium sulfate and distilled under reduced pressure. The obtained primary compound was purified by silica gel column chromatography to give 66 mg (yield: 3.92%) of the title compound.

¹ H NMR (500 MHz, CDCl ₃ ): 11.36 (s, 1H), 8.92 (s, 1H), 8.39-8.37 (m, 1H), 8.13 (d, J = 8.0Mz, 1H), 7.93 (d, J = 9.0Mz, 3H), 7.75-7.71 (m, 1H), 7.56-7.54 (m, 3H), 7.10-7.08 (m, 1H)

LC-MS (M ⁺ H): 298

Example  80-84  :

In the same manner as described in Example 78, the compounds of Examples 80 to 84 were prepared. Structural formulas, MS data and ¹ H NMR data of the compounds of Examples 80 to 84 prepared above are shown in Table 11.

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 80

292

81

283

82

341

83

278

84

250

Examples 85-99  :

The structural formulas, MS data and ¹ H NMR data of the compounds of Examples 85 to 99 are shown in Table 12.

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 85

320

86

294

87

285

88

266 89

278

90

305

91

257

92

286

93

313

94

328

95

328 96

272

97

271

98

297

99

341

Example  100  :

The compound of Example 94 was prepared by the same method as described in Example 78 (Scheme 4). The structural formula, MS data and ¹ H NMR data of the compound of Example 100 prepared above are shown in Table 13.

Example rescue LC-MS
(M ⁺ H) ¹ H NMR 100

277

Experimental Example  One  : ≪ / RTI & Thiourea  or Urea  Derivative HIV  Measurement of inhibitory activity

In order to confirm the HIV inhibitory activity of the thiourea or urea derivative of the present invention, the following experiment was performed.

One. HIV  Virus preparation

PNL4-3 vector expressing the HIV genome was transduced into 293FT cells. The HIV genome of pNL4-3 is not infected by the human body because the EGFP gene is substituted at the nef position. 293FT cells of about 3.0 × 10 ⁵ in 6-well plates were inoculated in DMEM containing 10% FBS without antibiotics and incubated for 48 hours. 90 ~ 95% of confluency was shown during transduction.

DNA (pNL4-3) was added to 250 μl of Opti-MEM I (GIBCO ^{™ ,} USA) medium at a low serum medium to a final concentration of 10 ng / ml, and 4 μl of 250 μl of Opti-MEM I (GIBCO ^™ ) medium. Lipofectamine 2000 (lipofectamine ^TM 2000, Invitrogen, USA). After 5 minutes at room temperature, DNA (pNL4-3) and lipofectamine were mixed 1: 2 and reacted at room temperature for 20 minutes. Subsequently, the culture medium was removed from the cell culture solution prepared above, followed by incubation for 4 hours in a carbon dioxide cell incubator with the addition of the DNA-lipopeptamine complex. Then, incubated again for 48 hours. After the culture containing HIV was recovered by centrifugation at 1,500 rpm for 5 minutes, the virus supernatant was obtained.

MT-4 cells were inoculated at 1.0 × 10 ⁶ cells / ml in RPMI cultures containing 10% FBS in 6-well plates, and virus supernatants obtained above were infected at a 1: 1 ratio after 4 hours of incubation. After 48 hours of incubation in a carbon dioxide cell incubator, the cells were replaced with fresh medium and incubated again for 72 hours. The amplified virus supernatant was then collected by centrifugation at 1500 rpm for 5 minutes and virus concentration was measured using the Virononstika HIV-1 Antigen Microelisa system kit (bioMerieux, Inc. Netherland).

2. HIV  Measurement of inhibitory activity

The thiourea or urea derivatives prepared in Examples 1 to 94 were dissolved in DMSO, prepared as 10 mM or 20 mM stock solutions, and stored at -20 ° C. The stock solution thus prepared was diluted with DMSO to make a starting concentration of 200 μM and used for the experiment.

In a 24-well plate, 4 × 10 ⁵ MT-4 cells were suspended in 200 μl of RPMI1640 (Gibco, 10% FBS) medium and infected with 200 μl of 200,000 pg / ml virus solution to a total volume of 400 μl. . 200 μM stock solution or stock solution was treated with 2 μl of thiourea or urea derivatives, each diluted 10-fold with DMSO, to a final concentration of 1 μM or lower. 10 μM AZT (azidothymidine, sigma, USA) was used as a positive control to a final concentration of 50 nM and DMSO as a negative control was used to a final concentration of 0.5%. After 48 hours of incubation in a carbon dioxide cell incubator (37 ° C., 5% CO ₂ ), the cells were replaced with fresh RPMI1640 cultures treated with thiourea or urea derivatives with a final concentration of 1 μM and incubated for another 48 hours. Each cell and virus soup was centrifuged at 1500 rpm for 5 minutes and once more at 13000 rpm for 5 minutes to remove cell residue. The resulting virus was measured for concentration by ELISA for p24 antigen using Virononstika HIV-1 Antigen Microelisa sytem kit (bioMerieux, Inc. Netherland) to determine the HIV inhibitory activity of thiourea or urea derivatives.

The HIV inhibitory activity concentration (μM) of the thiourea or urea derivative of the present invention is shown in Table 14.

Example HIV inhibitory activity concentration (μM) One 0.03 16 0.5 37 0.5 38 0.3 50 1.0 Positive control group (AZT) 0.005

As shown in Table 6, it was confirmed that the thiourea or urea derivative of the present invention has excellent HIV inhibitory activity.

Examples of formulations for the composition of the present invention are illustrated below.

Formulation example  One  : Sanje  Produce

0.1 g thiourea or urea derivative of the present invention

Lactose 1.5 g

Talc 0.5 g

The above ingredients were mixed and filled in an airtight container to prepare powders.

Formulation Example 2  : Preparation of Tablet

0.1 g thiourea or urea derivative of the present invention

Lactose 7.9 g

1.5 g of crystalline cellulose

0.5 g of magnesium stearate

After mixing the above components, a tablet was prepared by a direct tableting method.

Formulation Example 3 : Preparation of Capsule

0.1 g thiourea or urea derivative of the present invention

5 g of corn starch

4.9 g of carboxy cellulose

After the powder was prepared by mixing the above components, the powder was filled in a hard capsule according to the conventional method for preparing a capsule to prepare a capsule.

Formulation Example 4  : Preparation of Injection

0.1 g thiourea or urea derivative of the present invention

Appropriate sterile distilled water for injection

pH adjuster

Stabilizer

According to the conventional method for preparing an injection, the amount of the above-mentioned ingredient was prepared per ampoule (2 ml).

Formulation Example 5  : Manufacture of liquid

0.1 g thiourea or urea derivative of the present invention

10 g of isomerized sugar

5 g of mannitol

Purified water

Each component was dissolved in purified water in accordance with a conventional method for producing a liquid agent, and the lemon flavor was added in an appropriate amount, followed by mixing the above components. Then, purified water was added thereto to adjust the total volume to 100 ml, and then filled in a brown bottle and sterilized to prepare a liquid.

Claims (3)

1- (4-tert-butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-dimethylamino-propyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-dimethylamino-propyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),
4-tert-butyl-N- (4-ethyl-piperazine-1-carbothioyl) -benzoamide
(4-tert-Butyl-N- (4-ethyl-piperazine-1-carbothioyl) -benzamide),
3- (4-tert-butyl-benzoyl) -1- (2-diethylamino-ethyl) -1-methyl-thiourea
(3- (4-tert-Butyl-benzoyl) -1- (2-diethylamino-ethyl) -1-methyl-thiourea),
3- (4-tert-butyl-benzoyl) -1- (2-dimethylamino-ethyl) -1-methyl-thiourea
(3- (4-tert-Butyl-benzoyl) -1- (2-dimethylamino-ethyl) -1-methyl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (4-diethylamino-1-methyl-butyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-diethylamino-1-methyl-butyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (4-methyl-benzyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-methyl-benzyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (2-methyl-benzyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (2-methyl-benzyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-propylamino-propyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-propylamino-propyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3-phenethyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-phenethyl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (4-chloro-benzyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-chloro-benzyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-chloro-benzyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-chloro-benzyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3-naphthalen-2-ylmethyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-naphthalen-2-ylmethyl-thiourea),
4-tert-butyl-N- [4- (4-fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide
(4-tert-Butyl-N- [4- (4-fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide),
1- (4-tert-butyl-benzoyl) -3-cyclohexyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-cyclohexyl-thiourea),
1-benzoyl-3-naphthalen-2-ylmethyl-thiourea
(1-Benzoyl-3-naphthalen-2-ylmethyl-thiourea),
1-benzoyl-3- (4-diethylamino-1-methyl-butyl) -thiourea
(1-Benzoyl-3- (4-diethylamino-1-methyl-butyl) -thiourea),
3-benzoyl-1- (2-diethylamino-ethyl) -1-methyl-thiourea
(3-Benzoyl-1- (2-diethylamino-ethyl) -1-methyl-thiourea),
N- (4-Ethyl-piperazine-1-carbosanyl) -4-methyl-benzamide
(N- (4-Ethyl-piperazine-1-carbothioyl) -4-methyl-benzamide),
1-cyclohexyl-3- (4-methyl-benzoyl) -thiourea
(1-Cyclohexyl-3- (4-methyl-benzoyl) -thiourea),
1- (4-Chloro-benzyl) -3- (4-methyl-benzoyl) -thiourea
(1- (4-Chloro-benzyl) -3- (4-methyl-benzoyl) -thiourea),
1- (3-dimethylamino-propyl) -3- (4-methyl-benzoyl) -thiourea
(1- (3-Dimethylamino-propyl) -3- (4-methyl-benzoyl) -thiourea),
1- (4-Methyl-benzoyl) -3- (3-methyl-benzyl) -thiourea
(1- (4-Methyl-benzoyl) -3- (3-methyl-benzyl) -thiourea),
1- (4-Methyl-benzoyl) -3- (4-methyl-phenyl-butyl) -thiourea
(1- (4-Methyl-benzoyl) -3- (4-phenyl-butyl) -thiourea),
1- (4-Methyl-benzoyl) -3- (3-phenyl-propyl) -thiourea
(1- (4-Methyl-benzoyl) -3- (3-phenyl-propyl) -thiourea),
1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -thiourea
(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -thiourea),
1-benzoyl-3- [2- (4-fluoro-phenyl) -ethyl] -thiourea
(1-Benzoyl-3- [2- (4-fluoro-phenyl) -ethyl] -thiourea),
1- (4-Methyl-benzoyl) -3-pyridin-3-ylmethyl-thiourea
(1- (4-Methyl-benzoyl) -3-pyridin-3-ylmethyl-thiourea),
1- (4-Methyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea
(1- (4-Methyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea),
1- [2- (3-Bromo-phenyl) -ethyl] -3- (4-methyl-benzoyl) -thiourea
(1- [2- (3-Bromo-phenyl) -ethyl] -3- (4-methyl-benzoyl) -thiourea),
1- (4-Methyl-benzoyl) -3- (2-pyridin-2-yl-ethyl) -thiourea
(1- (4-Methyl-benzoyl) -3- (2-pyridin-2-yl-ethyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3-pyridin-2-yl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-pyridin-2-yl-thiourea)
1- (4-Chloro-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea
(1- (4-Chloro-benzoyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),
1- (4-Chloro-benzoyl) -3-naphthalen-2-ylmethyl-thiourea
(1- (4-Chloro-benzoyl) -3-naphthalen-2-ylmethyl-thiourea),
1- (4-Chloro-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea
(1- (4-Chloro-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea),
1- (4-phenoxy-benzoyl) -3-pyridin-2-yl-thiourea
(1- (4-Phenoxy-benzoyl) -3-pyridin-2-yl-thiourea),
1- (biphenyl-4-carbonyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea
(1- (Biphenyl-4-carbonyl) -3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),
1- (4'-tert-butyl-biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea
(1- (4'-tert-Butyl-biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea),
1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (naphthalene-2-carbonyl) -thiourea
(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (naphthalene-2-carbonyl) -thiourea),
1- (biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea
(1- (Biphenyl-4-carbonyl) -3- (3-chloro-phenyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (5,6,7,8-tetrahydro-naphthalen-1-yl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (5,6,7,8-tetrahydro-naphthalen-1-yl) -thiourea),
1- (4-tert-butyl-benzoyl) -3-quinolin-5-yl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-quinolin-5-yl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (4-tert-butyl-phenyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-tert-butyl-phenyl) -thiourea),
1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-isopropoxy-benzoyl) -thiourea
(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-isopropoxy-benzoyl) -thiourea),
1- (4-isopropoxy-benzoyl) -3-naphthalen-1-yl-thiourea
(1- (4-Isopropoxy-benzoyl) -3-naphthalen-1-yl-thiourea),
1- (5-hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea
(1- (5-Hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea),
1- (4-isopropoxy-benzoyl) -3-pyridin-2-yl-thiourea
(1- (4-Isopropoxy-benzoyl) -3-pyridin-2-yl-thiourea),
1- (4-isopropoxy-benzoyl) -3-m-tolyl-thiourea
(1- (4-Isopropoxy-benzoyl) -3-m-tolyl-thiourea),
1- (4-tert-butyl-benzoyl) -3 (-4-phenyl-butyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-phenyl-butyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-phenyl-propyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-phenyl-propyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- [2- (2-chloro-phenyl) -ethyl] -thiourea
(1- (4-tert-Butyl-benzoyl) -3- [2- (2-chloro-phenyl) -ethyl] -thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-methyl-benzyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-methyl-benzyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3-quinolin-8-yl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-quinolin-8-yl-thiourea),
1- (4-tert-butyl-benzoyl) -3-pyrazin-2-yl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-pyrazin-2-yl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-hydroxy-phenyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-hydroxy-phenyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (7-hydroxy-naphthalen-1-yl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (7-hydroxy-naphthalen-1-yl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (2-chloro-pyridin-4-yl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (2-chloro-pyridin-4-yl) -thiourea),
1- (4-tert-butyl-benzoyl) -3- (4-hydroxy-biphenyl-3-yl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-hydroxy-biphenyl-3-yl) -thiourea),
1-biphenyl-3-yl-3- (4-tert-butyl-benzoyl) -thiourea
(1-Biphenyl-3-yl-3- (4-tert-butyl-benzoyl) -thiourea),
1- (2-Fluoro-phenyl) -3- (4-isopropoxy-benzoyl) -thiourea
(1- (2-Fluoro-phenyl) -3- (4-isopropoxy-benzoyl) -thiourea),
1- (4-tert-butylphenyl) -3- (4-isopropoxy-benzoyl) -thiourea
(1- (4-tert-Butyl-phenyl) -3- (4-isopropoxy-benzoyl) -thiourea),
1- (biphenyl-3-yl-3- (4-isopropoxy-benzoyl) -thiourea
(1-Biphenyl-3-yl-3- (4-isopropoxy-benzoyl) -thiourea),
1- (7-hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea
(1- (7-Hydroxy-naphthalen-1-yl) -3- (4-isopropoxy-benzoyl) -thiourea),
1- (4-tert-butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea
(1- (4-tert-Butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -thiourea),
1- (4-tert-butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -urea
(1- (4-tert-Butyl-benzyl) -3- (5-hydroxy-naphthalen-1-yl) -urea),
1- (4-tert-butyl-benzyl) -3-cyclohexyl-urea
(1- (4-tert-Butyl-benzyl) -3-cyclohexyl-urea),
1- (4-tert-butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -urea
(1- (4-tert-Butyl-benzoyl) -3- (5-hydroxy-naphthalen-1-yl) -urea),
1- (4-tert-butyl-benzoyl) -3-pyridin-2-yl-urea
(1- (4-tert-Butyl-benzoyl) -3-pyridin-2-yl-urea),
1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -urea
(1- (3-Dimethylamino-2,2-dimethyl-propyl) -3- (4-methyl-benzoyl) -urea),
1-cyclohexyl-3- (4-methyl-benzoyl) -urea
(1-Cyclohexyl-3- (4-methyl-benzoyl) -urea),
1- (4-Methyl-benzoyl) -3-naphthalen-2-ylmethyl-urea
(1- (4-Methyl-benzoyl) -3-naphthalen-2-ylmethyl-urea),
1-benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -urea
(1-Benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -urea),
3-benzoyl-1- (2-dimethylamino-ethyl) -1-methyl-urea
(3-Benzoyl-1- (2-dimethylamino-ethyl) -1-methyl-urea),
1-benzoyl-3-phenyl-thiourea
(1-Benzoyl-3-phenyl-thiourea),
1- (4-tert-butyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-pyridin-2-ylmethyl-thiourea),
1- (4-tert-butyl-benzoyl) -3-pyridin-4-ylmethyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-pyridin-4-ylmethyl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (4-hydroxy-phenyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (4-hydroxy-phenyl) -thiourea), and
1- (4-tert-butyl-benzoyl) -3- (5-hydroxy-naphthalen-2-yl) -thiourea
A compound selected from the group consisting of (1- (4-tert-Butyl-benzoyl) -3- (5-hydroxy-naphthalen-2-yl) -thiourea), or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition for preventing or treating AIDS, comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
N- [4- (4-Fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide
(N- [4- (4-Fluoro-phenyl) -piperazine-1-carbothioyl] -benzamide),
1- (4-tert-butyl-benzoyl) -3-naphthalen-1-yl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-naphthalen-1-yl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (3-chloro-phenyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (3-chloro-phenyl) -thiourea),
1- (4-Methyl-benzoyl) -3-naphthalen-1-yl-thiourea
(1- (4-Methyl-benzoyl) -3-naphthalen-1-yl-thiourea),
1- (4-tert-butyl-benzoyl) -3-naphthalen-1-yl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-naphthalen-1-yl-thiourea),
1- (4-tert-butyl-benzoyl) -3-m-tolyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-m-tolyl-thiourea),
1- (4-tert-butyl-benzoyl) -3- (2-fluoro-phenyl) -thiourea
(1- (4-tert-Butyl-benzoyl) -3- (2-fluoro-phenyl) -thiourea),
4-tert-butyl-N- (4-methyl-piperazine-1-carbothioyl) -benzamide
(4-tert-Butyl-N- (4-methyl-piperazine-1-carbothioyl) -benzamide),
1-benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea
(1-Benzoyl-3- (3-dimethylamino-2,2-dimethyl-propyl) -thiourea),
1-benzoyl-3- (4-methyl-benzyl) -thiourea
(1-Benzoyl-3- (4-methyl-benzyl) -thiourea),
1-benzoyl-3- (3-dimethylamino-propyl) -thiourea
(1-Benzoyl-3- (3-dimethylamino-propyl) -thiourea),
N- (4-Ethyl-piperazine-1-carbosacyl) -benzamide
(N- (4-Ethyl-piperazine-1-carbothioyl) -benzamide),
1-benzoyl-3- (4-chloro-benzyl) -thiourea
(1-Benzoyl-3- (4-chloro-benzyl) -thiourea),
1-benzoyl-3- (2-pyridin-2-yl-ethyl) -thiourea
(1-Benzoyl-3- (2-pyridin-2-yl-ethyl) -thiourea),
1- (4-tert-butyl-benzoyl) -3-phenyl-thiourea
(1- (4-tert-Butyl-benzoyl) -3-phenyl-thiourea),
1- (4-Methyl-benzoyl) -3-pyridin-2-yl-thiourea
(1- (4-Methyl-benzoyl) -3-pyridin-2-yl-thiourea),
1- (4-Methyl-benzoyl) -3-phenyl-thiourea
(1- (4-Methyl-benzoyl) -3-phenyl-thiourea),
1- (4-Chloro-benzoyl) -3-cyclohexyl-thiourea
(1- (4-Chloro-benzoyl) -3-cyclohexyl-thiourea),
1- (4-Chloro-benzoyl) -3-naphthalen-1-yl-thiourea
(1- (4-Chloro-benzoyl) -3-naphthalen-1-yl-thiourea), and
1-benzoyl-3-benzyl-urea
A pharmaceutical composition for preventing or treating AIDS, comprising a compound selected from the group consisting of (1-Benzoyl-3-benzyl-urea), or a pharmaceutically acceptable salt thereof as an active ingredient.