The invention relates to a novel process for preparing Spiro derivatives, in particular 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one, and to novel intermediates for use in said process along with processes for preparing said intermediates.

This invention relates to cocrystals of naloxone and of naltrexone and their use as opioid antagonists. The cocrystals of the invention include naloxone isonicotinamide cocrystal, naloxone hydrochloride piperazine cocrystal, naltrexone menthol cocrystal, naltrexone thymine cocrystal, naltrexone 2,5-dihydroxybenzoic acid cocrystal, naltrexone salicylic acid cocrystal, naltrexone hydrochloride piperazine cocrystal and naltrexone hydrochloride sulfathiazole cocrystal. A drug-in¬ adhesive transdermal patch containing the opioid analgesic fentanyl or an analog thereof and a cocrystal of naloxone or naltrexone is disclosed. Also disclosed is a method of treating pain, such as acute, chronic or intermittent pain, by applying a drug-in-adhesive transdermal patch of the invention to the skin of a patient in need thereof. Also disclosed is an improved transdermal patch for administering fentanyl or an analog thereof, or for administering a mu opioid agonist, the improvement wherein the transdermal patch contains a cocrystal of the invention in an abuse limiting amount. The improved transdermal patch may be a drug-in-adhesive transdermal patch or a reservoir transdermal patch.

This invention relates to cocrystals of naloxone and of naltrexone and their use as opioid antagonists. The cocrystals of the invention include naloxone isonicotinamide cocrystal, naloxone hydrochloride piperazine cocrystal, naltrexone menthol cocrystal, naltrexone thymine cocrystal, naltrexone 2,5-dihydroxybenzoic acid cocrystal, naltrexone salicylic acid cocrystal, naltrexone hydrochloride piperazine cocrystal and naltrexone hydrochloride sulfathiazole cocrystal. A drug-in¬ adhesive transdermal patch containing the opioid analgesic fentanyl or an analog thereof and a cocrystal of naloxone or naltrexone is disclosed. Also disclosed is a method of treating pain, such as acute, chronic or intermittent pain, by applying a drug-in-adhesive transdermal patch of the invention to the skin of a patient in need thereof. Also disclosed is an improved transdermal patch for administering fentanyl or an analog thereof, or for administering a mu opioid agonist, the improvement wherein the transdermal patch contains a cocrystal of the invention in an abuse limiting amount. The improved transdermal patch may be a drug-in-adhesive transdermal patch or a reservoir transdermal patch.

Provided herein are free base crystalline forms, crystalline salts, and an amorphous salts of omecamtiv mecarbil.

Disclosed are a carboxylate represented by formula (I), and a carboxylic acid generator and a resist composition, including the same:

##STR00001## wherein R.sup.1 represents a fluorine atom or a fluorinated alkyl group having 1 to 4 carbon atoms; R.sup.2, R.sup.3 and R.sup.4 each independently represent a halogen atom, a fluorinated alkyl group having 1 to 4 carbon atoms or a hydrocarbon group having 1 to 12 carbon atoms, and —CH.sub.2— included in the hydrocarbon group may be replaced by —O— or —CO—; m2 and m3 represent an integer of 0 to 4, and m4 represents an integer of 0 to 5; and X.sup.0 represents a hydrocarbon group having 1 to 72 carbon atoms which may have a substituent, and —CH.sub.2— included in the hydrocarbon group may be replaced by —O—, —S—, —CO— or —SO.sub.2—.

Disclosed are a carboxylate represented by formula (I), and a carboxylic acid generator and a resist composition, including the same:

##STR00001## wherein R.sup.1 represents a fluorine atom or a fluorinated alkyl group having 1 to 4 carbon atoms; R.sup.2, R.sup.3 and R.sup.4 each independently represent a halogen atom, a fluorinated alkyl group having 1 to 4 carbon atoms or a hydrocarbon group having 1 to 12 carbon atoms, and —CH.sub.2— included in the hydrocarbon group may be replaced by —O— or —CO—; m2 and m3 represent an integer of 0 to 4, and m4 represents an integer of 0 to 5; and X.sup.0 represents a hydrocarbon group having 1 to 72 carbon atoms which may have a substituent, and —CH.sub.2— included in the hydrocarbon group may be replaced by —O—, —S—, —CO— or —SO.sub.2—.

A resist composition comprising a quencher containing a sulfonium salt having the formula (A).

##STR00001##

A resist composition comprising a quencher containing a sulfonium salt having the formula (A).

##STR00001##

A radiation-sensitive resin composition includes a polymer including a phenolic hydroxyl group, a compound represented by formula (1-1) or formula (1-2), and a compound represented by formula (2). In the formula (1-1), a sum of a, b, and c is no less than 1; at least one of R.sup.1, R.sup.2, and R.sup.3 represents a fluorine atom or the like; and R.sup.4 and R.sup.5 each independently represent a hydrogen atom, a fluorine atom, or the like. In the formula (1-2), in a case in which d is 1, R.sup.6 represents a fluorine atom or the like, and in a case in which d is no less than 2, at least one of the plurality of R.sup.6s represents a fluorine atom or the like; and R.sup.8 represents a single bond or a divalent organic group having 1 to 20 carbon atoms.

##STR00001##

A radiation-sensitive resin composition includes a polymer including a phenolic hydroxyl group, a compound represented by formula (1-1) or formula (1-2), and a compound represented by formula (2). In the formula (1-1), a sum of a, b, and c is no less than 1; at least one of R.sup.1, R.sup.2, and R.sup.3 represents a fluorine atom or the like; and R.sup.4 and R.sup.5 each independently represent a hydrogen atom, a fluorine atom, or the like. In the formula (1-2), in a case in which d is 1, R.sup.6 represents a fluorine atom or the like, and in a case in which d is no less than 2, at least one of the plurality of R.sup.6s represents a fluorine atom or the like; and R.sup.8 represents a single bond or a divalent organic group having 1 to 20 carbon atoms.

##STR00001##