194350-95-3

The invention discloses a synthesis process for 4-(4-ethyl-4,7-diazaspiro[3,3]octyl)-2-nitroaniline. The synthesis process comprises the following concrete steps: step 1, reacting 2-piperazinone and aposition-4 nitrogen-protected derivative thereof with ethyl bromide under basic conditions so as to obtain a compound 1; step 2, reacting the compound 1 with a titanium catalyst so as to obtain a compound 2; step 3, subjecting the compound 2 to deprotection to produce the free base 1-ethyl-2-cyclopropyl-piperazine or a hydrochloride thereof; step 4, reacting 1-ethyl-2-cyclopropyl-piperazine or the hydrochloride thereof with a compound 3 so as to obtain a compound 4 is obtained; and step 5, subjecting the compound 4 to deprotection so as to obtain the product 4-(4-ethyl-4,7-diazaspiro[3,3]octyl)-2-nitroaniline. The synthesis process of the invention is simple in synthesis conditions and uses cheap raw materials; and through the selection of a deprotecting agent, the formation of by-products can be reduced, and the yield of the product can be increased, as high as 80%.

The invention discloses a new class of containing piperazinone quinazoline - 2, 4 (1 H, 3 H) - dione PARP - 1/2 inhibitor, and its preparation and pharmaceutical composition and use. Specifically, the invention relates to the general formula I shown containing of the piperazinone quinazoline - 2, 4 (1 H, 3 H) - dione derivatives and their pharmaceutically acceptable salt, and its preparation method, comprising one or more of the compounds of the composition, and the compounds in the preparation, the prevention and/or treatment with PARP - 1/2 of a disease associated with the use of the medicament. (by machine translation)

The present disclosure provides compounds of Formula (LA) and/ or pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BTK, and are potentially useful for the treatment of diseases treatable by inhibition of ty r-osine kinases such as cancer, inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and/or pharmaceutically acceptable salts thereof and processes for preparing such compounds and p h ar-maceutically acceptable salts thereof

Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2′ pocket.

A series of 2-oxopiperazine, 4-aminomethyl-, 3-amino- and 3-aminomethylpiperidine analogues of DM235 (sunifiram) and MN19 (sapunifiram), two previously reported potent cognition-enhancers, have been synthesized and tested in the mouse passive-avoidance test. The compounds display minimal effective doses in the range 0.3-10 mg/kg. Although the new substances do not show improved activity when compared to the parent compounds, some useful information has been obtained to understand structure-activity relationships. In addition, the 3-aminopiperidine moiety appears to be a promising scaffold to synthesize new drugs endowed with cognition-enhancing activity.

A compound represented by formula (I): (wherein Ar1 represents a phenyl group which may have 1 to 3 substituents, or a non-substituted 5- or 6-membered aromatic heterocyclic group; Ar2 represents (i) a non-substituted phenyl group, (ii) a phenyl group which has been substituted by a lower alkyl group having 1 to 3 groups or atoms selected from among a carbamoyl group, an amino group, a hydroxyl group, a lower alkoxy group, and a halogen atom, or (iii) a 5- or 6-membered nitrogen-containing aromatic heterocyclic group which has been substituted by 1 to 3 groups or atoms selected from among a lower alkyl group, a lower alkynyl group, a lower alkanoyl group, a carbamoyl group, a cyano group, an amino group, a hydroxyl group, a lower alkoxy group, and a halogen atom; and X represents a group represented by formula (II): (wherein the ring structure represents a 4- to 7-membered heterocyclic group which may have, in addition to the nitrogen atom shown in formula (II), one heteroatom selected from among nitrogen, oxygen, and sulfur, and which may be substituted by 1 to 4 groups or atoms selected from among a lower alkyl group, a carbamoyl group, an amino group, a hydroxyl group, a lower alkoxy group, an oxo group, a lower alkanoyl group, a lower alkylsulfonyl group, and a halogen atom)), a salt thereof, a solvate of the compound or the salt, and a drug.

A compound represented by Formula (I): wherein Ar1 represents Formula (II): Ar2 represents a 5- or 6-membered aromatic heterocyclic group which may be substituted; and X represents Formula (III): a salt thereof, or a solvate of the compound or the salt. A potent platelet aggregation suppressant which does not inhibit COX-1 and COX-2 is provided.

PCT No. PCT/GB97/00169 Sec. 371 Date Jul. 27, 1998 Sec. 102(e) Date Jul. 27, 1998 PCT Filed Jan. 21, 1997 PCT Pub. No. WO97/27188 PCT Pub. Date Jul. 31, 1997The invention concerns a compound of formula (I) wherein: R1 is of the formula -NHC(=O)(1-4C)alkyl, -NHS(O)n(1-4C)alkyl wherein n is 0, 1 or 2 or R1 is hydroxy; R2 and R3 are independently hydrogen or fluoro; R4 is hydrogen, methyl, ethyl or oxo; R5 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or of the formula R6(CH2)m- wherein either m is 1-4 and R6 is, for example, trifluoromethyl, difluoromethyl, fluoromethyl, (1-4C)alkoxy, (1-4C)alkyl S(O)p- wherein p is 0, 1 or 2, (1-6C)alkanoyloxy, di-(+E,uns N+EE -(1-4C)alkyl)amino, +E,uns N+EE -((1-4C)alkyl)(1-4C)alkanoylamino, cyano, carboxy, (1-4C)alkoxycarbonyl, carbamoyl, di-(+E,uns N+EE -(1-4C)alkyl)carbamoyl, +E,uns N+EE -((1-4C)alkyl)(1-4C)alkanesulphonamido, +E,uns N+EE 1-((1-4C)alkyl)-di-(+E,uns N+EE 3-(1-4C)alkyl)ureido, or of the formula -OC(=O)NR7(R8) or -N(R9)SO2NR7(R8) wherein R7 and R8 are independently hydrogen or (1-4C)alkyl and R9 is (1-4C)alkyl; or m is 2-4 and R6 is, for example, hydroxy, (1-4C)alkanoylamino, amino, (1-4C)alkylamino, (1-4C)alkanesulphonamido, ureido, di-(+E,uns N+EE 3-(1-4C)alkyl)ureido or of the formula -NHSO2NR7(R8); and pharmaceutically-acceptable salts thereof; processes for their preparation; pharmaceutical compositions containing them and their use as antibacterial agents.