Pyrazole derivatives and processes for the preparation thereof

Details Pyrazole derivatives and processes for the preparation thereof Pyrazole derivatives and processes for the preparation thereof

1997-10-03

1999-11-09

Shah, Mukund J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

544262, A61K 31505, C07D48704

Patent

active

059815337

DESCRIPTION:

BRIEF SUMMARY
The invention relates to 4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives and intermediates and to processes for the preparation thereof, to pharmaceutical formulations comprising such derivatives, and to the use of those derivatives as medicaments.
The invention relates to 4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives of formula I ##STR2## wherein m and n are each independently of the other an integer from 0 up to and including 3, alkanoyloxy, carboxy, lower alkoxycarbonyl, carbamoyl, N-lower alkylcarbamoyl, or lower alkyl that is unsubstituted or substituted by amino or by cyano, it being possible when several phenyl substituents R.sub.1 are present for those substituents to be identical or different from one another, and including 3 and R.sub.7 is hydrogen or lower alkyl, or the group (C[R.sub.3 ]--R.sub.4).sub.q wherein q is an integer from 0 up to and including 3, R.sub.3 is hydrogen or lower alkyl and R.sub.4 is hydrogen or lower alkyl, and R.sub.2 is halogen, nitro, cyano, trifluoromethyl, carboxy, lower alkoxycarbonyl, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylcarbamoyl, azido, amino, lower alkylamino, di-lower alkylamino, di-lower alkylamino-lower alkyleneamino, benzylamino; acylated or sulfonated amino each having up to 10 carbon atoms; hydroxy, lower alkanoyloxy, oxa-lower alkoxy, lower alkoxy that is unsubstituted or substituted by carboxy, lower alkoxycarbonyl, carbamoyl or by N-lower alkylcarbamoyl, or lower alkyl that is unsubstituted or substituted by amino, lower alkanoylamino, benzoylamino, lower alkoxycarbonylamino, sulfonated amino, cyano, hydroxy, lower alkanoyloxy, lower alkoxycarbonyloxy or by lower alkoxy, it being possible when several phenyl substituents R.sub.2 are present for those substituents to be identical or different from one another and for two vicinal radicals R.sub.2 together also to form methylenedioxy, and to salts and tautomers of such compounds.
When m or n is 0, the phenyl ring in question does not carry a substituent R.sub.1 or R.sub.2, respectively. Preferably, m and n are each independently of the other an integer from 0 up to and including 2. When m and/or n is/are 1, the phenyl substituent R.sub.1 and/or R.sub.2 is/are primarily in the 4-position, i.e. in the para-position, or especially in the 3-position, i.e. in the meta-position. When m and/or n is/are 2, the two phenyl substituents R.sub.1 and/or R.sub.2 are preferably in the 3- and 4-positions.
When v is 0, the (R.sub.1).sub.m phenyl radical is bonded directly to the nitrogen atom in the 4-position of the 1H-pyrazolo[3,4-d]pyrimidine derivative.
Halogen R.sub.1 or R.sub.2 is fluorine, bromine, iodine or, preferably, chlorine.
Lower alkoxy R.sub.1 or R.sub.2 is, for example, methoxy.
Lower alkanoyloxy R.sub.1 or R.sub.2 is, for example, acetoxy.
Lower alkoxycarbonyl R.sub.1 or R2 is, for example, methoxycarbonyl.
N-Lower alkylcarbamoyl R.sub.1 or R.sub.2 is, for example, N-methylcarbamoyl.
Lower alkyl R.sub.1 or R.sub.2 that is substituted by amino or by cyano is, for example, --(CH.sub.2).sub.x --NH.sub.2 or --(CH.sub.2).sub.x --CN, wherein x is in each case from 1 to 4.
The group NH(CH--R.sub.7).sub.t that is represented by the symbol X represents, when t is 0, the bivalent group NH. When t is from 1 to 3 and R.sub.7 is hydrogen, the group NH(CH--R.sub.7).sub.t represents the bivalent radicals NHCH.sub.2, NH--CH.sub.2 --CH.sub.2 and NH--CH.sub.2 --CH.sub.2 --CH.sub.2, respectively, each of which is bonded by its nitrogen atom to the pyrazole ring and by its terminal carbon atom to the phenyl ring. When t is 1 and R.sub.7 is lower alkyl, the group NH(CH--R.sub.7).sub.t represents the bivalent radical NH--CH(lower alkyl), for example the radical NH--CH(CH.sub.3). X is preferably NH, NH--CH.sub.2 or NH--CH(CH.sub.3).
The group (C[R.sub.3 ]--R.sub.4).sub.q that is represented by the symbol X is, when q is 1, bonded by the underlined carbon atom (C[R.sub.3 ]--R.sub.4).sub.q both to the pyrazole ring and to the phenyl ring and is preferably CH.sub.2 or CH(lower alkyl). When q in the group (C[R.su

REFERENCES:
patent: 5686457 (1997-11-01), Traxler et al.
G. Dodin, et al., vol. 99, pp. 7257-7265, J. Am. Chem. Soc., 1977.
K. Klem, vol. 114, No. 6, pp. 2001-2018, Chem. Ber., 1981.
Traxler et al., "Use of Pharmacophore Model for the Design of EGF-R Tyrosine Kinase Inhibitors: 4-(Phenylamino) pyrazolo[3,4-d]pyrimidines," J. Med. Chem., vol. 40, No. 22, pp. 3601-3616, Oct. 24, 1997.
Burke, "Protein-Tyrosine Kinases: Potential Targets for Anticancer Drug Development," Stem Cells, vol. 12, pp. 1-6, 1994.

Affiliated with

Also associated with

Rating

Pyrazole derivatives and processes for the preparation thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Pyrazole derivatives and processes for the preparation thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrazole derivatives and processes for the preparation thereof will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1456291