RU98117389A

RU98117389A - CONDENSED PYRROLO (2,3-C) CARBAZOLE-6-ONES THAT ENHANCE THE INTERFERON GAMMA ACTIVITY

Info

Publication number: RU98117389A
Application number: RU98117389/04A
Authority: RU
Inventors: Роберт Л. Хадкинз; Джеймс Л. Диебоулд; Эрнст Найт (младший)
Original assignee: Сефалон, Инк.
Priority date: 1996-02-21
Filing date: 1997-02-20
Publication date: 2000-07-20

Claims

1. Condensed pyrrolo [2,3-c] carbazol-6-one represented by the formula selected from the group consisting of:

where a) R ^{1 is} selected from the group consisting of H, alkyl with 1-4 carbons, substituted or unsubstituted aryl, arylalkyl, heteroaryl, heteroarylalkyl; C (= O) R ⁹ , where R ⁹ represents alkyl with 1-4 carbon or aryl; (CH ₂ ) _n OR ⁹ where n represents an integer of 1-4; OR ¹⁰ where R ¹⁰ represents H or alkyl with 1-4 carbons; (CH ₂ ) _n OR ¹⁴ , where R ¹⁴ represents the amino acid residue after removal of the hydroxyl group of the carboxyl group; OR ¹⁴ , NR ⁷ R ⁸ ; (CH ₂ ) _n NR ⁷ R ^8; and O (CH ₂ ) _n NR ⁷ R ₈ ; and either (1) R ⁷ and R ⁸ independently represent H or alkyl with 1-4 carbons; or (2) R ⁷ and R ^{8 are} joined together to form a linking group of the general formula - (CH ₂ ) ₂ —X ¹ - (CH ₂ ) ₂ -, where X ¹ is O, S or CH ₂ ; b) R ^{2 is} selected from the group consisting of H, SO ₂ R ⁹ , CO ₂ R ⁹ , C (= O) R ⁹ , alkyl with 1-8 carbon, alkenyl with 1-8 carbon, alkynyl with 1-8 carbon and a 5-7 carbon monosaccharide in which each hydroxyl group of said monosaccharide is independently selected from the group consisting of an unsubstituted hydroxyl and a moiety replacing said hydroxyl group selected from H, alkyl with 1-4 carbon, alkylcarbonyloxy with 2-5 carbon and alkoxy with 1-4 carbons; where either 1) each alkyl with 1-8 carbon, alkenyl with 1-8 carbon or alkynyl with 1-8 carbon is unsubstituted; or 2) each alkyl with 1-8 carbon, alkenyl with 1-8 carbon, or alkynyl with 1-8 carbon, independently, is substituted by 1-3 groups selected from the group consisting of aryl with 6-10 carbon, heteroaryl, F, CL, Br, I, CN, NO ₂ , OH, OR ⁹ , O (CH ₂ ) _n NR ⁷ R ⁸ , OCOR ⁹ , OCONHR ⁹ , O-tetrahydropyranyl, NH ₂ , NR ⁷ R ⁸ , NR ¹⁰ CO ₂ R ⁹ ; NR ¹⁰ CONR ⁷ R ⁸ , NHC (= NH) NH ₂ , NR ¹⁰ SO ₂ R ⁹ ; S (O) _y R ¹¹ , where R ¹¹ is H, alkyl with 1-4 carbon, aryl with 6-10 carbon, or heteroaryl; and y is 1 or 2; SR ¹¹ , CO ₂ R ⁹ , CONR ⁷ R ⁸ , CHO, COR ⁹ , CH ₂ OR ⁷ , CH ₂ OR ⁹ CH = NNR ¹¹ R ¹² , CH = NOR ¹¹ , CH = NR ⁹ CH = NNHCH (N = NH ) NH ₂ ; SO ₂ NR ¹² R ¹³ , where either (1a) R ¹² and R ¹³ independently represent H, alkyl with 1-4 carbon, aryl with 6-10 carbon or heteroaryl; or (2a) R ¹² and R ^{13 are} joined together to form - (CH ₂ ) ₂ —X ¹ - (CH ₂ ) ₂ linking group; PO (OR ¹¹ ) ₂ , NHR ¹⁴ , HR ¹⁰ R ¹⁴ , OR ¹⁴ and a monosaccharide with 5-7 carbon, in which each hydroxyl group of the specified monosaccharide is independently selected from the group consisting of unsubstituted hydroxyl and a fragment replacing the specified hydroxyl group selected from H, alkyl with 1-4 carbon, alkylcarbonyloxy with 2-5 carbon and alkoxy with 1-4 carbon; c) each R ³ and R ⁴ is independently selected from the group consisting of H, aryl with 6-10 carbons, heteroaryl, F, Cl, Br, I, CN, CF ₃ , NO ₂ , OH, OR ⁹ , O (CH ₂ ) _n NR ⁷ R ⁸ , OCOR ⁹ , OCONHR ⁹ NH ₂ , (CH ₂ ) _n OR ¹⁰ , (CH ₂ ) _n OR ¹⁴ ,
OR ¹⁴ , NHR ¹⁴ , NR ⁷ R ⁸ NR ⁷ (CH ₂ ) _n NR ⁷ R ⁸ , NR ¹⁰ COR ⁹ , NR ¹⁰ CONR ⁷ R ⁸ , SR ¹¹ , S (O) _y R ¹¹ ,
CO ₂ R ⁹ , COR ⁹ , CONR ⁷ R ⁸ , CHO, CH = NOR ¹¹ , CH = NR ⁹ , CH = NNR ¹¹ R ¹² , (CH ₂ ) _n SR ⁹ , (CH ₂ ) _n S (O) _y R ⁹ ; CH ₂ SR ¹⁵ where R ¹⁵ represents alkyl with 1-4 carbon; CH ₂ S (O) _y R ¹⁴ , (CH ₂ ) _n NR ⁷ R ⁸ , (CH ₂ ) _n NHR ¹⁴ , alkyl with 1-8 carbon, alkenyl with 1-8 carbon and alkynyl with 1-8 carbon; and either 1) each alkyl with 1-8 carbon, alkenyl with 1-8 carbon or alkynyl with 1-8 carbon is unsubstituted, or 2) each alkyl with 1-8 carbon, alkenyl with 1-8 carbon or alkynyl with 1- 8 carbon is independently substituted as described above in b) 2); d) R ^{5 is} selected from the group consisting of alkyl with 1-8 carbon, alkenyl with 1-8 carbon and alkynyl with 1-8 carbon; and either 1) each alkyl, alkenyl or alkynyl group is unsubstituted; or 2) each alkyl, alkenyl or alkynyl group is substituted by 1-3 groups selected from the group consisting of F, Cl, Br, I, CN, CF ₃ , NO ₂ , OH, OR ⁹ , O (CH ₂ ) _n NR ⁷ R ⁸ , OCOR ⁹ , OCONHR ⁹ NH ₂ , (CH ₂ ) _n OR ⁹ , (CH ₂ ) _n OR ¹⁴ , NR ⁷ R ⁸ , NR ⁷ (CH ₂ ) _n NR ⁷ R ⁸ , NR ¹⁰ COR ⁹ , NR ¹⁰ CONR ⁷ R ⁸ , SR ¹¹ , S (O) _y R ¹¹ , CO ₂ R ⁹ , COR ⁹ , CONR ⁷ R ⁸ , CHO, CH = NOR ¹¹ , CH = NR ⁹ , CH = NNR ¹¹ R ¹² , (CH ₂ ) _n SR ⁹ , (CH ₂ ) _n S (O) _y R ⁹ CH ₂ SR ¹⁵ , CH ₂ S (O) _y R ¹⁴ , (CH ₂ ) _n NR ⁷ R ⁸ and (CH ₂ ) _n NHR ¹⁴ ; e) X is selected from the group consisting of -N-, -O-, -S-, -S (= O) -, -S (= O) ₂ -, alkylene with 1-3 carbons, -C (= O ) -, -C (R ² ) = C (R ² ) -, -C (R ² ) ₂ -, -CH = CH-, -CH (OH) -CH (OH) -, -C (= NOR ¹¹ ) -, -C (OR ¹¹ ) (R ¹¹ ) -, -C (= O) CH (R ¹⁵ ) -, -CH (R ¹⁵ ) C (= O) -, -CH ₂ -Z-, -Z -CH ₂ -, -CH ₂ ZCH ₂ -, where Z is selected from the group consisting of -C (OR ¹¹ ) (R ¹¹ ) -, O, S, C (= O) and NR ¹¹ ; and alkylene with 1-3 carbons substituted by a group selected from the group consisting of one R ⁵ substituent group, SR ¹⁰ , OR ¹⁰ , OR ¹⁴ , R ¹⁵ , phenyl, naphthyl and arylalkyl with 7-14 carbons.

2. The compound according to claim 1, where R ⁹ selected from the group consisting of alkyl with 1-4 carbons, phenyl, and naphthyl.

3. The compound according to claim 1, where R ¹¹ , R ¹² , and R ¹³ are each independently selected from the group consisting of H, alkyl with 1-4 carbons, phenyl, naphthyl, and heteroaryl.

4. The compound according to claim 1, where R ^{1 is} selected from the group consisting of H, alkyl with 1-4 carbons, substituted phenyl, unsubstituted phenyl, OR ¹⁰ and O (CH ₂ ) _n NR ⁷ R ⁸ .

5. The compound according to claim 1, where R ² selected from the group consisting of H, C (= O) R ⁹ , alkyl with 1-8 carbon and alkyl with 1-8 carbon, substituted by one group selected from the group consisting of from OR ⁹ , OH, OCOR ⁹ , NR ⁷ R ⁸ , NH ₂ , NR ¹⁰ COR ⁹ and NR ¹⁰ R ¹⁴ .

6. The compound according to claim 1, where R ³ and R ⁴ each independently selected from the group consisting of H, halogen, CN, OH, OR ⁹ , OR ¹⁴ , NH ₂ , NR ⁷ R ⁸ , (CH ₂ ) _n OR ¹⁰ , (CH ₂ ) _n OR ¹⁴ , COR ⁹ , NR ¹⁰ COR ⁹ , NHR ¹⁴ and O (CH ₂ ) _n NR ⁷ R ⁸ .

7. The compound according to claim 1, where R ⁵ selected from the group consisting of H and alkyl with 1-4 carbons.

8. The compound according to claim 1, where X is selected from the group consisting of -N-, -O-, -S-, alkylene with 1-3 carbons, -C = O-, -CH ₂ -Z- and -Z -CH ₂ .

9. The compound of claim 8, wherein X is selected from the group consisting of —N—, —O—, —S—, and —CH ₂ -.

10. The compound according to claim 9, where R ¹ , R ² , R ³ , R ⁴ and R ⁵ each represents N.

11. The compound according to claim 1, represented by formula I.

12. The compound according to claim 11, where R ^{1 is} selected from the group consisting of H, alkyl with 1-4 carbons, substituted phenyl, unsubstituted phenyl, OR ¹⁰ and O (CH ₂ ) _n NR ⁷ R ⁸ .

13. The compound of claim 11, wherein R ^{2 is} selected from the group consisting of H, C (= O) R ⁹ , alkyl with 1-8 carbons and alkyl with 1-8 carbons, substituted with one group selected from the group consisting of from OR ⁹ , OH, OCOR ⁹ , NR ⁷ R ⁸ , NH ₂ , NR ¹⁰ COR ⁹ and NR ¹⁰ R ¹⁴ .

14. The compound of claim 11, wherein R ³ and R ⁴ are each independently selected from the group consisting of H, halogen, CN, OH, OR ⁹ , OR ¹⁴ , NH ₂ , NR ⁷ R ⁸ , (CH ₂ ) _n OR ¹⁰ , (CH ₂ ) _n OR ¹⁴ , COR ⁹ , NR ¹⁰ COR ⁹ , NHR ¹⁴ and O (CH ₂ ) _n NR ⁷ R ⁸ .

15. The compound according to claim 11, where R ⁵ selected from the group consisting of H and alkyl with 1-4 carbons.

16. The compound according to claim 11, where X is selected from the group consisting of -N-, -O-, -S-, alkylene with 1-3 carbons, -C = O-, -CH ₂ -Z- and -Z -CH ₂ -.